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Vouzouneraki, K., Karlsson, F., Holmberg, J., Olsson, T., Berinder, K., Höybye, C., . . . Dahlqvist, P. (2025). Digital voice analysis as a biomarker of acromegaly. Journal of Clinical Endocrinology and Metabolism, 110(4), 983-990, Article ID dgae689.
Open this publication in new window or tab >>Digital voice analysis as a biomarker of acromegaly
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2025 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 110, no 4, p. 983-990, article id dgae689Article in journal (Refereed) Published
Abstract [en]

Context: There is a considerable diagnostic delay in acromegaly, contributing to increased morbidity. Voice changes due to orofacial and laryngeal changes are common in acromegaly.

Objective: Our aim was to explore the use of digital voice analysis as a biomarker for acromegaly using broad acoustic analysis and machine learning.

Methods: Voice recordings from patients with acromegaly and matched controls were collected using a mobile phone at Swedish university hospitals. Anthropometric and clinical data and the Voice Handicap Index (VHI) were assessed. Digital voice analysis of a sustained and stable vowel [a] resulted in 3274 parameters, which were used for training of machine learning models classifying the speaker as “acromegaly” or “control.” The machine learning models were trained with 76% of the data and the remaining 24% was used to assess their performance. For comparison, voice recordings of 50 pairs of participants were assessed by 12 experienced endocrinologists.

Results: We included 151 Swedish patients with acromegaly (13% biochemically active and 10% newly diagnosed) and 139 matched controls. The machine learning model identified patients with acromegaly more accurately (area under the receiver operating curve [ROC AUC] 0.84) than experienced endocrinologists (ROC AUC 0.69). Self-reported voice problems were more pronounced in patients with acromegaly than matched controls (median VHI 6 vs 2, P < .01) with higher prevalence of clinically significant voice handicap (VHI ≥20: 22.5% vs 3.6%).

Conclusion: Digital voice analysis can identify patients with acromegaly from short voice recordings with high accuracy. Patients with acromegaly experience more voice disorders than matched controls.

Place, publisher, year, edition, pages
Oxford University Press, 2025
Keywords
Voice Handicap Index, acromegaly, digital voice analysis, machine learning
National Category
Endocrinology and Diabetes
Research subject
computational linguistics; computational linguistics
Identifiers
urn:nbn:se:umu:diva-231262 (URN)10.1210/clinem/dgae689 (DOI)001341029100001 ()39363748 (PubMedID)2-s2.0-105000481113 (Scopus ID)
Funder
Swedish Research Council, 2018-2024Swedish Research Council, 2017-00626Swedish Association of Local Authorities and RegionsThe Kempe Foundations
Available from: 2024-10-30 Created: 2024-10-30 Last updated: 2025-04-28Bibliographically approved
Imamovic, M., Dahlqvist, P., Ragnarsson, O. & Einarsdottir, M. (2025). [Medicinens ABC] Glukokortikoidinducerad binjurebarkssvikt hos vuxna: [Glucocorticoid-induced adrenal insufficiency]. Läkartidningen, 122(7-8), Article ID 24090.
Open this publication in new window or tab >>[Medicinens ABC] Glukokortikoidinducerad binjurebarkssvikt hos vuxna: [Glucocorticoid-induced adrenal insufficiency]
2025 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 122, no 7-8, article id 24090Article in journal (Refereed) Published
Abstract [sv]

Glukokortikoidinducerad binjurebarkssvikt är ett underdiagnostiserat tillstånd som troligen bidrar till ökad mortalitet bland patienter med pågående eller nyligen avslutad kortisonbehandling. Konsensus om handläggning av glukokortikoidinducerad binjurebarkssvikt hos patienter med kortisonbehandling har tidigare saknats, men internationella riktlinjer har nyligen publicerats och sammanfattas i stora drag i denna ABC-artikel. Dessutom presenteras ett nytt svenskt kortisonkort som är avsett att delas ut till patienter som sätts in på prednisolon >5 mg dagligen eller motsvarande i >3–4 veckor, för att informera patient och vårdpersonal om risken för potentiellt livshotande binjurebarkssvikt.

Abstract [en]

Glucocorticoid-induced adrenal insufficiency is an underdiagnosed condition that possibly contributes to increased mortality. Consensus regarding management of glucocorticoid-induced adrenal insufficiency in patients receiving glucocorticoid therapy has previously been lacking, but the European Society of Endocrinology and the Endocrine Society have recently published joint international guidelines on the diagnosis and treatment, summarized in this article. To further support patients and healthcare professionals, and to prevent a potentially fatal adrenal crisis, a national blue corticosteroid treatment card has been introduced. The card is intended to be provided to patients treated with prednisolone >5 mg daily (or equivalent) for >3-4 weeks.

Place, publisher, year, edition, pages
Läkartidningen förlag, 2025
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-237105 (URN)39935313 (PubMedID)
Available from: 2025-04-01 Created: 2025-04-01 Last updated: 2025-04-02Bibliographically approved
Arlien-Søborg, M. C., Dal, J., Heck, A., Stochholm, K., Husted, E., Feltoft, C. L., . . . Jørgensen, J. O. (2024). Acromegaly management in the nordic countries: a Delphi consensus survey. Clinical Endocrinology, 101(3), 263-273
Open this publication in new window or tab >>Acromegaly management in the nordic countries: a Delphi consensus survey
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2024 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 101, no 3, p. 263-273Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
acromegaly, Delphi, dopamine agonist, growth hormone, growth hormone receptor antagonist, insulin-like growth factor i, somatostatin
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-226954 (URN)10.1111/cen.15095 (DOI)001244261400001 ()38865284 (PubMedID)2-s2.0-85195918201 (Scopus ID)
Funder
Pfizer AB
Available from: 2024-06-24 Created: 2024-06-24 Last updated: 2024-08-20Bibliographically approved
Robèrt, J., Tsatsaris, E., Berinder, K., Bonelli, L., Burman, P., Dahlqvist, P., . . . Edén Engström, B. (2024). Establishing a valid cohort of patients with acromegaly by combining the national patient register with the Swedish pituitary register. Journal of Endocrinological Investigation, 47(4), 995-1003
Open this publication in new window or tab >>Establishing a valid cohort of patients with acromegaly by combining the national patient register with the Swedish pituitary register
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2024 (English)In: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 47, no 4, p. 995-1003Article in journal (Refereed) Published
Abstract [en]

Purpose: The aim of this study was to establish a valid national cohort of patients diagnosed with acromegaly by combining data from the general National Patient Register (NPR) and the disease-specific Swedish Pituitary Register (SPR).

Methods: Patients ≥ 18 years of age at diagnosis of acromegaly reported from 1991 to 2018 who were registered in the NPR and/or SPR were included. The diagnosis of acromegaly was considered correct for patients identified in both registers or confirmed through chart review. Medical records were reviewed in two of Sweden´s six health care regions if the patient was reported only in the NPR. An algorithm for the NPR, with criteria requiring multiple diagnosis registrations and tumour and/or surgery codes, was constructed to reduce the number of patients to review in the remaining four regions.

Results: A total of 1866 patients were identified. Among these, 938 were reported in both registers. After application of the algorithm and chart review, the diagnosis was confirmed for 83 of the 906 patients found only in the NPR. Among 22 patients only registered in the SPR, a review of medical records confirmed acromegaly in 13. This resulted in a total of 1034 cases with acromegaly during the study period. The incidence rate of acromegaly in Sweden 1991–2018 was calculated to 4.0/million/year in the entire population and 5.1/million/year among subjects ≥ 18 years of age.

Conclusion: The combination of the SPR and NPR established a valid cohort of patients diagnosed with acromegaly and increased the estimated incidence in Sweden.

Place, publisher, year, edition, pages
Springer, 2024
Keywords
Acromegaly, ICD codes, Incidence, Patient register
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-215868 (URN)10.1007/s40618-023-02217-x (DOI)001086152500001 ()37851314 (PubMedID)2-s2.0-85174407981 (Scopus ID)
Funder
Region UppsalaRegion ÖstergötlandPfizer AB
Available from: 2023-11-01 Created: 2023-11-01 Last updated: 2024-08-15Bibliographically approved
Faresjö, Å., Theodorsson, E., Stomby, A., Quist, H., Jones, M. P., Östgren, C. J., . . . Faresjö, T. (2024). Higher hair cortisol levels associated with previous cardiovascular events and cardiovascular risks in a large cross-sectional population study. BMC Cardiovascular Disorders, 24(1), Article ID 536.
Open this publication in new window or tab >>Higher hair cortisol levels associated with previous cardiovascular events and cardiovascular risks in a large cross-sectional population study
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2024 (English)In: BMC Cardiovascular Disorders, E-ISSN 1471-2261, Vol. 24, no 1, article id 536Article in journal (Refereed) Published
Abstract [en]

Background: Stress is today a common feature of patients seeking medical care and a growing public health issue in society. A method has been developed to measure biological chronic stress by Hair Cortisol Concentrations (HCC). This biomarker, for chronic stress, captures information about cumulative cortisol levels over the course of several months. Long-term stress might be one of the factors contributing to the onset of cardiovascular conditions and also affecting different risk factors. The aim of this study was to analyse the association between Hair Cortisol Concentrations and previous cardiovascular diseases and cardiovascular risk factors.

Methods: The method of measuring chronic stress by Hair Cortisol Concentration was applied in a large Swedish national observational cross-sectional study. A population-based random sample of N = 4,821 Swedish middle-aged men and women was analysed for hair cortisol levels in relation to diagnosed previous cardiovascular diseases and biologically measured cardiovascular risk factors.

Results: Long-term stress, measured by hair cortisol, was significantly associated with the classical cardiovascular risk factors hypertension and high cholesterol, but not smoking. Those with elevated HCC levels also had a significantly increased pre-history of myocardial infarction, type 2 diabetes, atrial fibrillation and by-pass surgery, but not regarding stroke, angina pectoris or sleep apnoea. Higher HCC was significantly associated (p < 0.001) with Body mass index and waist circumference, but only for females. HCC was also associated with the risk markers leukocytes, and high-sensitivity CRP, indicating a possible linkage between HCC and inflammation and hypothetically also the bodily immune defense. No association was found between perceived stress and HCC.

Conclusions: An overall conclusion of our results is that health care should put more emphasis on patients reporting that they have been exposed to long term stress. Altogether, these analyses of Hair cortisol levels in a large middle-aged population show that chronically elevated cortisol levels represent a relevant and significant factor associated with cardiovascular diseases and classical cardiovascular risk factors.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2024
Keywords
Cardiovascular diseases, Cardiovascular risks, Cortisol, Hair, Stress
National Category
Cardiology and Cardiovascular Disease Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:umu:diva-230967 (URN)10.1186/s12872-024-04221-2 (DOI)001328965700001 ()39367323 (PubMedID)2-s2.0-85205818747 (Scopus ID)
Funder
AFA Insurance, 160340Region Östergötland
Available from: 2024-10-29 Created: 2024-10-29 Last updated: 2025-02-20Bibliographically approved
Imamovic, M., Vågberg, M., Cederquist, K. & Dahlqvist, P. (2024). Hyperinsulinemic hypoglycemia in a patient with a mutation in the insulin receptor. JCEM Case Reports, 2(12), Article ID luae221.
Open this publication in new window or tab >>Hyperinsulinemic hypoglycemia in a patient with a mutation in the insulin receptor
2024 (English)In: JCEM Case Reports, E-ISSN 2755-1520, Vol. 2, no 12, article id luae221Article in journal (Refereed) Published
Abstract [en]

Hyperinsulinemic hypoglycemias resulting from variants in the insulin receptor (INSR) gene are rare but clinically important disorders. We present a male patient in his 30s, experiencing recurrent postprandial hypoglycemic events. Endocrine evaluation revealed an elevated insulin-to-C-peptide ratio. A hypoglycemia gene panel, using next-generation sequencing, identified a heterozygous nonsense variant in the INSR gene (NM_000208.4) c.3079C > T, p.(Arg1027*). Initial treatment with diazoxide reduced hypoglycemic symptoms and led to weight loss and decreased hemoglobin A1c due to reduced compensatory carbohydrate intake. However, limiting side effects on diazoxide prompted a treatment switch to lanreotide with maintained absence of hypoglycemic events. This case highlights the importance of considering variants in the INSR gene as a differential diagnosis in hyperinsulinemic hypoglycemia cases, even in adults.

Place, publisher, year, edition, pages
Endocrine Society, 2024
Keywords
INSR, insulin receptor gene, hyperinsulinemia, hypoglycemia, insulin-to-c-peptide ratio
National Category
Endocrinology and Diabetes
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-237103 (URN)10.1210/jcemcr/luae221 (DOI)
Available from: 2025-04-01 Created: 2025-04-01 Last updated: 2025-05-07Bibliographically approved
Lakshmikanth, T., Consiglio, C., Sardh, F., Forlin, R., Wang, J., Tan, Z., . . . Brodin, P. (2024). Immune system adaptation during gender-affirming testosterone treatment. Nature, 633(8028), 155-164
Open this publication in new window or tab >>Immune system adaptation during gender-affirming testosterone treatment
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2024 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 633, no 8028, p. 155-164Article in journal (Refereed) Published
Abstract [en]

Infectious, inflammatory and autoimmune conditions present differently in males and females. SARS-CoV-2 infection in naive males is associated with increased risk of death, whereas females are at increased risk of long COVID1, similar to observations in other infections2. Females respond more strongly to vaccines, and adverse reactions are more frequent3, like most autoimmune diseases4. Immunological sex differences stem from genetic, hormonal and behavioural factors5 but their relative importance is only partially understood6–8. In individuals assigned female sex at birth and undergoing gender-affirming testosterone therapy (trans men), hormone concentrations change markedly but the immunological consequences are poorly understood. Here we performed longitudinal systems-level analyses in 23 trans men and found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. These findings in trans men are corroborated by sex-divergent responses in public datasets and illustrate the dynamic regulation of human immunity by sex hormones, with implications for the health of individuals undergoing hormone therapy and our understanding of sex-divergent immune responses in cisgender individuals.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-229631 (URN)10.1038/s41586-024-07789-z (DOI)001320019300001 ()39232147 (PubMedID)2-s2.0-85203192791 (Scopus ID)
Funder
Swedish Research Council, 2019-01495Swedish Research Council, 2020-06190Swedish Research Council, 2020-02889Swedish Research Council, 2021-06529Swedish Research Council, 2021-05450Swedish Research Council, 2022-01567Swedish Research Council, 2021-03118Swedish Research Council, 2020-02608Karolinska Institute, 2018-02229Karolinska Institute, 2019-00975Karolinska Institute, 2020-02139Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, GG2020-0040Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, 2141Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, 2227Knut and Alice Wallenberg Foundation, 2023-0344Knut and Alice Wallenberg Foundation, 2019.0191Knut and Alice Wallenberg Foundation, 2018.0325Knut and Alice Wallenberg Foundation, 2022.0146Tore Nilsons Stiftelse för medicinsk forskningMagnus Bergvall FoundationSwedish Society for Medical Research (SSMF), CG-22-0148-H-02Swedish Society of Medicine
Note

Correction: Tadepally Lakshmikanth, Camila Consiglio, Fabian Sardh, Rikard Forlin, Jun Wang, Ziyang Tan et. al. Author Correction: Immune system adaptation during gender-affirming testosterone treatment, Nature, 2024, Vol. 634, Issue 8033, Pages E5, DOI: 10.1038/s41586-024-08081-w

Available from: 2024-09-16 Created: 2024-09-16 Last updated: 2025-04-24Bibliographically approved
Bergthorsdottir, R., Esposito, D., Olsson, D. S., Ragnarsson, O., Dahlqvist, P., Bensing, S., . . . Nyberg, F. (2024). Increased risk of hospitalization, intensive care and death due to covid-19 in patients with adrenal insufficiency: a Swedish nationwide study. Journal of Internal Medicine, 295(3), 322-330
Open this publication in new window or tab >>Increased risk of hospitalization, intensive care and death due to covid-19 in patients with adrenal insufficiency: a Swedish nationwide study
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2024 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 295, no 3, p. 322-330Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
adrenal insufficiency, COVID-19, death, glucocorticoids, hospitalization, intensive care
National Category
General Practice Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:umu:diva-215852 (URN)10.1111/joim.13731 (DOI)001087945500001 ()37850585 (PubMedID)2-s2.0-85174246552 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation, KAW 2020.0299Swedish Research Council, 2021-05045Swedish Research Council, 2021-05450Swedish Research Council, 2019‐01112Swedish Association of Local Authorities and Regions, ALFGBG‐938453Swedish Association of Local Authorities and Regions, ALFGBG‐971130Swedish Association of Local Authorities and Regions, ALFGBG‐960884Swedish Association of Local Authorities and Regions, ALFGBG‐978954Swedish Association of Local Authorities and Regions, ALFGBG‐966066Swedish Research Council Formas, 2020-02828Forte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2023-10-30 Created: 2023-10-30 Last updated: 2025-04-24Bibliographically approved
Imamovic, M., Bäcklund, N., Lundstedt, S., Brattsand, G., Aardal, E. & Dahlqvist, P. (2024). Salivary cortisol and cortisone are stable after long-term storage. Scandinavian Journal of Clinical and Laboratory Investigation, 84(6), 405-409
Open this publication in new window or tab >>Salivary cortisol and cortisone are stable after long-term storage
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2024 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 84, no 6, p. 405-409Article in journal (Refereed) Published
Abstract [en]

Frozen saliva samples are often used for later determination of salivary glucocorticoids in research studies on stress and endocrine disorders. We studied the stability of cortisol and cortisone in saliva after six years of storage at −80 °C by repeated analysis of 153 stored aliquots, collected with Salivette®, using liquid chromatography tandem mass spectrometry. We found a very high agreement between the first and the repeated measurement after six years at −80 °C, for both cortisol and cortisone concentrations (rs= 0.96 and rs= 0.98, respectively). Passing-Bablok regression equations were y = 0.02 + 1.00x and y = 0.02 + 1.14x for cortisol and cortisone, respectively. We conclude that salivary cortisol and cortisone concentrations remain essentially unaltered after six years of storage at −80 °C.

Place, publisher, year, edition, pages
Taylor & Francis, 2024
Keywords
biobanking, Liquid chromatography, long-term storage, mass spectrometry, pre-analytical phase, salivary cortisol, salivary cortisone, stability, ultra-low temperature
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:umu:diva-229901 (URN)10.1080/00365513.2024.2403005 (DOI)001310442200001 ()39263928 (PubMedID)2-s2.0-85203711428 (Scopus ID)
Funder
Region Västerbotten
Available from: 2024-09-25 Created: 2024-09-25 Last updated: 2025-03-25Bibliographically approved
Bäcklund, N., Lundstedt, S., Tornevi, A., Wihlbäck, A.-C., Olsson, T., Dahlqvist, P. & Brattsand, G. (2024). Salivary cortisol and cortisone can circumvent confounding effects of oral contraceptives in the short synacthen test. Journal of Clinical Endocrinology and Metabolism, 109(7), 1899-1906
Open this publication in new window or tab >>Salivary cortisol and cortisone can circumvent confounding effects of oral contraceptives in the short synacthen test
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2024 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 109, no 7, p. 1899-1906Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Oxford University Press, 2024
Keywords
short Synacthen test, salivary cortisol, salivary cortisone, oral contraceptives, adrenal insufficiency, reference limits
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-222629 (URN)10.1210/clinem/dgad763 (DOI)001140071500001 ()38173358 (PubMedID)2-s2.0-85196301347 (Scopus ID)
Funder
Region VästerbottenUmeå University
Available from: 2024-03-22 Created: 2024-03-22 Last updated: 2024-07-02Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6471-9503

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