umu.sePublications
Change search
Refine search result
1 - 40 of 40
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    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
    Kirurgi, Sahlgrenska, Göteborg.
    Naredi, Silvana
    Anestesiologi, Sahlgrenska, Göteborg.
    Liver resection is not associated with decreased cortisol levels.Article in journal (Refereed)
    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.

    Key words: gastrointestinal surgical procedures, adrenal insufficiency, hydrocortisone

  • 2.
    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.

  • 3.
    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.

  • 4. 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.

  • 5.
    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

  • 6.
    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.

  • 7.
    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 (Basingstoke), 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.

  • 8.
    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)
  • 9.
    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.

  • 10.
    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)
  • 11.
    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, 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.

  • 12.
    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.

  • 13. 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.

  • 14. 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.

  • 15. 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, ISSN 2045-2322, 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.

  • 16. 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.

  • 17.
    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.

  • 18. 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)
  • 19.
    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.

  • 20. 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.

  • 21.
    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.

  • 22. 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, ISSN 1932-6203, 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.

  • 23. 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.

  • 24. 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.

  • 25.
    Olivecrona, Zandra
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and 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.
    Acute neuro-endocrine profile and prediction of outcome after severe brain injury2013In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, 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.

  • 26.
    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)
  • 27. 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.

  • 28. 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)
  • 29. Ragnarsson, Oskar
    et al.
    Johannsson, Gudmundur
    Geterud, Kjell
    Lodding, Par
    Dahlqvist, Per
    Department of Endocrinology, Diabetes and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Inadequate testosterone suppression after medical and subsequent surgical castration in a patient with prostate cancer.2013In: BMJ case reports, ISSN 1757-790X, Vol. 2013Article in journal (Refereed)
    Abstract [en]

    Androgen deprivation is a cornerstone in prostate cancer management. We present a 69-year-old man, with a poorly differentiated prostate cancer with skeletal and lymph node metastases. After medical and subsequent surgical castration serum testosterone concentrations remained inappropriately high (4.9 and 4.5 nmol/L; castration range < 0.5). For cancer staging a CT was performed which showed bilateral adrenal enlargement. Endocrine workup revealed elevated levels of adrenal androgens and adrenal precursors. Mutation analysis confirmed a non-classical 21-hydroxylase deficiency, that is, a mild form of congenital adrenal hyperplasia (CAH). To suppress adrenocorticotrophic hormone and the excess adrenal androgen secretion, treatment with hydrocortisone and prednisolone was started with success. Inadequate testosterone suppression after castration due to previously undiagnosed CAH has not previously been reported. Considering the estimated prevalence of 1% in selected populations, non-classical CAH should be considered when testosterone is not adequately suppressed after castration in men with prostate cancer.

  • 30. Ragnarsson, Oskar
    et al.
    Olsson, Daniel S.
    Chantzichristos, Dimitrios
    Papakokkinou, Eleni
    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 Engström, Britt
    Burman, Pia
    Bonelli, Lorenza
    Follin, Cecilia
    Petranek, David
    Erfurth, Eva Marie
    Wahlberg, Jeanette
    Ekman, Bertil
    Åkerman, Anna-Karin
    Schwarcz, Erik
    Bryngelsson, Ing-Liss
    Johannsson, Gudmundur
    The incidence of Cushing's disease: a nationwide Swedish study2019In: Pituitary, ISSN 1386-341X, E-ISSN 1573-7403, Vol. 22, no 2, p. 179-186Article in journal (Refereed)
    Abstract [en]

    Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.

    Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.

    Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05).

    Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.

  • 31. Ragnarsson, Oskar
    et al.
    Olsson, Daniel S.
    Papakokkinou, Eleni
    Chantzichristos, Dimitrios
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Segerstedt, Elin
    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.
    Petersson, Maria
    Berinder, Katarina
    Bensing, Sophie
    Höybye, Charlotte
    Edén-Engstrom, Britt
    Burman, Pia
    Bonelli, Lorenza
    Follin, Cecilia
    Petranek, David
    Erfurth, Eva Marie
    Wahlberg, Jeanette
    Ekman, Bertil
    Åkerman, Anna-Karin
    Schwarcz, Erik
    Bryngelsson, Ing-Liss
    Johannsson, Gudmundur
    Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study2019In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 6, p. 2375-2384Article in journal (Refereed)
    Abstract [en]

    Context: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable.

    Objective: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD.

    Design, Patients, and Methods: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality.

    Results: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome.

    Conclusion: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.

  • 32. Ragnarsson, Oskar
    et al.
    Stomby, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Ryhov County Hospital, Jönköping, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Evang, Johan A.
    Ryberg, Mats
    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.
    Bollerslev, Jens
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Johannsson, Gudmundur
    Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 82, p. 117-125Article in journal (Refereed)
    Abstract [en]

    Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 commis matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p < 0.001) and in the right inferior occipital gyrus (p < 0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p = 0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p < 0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p < 0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function.

  • 33. Risedal, Anette
    et al.
    Mattsson, Bengt
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nordborg, Claes
    Olsson, Tommy
    Johansson, Barbro B
    Environmental influences on functional outcome after a cortical infarct in the rat.2002In: Brain Research Bulletin, ISSN 0361-9230, E-ISSN 1873-2747, Vol. 58, no 3, p. 315-21Article in journal (Refereed)
    Abstract [en]

    The effect of postoperative housing conditions on functional outcome and brain-derived neurotrophic factor (BDNF) gene expression was evaluated 1 month after a distal ligation of the right middle cerebral artery (MCA) in spontaneously hypertensive rats. Two days postoperatively the rats were randomized into four groups; individually housed with no equipment (deprived group), individually housed with free access to a connected running wheel (running group), housed together in a large cage with no equipment (social group) or in the same size of cage furnished with bars, chains and various things to manipulate (enriched group). The enriched rats had significantly higher scores when crossing a rotating horizontal rod than deprived and running rats. The social group performed significantly better than the deprived group. The BDNF gene expression in the ipsi- and contralateral cortex, thalamus, hippocampus and cerebellum did not significantly differ between the groups. The weight of the adrenal glands was significantly increased in running rats suggesting that postischemic running may be stressful. We conclude that the beneficial effect of postischemic environmental enrichment is likely to be a combination of social and various physical activities, and that BDNF gene expression 1 month after a cortical infarct did not correlate with functional outcome.

  • 34. Rosén, Thord
    et al.
    Burman, Pia
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dahm, Peter
    Edén-Engström, Britt
    Ekman, Bertil
    Höybye, Charlotte
    Jakobsson, Karl-Erik
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Tölli, Anna
    Valdemarsson, Stig
    Ulfarsson, Trandur
    [Traumatic brain injury can cause pituitary deficiency. Suggestions for guidelines for assessment of pituitary function.]2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 12, p. 629-632Article in journal (Other academic)
    Abstract [sv]

    Traumatisk hjärnskada (traumatic brain injury, TBI) är en av de vanligaste orsakerna till död och nedsatt funktion hos människor i arbetsför ålder. Patienter som överlever svåra skallskador utgör en växande patientkategori inom dagens sjukvård. På senare år har det aktualiserats att allvarligt skalltrauma kan ge skador i hypofys–hypotalamusregionen. Det är angeläget att dessa patienter utreds för eventuell hypofyssvikt så att hormonell substitutionsterapi kan inledas om endokrin insufficiens fastställs. Detta kan förhoppningsvis underlätta efterföljande rehabilitering och därmed förbättra pro­gnosen. Vi presenterar här ett förslag till riktlinjer för utvärdering av hypofysfunktionen hos TBI-patienter. Samtidigt vill vi informera en bredare läsekrets om TBI-begreppet.

  • 35.
    Rönnbäck, Annica
    et al.
    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.
    Bergström, Sven-Anders
    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.
    Diurnal effects of enriched environment in immediate early gene expression in the rat brain2005In: Brain research, ISSN 0006-8993, Vol. 1046, no 1-2, p. 137-144Article in journal (Refereed)
    Abstract [en]

    Rodents housed in an enriched environment (EE) show increased neuronal plasticity with enhanced long-term potentiation and memory performance. We report an EE-induced increase in NGFI-A and Krox-20 mRNA expression exclusively during the dark period of the day. In addition, EE-housed rats showed considerable diurnal variation in NGFI-A, Krox-20, and NGFI-B mRNA expression which was absent in single-housed rats. Thus, EE-induced molecular changes are more evident during the dark phase when the rats have higher motor and exploratory activity. This is important to take into account in future studies of molecular mediators of experience-dependent neuronal plasticity.

  • 36.
    Rönnbäck, Annica
    et al.
    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.
    Svensson, Per-Arne
    Jernås, Margareta
    Carlsson, Björn
    Carlsson, Lena M S
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Gene expression profiling of the rat hippocampus one month after focal cerebral ischemia followed by enriched environment2005In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 385, no 2, p. 173-178Article in journal (Refereed)
    Abstract [en]

    Functional recovery after experimental stroke in rats is enhanced by environmental enrichment by stimulating plastic changes in brain regions outside the lesion, but the molecular mechanisms are not known. We investigated the effect of environmental enrichment after focal cerebral ischemia on cognitive recovery and hippocampal gene expression using microarray analysis. Rats placed in enriched environment (EE) for 1 month after middle cerebral artery occlusion (MCAo) showed significantly improved spatial memory in the Morris water maze compared to rats housed alone after MCAo. Microarray analysis suggested several EE-induced differences in neuronal plasticity-related genes, but these changes could not be confirmed by quantitative real-time PCR. This study highlights some of the potential problems associated with gene expression profiling of brain tissues. Further studies at earlier time points and in additional subregions of the brain are of interest in the search for molecular mechanisms behind EE-induced neuronal plasticity after ischemic stroke.

  • 37. Saevik, Å B
    et al.
    Åkerman, A-K
    Grønning, K
    Nermoen, I
    Valland, S F
    Finnes, T E
    Isaksson, M
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bergthorsdottir, R
    Ekwall, O
    Skov, J
    Nedrebø, B G
    Hulting, A-L
    Wahlberg, J
    Svartberg, J
    Höybye, C
    Bleskestad, I H
    Jørgensen, A P
    Kämpe, O
    Øksnes, M
    Bensing, S
    Husebye, E S
    Clues for early detection of autoimmune Addison's disease - myths and realities2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 2, p. 190-199Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Early detection of autoimmune Addison's disease (AAD) is important as delay in diagnosis may result in a life-threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well-described, but methodical investigations are scarce.

    OBJECTIVE: Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD.

    MATERIAL AND METHODS: A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978-2016. Scrutiny of medical records provided patient data and laboratory values.

    RESULTS: Low sodium occurred in 207 of 247 (84%), but only one-third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty-three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L(-1) [1-668]) and significantly lower in individuals with adrenal crisis (38 nmol L(-1) [2-442]) than in those without (81 nmol L(-1) [1-668], P < 0.001).

    CONCLUSION: The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD, and on clinical suspicion bring about assay of cortisol and ACTH. Presence of 21-hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis.

  • 38.
    Stomby, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Region Jönköping County, Jönköping, Sweden.
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Evang, Johan Arild
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bollerslev, Jens
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johannsson, Gudmundur
    Ragnarsson, Oskar
    Elevated resting-state connectivity in the medial temporal lobe and the prefrontal cortex among patients with Cushing's syndrome in remission2019In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 180, no 5, p. 329-338Article in journal (Refereed)
    Abstract [en]

    Objective: Cushing's syndrome is associated with long-term cognitive deficits and affective symptoms such as depression and anxiety. The alterations in brain function under lying these deficits after Cushing's syndrome are unclear and therefore we aimed to explore alterations in resting-state functional connectivity in patients with Cushing's syndrome in remission. Design: Cross-sectional case-control study. Methods: Nineteen women with Cushing's syndrome in remission for a median time of 7 years (IQR: 6-10) and a mean age of 45 years were included at three university clinics. These patients and 38 age-matched female controls underwent brain imaging at a single center. The main outcome measure was functional connectivity at rest, measured with functional magnetic resonance imaging. Results: The medial temporal lobe (MTL) and prefrontal cortex networks, exhibited elevated functional connectivity among patients compared to controls. The degree of elevated functional connectivity in the MTL was negatively associated with time in remission. Conclusions: Resting-state functional connectivity within glucocorticoid receptor-rich regions, particularly the MTL and medial prefrontal cortex, was increased in patients. These differences in connectivity may provide a neural basis for the cognitive deficits and affective symptoms commonly experienced by patients with Cushing's syndrome in remission.

  • 39. Ueland, Grethe Å.
    et al.
    Methlie, Paal
    Øksnes, Marianne
    Thordarson, Hrafnkell B.
    Sagen, Jørn
    Kellmann, Ralf
    Mellgren, Gunnar
    Ræder, Maria
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Dahl, Sandra R.
    Thorsby, Per M.
    Løvås, Kristian
    Husebye, Eystein S.
    The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS2018In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 4, p. 1696-1703Article in journal (Refereed)
    Abstract [en]

    Background: The cosyntropin test is used to diagnose adrenal insufficiency (AI) and nonclassical congenital adrenal hyperplasia (NCCAH). Current cutoffs for cortisol and 17-hydroxyprogesterone (17-OHP) are derived from nonstandardized immunoassays. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers direct measurement of steroids, prompting the need to re-establish normal ranges. Objective: The goal of this study was to define cutoff values for cortisol and 17-OHP in serum by LC-MS/MS 30 and 60 minutes after intravenous administration of 250 µg tetracosactide acetate to healthy volunteers and to compare the results with LC-MS/MS with routine immunoassays. Methods: Cosyntropin testing was performed in healthy subjects (n = 138) and in patients referred for evaluation of adrenocortical function (n = 94). Steroids were assayed by LC-MS/MS and compared with two immunoassays used in routine diagnostics (Immulite and Roche platforms). The cutoff level for cortisol was defined as the 2.5% percentile in healthy subjects not using oral estrogens (n = 121) and for 17-OHP as the 97.5% percentile. Results: Cortisol cutoff levels for LC-MS/MS were 412 and 485 nmol/L at 30 and 60 minutes, respectively. Applying the new cutoffs, 13 of 60 (22%) subjects who had AI according to conventional criteria now had a normal test result. For 17-OHP, the cutoff levels were 8.9 and 9.0 nmol/L at 30 and 60 minutes, respectively. Conclusions: LC-MS/MS provides cutoff levels for cortisol and 17-OHP after cosyntropin stimulation that are lower than those based on immunoassays, possibly because cross-reactivity between steroid intermediates and cortisol is eliminated. This reduces the number of false-positive tests for AI and false-negative tests for NCCAH.

  • 40.
    Vouzouneraki, Konstantina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Forsgren, Maria
    Wärn, Maria
    Persson, Jenny Tiberg
    Wik, Helena
    Dahlgren, Christina
    Nilsson, Ann-Sofie
    Alkebro, Caroline
    Burman, Pia
    Erfurth, Eva-Marie
    Wahlberg, Jeanette
    Åkerman, Anna-Karin
    Høbye, Charlotte
    Ragnarsson, Oskar
    Edén Engström, Britt
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Temporal relationship of sleep apnea and acromegaly: a nationwide study2018In: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 62, no 2, p. 456-463Article in journal (Refereed)
    Abstract [en]

    Purpose:

    Patients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis.

    Methods: Cross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients' follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea investigations.

    Results: Of the 259 participants, 75 (29%) were diagnosed with sleep apnea before the study start. In 43 (57%) of these patients, sleep apnea had been diagnosed before the diagnosis of acromegaly. After clinical assessment and sleep studies, sleep apnea was diagnosed in an additional 20 patients, yielding a total sleep apnea prevalence of 37%. Higher sleep apnea risk was associated with higher BMI, waist circumference, and index finger circumference. Sleep apnea was more frequent among patients with S-IGF-1 levels in the highest quartile.

    Conclusion: Sleep apnea is common among patients with acromegaly, and is often diagnosed prior to their acromegaly diagnosis. These results support early screening for sleep apnea in patients with acromegaly and awareness for acromegaly in patients with sleep apnea.

1 - 40 of 40
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf