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  • 1.
    Al-Shamkhi, Nasrin
    et al.
    Department of Internal Medicine, Örebro University Hospital and School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Endocrinology and Diabetology, Uppsala University Hospital, Uppsala, Sweden.
    Berinder, Katarina
    Department of Endocrinology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Borg, Henrik
    Department of Endocrinology, Skåne University Hospital, Lund University, Lund, Sweden.
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Höybye, Charlotte
    Department of Endocrinology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Olsson, Daniel S.
    Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Ragnarsson, Oskar
    Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Göteborg, Sweden.
    Ekman, Bertil
    Departments of Endocrinology in Linköping and Norrköping, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Engström, Britt Eden
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
    Pituitary function before and after surgery for nonfunctioning pituitary adenomas-data from the Swedish pituitary register2023In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 189, no 2, p. 217-224Article in journal (Refereed)
    Abstract [en]

    Objective: Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA).

    Design and methods: Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded.

    Results: Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm(3). Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively.

    Conclusions: Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.

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  • 2.
    Arlien-Søborg, Mai C.
    et al.
    Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
    Dal, Jakob
    Department of Endocrinology, Aalborg University Hospital, Aarhus, Denmark; Steno Diabetes Center North Jutland, Aalborg, Denmark.
    Heck, Ansgar
    Oslo University Hospital, Oslo, Norway.
    Stochholm, Kirstine
    Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
    Husted, Eigil
    Department of Endocrinology, Aalborg University Hospital, Aarhus, Denmark.
    Feltoft, Claus Larsen
    Copenhagen University Hospital—Herlev and Gentofte, Kobenhavn, Denmark.
    Rasmussen, Åse Krogh
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Feldt-Rasmussen, Ulla
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Andreassen, Mikkel
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Klose, Marianne Christina
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Nielsen, Torben Leo
    Odense University Hospital, Odense, Denmark.
    Andersen, Marianne Skovsager
    Odense University Hospital, Odense, Denmark.
    Christensen, Louise Lehmann
    Odense University Hospital, Odense, Denmark.
    Krogh, Jesper
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Jarlov, Anne
    Copenhagen University Hospital, Kobenhavn, Denmark.
    Bollerslev, Jens
    Oslo University Hospital, Oslo, Norway.
    Nermoen, Ingrid
    Akershus University Hospital, lørenskog, Norway.
    Oksnes, Marianne
    Haukeland University Hospital, Bergen, Norway.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Norrlands University Hospital, Umeå, Sweden.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Norrlands University Hospital, Umeå, Sweden.
    Berinder, Katarina
    Karolinska University Hospital, Sweden.
    Hoybye, Charlotte
    Karolinska University Hospital, Sweden.
    Petersson, Maria
    Karolinska University Hospital, Sweden.
    Akerman, Anna-karin
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Sweden; Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Wahlberg, Jeanette
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ekman, Bertil
    Department of Endocrinology and the Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Engstrom, Britt Eden
    Uppsala University Hospital, Uppsala, Sweden.
    Johannsson, Gudmundur
    Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg & Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ragnarsson, Oskar
    Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Olsson, Daniel
    Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg & Sahlgrenska University Hospital, Gothenburg, Sweden; Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Sigurjónsdóttir, Helga Ágústa
    The National University Hospital of Iceland, Gothenburg, Iceland; School of Medicine, University of Iceland, Reykjavik, Iceland.
    Fougner, Stine Lyngvi
    Department of Endocrinology, St. Olavs hospital, Trondheim University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Matikainen, Niina
    Helsinki University Hospital, Helsinki, Finland.
    Vehkavaara, Satu
    Helsinki University Hospital, Helsinki, Finland.
    Metso, Saara
    Tampere University Hospital, Tampere, Finland.
    Jaatinen, Pia
    Tampere University Hospital, Tampere, Finland.
    Hämäläinen, Päivi
    Tampere University Hospital, Tampere, Finland.
    Rintamäki, Reeta
    Kuopio University Hospital, Kuopio, Finland.
    Yliaska, Iina
    Oulu University Hospital, Oulu, Finland.
    Immonen, Heidi
    Turku University Hospital, Turku, Finland.
    Mäkimattila, Sari
    Helsinki University Hospital, Helsinki, Finland.
    Cederberg-Tamminen, Henna
    Helsinki University Hospital, Helsinki, Finland.
    Viukari, Marianna
    Helsinki University Hospital, Helsinki, Finland.
    Nevalainen, Pasi
    Tampere University Hospital, Tampere, Finland.
    Nuutila, Pirjo
    Turku University Hospital, Turku, Finland.
    Schalin-Jäntti, Camilla
    Helsinki University Hospital, Helsinki, Finland.
    Burman, Pia
    Skåne University Hospital, Lund University, Malmö, Sweden.
    Jørgensen, Jens Otto Lunde
    Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
    Acromegaly management in the nordic countries: a Delphi consensus survey2024In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265Article in journal (Refereed)
    Abstract [en]

    Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.

    Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.

    Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.

    Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

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  • 3.
    Arnardóttir, Steinunn
    et al.
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department of Endocrinology and Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Järås, Jacob
    Regional Cancer Center (RCC) Stockholm Gotland, Stockholm, Sweden.
    Burman, Pia
    Department of Endocrinology, Skånes University Hospital, University of Lund, Malmö, Sweden.
    Berinder, Katarina
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Erfurth, Eva Marie
    Department of Endocrinology, Skånes University Hospital, University of Lund, Malmö, Sweden.
    Höybye, Charlotte
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Larsson, Karin
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department of Endocrinology and Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Ragnarsson, Oskar
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ekman, Bertil
    Department of Endocrinology in Linköping, Department of Internal Medicine in Norrköping, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Edén Engström, Britt
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department of Endocrinology and Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Long-term outcomes of patients with acromegaly: a report from the Swedish Pituitary Register2022In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 186, no 3, p. 329-339Article in journal (Refereed)
    Abstract [en]

    Objective: To describe the treatment and long-term outcomes of patients with acromegaly from all healthcare regions in Sweden.

    Design and methods: Analysis of prospectively reported data from the Swedish Pituitary Register of 698 patients (51% females) with acromegaly diagnosed from 1991 to 2011. The latest clinical follow-up date was December 2012, while mortality data were collected for 28.5 years until June 2019.

    Results: The annual incidence was 3.7/million; 71% of patients had a macroadenoma, 18% had visual field defects, and 25% had at least one pituitary hormone deficiency. Eighty-two percent had pituitary surgery, 10% radiotherapy, and 39% medical treatment. At the 5- and 10-year follow-ups, insulin-like growth factor 1 levels were within the reference range in 69 and 78% of patients, respectively. In linear regression, the proportion of patients with biochemical control including adjuvant therapy at 10 years follow-up increased over time by 1.23% per year. The standardized mortality ratio (SMR) (95% CI) for all patients was 1.29 (1.11-1.49). For patients with biochemical control at the latest follow-up, SMR was not increased, neither among patients diagnosed between 1991 and 2000, SMR: 1.06 (0.85-1.33) nor between 2001 and2011, SMR: 0.87 (0.61-1.24). In contrast, non-controlled patients at the latest follow-up from both decades had elevated SMR, 1.90 (1.33-2.72) and 1.98 (1.24-3.14), respectively.

    Conclusions: The proportion of patients with biochemical control increased over time. Patients with biochemically controlled acromegaly have normal life expectancy, while non-controlled patients still have increased mortality. The high rate of macroadenomas and unchanged age at diagnosis illustrates the need for improvements in the management of patients with acromegaly.

  • 4. Bengtsson, Daniel
    et al.
    Ragnarsson, Oskar
    Berinder, Katarina
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Edén Engström, Britt
    Ekman, Bertil
    Höybye, Charlotte
    Burman, Pia
    Wahlberg, Jeanette
    Psychotropic drugs in patients with Cushing's disease before diagnosis and at long-term follow-up: a nationwide study2021In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, no 6, p. 1750-1760Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Psychiatric symptoms are common in Cushing's disease (CD) and seem only partly reversible following treatment.

    OBJECTIVE: To investigate drug dispenses associated to psychiatric morbidity in CD patients before treatment and during long-term follow-up.

    DESIGN: Nationwide longitudinal register-based study.

    SETTING: University Hospitals in Sweden.

    SUBJECTS: CD patients diagnosed between 1990 and 2018 (N=372) were identified in the Swedish Pituitary Register. Longitudinal data was collected from 5 years before, at diagnosis and during follow-up. Four matched controls per patient were included. Cross-sectional subgroup analysis of 76 patients in sustained remission was also performed.

    MAIN OUTCOME MEASURES: Data from the Swedish Prescribed Drug Register and the Patient Register.

    RESULTS: In the 5-year period before, and at diagnosis, use of antidepressants (OR 2.2[95%CI 1.3-3.7] and 2.3[1.6-3.5]), anxiolytics (2.9[1.6-5.3] and 3.9[2.3-6.6]) and sleeping pills (2.1[1.2-3.7] and 3.8[2.4-5.9]) was more common in CD than controls. ORs remained elevated at 5-year follow-up for antidepressants (2.4[1.5-3.9]) and sleeping pills (3.1[1.9-5.3]). Proportions of CD patients using antidepressants (26%) and sleeping pills (22%) were unchanged at diagnosis and 5-year follow-up, whereas drugs for hypertension and diabetes decreased. Patients in sustained remission for median 9.3 years (IQR 8.1-10.4) had higher use of antidepressants (OR 2.0[1.1-3.8]) and sleeping pills (2.4[1.3-4.7]), but not of drugs for hypertension.

    CONCLUSIONS: Increased use of psychotropic drugs in CD was observed before diagnosis and remained elevated regardless of remission status, suggesting persisting negative effects on mental health. The study highlights the importance of early diagnosis of CD, and the need for long-term monitoring of mental health.

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  • 5.
    Bengtsson, Daniel
    et al.
    Department Of Biomedical And Clinical Sciences, Linköping University, Linköping, Sweden.
    Ragnarsson, Oskar
    Department Of Internal Medicine And Clinical Nutrition, Institute Of Medicine, Sahlgrenska Academy, University Of Gothenburg, Gothenburg, Sweden; Department Of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Berinder, Katarina
    Department Of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department Of Molecular Medicine And Surgery, Karolinska Institutet, Stockholm, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Edén Engström, Britt
    Department Of Medical Sciences Endocrinology And Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department Of Endocrinology And Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Ekman, Bertil
    Department Of Endocrinology, Linköping University, Linköping, Sweden; Department Of Health Medicine And Caring Sciences, Linköping University, Linköping, Sweden.
    Höybye, Charlotte
    Department Of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department Of Molecular Medicine And Surgery, Karolinska Institutet, Stockholm, Sweden.
    Järås, Jacob
    Regional Cancer Centre, Stockholm/Gotland, Stockholm, Sweden.
    Valdemarsson, Stig
    Department Of Clinical Sciences, Skåne University Hospital, University Of Lund, Lund, Sweden.
    Burman, Pia
    Department Of Endocrinology, Skåne University Hospital, University Of Lund, Malmö, Sweden.
    Wahlberg, Jeanette
    Department Of Endocrinology, Linköping University, Linköping, Sweden; Department Of Health Medicine And Caring Sciences, Linköping University, Linköping, Sweden; Faculty Of Medical Sciences, Örebro University, Örebro, Sweden.
    Increased Mortality Persists after Treatment of Cushing's Disease: A Matched Nationwide Cohort Study2022In: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 6, no 6, article id bvac045Article in journal (Refereed)
    Abstract [en]

    Context: Whether biochemical remission normalizes life expectancy in Cushing's disease (CD) patients remains unclear. Previous studies evaluating mortality in CD are limited by using the expected number of deaths in the background population instead of the actual number in matched controls. Objective and setting: To study mortality by time-to-event analysis in an unselected nationwide CD patient cohort. Design and participants: Longitudinal data from the Swedish Pituitary Register of 371 patients diagnosed with CD from 1991 to 2018 and information from the Swedish Cause of Death Register were evaluated. Four controls per patient (n = 1484) matched at the diagnosis date by age, sex, and residential area were included. Main outcome measures: Mortality and causes of death. Results: The median diagnosis age was 44 years (interquartile range 32-56), and the median follow-up was 10.6 years (5.7-18.0). At the 1-, 5-, 10-, 15-, and 20-year follow-ups, the remission rates were 80%, 92%, 96%, 91%, and 97%, respectively. Overall mortality was increased in CD patients compared with matched controls [hazard ratio (HR) 2.1 (95% CI 1.5-2.8)]. The HRs were 1.5 (1.02-2.2) for patients in remission at the last follow-up (n = 303), 1.7 (1.03-2.8) for those in remission after a single pituitary surgery (n = 177), and 5.6 (2.7-11.6) for those not in remission (n = 31). Cardiovascular diseases (32/66) and infections (12/66) were overrepresented causes of death. Conclusions: Mortality was increased in CD patients despite biochemical remission compared to matched controls. The study highlights the importance of careful comorbidity monitoring, regardless of remission status.

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  • 6.
    Bergthorsdottir, Ragnhildur
    et al.
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Esposito, Daniela
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Olsson, Daniel S.
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden; Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Ragnarsson, Oskar
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden; Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bensing, Sophie
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital Stockholm, Sollentuna, Sweden.
    Nåtman, Jonatan
    Centre of Registers Västra Götaland, Gothenburg, Sweden.
    Johannsson, Gudmundur
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nyberg, Fredrik
    School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Increased risk of hospitalization, intensive care and death due to covid-19 in patients with adrenal insufficiency: a Swedish nationwide study2024In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 295, no 3, p. 322-330Article in journal (Refereed)
    Abstract [en]

    Background: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown.

    Methods: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis.

    Results: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59–2.43), intensive care admission (2.76, 1.49–5.09) and death (2.29, 1.60–3.28).

    Conclusion: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.

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  • 7.
    Berndt, Vendela
    et al.
    Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    de Verdier, Jennie
    Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden.
    Ryberg, Henrik
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden.
    Ragnarsson, Oskar
    Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    The diagnostic value of salivary cortisol and salivary cortisone in patients with suspected hypercortisolism2022In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 13, article id 1028804Article in journal (Refereed)
    Abstract [en]

    Background: Diagnosing endogenous hypercortisolism remains a challenge, partly due to a lack of biochemical tests with good diagnostic accuracy. Objectives: To evaluate the diagnostic value of salivary cortisol and cortisone in patients with suspected hypercortisolism. Methods: Retrospective study including 155 patients with adrenal incidentaloma, and 54 patients with suspected Cushing's syndrome (CS). Salivary samples were collected at home, at 11 p.m., and at 8 a.m. following an over-night dexamethasone suppression test (DST). Salivary cortisol and cortisone were measured with liquid chromatography-tandem mass spectrometry. Results: Ten of 155 patients with adrenal incidentaloma were considered to have autonomous cortisol secretion (ACS). Using previously established cut-offs, all patients with ACS had elevated plasma-cortisol (>50 nmol/L) following DST, 9/10 had elevated late-night salivary cortisone (>15 nmol/L) whereas only 4/10 had elevated late-night salivary cortisol (LNSC; >3 nmol/L) compared to 35%, 9% and 8%, respectively, of the 145 patients with non-functioning adrenal incidentaloma. Six (60%) patents with ACS had elevated salivary cortisol and cortisone at 8 a.m. following DST compared to 9% and 8%, respectively, of patients with non-functioning adrenal incidentaloma. One of 6 patients with overt CS had a normal LNSC and one had normal late-night salivary cortisone, while all had increased salivary cortisol and cortisone following DST. Conclusion: LNSC is not sufficiently sensitive or specific to be used for screening patients with suspected hypercortisolism. Instead, late-night salivary cortisone seems to be a promising alternative in patients with adrenal incidentaloma and salivary cortisone at 8 a.m. following DST in patients with suspected CS. Larger studies are needed to confirm these findings.

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  • 8.
    Beun, Johan G.
    et al.
    AdrenalNET, The Netherlands.
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital, Lund University, Sweden.
    Kampe, Olle
    Department of Medicine (Solna), Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Diabetes and Metabolism, Karolinska University Hospital, Stockholm, Sweden.
    Husebye, Eystein S.
    Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway.
    Hahner, Stephanie
    Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Germany.
    Kristensen, Jette
    Addison Foreningen i Danmark, Denmark.
    Noordzij, Alida
    AdrenalNET, The Netherlands.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Doctors, teach your adrenal insufficiency patients well: provide them with a European Emergency Card!2022In: Endocrine Connections, E-ISSN 2049-3614, Vol. 12, no 1, article id e220345Article, review/survey (Refereed)
    Abstract [en]

    Adrenal insufficiency is a life-threatening condition requiring chronic glucocorticoid replacement therapy, as well as stress adaptation to prevent adrenal crises. To increase patients' self-sustainability, education on how to tackle an adrenal crisis is crucial. All patients should carry the European Emergency Card.

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  • 9.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundberg, Owe
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Naredi, Silvana
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Liver resection is not associated with decreased cortisol levels.Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Adrenal hormones are synthesized from cholesterol, produced and stored in the liver. Liver failure has been reported to be associated with adrenal insufficiency. A possible mechanism could be a limited supply of substrate for cortisol synthesis. The aims of this study was to evaluate the occurrence of total serum cortisol <200 nmol/L after major liver resection (≥ 30%) and other major surgery (hemicolectomy) and to assess associations between cholesterol and corti­sol levels after liver resection.

    Methods: Prospective, observational study. 40 patients were included (major liver resection n=15, hemicolectomy n=25). Serum and salivary cortisol were followed from morning before surgery up to five days postoperatively. Sulphated dehy­droepiandrosterone (DHEAS) and lipids (cholesterol, low density lipoproteins, high density lipoproteins and triglycerides) were obtained in liver resection patients.

    Results: 8/25 (32%, hemicolectomy patients), and 3/15 (20%, liver resection patients) had serum cortisol <200 nmol/L. Neither hemicolectomy nor liver resec­tion was significantly associated with serum cortisol <200 nmol/L, p=0.49. Serum cortisol <200 nmol/L was not significantly associated with lipids below normal limits, (cholesterol; p=1.0 day 1, p=0.46 day 4, LDL; p=0.56 day 1, p=1.0 day 4, and HDL; p=0.27 day 1, p=1.0 day 4). Serum and salivary cortisol correlated sig­nificantly (rs=0.83, p<0.0001, hemicolectomy, rs=0.80, p<0.0001, liver resection).

    Conclusion: Serum cortisol levels <200 nmol/L was found in 32% (hemicolec­tomy) and 20% (liver resection) postoperatively. Compared to after hemicolec­tomy, serum cortisol <200 nmol/L was not significantly more common after liver resection. Lipids below normal limits were not associated with serum cortisol <200 nmol/L after liver resection.

  • 10.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Leif
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Saliva stimulation with glycerine and citric acid does not affect salivary cortisol levels2014In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 81, no 2, p. 244-248Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    In critically ill patients with hypotension, who respond poorly to fluids and vasoactive drugs, cortisol insufficiency may be suspected. In serum over 90% of cortisol is protein-bound, thus routine measures of total serum cortisol may yield 'false lows' due to hypoproteinaemia. Thus, the occurrence of cortisol insufficiency could be overestimated in critically ill patients. Salivary cortisol can be used as a surrogate for free serum cortisol, but in critically ill patients saliva production is decreased, and insufficient volume of saliva for analysis is a common problem. The aim of this study was to investigate if a cotton-tipped applicator with glycerine and citric acid could be used for saliva stimulation without affecting salivary cortisol levels.

    DESIGN:

    Prospective, observational study.

    PARTICIPANTS:

    Thirty-six volunteers (six males, 30 females), age 49 ± 9 years, without known oral mucus membrane rupture in the mouth.

    MEASUREMENTS:

    Forty-two pairs of saliva samples (22 paired morning samples, 20 paired evening samples) were obtained before and after saliva stimulation with glycerine and citric acid. Salivary cortisol was analysed using Spectria Cortisol RIA (Orion Diagnostica, Finland).

    RESULTS:

    The paired samples correlated significantly (P < 0·0001) and there was no significant difference between un-stimulated and stimulated salivary cortisol levels.

    CONCLUSIONS:

    Saliva stimulation with a cotton-tipped applicator containing glycerine and citric acid did not significantly influence salivary cortisol levels in healthy volunteers. This indicates that salivary cortisol measurement after saliva stimulation may be a useful complement when evaluating cortisol status in critically ill patients.

  • 11.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Leif
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Thunberg, Johan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Sylvan, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Adrenal response after trauma is affected by time after trauma and sedative/analgesic drugs2014In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 45, no 8, p. 1149-1155Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The adrenal response in critically ill patients, including trauma victims, has been debated over the last decade. The aim of this study was to assess the early adrenal response after trauma. METHODS: Prospective, observational study of 50 trauma patients admitted to a level-1-trauma centre. Serum and saliva cortisol were followed from the accident site up to five days after trauma. Corticosteroid binding globulin (CBG), dehydroepiandrosterone (DHEA) and sulphated dehydroepiandrosterone (DHEAS) were obtained twice during the first five days after trauma. The effect of time and associations between cortisol levels and; severity of trauma, infusion of sedative/analgesic drugs, cardiovascular dysfunction and other adrenocorticotropic hormone (ACTH) dependent hormones (DHEA/DHEAS) were studied. RESULTS: There was a significant decrease over time in serum cortisol both during the initial 24 h, and from the 2nd to the 5th morning after trauma. A significant decrease over time was also observed in calculated free cortisol, DHEA, and DHEAS. No significant association was found between an injury severity score >/= 16 (severe injury) and a low (< 200 nmol/L) serum cortisol at any time during the study period. The odds for a serum cortisol < 200 nmol/L was eight times higher in patients with continuous infusion of sedative/analgesic drugs compared to patients with no continuous infusion of sedative/analgesic drugs. CONCLUSION: Total serum cortisol, calculated free cortisol, DHEA and DHEAS decreased significantly over time after trauma. Continuous infusion of sedative/analgesic drugs was independently associated with serum cortisol < 200 nmol/L.

  • 12. Burman, P.
    et al.
    Mattsson, A. F.
    Johannsson, G.
    Höybye, C.
    Holmer, H.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Berinder, K.
    Engström, B. E.
    Ekman, B.
    Erfurth, E. M.
    Svensson, J
    Wahlberg, J.
    Karlsson, F. A.
    Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality2013In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 4, p. 1466-1475Article in journal (Refereed)
    Abstract [en]

    Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified.

    Objective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up.

    Design and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed.

    Main Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up.

    Results: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy.

    Conclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

  • 13. Byhamre, Marja Lisa
    et al.
    Blankenberg, Stefan
    Dahlqvist, Per
    Eriksson, Marie
    Oskarsson, Viktor
    Söderberg, Stefan
    Zeller, Tanja
    Wennberg, Patrik
    Associations between snus use and concentrations of CRP, 25(OH)D and testosterone – a population-based studyManuscript (preprint) (Other academic)
  • 14.
    Bäcklund, Nils
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Brattsand, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Israelsson, Marlen
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Ragnarsson, Oskar
    Burman, Pia
    Edén Engström, Britt
    Høybye, Charlotte
    Berinder, Katarina
    Wahlberg, Jeanette
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome2020In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 182, no 6, p. 569-582Article in journal (Refereed)
    Abstract [en]

    Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST).

    Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves.

    Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h.

    Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.

  • 15.
    Bäcklund, Nils
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Brattsand, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lundstedt, Staffan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Aardal, Elisabeth
    Department of Clinical Chemistry, Linköping University, Linköping, Sweden; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Bartuseviciene, Inga
    Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
    Berinder, Katarina
    Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Höybye, Charlotte
    Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital, Malmö, Sweden.
    Edén Engström, Britt
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department of Endocrinology and Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Isaksson, Anders
    Department of Clinical Chemistry and Pharmacology, Lund University, Lund, Sweden.
    Blomgren, Anders
    Department of Clinical Chemistry and Pharmacology, Lund University, Lund, Sweden.
    Ragnarsson, Oskar
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Rüetschi, Ulrika
    Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Wahlberg, Jeanette
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Salivary cortisol and cortisone in diagnosis of Cushing's syndrome: a comparison of six different analytical methods2023In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 61, no 10, p. 1780-1791Article in journal (Refereed)
    Abstract [en]

    Objectives: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing’s syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS.

    Methods: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves.

    Results: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4–3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7–1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5–16.6 nmol/L at 23:00 h and 3.0–3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs ≥0.96.

    Conclusions: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.

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  • 16.
    Bäcklund, Nils
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundstedt, Staffan
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Tornevi, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Wihlbäck, Anna-Carin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Brattsand, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Comparison of plasma cortisol-, salivary cortisol- and salivary cortisone-response to the short Synacthen test in women using oral contraceptivesManuscript (preprint) (Other academic)
  • 17.
    Bäcklund, Nils
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundstedt, Staffan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Tornevi, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wihlbäck, Anna-Carin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Brattsand, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Salivary cortisol and cortisone can circumvent confounding effects of oral contraceptives in the short synacthen test2024In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 109, no 7, p. 1899-1906Article in journal (Refereed)
    Abstract [en]

    Context: Adrenal insufficiency (AI) is usually diagnosed by low plasma cortisol levels following a short Synacthen test (SST). Most plasma cortisol is bound to corticosteroid-binding globulin, which is increased by estrogen in combined estrogen-progestin oral contraceptives (COCs). Women with AI using COCs are therefore at risk of having an apparently normal plasma cortisol level during SST, which would not adequately reflect AI.

    Objective: To test whether salivary cortisol or cortisone during SST is more robust against the COC effect and to calculate the lower reference limits (LRLs) for these to be used as tentative diagnostic cutoffs to exclude AI.

    Methods: Forty-one healthy women on COCs and 46 healthy women without exogenous estrogens performed an SST with collection of plasma and salivary samples at 0, 30, and 60 min after Synacthen injection. The groups were compared using regression analysis with age as covariate and the LRLs were calculated parametrically.

    Results: SST-stimulated plasma cortisol levels were significantly higher in the COC group versus controls, while mean salivary cortisol and cortisone levels were slightly lower in the COC group. Importantly, COC use did not significantly alter LRLs for salivary cortisol or cortisone. The smallest LRL difference between groups was seen for salivary cortisone.

    Conclusion: Salivary cortisol and especially salivary cortisone are considerably less affected by COC use than plasma cortisol during SST. Due to similar LRLs, a common cutoff for salivary cortisol and cortisone during SST can be used to exclude AI in premenopausal women irrespective of COC use.

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  • 18.
    Dahlqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bensing, Sophie
    Ekwall, Olov
    Wahlberg, Jeanette
    Bergthorsdottir, Ragnhildur
    Hulting, Anna-Lena
    Nationellt kort vid binjurbarksvikt: nytt varningskort kan leda till bättre handläggning och ökad patientsäkerhet2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 44, p. 2226-2227Article in journal (Refereed)
    Abstract [sv]

    Akut binjurebarkssvikt (akut kortisolbrist/Addisonkris) är en ovanlig men viktig differentialdiagnos vid akut cirkulationssvikt. De flesta fall av Addisonkris drabbar patienter med känd binjurebarkssvikt, oftast i samband med gastroenterit eller annan infektion. Noggrann och tydlig information och utbildning av patienter, anhöriga och sjukvårdspersonal behövs för att undvika sjuklighet och dödsfall i akut binjurebarkssvikt. Ett nationellt varningskort i kreditkortsformat har tagits fram till patienter med binjurebarkssvikt för att uppmärksamma och förbättra handläggningen av detta potentiellt livshotande tillstånd

  • 19.
    Dahlqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Isaksson, Magnus
    Bensing, Sophie
    Is adrenal insufficiency a rare disease?2016In: Cortisol excess and insufficiency / [ed] E. Arvat, A. Falorni, Basel: S. Karger, 2016, Vol. 46, p. 106-114Chapter in book (Refereed)
    Abstract [en]

    Adrenal insufficiency (AI) is a potentially life-threatening condition and it is of utmost importance to identify and adequately manage affected individuals. Diagnosis is often delayed, probably partly because diseases of the adrenal or pituitary region that cause primary AI (PAI) or central AI are relatively rare conditions. However, iatrogenic AI, i.e. the physiological downregulation of the hypothalamic-pituitary-adrenal axis and adrenal atrophy caused by glucocorticoid treatment for different inflammatory conditions is likely to be considerably more common. The type of glucocorticoid, dose and duration of treatment are factors to consider when trying to predict the risk of developing symptoms of AI. However, the considerable individual variation in the sensitivity for developing iatrogenic AI impedes prediction. In industrialized countries, autoimmune adrenalitis accounts for the majority of cases of PAI. Among children, genetic conditions - in particular congenital adrenal hyperplasia - need to be considered. Important risk groups for central AI are patients with tumours in the hypothalamic-pituitary region, moderate-to-severe traumatic head injury and patients who receive cranial radiotherapy or cytotoxic T-lymphocyte antigen 4 blockade treatment. Structured endocrine follow-up is essential in these groups. Health workers need to be attentive to these potentially fatal conditions and at-risk populations should be carefully informed about symptoms and signs of AI.

  • 20.
    Dahlqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hägg, Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Testicular enlargement in a patient with a FSH-secreting pituitary adenoma2010In: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 37, no 2, p. 289-293Article in journal (Refereed)
    Abstract [en]

    Clinically non-functional pituitary adenomas are often derived from gonadotropin producing cells. However, gonadotropinomas causing elevated serum levels of follicle-stimulating hormone (FSH) and clinical signs of FSH hypersecretion are very rarely described. Our patient, a 56-year-old man, was referred to our clinic with signs of hypogonadism. Magnetic resonance imaging (MRI) and biochemical examinations showed a large pituitary adenoma and excessive levels of serum FSH. Clinical examination and ultrasound measurement revealed bilaterally enlarged testes. After pituitary surgery, serum FSH levels normalized and there was a decrease in testicular volume. This case suggests that supraphysiological levels of FSH from a gonadotropinoma can cause a clinically observable effect, i.e. testicular enlargement. This is in line with experimental studies showing biological effect of FSH from pituitary adenomas and previous occasional reports of ovarian hyperstimulation and testicular enlargement in patients with FSH-secreting gonadotropinomas.

  • 21.
    Dahlqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mattsson, Cecilia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olivecrona, Zandra
    Koskinen, Lars-Owe D
    Pituitary Function after Severe Traumatic Brain Injury (TBI) in Northern Sweden2011In: Contents:June 2011, Volume 32, Issue 03_MeetingAbstracts / [ed] E Chester Ridway, 2011, p. 396-Conference paper (Other academic)
  • 22.
    Dahlqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Rönnbäck, Annica
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bergström, Sven-Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Söderström, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Environmental enrichment reverses learning impairment in the Morris water maze after focal cerebral ischemia in rats2004In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 19, no 8, p. 2288-2298Article in journal (Refereed)
    Abstract [en]

    Cognitive impairment is common after ischemic stroke. In rodent stroke models using occlusion of the middle cerebral artery (MCA) this is reflected by impaired spatial memory associated with the size of the ischemic lesion. Housing in an enriched environment enhances brain plasticity and improves recovery of sensorimotor functions after experimental stroke in rats. In this study we report that postischemic housing in an enriched environment also attenuates the long-term spatial memory impairment after MCA occlusion and extinguishes the association between spatial memory and infarct volume. An enriched environment did not significantly alter the expression of selected neuronal plasticity-associated genes 1 month after MCA occlusion, indicating that most of the adaptive changes induced by an enriched environment have already occurred at this time point. We conclude that the attenuated memory impairment induced by environmental enrichment after MCA occlusion provides a useful model for further studies on the neurobiological mechanisms of recovery of cognitive functions after ischemic stroke.

  • 23.
    Dahlqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rönnbäck, Annica
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Risedal, Anette
    Nergårdh, Richard
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Seckl, Jonathan R
    Johansson, Barbro B
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Effects of postischemic environment on transcription factor and serotonin receptor expression after permanent focal cortical ischemia in rats2003In: Neuroscience, Vol. 119, no 3, p. 643-652Article in journal (Refereed)
  • 24.
    Dahlqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, and Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg.
    Spencer, Rupert
    Marques, Pedro
    Dang, Mary N.
    Glad, Camilla A. M.
    Johannsson, Gudmundur
    Korbonits, Márta
    Pseudoacromegaly: A Differential Diagnostic Problem for Acromegaly With a Genetic Solution2017In: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 1, no 8, p. 1104-1109Article in journal (Refereed)
    Abstract [en]

    Acromegaly is usually not a difficult condition to diagnose once the possibility of this disease has been raised. However, a few conditions present with some aspects of acromegaly or gigantism but without growth hormone (GH) excess. Such cases are described as "pseudoacromegaly" or "acromegaloidism". Here we describe a female patient investigated for GH excess at 10 years of age for tall stature since infancy (height and weight > +3 standard deviations) and typical acromegalic features, including large hands/feet, large jaw, tongue, hoarse deep voice, and headache. Results of radiography of the sella turcica and GH response at an oral glucose tolerance test and insulin-arginine- thyrotrophin-luteinizing hormone-releasing hormone test were normal. Ethinylestradiol and medroxyprogesterone were given for 2 years; this successfully stopped further height increase. Although the patient's growth rate plateaued, coarsening of the facial features and acral enlargement also led to investigations for suspicion of acromegaly at 23 and 36 years of age, both with negative results. On referral at the age of 49 years, she had weight gain, sweating, sleep apnea, headaches, joint pain, and enlarged tongue. Endocrine assessment again showing normal GH axis was followed by genetic testing with a macrocephaly/overgrowth syndrome panel. A denovo mutation in the NSD1 gene (c.6605G>C; p.Cys2202Ser) was demonstrated. Mutations affecting the same cysteine residue have been identified in patients with Sotos syndrome. In summary, Sotos syndrome and other overgrowth syndromes can mimic the clinical manifestations of acromegaly or gigantism. Genetic assessment could be helpful in these cases.

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  • 25.
    Dahlqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Zhao, L
    Johansson, I M
    Mattsson, B
    Johansson, B B
    Seckl, J R
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats.1999In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 93, no 2, p. 527-35Article in journal (Refereed)
    Abstract [en]

    Housing rats in an enriched environment after focal brain ischemia improves functional outcome without changes in infarct volume, suggesting neuroplastic changes outside the lesion. In this study, permanent occlusion of the middle cerebral artery was followed by housing in an enriched or a standard environment. Nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression were determined by in situ hybridization two to 30 days after middle cerebral artery occlusion. Stroke induced a decrease in nerve growth factor-induced gene A messenger RNA expression in cortical areas outside the ischemic lesion and in the CA1 subregion of the hippocampus two to three days after ischemia. This decrease was more prolonged with environmental enrichment, lasting until 20 days. However, 30 days after focal cerebral ischemia, environmental enrichment increased nerve growth factor-induced gene A expression compared to standard housing. A reduction of hippocampal glucocorticoid receptor (type II) messenger RNA two to 12 days after stroke in standard housed rats was restored by environmental enrichment. These data suggest that improved functional outcome induced by environmental enrichment after middle cerebral artery occlusion is associated with dynamically altered expression of nerve growth factor-induced gene A messenger RNA in brain regions outside the ischemic lesion, and sustained levels of hippocampal glucocorticoid receptor messenger RNA expression.

  • 26. Dalin, Frida
    et al.
    Nordling Eriksson, Gabriel
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hallgren, Åsa
    Wahlberg, Jeanette
    Ekwall, Olov
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Rönnelid, Johan
    Olcén, Per
    Winqvist, Ola
    Catrina, Sergiu-Bogdan
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Laudius, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Isaksson, Magnus
    Halldin Stenlid, Maria
    Gustafsson, Jan
    Gebre-Medhin, Gennet
    Björnsdottir, Sigridur
    Janson, Annika
    Åkerman, Anna-Karin
    Åman, Jan
    Duchen, Karel
    Bergthorsdottir, Ragnhildur
    Johannsson, Gudmundur
    Lindskog, Emma
    Landin-Olsson, Mona
    Elfving, Maria
    Waldenström, Erik
    Hulting, Anna-Lena
    Kämpe, Olle
    Bensing, Sophie
    Clinical and immunological characteristics of Autoimmune Addison's disease: a nationwide Swedish multicenter study2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 2, p. 379-389Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.

    OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.

    DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.

    MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.

    RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).

    CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.

  • 27. Eriksson, D
    et al.
    Bianchi, M
    Landegren, N
    Nordin, J
    Dalin, F
    Mathioudaki, A
    Eriksson, G N
    Hultin-Rosenberg, L
    Dahlqvist, J
    Zetterqvist, H
    Karlsson, Å
    Hallgren, Å
    Farias, F H G
    Murén, E
    Ahlgren, K M
    Lobell, A
    Andersson, G
    Tandre, K
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Söderkvist, P
    Rönnblom, L
    Hulting, A-L
    Wahlberg, J
    Ekwall, O
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Meadows, J R S
    Bensing, S
    Lindblad-Toh, K
    Kämpe, O
    Pielberg, G R
    Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 6, p. 595-608Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.

    METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.

    RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.

    CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

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  • 28. Eriksson, Daniel
    et al.
    Bianchi, Matteo
    Landegren, Nils
    Dalin, Frida
    Skov, Jakob
    Hultin-Rosenberg, Lina
    Mathioudaki, Argyri
    Nordin, Jessika
    Hallgren, Åsa
    Andersson, Göran
    Tandre, Karolina
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Söderkvist, Peter
    Rönnblom, Lars
    Hulting, Anna-Lena
    Wahlberg, Jeanette
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Ekwall, Olov
    Meadows, Jennifer R. S.
    Lindblad-Toh, Kerstin
    Bensing, Sophie
    Pielberg, Gerli Rosengren
    Kämpe, Olle
    Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison's disease in Sweden2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 8395Article in journal (Refereed)
    Abstract [en]

    Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.

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  • 29. Eriksson, Daniel
    et al.
    Dalin, Frida
    Eriksson, Gabriel Nordling
    Landegren, Nils
    Bianchi, Matteo
    Hallgren, Asa
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wahlberg, Jeanette
    Ekwall, Olov
    Winqvist, Ola
    Catrina, Sergiu-Bogdan
    Ronnelid, Johan
    Hulting, Anna-Lena
    Lindblad-Toh, Kerstin
    Alimohammadi, Mohammad
    Husebye, Eystein S.
    Knappskog, Per Morten
    Pielberg, Gerli Rosengren
    Bensing, Sophie
    Kampe, Olle
    Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS12018In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 1, p. 179-186Article in journal (Refereed)
    Abstract [en]

    Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.

    Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.

    Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.

    Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.

    Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.

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  • 30. Eriksson, Daniel
    et al.
    Røyrvik, Ellen Christine
    Aranda-Guillén, Maribel
    Holte Berger, Amund
    Landegren, Nils
    Artaza, Haydee
    Hallgren, Åsa
    Aardal Grytaas, Marianne
    Ström, Sara
    Bratland, Eirik
    Botusan, Ileana Ruxandra
    Eikeland Oftedal, Bergithe
    Breivik, Lars
    Vaudel, Marc
    Helgeland, Øyvind
    Falorni, Alberto
    Palmstrøm Jørgensen, Anders
    Hulting, Anna-Lena
    Svartberg, Johan
    Ekwall, Olov
    Fougner, Kristian Johan
    Wahlberg, Jeanette
    Nedrebø, Bjørn Gunnar
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Knappskog, Per Morten
    Wolff, Anette Susanne Bøe
    Bensing, Sophie
    Johansson, Stefan
    Kämpe, Olle
    Husebye, Eystein Sverre
    GWAS for autoimmune Addison's disease identifies multiple risk loci and highlights AIRE in disease susceptibility2021In: Nature Communications, E-ISSN 2041-1723, Vol. 12, no 1, article id 959Article in journal (Refereed)
    Abstract [en]

    Autoimmune Addison's disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here report the first genome-wide association study on AAD, which identifies nine independent risk loci (P < 5 × 10-8). In addition to loci implicated in lymphocyte function and development shared with other autoimmune diseases such as HLA, BACH2, PTPN22 and CTLA4, we associate two protein-coding alterations in Autoimmune Regulator (AIRE) with AAD. The strongest, p.R471C (rs74203920, OR = 3.4 (2.7-4.3), P = 9.0 × 10-25) introduces an additional cysteine residue in the zinc-finger motif of the second PHD domain of the AIRE protein. This unbiased elucidation of the genetic contribution to development of AAD points to the importance of central immunological tolerance, and explains 35-41% of heritability (h2).

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  • 31. Espiard, Stéphanie
    et al.
    McQueen, Johanna
    Sherlock, Mark
    Ragnarsson, Oskar
    Bergthorsdottir, Ragnhildur
    Burman, Pia
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Ekman, Bertil
    Engström, Britt Edén
    Skrtic, Stanko
    Wahlberg, Jeanette
    Stewart, Paul M
    Johannsson, Gudmundur
    Improved Urinary Cortisol Metabolome in Addison's disease: a Prospective Trial of Dual-Release Hydrocortisone2021In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, no 3, p. 814-825Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism.

    OBJECTIVE: To study cortisol metabolism during DR-HC and TID-HC.

    DESIGN: Randomized, 12-week, crossover study.

    INTERVENTION AND PARTICIPANTS: DC-HC and same daily dose of TID-HC in patients with primary adrenal insufficiency (n=50) versus healthy subjects (n=124) as control.

    MAIN OUTCOME MEASURES: Urinary corticosteroid metabolites measured by gas chromatography/mass spectrometry on 24-hour urinary collections.

    RESULTS: Total cortisol metabolites decreased during DR-HC compared to TID-HC (P < 0.001) and reached control values (P = 0.089). During DR-HC, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity measured by tetrahydrocortisol+5α-tetrahydrocortisol/tetrahydrocortisone ratio was reduced compared to TID-HC (P < 0.05), but remained increased versus controls (P < 0.001). 11β-HSD2 activity measured by urinary free cortisone/free cortisol ratio was decreased with TID-HC versus controls (P < 0.01) but normalized with DR-HC (P = 0.358). 5α- and 5β-reduced metabolites were decreased with DR-HC compared to TID-HC. Tetrahydrocortisol/5α-tetrahydrocortisol ratio was increased during both treatments, suggesting increased 5β-reductase activity.

    CONCLUSIONS: The urinary cortisol metabolome shows striking abnormalities in patients receiving conventional TID-HC replacement therapy with increased 11β-HSD1 activity that may account for the unfavorable metabolic phenotype in primary adrenal insufficiency. Its change towards normalization with DR-HC may mediate beneficial metabolic effects. The urinary cortisol metabolome may serve as a tool to assess optimal cortisol replacement therapy.

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  • 32.
    Himonakos, Christos
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Internal Medicine, Center for Endocrinology and Diabetes, Karlstad Central Hospital, Karlstad, Sweden.
    Burman, Pia
    Department of Endocrinology, Lund University, Skåne University Hospital, Malmö, Sweden.
    Borg, Henrik
    Department of Endocrinology, Lund University, Skåne University Hospital, Lund, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Engström, Britt Edén
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
    Ekman, Bertil
    Department of Endocrinology and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Emilsson, Louise
    Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway; Nysäter Health Care Center and Center for Clinical Research, County Council of Värmland, Karlstad, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Olsson, Daniel S.
    Department of Endocrinology at Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Ragnarsson, Oskar
    Department of Endocrinology at Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Wahlberg, Jeanette
    Department of Medicine, Örebro University Hospital, Sweden; School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Sweden.
    Åkerman, Anna-Karin
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Medicine, Örebro University Hospital, Sweden.
    Hoybye, Charlotte
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Berinder, Katarina
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Long-term follow-up of 84 patients with giant prolactinomas: a swedish nationwide study2023In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 108, no 12, p. e1506-e1514Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas.

    Methods: Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 & mu;g/L, tumor diameter & GE;40 mm] identified in the Swedish Pituitary Register 1991-2018.

    Results: Eighty-four patients [mean age 47 (SD & PLUSMN;16) years, 89% men] were included in the study. At diagnosis, the median PRL was 6305 & mu;g/L (range 1450-253 000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received 1 or more additional therapies, including surgery (n = 19), radiotherapy (n = 6), other medical treatments (n = 4), and chemotherapy (n = 2). Ki-67 was & GE;10% in 4/14 tumors. At the last follow-up [median 9 years (interquartile range (IQR) 4-15)], the median PRL was 12 & mu;g/L (IQR 4-126), and the median tumor diameter was 22 mm (IQR 3-40). Normalized PRL was achieved in 55%, significant tumor reduction in 69%, and combined response (normalized PRL and significant tumor reduction) in 43%. In the primary DA-treated patients (n = 79), the reduction in PRL or tumor size after the first year predicted the combined response at the last follow-up (P < .001 and P = .012, respectively).

    Conclusion: DAs effectively reduced PRL and tumor size, but approximately 1 patient out of 4 needed multimodal treatment. Our results suggest that the response to DA after 1 year is useful for identifying patients who need more careful monitoring and, in some cases, additional treatment.

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  • 33.
    Hu, Xiao-Lei
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bergström, Sven-Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Brink, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rönnbäck, Annica
    Karolinska Institute, Dept NVS, KI-Alzheimer Disease Research Center, KASPAC, Novum, SE-141 57 Huddinge, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Enriched environment increases spinophilin mRNA expression and spinophilin immunoreactive dendritic spines in hippocampus and cortex2010In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 476, no 2, p. 79-83Article in journal (Refereed)
    Abstract [en]

    Housing rodents in an enriched environment (EE) induces structural and functional plasticity in the adult brain, including increased dendritic sprouting and number of dendritic spines. However, the molecular mechanisms behind EE-induced brain plasticity remain largely unknown. Circadian rhythm plays an important role in memory processing but the neurobiological mechanisms of how circadian rhythm affects memory and brain plasticity remain controversial. In the current study, we studied the expression of spinophilin, a protein highly enriched in dendritic spines and involved in spine morphology and synaptic plasticity, to examine the effects of EE and circadian rhythm in rats housed in EE for different periods of time. Spinophilin mRNA expression was studied by in situ hybridization and the density of spinophilin immunoreactive puncta was quantified after immunohistochemical staining. Compared to rats living in a deprived environment (DE), we found a transient increase in the density of spinophilin immunoreactive puncta in hippocampus and cortex after 1 week of EE housing and persistent elevations of spinophilin mRNA expression during 1-4 weeks of environmental enrichment. Increased spinophilin expression was found during the light phase of the diurnal cycle, but not the dark phase. Thus, enriched housing altered the diurnal variation in spinophilin mRNA expression, suggesting that circadian modulation is likely to be important for experience dependent plasticity. The current results suggest a possible role for spinophilin in neuronal plasticity induced by environmental enrichment, but further studies are needed to establish a cause-effect relation.

  • 34. Husebye, Eystein Sverre
    et al.
    Erichsen, Martina Moter
    Myhre, Anne-Grethe
    Bratke, Heiko
    Jørgensen, Anders Palmstrøm
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Løvås, Kristian
    Nytt steroidkort ved binyrebarksvikt2012In: Tidsskrift for Den norske lægeforening, ISSN 0029-2001, E-ISSN 0807-7096, Vol. 132, no 18, p. 2043-2044Article in journal (Refereed)
  • 35.
    Ibrahim, Aghil
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundgren, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The clinical course after glucocorticoid treatment in patients with inflammatory bowel disease is linked to suppression of the hypothalamic-pituitary-adrenal axis: a retrospective observational study2017In: Therapeutic Advances in Gastroenterology, ISSN 1756-283X, E-ISSN 1756-2848, Vol. 10, no 11, p. 829-836Article in journal (Refereed)
    Abstract [en]

    Background: Adrenal insufficiency (AI) secondary to treatment with glucocorticoids (GCs) is common in patients with inflammatory bowel disease (IBD), but little is known about the relationship between AI and the clinical course in IBD. The aim of the study was to compare the clinical course in IBD patients with normal adrenal function versus patients with subnormal adrenal function.

    Methods: A retrospective observational study on 63 patients with IBD who had performed a low-dose short Synacthen test (LDSST) (1 μg) immediately (1-7 days) after a standard course of GCs. A subnormal LDSST was defined as serum cortisol <550 nmol/L. Outcomes were time to next flare and fecal calprotectin levels.

    Results: Sixty-three percent (n = 40) of the IBD patients had a subnormal LDSST. Patients who were steroid-free (n = 41) after the LDSST were observed for 3 years. Patients with a peak serum cortisol <400 nmol/L immediately after GC treatment had significantly longer time until the next flare-up of their IBD and tended to use a lower cumulative prednisolone dose during the study period in comparison to the other subgroups. Fecal calprotectin levels were significantly lower in patients with a peak s-cortisol <550 nmol/L versus patients with peak s-cortisol ⩾550 nmol/L (median 336 µg/g (IQR 521) versus 955 µg/g (IQR 1867); p = 0.012).

    Conclusions: GC-induced AI is common in patients with IBD and is associated with lower disease activity. This suggests a link between responsiveness to GC treatment and suppression of the hypothalamic-pituitary-adrenal axis in IBD.

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  • 36.
    Imamovic, Marcus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bäcklund, Nils
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundstedt, Staffan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Brattsand, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Aardal, Elisabeth
    Department of Clinical Chemistry and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Confounding effects of liquorice, hydrocortisone, and blood contamination on salivary cortisol but not cortisone2023In: Endocrine Connections, E-ISSN 2049-3614, Vol. 12, no 1, article id e220324Article in journal (Refereed)
    Abstract [en]

    Objective: To determine the effects of liquorice consumption, topical hydrocortisone, and blood contamination on salivary cortisol and cortisone concentrations.

    Design and methods: Thirty healthy volunteers were randomized to a low, medium, or high dose of liquorice. Late-night saliva samples were collected using a Salivette® collection device at baseline, during 1 week of daily liquorice consumption, and during 4 weeks' washout. Saliva sampling was also performed before and after the application of topical hydrocortisone on the skin. Furthermore, in a subgroup (n  = 16), saliva and venous blood were collected from each individual and mixed to achieve graded blood contamination in saliva. Salivary cortisol and cortisone were analyzed with liquid chromatography-tandem mass spectrometry.

    Results: Significant increases in salivary cortisol concentrations were observed during medium- (+49%) and high-dose (+97%) liquorice intake, which returned to baseline 4 days after liquorice withdrawal. Topical hydrocortisone on fingers holding the collection swab increased salivary cortisol concentrations >1000-fold with concomitant pronounced elevation of the cortisol:cortisone ratio. Salivary cortisol increased significantly after contamination with blood ≥0.5%. Visual examination could safely detect these samples. Salivary cortisone concentrations were unaffected by liquorice consumption and blood contamination, and only marginally affected by topical hydrocortisone.

    Conclusion: Liquorice, topical hydrocortisone, and blood contamination may all cause elevated salivary cortisol concentrations. Improved sampling instructions and visual examination of the sample may minimize these risks. Salivary cortisone is essentially unaffected by the different preanalytical confounders and may be used as a first-line screening test for Cushing's syndrome.

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  • 37.
    Jacobson, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Johansson, Mattias
    Svensson, Johan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Billing, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Franklin, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Hyperglycemia as a risk factor in pancreatic cancer: A nested case-control study using prediagnostic blood glucose levels2021In: Pancreatology (Print), ISSN 1424-3903, E-ISSN 1424-3911, Vol. 21, no 6, p. 1112-1118Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples.

    METHODS: Prospective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t-test and log rank test.

    RESULTS: The unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05-1.60, P = .015). Impaired fasting glucose (≥6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05-2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26-12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08-8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04-2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival.

    CONCLUSIONS: High fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer.

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  • 38. Johannsson, G
    et al.
    Nilsson, AG
    Bergthorsdottir, R
    Burman, P
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ekman, B
    Engström, BE
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ragnarsson, O
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wahlberg, J
    Biller, BMK
    Monson, JP
    Stewart, PM
    Lennernäs, H
    Skrtic, S
    Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation2012In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 97, no 2, p. 473-481Article in journal (Refereed)
    Abstract [en]

    Context: Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.

    Objective: The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.Design and Setting:We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.

    Patients: The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).

    Intervention: The same daily dose of hydrocortisone was administered as OD dual-release or TID.

    Main Outcome Measure: We evaluated cortisol pharmacokinetics.

    Results: Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004).

    Conclusion: The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.

  • 39.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nilsson, Leif
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Cortisol levels are influenced by sedation in the acute phase after subarachnoid haemorrhage2013In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 4, p. 452-460Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Subarachnoid haemorrhage (SAH) is a life-threatening condition that may be aggravated by acute pituitary damage and cortisol insufficiency. Robust diagnostic criteria for critical illness-related corticosteroid insufficiency (CIRCI) are lacking. The aim of this study was to assess the frequency of CIRCI in the acute phase (0-240 h) after SAH and to evaluate associations between cortisol levels and clinical parameters (sedation, circulatory failure, gender, age, severity of disease, treatment). CIRCI was defined as a single morning serum cortisol (mSC) < 200 nmol/L. The lower limit for calculated free cortisol (cFC) was set at < 22 nmol/L, and for saliva cortisol at < 7.7 nmol/L.

    METHODS: Fifty patients were included. Serum/saliva cortisol and corticosteroid-binding globulin were obtained every second morning. A logistic regression model was used for multivariate analysis comparing cortisol levels with clinical parameters.

    RESULTS: Of the patients, 21/50 (42%) had an mSC < 200 nmol/L and 30/50 (60%) had a cFC < 22 nmol/L. In patients with continuous intravenous sedation, the odds ratio for a mSC to be < 200 nmol/L was 18 times higher (95% confidence interval 4.2-85.0, P < 0.001), and the odds ratio for a cFC to be < 22 nmol/L was 2.4 times higher (95% confidence interval 1.2-4.7, P < 0.05) compared with patients with no continuous intravenous sedation.

    CONCLUSIONS: Continuous intravenous sedation was significantly associated with cortisol values under defined limits (mSC < 200, cFC < 22 nmol/L). The possibility that sedating drugs per se may influence cortisol levels should be taken into consideration before CIRCI is diagnosed.

  • 40. Mitchell, Anna L.
    et al.
    Macarthur, Katie D. R.
    Gan, Earn H.
    Baggott, Lucy E.
    Wolff, Anette S. B.
    Skinningsrud, Beate
    Platt, Hazel
    Short, Andrea
    Lobell, Anna
    Kampe, Olle
    Bensing, Sophie
    Betterle, Corrado
    Kasperlik-Zaluska, Anna
    Zurawek, Magdalena
    Fichna, Marta
    Kockum, Ingrid
    Eriksson, Gabriel Nordling
    Ekwall, Olov
    Wahlberg, Jeanette
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hulting, Anna-Lena
    Penna-Martinez, Marissa
    Meyer, Gesine
    Kahles, Heinrich
    Badenhoop, Klaus
    Hahner, Stephanie
    Quinkler, Marcus
    Falorni, Alberto
    Phipps-Green, Amanda
    Merriman, Tony R.
    Ollier, William
    Cordell, Heather J.
    Undlien, Dag
    Czarnocka, Barbara
    Husebye, Eystein
    Pearce, Simon H. S.
    Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 3, p. e88991-Article in journal (Refereed)
    Abstract [en]

    Background:

    Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.

    Aim:

    To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.

    Methods:

    A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity.

    Results:

    We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-kappa B1 and IL23A genes in the UK and Italian cohorts respectively.

    Conclusions:

    Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.

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  • 41. Nilsson, A G
    et al.
    Marelli, C
    Fitts, D
    Bergthorsdottir, R
    Burman, P
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ekman, B
    Engström, B Edén
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ragnarsson, O
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wahlberg, J
    Lennernäs, H
    Skrtic, S
    Johannsson, G
    Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency2014In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 171, no 3, p. 369-377Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI).

    DESIGN: Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden.

    METHODS: Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness).

    RESULTS: In stage 1, patients had a median 1.5 (range, 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure.

    CONCLUSIONS: This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy.

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  • 42. Nilsson, Anna G.
    et al.
    Bergthorsdottir, Ragnhildur
    Burman, Pia
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ekman, Bertil
    Engstrom, Britt Eden
    Ragnarsson, Oskar
    Skrtic, Stanko
    Wahlberg, Jeanette
    Achenbach, Heinrich
    Uddin, Sharif
    Marelli, Claudio
    Johannsson, Gudmundur
    Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study2017In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 176, no 6, p. 715-725Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI).

    Design: Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden.

    Methods: Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires.

    Results: Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6–5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008).

    Conclusions: In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.

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  • 43.
    Olivecrona, Zandra
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Acute neuro-endocrine profile and prediction of outcome after severe brain injury2013In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, E-ISSN 1757-7241, Vol. 21, no 33Article in journal (Refereed)
    Abstract [en]

    Object: The aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome.

    Methods: Prospective study, including consecutive patients, 15-70 years, with sTBI, Glasgow Coma Scale (GCS) score <= 8, initial cerebral perfusion pressure > 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08-10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17-19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E.

    Results: Profound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. < 276 nmol/L (= 10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3 and TSH at day 4 in patients with a poor outcome at 3 months. 5) A higher Marshall CT score was associated with higher day 1 LH/FSH-and lower day 4 TSH levels 6) In general no significant correlation between GCS, ICP or CPP and hormone levels were detected. Only ICPmax and LH day 1 in men was significantly correlated.

    Conclusion: Profound dynamic changes in hormone levels are found in the acute phase of sTBI. This is consistent with previous findings in different groups of critically ill patients, most of which are likely to be attributed to physiological adaptation to acute illness. Low cortisol levels were a common finding, and not associated with unfavorable outcome. A retained ability to a dynamic hormonal response, i.e. fast and strong suppression of the pituitary-gonadal axis (day 1) and ability to restore activity in the pituitary-thyroid axis (day 4) was associated with less severe injury according to CT-findings and favorable outcome.

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  • 44.
    Olsson, Tommy
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson,
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rönnbäck, A
    Wieloch, T
    Johansson, B
    Glucocorticoid axis abnormalities related to brain damage.1999In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 167, no 2, p. A9-Article in journal (Refereed)
  • 45. Onnestam, Lisa
    et al.
    Berinder, Katarina
    Burman, Pia
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Engström, Britt Edén
    Wahlberg, Jeanette
    Nyström, Helena Filipsson
    National Incidence and Prevalence of TSH-Secreting Pituitary Adenomas in Sweden2013In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 2, p. 626-635Article in journal (Refereed)
    Abstract [en]

    Context: TSH-secreting pituitary adenomas (TSHomas) are rare. Epidemiological data are scant and there are no reports on national incidence. Objective: The objective of the study was to estimate the national Swedish incidence and prevalence of TSHomas. Design: This was an observational study. Setting: The study was conducted at tertiary referral centers. Patients: The Swedish Pituitary Registry and World Health Organization International Statistical Classification of Diseases and Related Health Problems coding at all university hospitals were used to identify patients diagnosed with TSHomas 1990-2010. The identified patients' medical records were studied until the latest follow-up [median 5.0 years (range < 1-20 years)]. Main Outcome Measurements: Incidence, prevalence, demographics, tumor characteristics, treatment outcome, and thyroid hormone level at diagnosis were measured. Results: The age-standardized national incidence of 28 TSHoma patients was 0.15 per 1 million inhabitants per year, with an increasing incidence over time (0.05 per 1 million per year in 1990-1994 to 0.26 per 1 million per year in 2005-2009). The national prevalence in 2010 was 2.8 per 1 million inhabitants, in which 0.85 per 1 million had active disease. Most patients (n = 22) underwent pituitary surgery, 5 had radiotherapy, and 6 had somatostatin analogues. Eighteen patients were considered cured at the latest follow-up; 25% remained uncontrolled. Subjects treated for putative primary hyperthyroidism prior to diagnosis had TSH levels more than double those with intact thyroid at diagnosis (P = .013). The median time to diagnosis was longer for women than men (4 vs < 1 year, P = .026). More women than men were treated surgically (94.1% vs 54.5%, P = .022). Conclusion: This is the first estimate of a national incidence of TSHoma. Additional epidemiological studies are needed to compare these results with other geographical areas. This study suggests an increased incidence of TSHomas, in agreement with reports on other pituitary adenomas.

  • 46. Papakokkinou, Eleni
    et al.
    Olsson, Daniel S.
    Chantzichristos, Dimitrios
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Segerstedt, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Petersson, Maria
    Berinder, Katarina
    Bensing, Sophie
    Hoybye, Charlotte
    Eden-Engstrom, Britt
    Burman, Pia
    Bonelli, Lorenza
    Follin, Cecilia
    Petranek, David
    Erfurth, Eva Marie
    Wahlberg, Jeanette
    Ekman, Bertil
    Akerman, Anna-Karin
    Schwarcz, Erik
    Bryngelsson, Ing-Liss
    Johannsson, Gudmundur
    Ragnarsson, Oskar
    Excess Morbidity Persists in Patients With Cushing's Disease During Long-term Remission: A Swedish Nationwide Study2020In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 105, no 8, p. 2616-2624Article in journal (Refereed)
    Abstract [en]

    Context: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.

    Objective: To investigate comorbidities in patients with CD.

    Design, Setting, and Patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.

    Main Outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (Os) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.

    Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.

    Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.

  • 47.
    Papakokkinou, Eleni
    et al.
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Piasecka, Marta
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlsen, Hanne Krage
    Department of Environmental and Occupational Health School of Public Health and Community Medicine, University of Gothenburg, Gothenburg, Sweden.
    Chantzichristos, Dimitrios
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Olsson, Daniel S.
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Petersson, Maria
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Berinder, Katarina
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Bensing, Sophie
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Höybye, Charlotte
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Engström, Britt Edén
    Department of Endocrinology and Diabetes, Uppsala University Hospital, and Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden.
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital, University of Lund, Malmö, Sweden.
    Follin, Cecilia
    Department of Endocrinology, Skåne University Hospital, Lund, Sweden.
    Petranek, David
    Department of Endocrinology, Skåne University Hospital, Lund, Sweden.
    Erfurth, Eva Marie
    Department of Endocrinology, Skåne University Hospital, Lund, Sweden.
    Wahlberg, Jeanette
    Department of Endocrinology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Department of Internal Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ekman, Bertil
    Department of Endocrinology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Åkerman, Anna-Karin
    Department of Internal Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Schwarcz, Erik
    Department of Internal Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Johannsson, Gudmundur
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Falhammar, Henrik
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Ragnarsson, Oskar
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; The Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Prevalence of Nelson’s syndrome after bilateral adrenalectomy in patients with cushing’s disease: a systematic review and meta-analysis2021In: Pituitary, ISSN 1386-341X, E-ISSN 1573-7403, Vol. 24, p. 797-809Article in journal (Refereed)
    Abstract [en]

    Purpose: Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson’s syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development.

    Data sources: Systematic literature search in four databases.

    Study Selection: Observational studies reporting the prevalence of NS after BA in adult patients with CD.

    Data extraction: Data extraction and risk of bias assessment were performed by three independent investigators.

    Data synthesis: Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22–31%), with moderate to high heterogeneity (I2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27–50%). The prevalence of treatment for NS was 21% (95% CI 18–26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5–1.6)] or pituitary surgery [0.6 (95% CI 0.4–1.0)].

    Conclusions: Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.

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  • 48.
    Petersson, Maria
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Berinder, Katarina
    Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Eden Engström, Britt
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
    Tsatsaris, Erika
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
    Ekman, Bertil
    Department of Endocrinology in Linköping and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Wahlberg, Jeanette
    Department of Endocrinology in Linköping and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Department of Internal Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital, University of Lund, Malmö, Sweden.
    Borg, Henrik
    Department of Endocrinology, Skåne University Hospital, University of Lund, Lund, Sweden.
    Siesjö, Peter
    Department of Neurosurgery, Skåne University Hospital, University of Lund, Lund, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Åkerman, Anna-Karin
    Department of Internal Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ragnarsson, Oskar
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Olsson, Martin
    Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
    Förander, Petter
    Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
    Bensing, Sophie
    Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Höybye, Charlotte
    Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Natural history and surgical outcome of Rathke's cleft cysts: A study from the Swedish Pituitary Registry2022In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 96, no 1, p. 54-61Article in journal (Refereed)
    Abstract [en]

    Objective: Rathke's cleft cysts are benign, embryological remnants in the pituitary gland. The majority of them are small and asymptomatic but a few may become large, and cause mass effects, pituitary hormone deficiencies and visual impairment. Recommendations for the follow-up of Rathke's cleft cysts vary since data on the natural history are sparse.

    Patients and Design: Data at diagnosis and at 1, 5 and 10 years for patients with a Rathke's cleft cyst (434 at diagnosis, 317 females) were retrieved from the Swedish Pituitary Registry. Cysts ≤3 mm in diameter were excluded from the study.

    Measurements: Data included demographics, cyst size, pituitary function, visual defects and surgery.

    Results: The mean age at diagnosis was 45 years. In patients with cysts <10 mm in diameter (n = 204) 2.9% had pituitary hormone deficiencies and 2% had visual field impairments. Cyst size did not progress during the 5 years. Cysts with a diameter of ≥10 mm that were not operated (n = 174) decreased in size over the years (p <.01). Pituitary hormone deficiencies and visual impairments were more frequent (18% and 5.7%, respectively) but were stable over time. Transphenoidal surgery was performed in 56 patients of whom 51 underwent surgery before the 1-year follow-up. The mean cyst diameter at diagnosis was 18 mm (range: 9─30 mm), 36% had pituitary hormone deficiency, 45% had visual field defects and 20% had impaired visual acuity. One year after surgery 60% had no cyst remnants, 50% had a pituitary deficiency, 26% had visual field defects and 12% had impaired visual acuity. No major changes were observed after 5 years. Twelve of the operated patients had a follow-up at 10 years, in eight the cyst remnants or recurrences increased in size over time (p <.05).

    Conclusions: Rathke's cleft cysts with a size less than 10 mm rarely grow and our results indicate that radiological follow-up can be restricted to 5 years. In contrast, progression of postoperative remnants or recurrent cysts is more likely and require long-term follow-up.

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  • 49. Quinkler, Marcus
    et al.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Husebye, Eystein S.
    Kampe, Olle
    A European Emergency Card for adrenal insufficiency can save lives2015In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 26, no 1, p. 75-76Article in journal (Refereed)
  • 50.
    Ragnarsson, Oskar
    et al.
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Muth, Andreas
    Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Calissendorff, Jan
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mineralocorticoid receptor antagonists for primary aldosteronism - appropriate or not?2023In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 188, no 3, p. L1-L2Article in journal (Other academic)
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