31 results on '"Øksnes, M."'
Search Results
2. Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response
- Author
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Helseth, R., Carlsen, S. M., Bollerslev, J., Svartberg, J., Øksnes, M., Skeie, S., and Fougner, S. L.
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- 2016
- Full Text
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3. The short cosyntropin test revisited - new normal reference range using LCMSMS
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Øksnes M, Løvås K, Ueland Gå, Sagen J, P. Methlie, Husebye Es, Kellmann R, Ræder M, Thordarson Hb, Dahlqvist P, Dahl, Mellgren G, and Thorsby Pm
- Subjects
New normal ,business.industry ,Cosyntropin test ,Reference range ,Nuclear medicine ,business ,Mathematics - Published
- 2018
4. Clues for early detection of autoimmune Addison's disease - myths and realities
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Saevik, Å B, Åkerman, A-K, Grønning, K, Nermoen, I, Valland, S F, Finnes, T E, Isaksson, M, Dahlqvist, Per, 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, Saevik, Å B, Åkerman, A-K, Grønning, K, Nermoen, I, Valland, S F, Finnes, T E, Isaksson, M, Dahlqvist, Per, 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, and Husebye, E S
- Abstract
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.
- Published
- 2018
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5. Clues for early detection of autoimmune Addison's disease : myths and realities
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Sævik, Åse Bjorvatn, Åkerman, A.‐K., Grønning, Kjersti, Nermoen, I., Valland, S. F., Finnes, T. E., Isaksson, M., Dahlqvist, P., Bergthorsdottir, R., Ekwall, O., Skov, J., Nedrebø, B. G., Hulting, A.‐L., Wahlberg, Jeanette, Svartberg, J., Höybye, C., Bleskestad, I. H., Jørgensen, A. P., Kämpe, O., Øksnes, M., Bensing, S., Husebye, E. S., Sævik, Åse Bjorvatn, Åkerman, A.‐K., Grønning, Kjersti, Nermoen, I., Valland, S. F., Finnes, T. E., Isaksson, M., Dahlqvist, P., Bergthorsdottir, R., Ekwall, O., Skov, J., Nedrebø, B. G., Hulting, A.‐L., Wahlberg, Jeanette, Svartberg, J., Höybye, C., Bleskestad, I. H., Jørgensen, A. P., Kämpe, O., Øksnes, M., Bensing, S., and Husebye, E. S.
- Abstract
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., Funding Agencies:Regional Health Authorities of Western NorwayUniversity of BergenThe Norwegian Research councilThe Swedish Research CouncilTorsten and Ragnar Söderberg FoundationsThe regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutetthe Swedish Society for Medical Research, the Swedish Society of MedicineTore Nilson's Foundation for Medical ResearchÅke Wiberg Foundation
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- 2018
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6. Clues for early detection of autoimmune Addison's disease - myths and realities
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Saevik, Å. B., primary, Åkerman, A.-K., additional, Grønning, K., additional, Nermoen, I., additional, Valland, S. F., additional, Finnes, T. E., additional, Isaksson, M., additional, Dahlqvist, P., additional, Bergthorsdottir, R., additional, Ekwall, O., additional, Skov, J., additional, Nedrebø, B. G., additional, Hulting, A.-L., additional, Wahlberg, J., additional, Svartberg, J., additional, Höybye, C., additional, Bleskestad, I. H., additional, Jørgensen, A. P., additional, Kämpe, O., additional, Øksnes, M., additional, Bensing, S., additional, and Husebye, E. S., additional
- Published
- 2017
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7. Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response
- Author
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Helseth, R., primary, Carlsen, S. M., additional, Bollerslev, J., additional, Svartberg, J., additional, Øksnes, M., additional, Skeie, S., additional, and Fougner, S. L., additional
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- 2015
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8. Preoperative octreotide treatment of acromegaly: long-term results of a randomised controlled trial
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Fougner, S L, primary, Bollerslev, J, additional, Svartberg, J, additional, Øksnes, M, additional, Cooper, J, additional, and Carlsen, S M, additional
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- 2014
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9. Improving diagnostic precision in primary ovarian insufficiency using comprehensive genetic and autoantibody testing.
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Vogt EC, Bratland E, Berland S, Berentsen R, Lund A, Björnsdottir S, Husebye E, and Øksnes M
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- Humans, Female, Mutation, Cross-Sectional Studies, Autoantibodies, Prospective Studies, Fragile X Mental Retardation Protein genetics, Primary Ovarian Insufficiency diagnosis, Primary Ovarian Insufficiency genetics
- Abstract
Study Question: Is it possible to find the cause of primary ovarian insufficiency (POI) in more women by extensive screening?, Summary Answer: Adding next generation sequencing techniques including a POI-associated gene panel, extended whole exome sequencing data, as well as specific autoantibody assays to the recommended diagnostic investigations increased the determination of a potential etiological diagnosis of POI from 11% to 41%., What Is Known Already: POI affects ∼1% of women. Clinical presentations and pathogenic mechanisms are heterogeneous and include genetic, autoimmune, and environmental factors, but the underlying etiology remains unknown in the majority of cases., Study Design, Size, Duration: Prospective cross-sectional study of 100 women with newly diagnosed POI of unknown cause consecutively referred to Haukeland University Hospital, Bergen, Norway, January 2019 to December 2021., Participants/materials, Setting, Methods: In addition to standard recommended diagnostic investigations including screening for chromosomal anomalies and premutations in the fragile X mental retardation 1 gene (FMR1) we used whole exome sequencing, including targeted analysis of 103 ovarian-related genes, and assays of autoantibodies against steroid cell antigens., Main Results and the Role of Chance: We identified chromosomal aberrations in 8%, FMR1 premutations in 3%, genetic variants related to POI in 16%, and autoimmune POI in 3%. Furthermore in 11% we identified POI associated genetic Variants of unknown signifcance (VUS). A homozygous pathogenic variant in the ZSWIM7 gene (NM_001042697.2) was found in two women, corroborating this as a novel cause of monogenic POI. No associations between phenotypes and genotypes were found., Limitations, Reasons for Caution: Use of candidate genetic and autoimmune markers limit the possibility to discover new markers. To further investigate the genetic variants, family studies would have been useful. We found a relatively high proportion of genetic variants in women from Africa and lack of genetic diversity in the genomic databases can impact diagnostic accuracy., Wider Implications of the Findings: Since no specific clinical or biochemical markers predicted the underlying cause of POI discussion of which tests should be part of diagnostic screening in clinical practice remains open. New technology has altered the availability and effectiveness of genetic testing, and cost-effectiveness analyses are required to aid sustainable diagnostics., Study Funding/competing Interest(s): The study was supported by grants and fellowships from Stiftelsen Kristian Gerhard Jebsen, the Novonordisk Foundation, the Norwegian Research Council, University of Bergen, and the Regional Health Authorities of Western Norway. The authors declare no conflict of interest., Trial Registration Number: NCT04082169., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)
- Published
- 2024
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10. Approach to the Patient: Diagnosis of Primary Adrenal Insufficiency in Adults.
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Øksnes M and Husebye ES
- Subjects
- Adult, Humans, Autoantibodies, Steroid 21-Hydroxylase, Addison Disease complications, Addison Disease diagnosis, Adrenal Cortex
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- 2023
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11. Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional study.
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Sævik ÅB, Ueland G, Åkerman AK, Methlie P, Quinkler M, Jørgensen AP, Höybye C, Debowska AWJ, Nedrebø BG, Dahle AL, Carlsen S, Tomkowicz A, Sollid ST, Nermoen I, Grønning K, Dahlqvist P, Grimnes G, Skov J, Finnes T, Valland SF, Wahlberg J, Holte SE, Kämpe O, Bensing S, Husebye ES, and Øksnes M
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- Humans, Male, Female, Cross-Sectional Studies, Quality of Life, Leptin, Glucocorticoids, Inflammation, Cosyntropin, Biomarkers, Neoplasm Proteins, Extracellular Matrix Proteins, Addison Disease complications, Cardiovascular Diseases diagnosis, Cardiovascular Diseases complications
- Abstract
Objective: Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood., Design: Cross-sectional study., Methods: We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH., Results: Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = -0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (-0.15 normalized protein expression [NPX], P = .0001, and -0.25 NPX, P = .0003, respectively)., Conclusions: We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)
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- 2023
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12. High-resolution daily profiles of tissue adrenal steroids by portable automated collection.
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Upton TJ, Zavala E, Methlie P, Kämpe O, Tsagarakis S, Øksnes M, Bensing S, Vassiliadi DA, Grytaas MA, Botusan IR, Ueland G, Berinder K, Simunkova K, Balomenaki M, Margaritopoulos D, Henne N, Crossley R, Russell G, Husebye ES, and Lightman SL
- Subjects
- Humans, Tetrahydrocortisol, Chromatography, Liquid, Steroids, Sleep
- Abstract
Rhythms are intrinsic to endocrine systems, and disruption of these hormone oscillations occurs at very early stages of the disease. Because adrenal hormones are secreted with both circadian and ultradian periods, conventional single-time point measurements provide limited information about rhythmicity and, crucially, do not provide information during sleep, when many hormones fluctuate from nadir to peak concentrations. If blood sampling is attempted overnight, then this necessitates admission to a clinical research unit, can be stressful, and disturbs sleep. To overcome this problem and to measure free hormones within their target tissues, we used microdialysis, an ambulatory fraction collector, and liquid chromatography-tandem mass spectrometry to obtain high-resolution profiles of tissue adrenal steroids over 24 hours in 214 healthy volunteers. For validation, we compared tissue against plasma measurements in a further seven healthy volunteers. Sample collection from subcutaneous tissue was safe, well tolerated, and allowed most normal activities to continue. In addition to cortisol, we identified daily and ultradian variation in free cortisone, corticosterone, 18-hydroxycortisol, aldosterone, tetrahydrocortisol and allo-tetrahydrocortisol, and the presence of dehydroepiandrosterone sulfate. We used mathematical and computational methods to quantify the interindividual variability of hormones at different times of the day and develop "dynamic markers" of normality in healthy individuals stratified by sex, age, and body mass index. Our results provide insight into the dynamics of adrenal steroids in tissue in real-world settings and may serve as a normative reference for biomarkers of endocrine disorders (ULTRADIAN, NCT02934399).
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- 2023
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13. Plasma-Metanephrines in Patients with Autoimmune Addison's Disease with and without Residual Adrenocortical Function.
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Åkerman AK, Sævik ÅB, Thorsby PM, Methlie P, Quinkler M, Jørgensen AP, Höybye C, Debowska AJ, Nedrebø BG, Dahle AL, Carlsen S, Tomkowicz A, Sollid ST, Nermoen I, Grønning K, Dahlqvist P, Grimnes G, Skov J, Finnes T, Wahlberg J, Holte SE, Simunkova K, Kämpe O, Husebye ES, Øksnes M, and Bensing S
- Abstract
Purpose: Residual adrenocortical function, RAF, has recently been demonstrated in one-third of patients with autoimmune Addison's disease (AAD). Here, we set out to explore any influence of RAF on the levels of plasma metanephrines and any changes following stimulation with cosyntropin., Methods: We included 50 patients with verified RAF and 20 patients without RAF who served as controls upon cosyntropin stimulation testing. The patients had abstained from glucocorticoid and fludrocortisone replacement > 18 and 24 h, respectively, prior to morning blood sampling. The samples were obtained before and 30 and 60 min after cosyntropin stimulation and analyzed for serum cortisol, plasma metanephrine (MN), and normetanephrine (NMN) by liquid-chromatography tandem-mass pectrometry (LC-MS/MS)., Results: Among the 70 patients with AAD, MN was detectable in 33%, 25%, and 26% at baseline, 30 min, and 60 min after cosyntropin stimulation, respectively. Patients with RAF were more likely to have detectable MN at baseline (p = 0.035) and at the time of 60 min ( p = 0.048) compared to patients without RAF. There was a positive correlation between detectable MN and the level of cortisol at all time points ( p = 0.02, p = 0.04, p < 0.001). No difference was noted for NMN levels, which remained within the normal reference ranges., Conclusion: Even very small amounts of endogenous cortisol production affect MN levels in patients with AAD.
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- 2023
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14. Premature ovarian insufficiency.
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Vogt EC, Russell HNB, Øksnes M, and Lund A
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- Female, Hormone Replacement Therapy adverse effects, Humans, Primary Ovarian Insufficiency diagnosis, Primary Ovarian Insufficiency drug therapy, Primary Ovarian Insufficiency etiology
- Abstract
Premature ovarian insufficiency is a complex condition with a heterogenous aetiology, and is defined as loss of ovarian function before the age of 40. Early diagnosis and initiation of hormone replacement therapy is essential to alleviate symptoms and prevent later complications as a result of premature oestrogen deficiency. In this clinical review article we present an update on the diagnostics and treatment of the condition.
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- 2022
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15. Premature menopause and autoimmune primary ovarian insufficiency in two international multi-center cohorts.
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Vogt EC, Real FG, Husebye ES, Björnsdottir S, Benediktsdottir B, Bertelsen RJ, Demoly P, Franklin KA, de Aja Gallastegui LS, González FJC, Heinrich J, Holm M, Jogi NO, Leynaert B, Lindberg E, Malinovschi A, Martínez-Moratalla J, Mayoral RG, Oudin A, Pereira-Vega A, Semjen CR, Schlünssen V, Triebner K, and Øksnes M
- Abstract
Objective: To investigate markers of premature menopause (<40 years) and specifically the prevalence of autoimmune primary ovarian insufficiency (POI) in European women., Design: Postmenopausal women were categorized according to age at menopause and self-reported reason for menopause in a cross-sectional analysis of 6870 women., Methods: Variables associated with the timing of menopause and hormone measurements of 17β-estradiol and follicle-stimulating hormone were explored using multivariable logistic regression analysis. Specific immunoprecipitating assays of steroidogenic autoantibodies against 21-hydroxylase (21-OH), side-chain cleavage enzyme (anti-SCC) and 17alpha-hydroxylase (17 OH), as well as NACHT leucine-rich-repeat protein 5 were used to identify women with likely autoimmune POI., Results: Premature menopause was identified in 2.8% of women, and these women had higher frequencies of nulliparity (37.4% vs 19.7%), obesity (28.7% vs 21.4%), osteoporosis (17.1% vs 11.6%), hormone replacement therapy (59.1% vs 36.9%) and never smokers (60.1% vs 50.9%) (P < 0.05), compared to women with menopause ≥40 years. Iatrogenic causes were found in 91 (47%) and non-ovarian causes in 27 (14%) women, while 77 (39%) women were classified as POI of unknown cause, resulting in a 1.1% prevalence of idiopathic POI. After adjustments nulliparity was the only variable significantly associated with POI (odds ratio 2.46; 95% CI 1.63-3.42). Based on the presence of autoantibodies against 21 OH and SCC, 4.5% of POI cases were of likely autoimmune origin., Conclusion: Idiopathic POI affects 1.1% of all women and almost half of the women with premature menopause. Autoimmunity explains 4.5% of these cases judged by positive steroidogenic autoantibodies.
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- 2022
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16. Sex-Specific Limitations in Physical Health in Primary Adrenal Insufficiency.
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Didriksen NM, Sævik ÅB, Sortland LS, Øksnes M, and Husebye ES
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- Adult, Aged, Comorbidity, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Sex Factors, Surveys and Questionnaires, Addison Disease psychology, Health Status, Quality of Life
- Abstract
Background: Patients with primary adrenal insufficiency (PAI) suffer reduced quality of life (QoL), but comparisons with large-scale normative data are scarce. The clinical characteristics associated with reduced QoL are largely unknown., Methods: Cross-sectional data on clinical characteristics and QoL scores from 494 patients were included. QoL was measured using RAND-36 (generic) and AddiQoL (-30 and -8, disease-specific). RAND-36 is reported as subdomain scores as well as physical (PCS) and metal (MCS) summary scores and compared with normative data., Results: Perception of physical role was consistently decreased across age groups in patients with PAI compared with normative data [75 (0-100) vs. 100 (50-100), p<0.001]. Men with PAI reported significantly lower scores for social functioning [88 (75-100) vs. 100 (75-100), p<0.001], as well as for vitality and physical role. In women, the greatest impairment was seen in physical role [50 (0-100) vs. 100 (50-100), p<0.001], followed by social functioning, vitality, physical function, general health, mental health, and emotional role. Overall, better QoL was associated with male sex (AddiQoL-30: 89 ± 13 vs. 82 ± 13, p<0.002), younger age (e.g. 20-29 vs. 80-89 years: PCS 59 [50-62] vs. 46 [37-53], p<0.001), autoimmune etiology [PCS: 53 (45-59) vs. . 45 (38-54), p<0.001], and absence of autoimmune comorbidity [PCS: 54 (45-59) vs. 50 (43-58), p<0.001]. There were no significant differences in QoL scores between different doses or dosing regimens of glucocorticoid or mineralocorticoid replacement., Conclusion: QoL is reduced in patients with PAI, especially perception of physical role in women and social functioning in men. Among patients with PAI, female sex, higher age, non-autoimmune etiology, and autoimmune comorbidity was associated with lower QoL-scores., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Didriksen, Sævik, Sortland, Øksnes and Husebye.)
- Published
- 2021
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17. Primary Ovarian Insufficiency in Women With Addison's Disease.
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Vogt EC, Breivik L, Røyrvik EC, Grytaas M, Husebye ES, and Øksnes M
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- Addison Disease complications, Adult, Autoantibodies blood, Autoantibodies immunology, Cholesterol Side-Chain Cleavage Enzyme immunology, Female, Hormone Replacement Therapy statistics & numerical data, Humans, Menopause, Premature blood, Norway epidemiology, Polymorphism, Single Nucleotide, Predictive Value of Tests, Prevalence, Primary Ovarian Insufficiency genetics, Primary Ovarian Insufficiency immunology, Registries, Addison Disease genetics, Addison Disease immunology, Menopause, Premature genetics, Menopause, Premature immunology, Primary Ovarian Insufficiency epidemiology
- Abstract
Context: Primary ovarian insufficiency (POI) is defined by menopause before 40 years of age. POI prevalence is higher among women with autoimmune Addison's disease (AAD) than in the general population, but their clinical characteristics are insufficiently studied., Objective: To assess the prevalence of POI in a large cohort of women with AAD and describe clinical, immunological, and genetic characteristics., Methods: An observational population-based cohort study of the Norwegian National Addison Registry. The Norwegian Prescription Database was used to assess prescription of menopausal hormone replacement therapy (HRT). A total of 461 women with AAD were studied. The primary outcome measure was prevalence of POI. Secondary outcomes were clinical characteristics, autoantibodies, and genome-wide single nucleotide polymorphism variation., Results: The prevalence of POI was 10.2% (47/461) and one-third developed POI before 30 years of age. POI preceded or coincided with AAD diagnosis in more than half of the women. The prevalence of concomitant autoimmune diseases was 72%, and AAD women with POI had more autoantibodies than AAD women without (≥2 autoantibodies in 78% vs 25%). Autoantibodies against side-chain cleavage enzyme (SCC) had the highest accuracy with a negative predictive value for POI of 96%. HRT use was high compared to the age adjusted normal population (11.3 % vs 0.7%)., Conclusion: One in 10 women with AAD have POI. Autoantibodies against SCC are the most specific marker for autoimmune POI. We recommend testing women with AAD <40 years with menstrual disturbances or fertility concerns for autoantibodies against SCC., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
- Published
- 2021
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18. Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addison's Disease.
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Sævik ÅB, Wolff AB, Björnsdottir S, Simunkova K, Hynne MS, Dolan DWP, Bratland E, Knappskog PM, Methlie P, Carlsen S, Isaksson M, Bensing S, Kämpe O, Husebye ES, Løvås K, and Øksnes M
- Abstract
Background: No reliable biomarkers exist to guide glucocorticoid (GC) replacement treatment in autoimmune Addison's disease (AAD), leading to overtreatment with alarming and persistent side effects or undertreatment, which could be fatal., Objective: To explore changes in gene expression following different GC replacement doses as a means of identifying candidate transcriptional biomarkers to guide GC replacement in AAD., Methods: Step 1: Global microarray expression analysis on RNA from whole blood before and after intravenous infusion of 100 mg hydrocortisone (HC) in 10 patients with AAD. In 3 of the most highly upregulated genes, we performed real-time PCR (rt-PCR) to compare gene expression levels before and 3, 4, and 6 hours after the HC infusion. Step 2: Rt-PCR to compare expression levels of 93 GC-regulated genes in normal versus very low morning cortisol levels in 27 patients with AAD., Results: Step 1: Two hours after infusion of 100 mg HC, there was a marked increase in FKBP5, MMP9, and DSIPI expression levels. MMP9 and DSIPI expression levels correlated with serum cortisol. Step 2: Expression levels of CEBPB, DDIT4, FKBP5, DSIPI , and VDR were increased and levels of ADARB1, ARIDB5, and POU2F1 decreased in normal versus very low morning cortisol. Normal serum cortisol levels positively correlated with DSIPI , DDIT4, and FKBP5 expression., Conclusions: We introduce gene expression as a novel approach to guide GC replacement in AAD. We suggest that gene expression of DSIPI, DDIT4, and FKBP5 are particularly promising candidate biomarkers of GC replacement, followed by MMP9, CEBPB, VDR, ADARB1, ARID5B , and POU2F1 ., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
- Published
- 2021
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19. Residual Corticosteroid Production in Autoimmune Addison Disease.
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Sævik ÅB, Åkerman AK, Methlie P, Quinkler M, Jørgensen AP, Höybye C, Debowska AJ, Nedrebø BG, Dahle AL, Carlsen S, Tomkowicz A, Sollid ST, Nermoen I, Grønning K, Dahlqvist P, Grimnes G, Skov J, Finnes T, Valland SF, Wahlberg J, Holte SE, Simunkova K, Kämpe O, Husebye ES, Bensing S, and Øksnes M
- Subjects
- Adult, Cosyntropin blood, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Addison Disease blood, Adrenal Cortex Hormones blood
- Abstract
Context: Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison disease (AAD) produce corticosteroids even years after diagnosis., Objective: To determine frequencies and clinical features of residual corticosteroid production in patients with AAD., Design: Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after > 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography-tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test., Results: Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P < 0.002) and in shorter disease duration (median 6 [0-44] vs 13 [0-53] years; P < 0.001). Residual MC production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs 13 [0-53] years; P < 0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs 0.100 [0.028-0.300] mg; P < 0.005), and higher plasma renin concentration (median 179 [22-915] vs 47.5 [0.6-658.0] mU/L; P < 0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r = 0.989; P < 0.001) and plasma adrenocorticotropic hormone (ACTH; r = -0.487; P < 0.001)., Conclusion: In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life., (© Endocrine Society 2020.)
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- 2020
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20. The effect of exhaustive exercise on the choice of technique and physiological response in classical roller skiing.
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Ettema G, Øksnes M, Kveli E, and Sandbakk Ø
- Subjects
- Biomechanical Phenomena physiology, Exercise Test, Humans, Male, Young Adult, Exercise physiology, Heart Rate physiology, Oxygen Consumption physiology, Physical Exertion physiology, Skiing physiology
- Abstract
Purpose: The aim of this study was to investigate the effect of exhaustive exercise on technique preference and the accompanying physiological response during classic skiing at constant workload, but with varying incline-speed combinations., Methods: Seven male competitive cross-country skiers performed four tests, each lasting 23 min, at constant 200 W workload roller skiing on a treadmill using classic style, three in unfatigued state, and one after exhaustion. The incline and speed combination (that determined the 200 W) were altered each minute during the tests. The athletes were allowed to change sub-technique at free will. Physiological variables and cycle rate were recorded continuously as well as the incline-speed combinations at which the sub-technique was changed., Results: Exhaustive exercise did not (or hardly) affect cycle rate and choice of technique. The physiological response was most prominent in slight incline-high speed conditions, independent of exercise duration. Exhaustive exercise affected the physiological response in a differentiated manner. HR and RER remained, respectively, higher and lower after fatigue, while [Formula: see text] (and thereby GE) were affected only during approximately the first 8 min of post-exhaustion exercise., Conclusions: Exhaustive exercise has a minimal effect on choice of technique in classic cross-country skiing with free choice of sub-technique, even though physiological stress is increased.
- Published
- 2018
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21. The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS.
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Ueland GÅ, Methlie P, Øksnes M, Thordarson HB, Sagen J, Kellmann R, Mellgren G, Ræder M, Dahlqvist P, Dahl SR, Thorsby PM, Løvås K, and Husebye ES
- Subjects
- Adolescent, Adrenal Hyperplasia, Congenital blood, Adrenal Insufficiency blood, Adult, Aged, Aged, 80 and over, Chromatography, Liquid, Female, Humans, Male, Middle Aged, Reference Values, Tandem Mass Spectrometry, Young Adult, 17-alpha-Hydroxyprogesterone blood, Adrenal Hyperplasia, Congenital diagnosis, Adrenal Insufficiency diagnosis, Cosyntropin, Hydrocortisone blood
- Abstract
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.
- Published
- 2018
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22. Clues for early detection of autoimmune Addison's disease - myths and realities.
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Saevik ÅB, Åkerman AK, Grønning K, Nermoen I, Valland SF, Finnes TE, Isaksson M, Dahlqvist P, Bergthorsdottir R, Ekwall O, Skov J, Nedrebø BG, Hulting AL, Wahlberg J, Svartberg J, Höybye C, Bleskestad IH, Jørgensen AP, Kämpe O, Øksnes M, Bensing S, and Husebye ES
- Subjects
- Addison Disease blood, Addison Disease complications, Adolescent, Adult, Aged, Biomarkers blood, Blood Glucose metabolism, Child, Child, Preschool, Female, Humans, Hydrocortisone blood, Hyperkalemia etiology, Hypoglycemia etiology, Hyponatremia etiology, Male, Middle Aged, Potassium blood, Retrospective Studies, Sodium blood, Thyrotropin blood, Young Adult, Addison Disease diagnosis, Early Diagnosis
- Abstract
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., (© 2017 The Association for the Publication of the Journal of Internal Medicine.)- Published
- 2018
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23. The role of speed and incline in the spontaneous choice of technique in classical roller-skiing.
- Author
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Ettema G, Kveli E, Øksnes M, and Sandbakk Ø
- Subjects
- Adult, Biomechanical Phenomena, Exercise Test methods, Heart Rate physiology, Humans, Male, Oxygen Consumption physiology, Young Adult, Skiing physiology
- Abstract
Cross-country skiers change technique depending on terrain (incline) and effort (work rate; speed at a particular incline or resistance). The literature is not unequivocal about the influence of incline or speed on the choice of technique, i.e., which of these act as a 'control parameter'. Identifying task related control parameters for spontaneous technique shifts assists elucidating which mechanisms are active for triggering technique transitions. The aim of this study was to investigate whether speed or incline acted as such control parameter for technique shifts during classic style roller skiing. In this study, we kept the exercise intensity constant while changing two potential control parameters (speed and incline). Thus, any effect of work rate was excluded. Eight male competitive cross-country skiers performed roller skiing on a treadmill while incline was altered from 3 to 11% and back to 3% each minute by 1% and speed changed accordingly to obtain a constant work rate. This protocol was performed at three submaximal work rates (170, 200, and 230W) to obtain various combinations of speed and incline. The athletes were free to choose their technique (double poling, double poling with kick and diagonal stride), which was identified using continuous phase analysis on the motion of the skis. Physiological response (heart rate, oxygen uptake) was recorded continuously. The incline seemed to affect choice of technique shift more than speed: the ANOVA for repeated measures on all work rates showed no significant effect of incline (p>0.2) and an effect for speed (p<0.001). No effect of protocol order (increasing versus decreasing incline) was found for transitions. The physiological response was lowest for conditions of steep incline-low speed and was affected by protocol order. Cycle rate was affected by incline only in the double poling technique. Possible mechanisms related to the triggering of technique transitions are discussed., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
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24. Assessment of diabetic polyneuropathy in Zanzibar: Comparison between traditional methods and an automated point-of-care nerve conduction device.
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Vogt EC, Øksnes M, Suleiman F, Juma BA, Thordarson HB, Ommedal O, and Søfteland E
- Abstract
Aim: Scant information is available about the prevalence of diabetic polyneuropathy, as well as the applicability of screening tools in sub-Saharan Africa. We aimed to investigate these issues in Zanzibar (Tanzania)., Methods: One hundred consecutive diabetes patients were included from the diabetes clinic at Mnazi Mmoja Hospital. Clinical characteristics were recorded. Further, we investigated: a) self-reported numbness of the lower limbs, b) ten-point monofilament test, c) the Sibbald 60-s Tool and d) nerve conduction studies (NCS, using an automated handheld point-of-care device, the NC-stat DPNCheck)., Results: Mean age was 54 years, 90% had type 2 diabetes, and with 9 year average disease duration. Mean HbA1c was 8.5% (69 mmol/mol), blood pressure 155/88 mmHg. Sixty-two% reported numbness, 61% had positive monofilament and 79% positive Sibbald tool. NCS defined neuropathy in 45% of the patients. Only the monofilament showed appreciable concordance with the NCS, Cohen's κ 0.43., Conclusions: The patient population was characterised by poor glycaemic control and hypertension. In line with this, neuropathy was rampant. The monofilament test tended to define more cases of probable neuropathy than the NCS, however specificity was rather low. Plantar skin thickening may have led to false positives in this population. Overall concordance was, however, appreciable, and could support continued use of monofilament as a neuropathy screening tool. The NC-stat DPNCheck could be useful in cases of diagnostic uncertainty or for research purposes in a low resource setting.
- Published
- 2017
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25. Effect of a pre-exercise hydrocortisone dose on short-term physical performance in female patients with primary adrenal failure.
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Simunkova K, Jovanovic N, Rostrup E, Methlie P, Øksnes M, Nilsen RM, Hennø H, Tilseth M, Godang K, Kovac A, Løvås K, and Husebye ES
- Subjects
- Adult, Blood Glucose analysis, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Epinephrine blood, Exercise Test, Fatty Acids, Nonesterified blood, Female, Health Status, Humans, Hydrocortisone blood, Middle Aged, Oxygen Consumption, Physical Endurance, Placebos, Surveys and Questionnaires, Time Factors, Addison Disease drug therapy, Addison Disease physiopathology, Exercise, Hydrocortisone administration & dosage
- Abstract
Objective: Many patients with primary adrenal insufficiency (Addison's disease) take extra doses of glucocorticoids during stressful events, but a benefit has not been demonstrated in controlled trials. Here, we investigated the effects of a pre-exercise hydrocortisone dose on cardiorespiratory, hormonal and metabolic parameters in response to short-term strenuous physical activity., Design: This was a randomized placebo-controlled, two-week cross-over clinical trial., Participants: Ten women with Addison's disease and 10 age-matched healthy females participated in the study., Measurements: All women in the study underwent maximal incremental exercise testing. A stress dose of 10 mg hydrocortisone or placebo was given 1 h prior to exercise on two occasions. Blood samples were drawn before, and 0, 15 and 30 min post exercise. Oxygen uptake, maximal aerobic capacity, endocrine and metabolic responses to physical activity, as well as health status by questionnaires were evaluated., Results: Maximal aerobic capacity and duration of exercise were significantly lower in patients than in healthy subjects and did not improve with the treatment. After an extra hydrocortisone dose serum cortisol was significantly higher than in the healthy subjects (P<0.001). Post-exercise glucose and adrenaline levels were significantly lower and free fatty acids insignificantly higher in patients irrespective of stress dose. Stress dosing did not alter other metabolic or hormonal parameters or quality of life after the exercise., Conclusions: The patients did not benefit from an extra dose of hydrocortisone in short strenuous exercise. Stress dosing may not be justified in this setting. Whether stress dosing is beneficial in other types of physical activity will have to be examined further., (© 2016 European Society of Endocrinology.)
- Published
- 2016
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26. Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.
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Björnsdottir S, Øksnes M, Isaksson M, Methlie P, Nilsen RM, Hustad S, Kämpe O, Hulting AL, Husebye ES, Løvås K, Nyström T, and Bensing S
- Subjects
- Adrenocorticotropic Hormone blood, Adult, Aged, Circadian Rhythm, Cross-Over Studies, Female, Glucose Clamp Technique, Humans, Hydrocortisone blood, Infusions, Subcutaneous, Male, Middle Aged, Norway, Sweden, Young Adult, Addison Disease drug therapy, Glucocorticoids administration & dosage, Hormone Replacement Therapy methods, Hydrocortisone administration & dosage, Insulin Resistance
- Abstract
Context: Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI)., Objective: The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD., Design and Setting: An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden., Patients: Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp., Intervention: Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment., Main Outcome Measure: We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity., Results: Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms., Conclusion: Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2015
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27. Modified-release hydrocortisone decreases BMI and HbA1c in patients with primary and secondary adrenal insufficiency.
- Author
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Quinkler M, Miodini Nilsen R, Zopf K, Ventz M, and Øksnes M
- Subjects
- Adrenal Hyperplasia, Congenital drug therapy, Adrenal Hyperplasia, Congenital psychology, Adrenal Insufficiency metabolism, Adrenal Insufficiency psychology, Adult, Aged, Aged, 80 and over, Anti-Inflammatory Agents administration & dosage, Delayed-Action Preparations, Female, Follow-Up Studies, Humans, Hydrocortisone administration & dosage, Lipids blood, Male, Middle Aged, Prospective Studies, Quality of Life, Surveys and Questionnaires, Adrenal Insufficiency drug therapy, Anti-Inflammatory Agents therapeutic use, Body Mass Index, Glycated Hemoglobin metabolism, Hydrocortisone therapeutic use
- Abstract
Objective: Patients with adrenal insufficiency (AI) have impaired health-related quality of life (HRQoL), which is thought to be in part due to unphysiological glucocorticoid replacement therapy. The aim was to compare once-daily hydrocortisone (HC) dual-release tablet (modified-release) with conventional HC therapy regarding clinical data and HRQoL., Design and Methods: We conducted an open, prospective trial at one endocrine center. There were 15 of 26 patients with primary AI, nine of 18 patients with secondary AI, and six congenital adrenal hyperplasia patients switched to modified-release HC therapy by their own decision. We evaluated clinical outcome and disease-specific HRQoL by using AddiQoL questionnaire at baseline and at follow-up (median 202 days (85-498))., Results: Patients on modified-release HC (n=30) showed significant decreases in BMI (26.0±0.75-25.6±0.71, P for change=0.006) and HbA1c (6.04±0.29-5.86±0.28, P for change=0.005), whereas patients remaining on conventional HC (n=20) showed no change in these parameters (P for interaction=0.029 and 0.017 respectively). No significant change in AddiQoL score were found in the modified-release HC group (83.8 baseline and 84.9 at follow-up; P for change=0.629). In the conventional HC group, there was a significant decrease in scores (84.0 baseline and 80.9 at follow-up; P for change=0.016), with a between-treatment P for interaction of 0.066. The fatigue subscore of AddiQoL showed the same pattern with a significant decrease (P for change=0.024) in patients on conventional HC therapy (P for interaction=0.116)., Conclusions: Modified-release HC decreases BMI and HbA1c compared with conventional HC treatment. In addition, it seems to stabilize HRQoL over time., (© 2015 European Society of Endocrinology.)
- Published
- 2015
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28. Optimal glucocorticoid replacement in adrenal insufficiency.
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Øksnes M, Ross R, and Løvås K
- Subjects
- Humans, Quality of Life, Adrenal Insufficiency drug therapy, Glucocorticoids therapeutic use, Hormone Replacement Therapy methods
- Abstract
Adrenal insufficiency (glucocorticoid deficiency) comprises a group of rare diseases, including primary adrenal insufficiency, secondary adrenal insufficiency and congenital adrenal hyperplasia. Lifesaving glucocorticoid therapy was introduced over 60 years ago, but since then a number of advances in treatment have taken place. Specifically, little is known about short- and long-term treatment effects, and morbidity and mortality. Over the past decade, systematic cohort and registry studies have described reduced health-related quality of life, an unfavourable metabolic profile and increased mortality in patients with adrenal insufficiency, which may relate to unphysiological glucocorticoid replacement. This has led to the development of new modes of replacement that aim to mimic normal glucocorticoid physiology. Here, evidence for the inadequacy of conventional glucocorticoid therapy and recent developments in treatment are reviewed, with an emphasis on primary adrenal insufficiency., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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29. Genetic, anthropometric and metabolic features of adult Norwegian patients with 21-hydroxylase deficiency.
- Author
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Nermoen I, Brønstad I, Fougner KJ, Svartberg J, Øksnes M, Husebye ES, and Løvås K
- Subjects
- Adrenal Hyperplasia, Congenital epidemiology, Adrenal Hyperplasia, Congenital physiopathology, Adult, Aged, Anthropometry, Blood Pressure genetics, Blood Pressure physiology, Bone Density genetics, Bone Density physiology, Cross-Sectional Studies, Female, Genetic Association Studies, Genotype, Humans, Male, Middle Aged, Mutation physiology, Norway epidemiology, Young Adult, Adrenal Hyperplasia, Congenital genetics, Adrenal Hyperplasia, Congenital metabolism, Body Weights and Measures, Steroid 21-Hydroxylase genetics
- Abstract
Objective: The aim of this study was to determine the genetic, anthropometric and metabolic features in an unselected population of adult Norwegian patients with 21-hydroxylase deficiency (21OHD). PATIENTS, METHODS AND DESIGN: Sixty-four 21OHD patients participated (23 men and 41 women; median age 38.5 years; range 19-72 years) in a cross-sectional study including DNA sequencing of CYP21A2, anthropometric measurements including dual X-ray absorptiometry scanning and biochemical analyses. The results were compared with reference cohorts from the general population., Results: We identified four novel and plausibly disease-causing CYP21A2 mutations. Gene deletions/conversions (42.1% of alleles), the splice mutation I2 splice (23.0%) and point mutation I172 N (22.2%) were common. The genotype corresponded to clinical phenotype in 92% of the patients. The prevalence of osteopenia was 48% in males and 34% in females. Both men and women had normal BMI but markedly increased fat mass compared with the normal population. Diastolic blood pressure was higher than normal. Thirty-nine per cent of the women had testosterone levels above the normal range; 13% of the men had testosterone levels below normal. Reduced final height was more pronounced in men (median -11.2 cm, -1.77 SDS) than in women (-6.3 cm, -1.07 SDS)., Conclusions: In this population-based survey of 21OHD, we identified four novel mutations and high concordance between genotype and phenotype. The patients had increased fat mass, increased diastolic blood pressure, reduced final height and high frequency of osteopenia among males. These results show unfavourable metabolic features in 21OHD patients indicating a need for improvement of treatment and follow-up.
- Published
- 2012
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30. Quality of life in European patients with Addison's disease: validity of the disease-specific questionnaire AddiQoL.
- Author
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Øksnes M, Bensing S, Hulting AL, Kämpe O, Hackemann A, Meyer G, Badenhoop K, Betterle C, Parolo A, Giordano R, Falorni A, Papierska L, Jeske W, Kasperlik-Zaluska AA, Chatterjee VK, Husebye ES, and Løvås K
- Subjects
- Addison Disease diagnosis, Addison Disease physiopathology, Adolescent, Adult, Aged, Europe, Female, Germany epidemiology, Humans, Italy epidemiology, Male, Middle Aged, Norway epidemiology, Poland epidemiology, Reproducibility of Results, Sweden epidemiology, Young Adult, Addison Disease epidemiology, Addison Disease psychology, Quality of Life, Surveys and Questionnaires
- Abstract
Context: Patients with Addison's disease (AD) self-report impairment in specific dimensions on well-being questionnaires. An AD-specific quality-of-life questionnaire (AddiQoL) was developed to aid evaluation of patients., Objective: We aimed to translate and determine construct validity, reliability, and concurrent validity of the AddiQoL questionnaire., Methods: After translation, the final versions were tested in AD patients from Norway (n = 107), Sweden (n = 101), Italy (n = 165), Germany (n = 200), and Poland (n = 50). Construct validity was examined by exploratory factor analysis and Rasch analysis, aiming at unidimensionality and fit to the Rasch model. Reliability was determined by Cronbach's coefficient-α and Person separation index. Longitudinal reliability was tested by differential item functioning in stable patient subgroups. Concurrent validity was examined in Norwegian (n = 101) and Swedish (n = 107) patients., Results: Exploratory factor analysis and Rasch analysis identified six items with poor psychometric properties. The 30 remaining items fitted the Rasch model and proved unidimensional, supported by appropriate item and person fit residuals and a nonsignificant χ(2) probability. Crohnbach's α-coefficient 0.93 and Person separation index 0.86 indicate high reliability. Longitudinal reliability was excellent. Correlation with Short Form-36 and Psychological General Well-Being Index scores was high. A shorter subscale comprising eight items also proved valid and reliable. Testing of AddiQoL-30 in this large patient cohort showed significantly worse scores with increasing age and in women compared with men but no difference between patients with isolated AD and those with concomitant diseases., Conclusion: The validation process resulted in a revised 30-item AddiQoL questionnaire and an eight-item AddiQoL short version with good psychometric properties and high reliability.
- Published
- 2012
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31. Gamma knife stereotactic radiosurgery of Nelson syndrome.
- Author
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Vik-Mo EO, Øksnes M, Pedersen PH, Wentzel-Larsen T, Rødahl E, Thorsen F, Schreiner T, Aanderud S, and Lund-Johansen M
- Subjects
- Adult, Brain Neoplasms diagnosis, Cross-Sectional Studies, Disease-Free Survival, Female, Follow-Up Studies, Glioblastoma diagnosis, Humans, Hypopituitarism diagnosis, Hypopituitarism prevention & control, Magnetic Resonance Imaging, Male, Middle Aged, Nelson Syndrome blood, Nelson Syndrome pathology, Pituitary Gland pathology, Postoperative Complications diagnosis, Postoperative Complications prevention & control, Retrospective Studies, Treatment Outcome, Adrenocorticotropic Hormone blood, Nelson Syndrome surgery, Pituitary Gland surgery, Radiosurgery adverse effects
- Abstract
Objective: Gamma knife radiosurgery (GKR) can be used as primary or adjuvant therapy for the treatment of an ACTH-producing pituitary tumor after bilateral adrenalectomy, called Nelson syndrome (NS). We have examined the effect of GKR on tumor growth and ACTH-hypersecretion, and characterized the adverse events of this treatment in patients with NS., Design: Cross-sectional follow-up study. First, retrospective data pre- and post-GKR were collected. Patients then underwent a predefined survey including radiological, endocrinological, ophthalmological, and neurosurgical evaluation., Subjects: Ten patients treated with GKR for NS after previous bilateral adrenalectomy. The mean follow-up was 7 years. No patient was lost to follow-up., Results: Tumor growth was stopped in all patients. The ACTH levels declined in eight patients, and normalized in one patient. There was a significant drop in ACTH levels, with a half-time of 2.8 years. No patient developed visual field defects or any other cranial nerve dysfunction as a result of treatment. Four patients started hormone substitution therapy during the follow-up period. The substitution therapy of three pituitary axes present at GKR treatment could be stopped during the same period. One patient developed a glioblastoma in the left parieto-occipital region 14 years after GKR, far from the field of treatment. As the radiation level was below 1Gy to this area, it is unlikely that the GKR treatment itself induced the malignant tumor., Conclusion: In patients with NS, GKR is an effective adjuvant treatment, carrying relatively few adverse effects. Although the risk of developing a secondary neoplasia after GKR is present, it is probably extremely low.
- Published
- 2009
- Full Text
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