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1.
  • Al-Shamkhi, Nasrin, 1985-, et al. (author)
  • Pituitary function before and after surgery for nonfunctioning pituitary adenomas-data from the Swedish Pituitary Register.
  • 2023
  • In: European journal of endocrinology. - : Bioscientifica. - 1479-683X .- 0804-4643. ; 189:2, s. 217-224
  • Journal article (peer-reviewed)abstract
    • Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA).Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded.Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm3. Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively.Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.
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2.
  • Arnardottir, Steinunn, et al. (author)
  • Long-term outcomes of patients with acromegaly: a report from the Swedish Pituitary Register
  • 2022
  • In: European Journal of Endocrinology. - : European Society of Endocrinology. - 1479-683X .- 0804-4643. ; 186:3, s. 329-339
  • Journal article (peer-reviewed)abstract
    • Objective: To describe the treatment and long-term outcomes of patients with acromegaly from all healthcare regions in Sweden. Design and methods: Analysis of prospectively reported data from the Swedish Pituitary Register of 698 patients (51% females) with acromegaly diagnosed from 1991 to 2011. The latest clinical follow-up date was December 2012, while mortality data were collected for 28.5 years until June 2019. Results: The annual incidence was 3.7/million; 71% of patients had a macroadenoma, 18% had visual field defects, and 25% had at least one pituitary hormone deficiency. Eighty-two percent had pituitary surgery, 10% radiotherapy, and 39% medical treatment. At the 5- and 10-year follow-ups, insulin-like growth factor 1 levels were within the reference range in 69 and 78% of patients, respectively. In linear regression, the proportion of patients with biochemical control including adjuvant therapy at 10 years follow-up increased over time by 1.23% per year. The standardized mortality ratio (SMR) (95% CI) for all patients was 1.29 (1.11-1.49). For patients with biochemical control at the latest follow-up, SMR was not increased, neither among patients diagnosed between 1991 and 2000, SMR: 1.06 (0.85-1.33) nor between 2001 and2011, SMR: 0.87 (0.61-1.24). In contrast, non-controlled patients at the latest follow-up from both decades had elevated SMR, 1.90 (1.33-2.72) and 1.98 (1.24-3.14), respectively. Conclusions: The proportion of patients with biochemical control increased over time. Patients with biochemically controlled acromegaly have normal life expectancy, while non-controlled patients still have increased mortality. The high rate of macroadenomas and unchanged age at diagnosis illustrates the need for improvements in the management of patients with acromegaly.
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3.
  • Backman, Samuel, et al. (author)
  • Whole genome sequencing of apparently mutation-negative MEN1 patients
  • 2020
  • In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 182:1, s. 35-45
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE:Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant syndrome usually caused by loss-of-function mutations in the MEN1-gene. However, a minority of patients who fulfill the criteria for MEN1 are not found to harbor MEN1-mutations. Besides, some of these individuals, present with a subtly different phenotype suggestive of sporadic disease. The aim of the present study was to investigate the genetic architecture of mutation-negative MEN1. DESIGN:Fourteen patients with a clinical diagnosis (n=13) or suspicion (n=1) of MEN1 who had negative genetic screening of the MEN1 gene were included. METHODS:Constitutional DNA from the included patients, as well as tumor DNA from six of the patients, was subjected to whole genome sequencing. Constitutional variants were filtered against population databases and somatic variants were studied under a tumor-suppressor model. RESULTS:Three patients carried pathogenic variants (two splice-site variants, one missense variant) in MEN1 that had not been detected during routine clinical sequencing, one patient carried a pathogenic variant in CASR and one patient carried a gross deletion on chromosome 1q which included the CDC73 gene. Analysis of matched tumor DNA from six patients without mutations did not detect any recurrent genes fulfilling Knudson's two-hit model. CONCLUSION:These results highlight the possibility of germline mutations being missed in routine screening, the importance of considering phenocopies in atypical or mutation-negative cases. The absence of apparent disease-causing mutations suggests that a fraction of MEN1 mutation negative MEN1 cases may be due to the chance occurrence of several endocrine tumors in one patient.
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4.
  • Bang, Peter, et al. (author)
  • Effectiveness and safety of rhIGF1 therapy n patients with or without Laron syndrome
  • 2021
  • In: European Journal of Endocrinology. - : BIOSCIENTIFICA LTD. - 0804-4643 .- 1479-683X. ; 184:2, s. 267-276
  • Journal article (peer-reviewed)abstract
    • Objective: The European Increlex (R) Growth Forum Database Registry monitors the effectiveness and safety of recombinant human insulin-like growth factor-1 (rhIGF1; mecasermin, Increlex (R)) therapy in patients with severe primary IGF1 deficiency (SPIGFD). We present data from patients with and without a reported genetic diagnosis of Laron syndrome (LS). Design: Ongoing, open-label, observational registry (NCT00903110). Methods: Children and adolescents receiving rhIGF1 therapy from 10 European countries were enrolled in 2008-2017 (n = 242). The treatment-naive/prepubertal (NPP) cohort (n = 138) was divided into subgroups based on reported genetic diagnosis of LS (n = 21) or non-LS (n = 117). Multivariate analysis of the NPP-non-LS subgroup was conducted to identify factors predictive of growth response (first-year-height standard deviation score (SDS) gain >= 0.3). Assessments included change in height and weight over 5 years and adverse events (AEs). Results: Height SDS gain from baseline was greater in the NPP-LS than the NPP-non-LS subgroup after 1 years treatment (P < 0.05). In the NPP-non-LS subgroup, 56% were responders; young age at baseline was a positive independent predictive factor (P < 0.001). NPP-non-LS-responders and the NPP-LS subgroup had a similar mean age (6.07 years vs 7.00 years) at baseline and height SDS gain in year 1 (0.64 vs 0.70), although NPP-non-LS-responders were taller (P < 0.001) at baseline. BMI SDS changes did not differ across subgroups. Treatment-emergent AEs were experienced by 65.3% of patients; hypoglycaemia was most common. Conclusions: In most NPP children with SPIGFD, with or without LS, rhIGF1 therapy promotes linear growth. The safety profile was consistent with previous studies.
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5.
  • Boguszewski, M. C. S., et al. (author)
  • Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement
  • 2022
  • In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 186:6
  • Journal article (peer-reviewed)abstract
    • Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.
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6.
  • Bäcklund, Nils, et al. (author)
  • Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome
  • 2020
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 182:6, s. 569-582
  • Journal article (peer-reviewed)abstract
    • Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves. Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h. Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better. © 2020 European Society of Endocrinology Printed in Great Britain.
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7.
  • Bäcklund, Nils, et al. (author)
  • Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing’s syndrome
  • 2020
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 182:6, s. 569-582
  • Journal article (peer-reviewed)abstract
    • Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST).Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves.Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h.Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.
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8.
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9.
  • Crona, Joakim, et al. (author)
  • ENSAT registry-based randomized clinical trials for adrenocortical carcinoma
  • 2021
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 184:2, s. R51-R59
  • Research review (peer-reviewed)abstract
    • Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.
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10.
  • Dogra, Prerna, et al. (author)
  • Rare benign adrenal lesions
  • 2023
  • In: European Journal of Endocrinology. - : Oxford University Press. - 0804-4643 .- 1479-683X. ; 188:4, s. 407-420
  • Journal article (peer-reviewed)abstract
    • While most benign lesions of the adrenal glands represent either an adrenocortical adenoma or a myelolipoma, the advent and frequent use of high-resolution radiological investigations have led to relatively increased incidental discovery of rare adrenal lesions, specifically benign adrenal cysts, adrenal ganglioneuromas, adrenal schwannomas, adrenal hemorrhage, and adrenal calcifications. Radiological characteristics of the different rare benign adrenal lesions could vary from distinct to indeterminate. Though typically nonfunctional, these rare lesions require evaluation for adrenal hormone excess, as they may phenotypically appear similar to pheochromocytoma or adrenocortical carcinoma and could sometimes be associated with or conceal an underlying functional adrenal tumor. In this review, we discuss the various rare benign adrenal lesions, emphasizing a practical perspective.
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11.
  • Eriksson, Jan W, et al. (author)
  • Tissue-specific glucose partitioning and fat content in prediabetes and type 2 diabetes: whole-body PET/MRI during hyperinsulinemia
  • 2021
  • In: European journal of endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 184:6, s. 879-899
  • Journal article (peer-reviewed)abstract
    • Objective: To obtain direct quantifications of glucose turnover, volumes an d fat content of several tissues in the development of type 2 diabetes (T2D) using a novel integrated a pproach for whole-body imaging. Design and methods: Hyperinsulinemic-euglycemic clamps and simultaneous whole-body integrated [18F]FDG-PET/MRI with automated analyses were performed in control (n = 12), prediabetes (n = 16) and T2D (n = 13) subjects matched for age, sex and BMI. Results: Whole-body glucose uptake (Rd) was reduced by approximately 25% in T2D vs control subjects, and partitioning to brain was increased from 3.8% of total Rd in co ntrols to 7.1% in T2D. In liver, subcutaneous AT, thigh muscle, total tissue glucose metabolic rates (MRglu) and their % of total Rd were reduced in T2D compared to contr ol subjects. The prediabetes group had intermediate findings. Total MRglu in heart, visceral AT, gluteus and calf muscle was similar across groups. Whole-body insulin sensitivity asses sed as glucose infusion rate correlated with liver MR glu but inversely with brain MRglu. Liver fat content correlated with MRglu in brain but inversely with MRglu in other tissues. Calf muscle fat was inversely associated with MR glu only in the same muscle group. Conclusions: This integrated imaging approach provides detailed quantification of tissue-specific glucose metabolism. During T2D development, insulin-stimulated glucose disposal is impaired and increasingly shifted away from muscle, liver and fat toward the brain. Altered glucose handling in the brain and liver fat accumulation may aggravate insulin resistance in several organs. © 2021 BioScientifica Ltd.. All rights reserved.
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12.
  • Fortuin-de Smidt, Melony C., et al. (author)
  • Effect of exercise training on insulin sensitivity, hyperinsulinemia and ectopic fat in black South African women : a randomized controlled trial
  • 2020
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 183:1, s. 51-61
  • Journal article (peer-reviewed)abstract
    • Objective: We investigated the effects of a 12-week exercise intervention on insulin sensitivity (SI) and hyperinsulinemia and associated changes in regional and ectopic fat.Research design and methods: Healthy, black South African women with obesity (mean age 23 ± 3.5 years) and of isiXhosa ancestry were randomised into a 12-week aerobic and resistance exercise training group (n = 23) and a no exercise group (control, n = 22). Pre and post-intervention testing included assessment of SI, insulin response to glucose (AIRg), insulin secretion rate (ISR), hepatic insulin extraction (FEL) and disposition index (DI) (AIRg × SI) (frequently sampled i.v. glucose tolerance test); fat mass and regional adiposity (dual-energy X-ray absorptiometry); hepatic, pancreatic and skeletal muscle fat content and abdominal s.c. and visceral adipose tissue volumes (MRI).Results: Exercise training increased VO2peak (mean ± s.d.: 24.9 ± 2.42 to 27.6 ± 3.39 mL/kg/min, P < 0.001), SI (2.0 (1.2–2.8) to 2.2 (1.5–3.7) (mU/l)−1 min−1, P = 0.005) and DI (median (interquartile range): 6.1 (3.6–7.1) to 6.5 (5.6–9.2) × 103 arbitrary units, P = 0.028), and decreased gynoid fat mass (18.5 ± 1.7 to 18.2 ± 1.6%, P < 0.001) and body weight (84.1 ± 8.7 to 83.3 ± .9.7 kg, P = 0.038). None of these changes were observed in the control group, but body weight increased (P = 0.030). AIRg, ISR and FEL, VAT, SAT and ectopic fat were unaltered after exercise training. The increase in SI and DI were not associated with changes in regional or ectopic fat.Conclusion: Exercise training increased SI independent from changes in hyperinsulinemia and ectopic fat, suggesting that ectopic fat might not be a principal determinant of insulin resistance in this cohort.
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13.
  • Haissaguerre, M, et al. (author)
  • Immunohistochemical characterization of a steroid-secreting oncocytic adrenal carcinoma responsible for paraneoplastic hyperparathyroidism
  • 2023
  • In: European journal of endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 188:4, s. K11-K16
  • Journal article (peer-reviewed)abstract
    • We report a unique case of a 44-year-old man with paraneoplastic hyperparathyroidism due to an oncocytic adrenocortical carcinoma (stage pT3N0R0M0, ENSAT 2 with a 4% Ki-67). Paraneoplastic hyperparathyroidism was associated with mild ACTH-independent hypercortisolism and increased estradiol secretion responsible for gynecomastia and hypogonadism. Biological investigations performed in blood samples from peripheral and adrenal veins revealed that the tumor secreted PTH and estradiol. Ectopic PTH secretion was confirmed by abnormally high expression of PTH mRNA and clusters of PTH immunoreactive cells in the tumor tissue. Double-immunochemistry studies and analysis of contiguous slides for the expression of PTH and steroidogenic markers (SRB-1, 3β-HSD and aromatase) were performed. The results suggested the presence of two tumor cells subtypes with large cells with voluminous nuclei producing only PTH and that were distinct from steroid producing cells.
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14.
  • Haissaguerre, M, et al. (author)
  • Immunohistochemical characterization of a steroid-secreting oncocytic adrenal carcinoma responsible for paraneoplastic hyperparathyroidism
  • 2023
  • In: European journal of endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 188:4, s. K11-K16
  • Journal article (peer-reviewed)abstract
    • We report a unique case of a 44-year-old man with paraneoplastic hyperparathyroidism due to an oncocytic adrenocortical carcinoma (stage pT3N0R0M0, ENSAT 2 with a 4% Ki-67). Paraneoplastic hyperparathyroidism was associated with mild ACTH-independent hypercortisolism and increased estradiol secretion responsible for gynecomastia and hypogonadism. Biological investigations performed in blood samples from peripheral and adrenal veins revealed that the tumor secreted PTH and estradiol. Ectopic PTH secretion was confirmed by abnormally high expression of PTH mRNA and clusters of PTH immunoreactive cells in the tumor tissue. Double-immunochemistry studies and analysis of contiguous slides for the expression of PTH and steroidogenic markers (SRB-1, 3β-HSD and aromatase) were performed. The results suggested the presence of two tumor cells subtypes with large cells with voluminous nuclei producing only PTH and that were distinct from steroid producing cells.
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15.
  • Isand, Kristina, et al. (author)
  • High prevalence of venous thrombotic events in Cushing's syndrome: data from ERCUSYN and details in relation to surgery.
  • 2024
  • In: European journal of endocrinology. - 0804-4643 .- 1479-683X. ; 190:1, s. 75-85
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to evaluate the prevalence of venous thromboembolism (VTE) in patients included in the European Registry on Cushing's syndrome (ERCUSYN), compare their clinical characteristics with those who did not develop VTE and identify risk factors for VTE.A retrospective observational cohort study.Data extraction from the registry was taken on February, 7, 2022. At the time there were 2174 patients diagnosed with Cushing's syndrome (CS) and 95 VTEs were reported in the database.Of 95 VTE events 70 (74%) were in pituitary-dependent CS patients, 12 (12.5%) in adrenal-dependant CS, 10 (10.5%) in ectopic CS, and 3 (3%) in CS due to other causes. Sex, 24-hour urinary free cortisol (UFC) value at diagnosis, as well as the number of operations remained statistically significant predictors of VTE. Of patients who were treated with at least one surgery, 12 (13%) VTE occurred before and 80 (87%) after the surgery. Nearly half of these VTEs occurred within six months since the operation (36; 45%). Over half of the centers that reported VTE did not routinely anticoagulate CS patients. Anticoagulation schemes varied widely.Patients with CS have an elevated risk of developing VTE for an extended period of time. From ERCUSYN cohort patients have higher risk for VTE if they need multiple surgeries to treat CS, are males and have high UFC values at the diagnosis of CS. Since there is no agreement on thromboprohpylaxis, a protocol for VTE prevention that is widely adopted appears to be necessary for patients with CS.
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16.
  • Kildemoes, R. J., et al. (author)
  • Dose-exposure-IGF-I response of once-weekly somapacitan in adults with GH deficiency
  • 2022
  • In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 187:1, s. 27-38
  • Journal article (peer-reviewed)abstract
    • Objective: Growth hormone (GH) replacement therapy in patients with adult growth hormone deficiency (AGHD) is individually titrated due to variable dose-responses among patients. The aim of this study was to provide clinical guidance on dosing and titration of the novel long-acting GH derivative somapacitan based on analyses of somapacitan dose-insulin-like growth factor I (IGF-I) responses in AGHD patients. Design: Analyses of dosing information, 4364 somapacitan concentration samples and 4880 IGF-I samples from 330 AGHD patients treated with somapacitan in three phase 3 trials. Methods: Pharmacokinetic/pharmacodynamic modelling was used to evaluate starting dose groups by age and oral oestrogen therapy, characterise the dose-IGF-I response in the overall AGHD population and patient subgroups, predict the IGF-I response to dose changes and simulate missed dosing. Results: The analyses supported the clinical recommendations of higher starting doses for younger patients and women on oral oestrogen replacement therapy. For patients switching from daily GH treatment, the mean maintenance dose ratio between somapacitan (mg/week) and somatropin (mg/day) was predicted to be 8.2 (observed interquartile range of 6.7-9.1). Simulations of IGF-I SDS profiles confirmed the appropriate time for IGF-I sampling to be 3-4 days after somapacitan dosing and supported somapacitan administration with up to 3 days delay in case of missed dosing. Subgroup analyses characterised the dose-exposure-IGF-I response in patient subgroups and indicated that dose requirements are mainly influenced by sex and oral oestrogen treatment. Conclusions: This study extends the knowledge of the somapacitan dose-IGF-I response and provides information on clinical dosing of once-weekly somapacitan in patients with AGHD.
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17.
  • Kufe, Clement N., et al. (author)
  • Increased risk for type 2 diabetes in relation to adiposity in middle-aged Black South African men compared to women
  • 2022
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 186:5, s. 523-533
  • Journal article (peer-reviewed)abstract
    • Aims: Despite a higher prevalence of overweight/obesity in Black South African women compared to men, the prevalence of type 2 diabetes (T2D) does not differ. We explored if this could be due to sex differences in insulin sensitivity, clearance and/or beta-cell function and also sex-specific associations with total and regional adiposity.Methods: This cross-sectional study included 804 Black South African men (n = 388) and women (n = 416). Dual-energy X-ray absorptiometry was used to measure total and regional adiposity. Insulin sensitivity (Matsuda index), secretion (C-peptide index) and clearance (C-peptide/insulin ratio) were estimated from an oral glucose tolerance test.Results: After adjusting for sex differences in the fat mass index, men were less insulin sensitive and had lower beta-cell function than women (P < 0.001), with the strength of the associations with measures of total and central adiposity being greater in men than women (P < 0.001 for interactions). Further, the association between total adiposity and T2D risk was also greater in men than women (relative risk ratio (95% CI): 2.05 (1.42-2.96), P < 0.001 vs 1.38 (1.03-1.85), P = 0.031).Conclusion: With increasing adiposity, particularly increased centralisation of body fat linked to decreased insulin sensitivity and beta-cell function, Black African men are at greater risk for T2D than their female counterparts.
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18.
  • Lundtoft, Christian, et al. (author)
  • Relation between HLA and copy number variation of steroid 21-hydroxylase in a Swedish cohort of patients with autoimmune Addison's disease.
  • 2023
  • In: European journal of endocrinology. - : Bioscientifica. - 1479-683X .- 0804-4643. ; 189:2, s. 235-241
  • Journal article (peer-reviewed)abstract
    • Autoantibodies against the adrenal enzyme 21-hydroxylase is a hallmark manifestation in autoimmune Addison's disease (AAD). Steroid 21-hydroxylase is encoded by CYP21A2, which is located in the human leucocyte antigen (HLA) region together with the highly similar pseudogene CYP21A1P. A high level of copy number variation is seen for the 2 genes, and therefore, we asked whether genetic variation of the CYP21 genes is associated with AAD.Case-control study on patients with AAD and healthy controls.Using next-generation DNA sequencing, we estimated the copy number of CYP21A2 and CYP21A1P, together with HLA alleles, in 479 Swedish patients with AAD and autoantibodies against 21-hydroxylase and in 1393 healthy controls.With 95% of individuals carrying 2 functional 21-hydroxylase genes, no difference in CYP21A2 copy number was found when comparing patients and controls. In contrast, we discovered a lower copy number of the pseudogene CYP21A1P among AAD patients (P = 5 × 10-44), together with associations of additional nucleotide variants, in the CYP21 region. However, the strongest association was found for HLA-DQB1*02:01 (P = 9 × 10-63), which, in combination with the DRB1*04:04-DQB1*03:02 haplotype, imposed the greatest risk of AAD.We identified strong associations between copy number variants in the CYP21 region and risk of AAD, although these associations most likely are due to linkage disequilibrium with disease-associated HLA class II alleles.
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19.
  • Majidi, Fatemeh, et al. (author)
  • Clinical spectrum of primary adrenal lymphoma: results of a multicenter cohort study
  • 2020
  • In: European Journal of Endocrinology. - : BIOSCIENTIFICA LTD. - 0804-4643 .- 1479-683X. ; 183:4, s. 453-462
  • Journal article (peer-reviewed)abstract
    • Purpose: We sought to refine the clinical picture of primary adrenal lymphoma (PAL), a rare lymphoid malignancy with predominant adrenal manifestation and risk of adrenal insufficiency. Methods: Ninety-seven patients from 14 centers in Europe, Canada and the United States were included in this retrospective analysis between 1994 and 2017. Results: Of the 81 patients with imaging data, 19 (23%) had isolated adrenal involvement (iPAL), while 62 (77%) had additional extra-adrenal involvement (PAL+). Among patients who had both CT and PET scans, 18FDG-PET revealed extra-adrenal involvement not detected by CT scan in 9/18 cases (50%). The most common clinical manifestations were B symptoms (55%), fatigue (45%), and abdominal pain (35%). Endocrinological assessment was often inadequate. With a median follow-up of 41.6 months, 3-year progression-free (PFS) and overall (OS) survival rates in the entire cohort were 35.5% and 39.4%, respectively. The hazard ratios of iPAL for PFS and OS were 40.1 (95% CI: 2.63-613.7, P = 0.008) and 2.69 (95% CI: 0.61-11.89, P = 0.191), respectively. PFS was much shorter in iPAL vs PAL+ (median 4 months vs not reached, P = 0.006), and OS also appeared to be shorter (median 16 months vs not reached), but the difference did not reach statistical significance (P = 0.16). Isolated PAL was more frequent in females (OR = 3.81; P = 0.01) and less frequently associated with B symptoms (OR = 0.159; P = 0.004). Conclusion: We found unexpected heterogeneity in the clinical spectrum of PAL. Further studies are needed to clarify whether clinical distinction between iPAL and PAL+ is corroborated by differences in molecular biology.
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20.
  • Naruse, Mitsuhide, et al. (author)
  • International multicenter survey on screening and confirmatory testing in primary aldosteronism.
  • 2023
  • In: European journal of endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 188:1
  • Journal article (peer-reviewed)abstract
    • Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized.In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated.We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers.Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.
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21.
  • Nilsson, Ola, 1970- (author)
  • Aggrecanopathies highlight the need for genetic evaluation of ISS children
  • 2020
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 183:2, s. C9-C10
  • Journal article (peer-reviewed)abstract
    • Short stature is one of the most common causes for referrals to pediatric endocrinologists. However, in a majority of the children, no underlying cause can be identified and the child instead receives the unhelpful diagnosis of idiopathic short stature (ISS), often after extensive work-up and testing. Recent advances in genetic methodology have allowed for the identification of a number of different monogenic conditions within the large cohort of ISS children. Isolated short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (MIM#165800) due to heterozygous aggrecan gene mutations exemplifies how this progress is changing the way we assess, counsel and treat children with non-endocrine growth disorders.
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22.
  • Oster, S., et al. (author)
  • Self-management and hospitalization in 615 Swedish patients with Addison's disease during the coronavirus disease 2019 pandemic: a retrospective study
  • 2023
  • In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 188:2
  • Journal article (peer-reviewed)abstract
    • Objective Autoimmune Addison's disease (AAD) entails a chronic adrenal insufficiency and is associated with an increased risk of severe infections. It is, however, unknown how patients with AAD were affected by the coronavirus disease 2019 (COVID-19) pandemic of 2020-2021. This study was aimed at investigating the incidence of COVID-19 in patients with AAD in Sweden, the self-adjustment of medications during the disease, impact on social aspects, and treatment during hospitalization. Additionally, we investigated if there were any possible risk factors for infection and hospitalization. Design and methods Questionnaires were sent out from April to October 2021 to 813 adult patients with AAD in the Swedish Addison Registry. The questionnaires included 55 questions inquiring about COVID-19 sickness, hospital care, medications, and comorbidities, focusing on the pre-vaccine phase. Results Among the 615 included patients with AAD, COVID-19 was reported in 17% of which 8.5% required hospital care. Glucocorticoid treatment in hospitalized patients varied. For outpatients, 85% increased their glucocorticoid dosage during sickness. Older age (P = .002) and hypertension (P = .014) were associated with an increased risk of hospital care, while younger age (P < .001) and less worry about infection (P = .030) were correlated with a higher risk of COVID-19. Conclusions In the largest study to date examining AAD during the COVID-19 pandemic, we observed that although one-fifth of the cohort contracted COVID-19, few patients required hospital care. A majority of the patients applied general recommended sick rules despite reporting limited communication with healthcare during the pandemic.
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23.
  • Pan, Xiong-Fei, et al. (author)
  • Circulating fatty acids and risk of gestational diabetes mellitus : prospective analyses in China
  • 2021
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 185:1, s. 87-97
  • Journal article (peer-reviewed)abstract
    • Objective: We aimed to examine prospective associations between circulating fatty acids in early pregnancy and incident gestational diabetes mellitus (GDM) among Chinese pregnant women.Methods: Analyses were based on two prospective nested case-control studies conducted in western China (336 GDM cases and 672 matched controls) and central China (305 cases and 305 matched controls). Fasting plasma fatty acids in early pregnancy (gestational age at enrollment: 10.4 weeks(s.d., 2.0)) and 13.2 weeks (1.0), respectively) were determined by gas chromatography-mass spectrometry, and GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Groups criteria during 24-28 weeks of gestation. Multiple metabolic biomarkers (HOMA-IR (homeostatic model assessment for insulin resistance), HbA1c, c-peptide, high-sensitivity C-reactive protein, adiponectin, leptin, and blood lipids) were additionally measured among 672 non-GDM controls at enrollment.Results: Higher levels of saturated fatty acids (SFAs) 14:0 (pooled odds ratio, 1.41 for each 1-s.d. increase; 95% CI: 1.25, 1.59) and 16:0 (1.19; 1.05, 1.35) were associated with higher odds of GDM. Higher levels of n-6 polyunsaturated fatty acid (PUFA) 18:2n-6 were strongly associated with lower odds of GDM (0.69; 0.60, 0.80). In non-GDM pregnant women, higher SFAs 14:0 and 16:0 but lower n-6 PUFA 18:2n-6 were generally correlated with unfavorable metabolic profiles.Conclusions: We documented adverse associations of 14:0 and 16:0 but a protective association of 18:2n-6 with GDM among Chinese pregnant women. Our findings highlight the distinct roles of specific fatty acids in the onset of GDM.
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24.
  • Quinkler, Marcus, et al. (author)
  • Characterization of patients with adrenal insufficiency and frequent adrenal crises
  • 2021
  • In: European Journal of Endocrinology. - : BioScientifica Ltd.. - 0804-4643 .- 1479-683X. ; 184:6, s. 761-771
  • Journal article (peer-reviewed)abstract
    • Objective: This study aimed to characterize the clinical and biochemical features of patients with primary (PAI) and secondary (SAI) adrenal insufficiency who developed adrenal crises (ACs) and estimate the incidence of ACs in these patients. Design: Retrospective case-control analysis of the European Adrenal Insufficiency Registry (EU-AIR; NCT01661387). Methods: Two thousand six hundred and ninety-four patients with AI (1054 PAI; 1640 SAI) enrolled in EU-AIR. Patients who developed >= 1 AC were matchd 1:3 with patients without ACs for age, sex and AI type. Data were collected at baseline and follow-up (mean +/- s.D.: PAI 3.2 +/- 1.7 years; SAI 2.9 +/- 1.7 years). Results: One hundred and forty-eight out of 2694 patients (5.5%; n = 84 PAI; n = 64 SAI) had an AC during the study: 6.53 (PAI) and 3.17 (SAI) ACs/100 patient-years. Of patients who experienced an AC, 16% (PAI) and 9.4% (SAI) experienced > 1 AC/year. The incidence of adverse events, infectious intercurrent illnesses and infectious serious adverse events were higher in patients with ACs than without ACs. No differences were observed in BMI, HbA1c, blood pressure and frequencies of diabetes mellitus or hypertension between subgroups (PAI and SAI, with and without ACs). At baseline, PAI patients with AC had higher serum potassium (4.3 +/- 0.5 vs 4.2 +/- 0.4 mmol/L; P = 0.03) and lower sodium (138.5 +/- 3.4 vs 139.7 +/- 2.9 mmol/L; P = 0.004) than patients without AC. At last observation, SAI patients with AC had higher hydrocortisone doses than patients without AC (11.9 +/- 5.1 vs 10.1 +/- 2.9 mg/m(2); P < 0.001). Conclusions: These results demonstrate that concomitant diseases and cardiovascular risk factors do not feature in the risk profile of AC; however, patients with AC had a higher incidence of infectious events.
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25.
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26.
  • Saevik, Ase Bjorvatn, et al. (author)
  • Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional study
  • 2023
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 189:4, s. 438-447
  • Journal article (peer-reviewed)abstract
    • Objective: Increased prevalence of cardiovascular disease has been reported in autoimmune Addisons 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 mu g 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.
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27.
  • Sandqvist, Patricia, et al. (author)
  • Primary hyperparathyroidism, a machine learning approach to identify multiglandular disease in patients with a single adenoma found at preoperative Sestamibi-SPECT/CT
  • 2022
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 187:2, s. 257-263
  • Journal article (peer-reviewed)abstract
    • Objective: Successful preoperative image localisation of all parathyroid adenomas (PTA) in patients with primary hyperparathyroidism (pHPT) and multiglandular disease (MGD) remains challenging. We investigate whether a machine learning classifier (MLC) could predict the presence of overlooked PTA at preoperative localisation with Tc-99m-Sestamibi-SPECT/CT in MGD patients.Design: This study is a retrospective study from a single tertiary referral hospital initially including 349 patients with biochemically confirmed pHPT and cured after surgical parathyroidectomy.Methods: A classification ensemble of decision trees with Bayesian hyperparameter optimisation and five-fold cross-validation was trained with six predictor variables: the preoperative plasma concentrations of parathyroid hormone, total calcium and thyroid-stimulating hormone, the serum concentration of ionised calcium, the 24-h urine calcium and the histopathological weight of the localised PTA at imaging. Two response classes were defined: patients with single-gland disease (SGD) correctly localised at imaging and MGD patients in whom only one PTA was localised on imaging. The data set was split into 70% for training and 30% for testing. The MLC was also tested on a subset of the original data based on CT image-derived PTA weights.Results: The MLC achieved an overall accuracy at validation of 90% with an area under the cross-validation receiver operating characteristic curve of 0.9. On test data, the MLC reached a 72% true-positive prediction rate for MGD patients and a misclassification rate of 6% for SGD patients. Similar results were obtained in the testing set with image-derived PTA weight.Conclusions: Artificial intelligence can aid in identifying patients with MGD for whom Tc-99m-Sestamibi-SPECT/CT failed to visualise all PTAs.
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28.
  • Skov, Jakob, et al. (author)
  • Co-aggregation and heritability of organ-specific autoimmunity : a population-based twin study
  • 2020
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 182:5, s. 473-480
  • Journal article (peer-reviewed)abstract
    • Objective: Co-aggregation of autoimmune diseases is common, suggesting partly shared etiologies. Genetic factors are believed to be important, but objective measures of environ mental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at estimating heritability and genetic overlap in seven organspecific autoimmune diseases.Design: Prospective twin cohort study.Methods: We used a cohort of 110 814 twins to examine co-aggregation and heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 diabetes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disease as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estimate the genetic influence on co-aggregation. Heritability for individual disorders was calculated using structural equational modeling adjusting for censoring and truncation of data.Results: Co-aggregation was more pronounced in monozygotic twins (media n HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moderate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0. 71) for Graves' disease to 0.97 (95% CI: 0.91- 1.00) for Addison's disease.Conclusions: Overall, co-aggregation was more pronounced in monozygotic than in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co-aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our results validate and refine previous heritability estimates based on smaller twin cohorts.
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29.
  • Skov, J., et al. (author)
  • Co-aggregation and heritability of organ-specific autoimmunity: a population-based twin study
  • 2020
  • In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 182:5, s. 473-480
  • Journal article (peer-reviewed)abstract
    • Objective: Co-aggregation of autoimmune diseases is common, suggesting pa rtly shared etiologies. Genetic factors are believed to be important, but objective measures of environ mental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at esti mating heritability and genetic overlap in seven organspecific autoimmune diseases. Design: Prospective twin cohort study. Methods: We used a cohort of 110 814 twins to examine co-aggregation an d heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 dia betes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disea se as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estim ate the genetic influence on co- aggregation. Heritability for individual disorders was calculated using stru ctural equational modeling adjusting for censoring and truncation of data. Results: Co-aggregation was more pronounced in monozygotic twins (media n HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moder ate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0. 71) for Graves' disease to 0.97 (95% CI: 0.91- 1.00) for Addison's disease. Conclusions: Overall, co-aggregation was more pronounced in monozygotic tha n in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co- aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our r esults validate and refine previous heritability estimates based on smaller twin cohorts.
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30.
  • Skov, J., et al. (author)
  • Shared etiology of type 1 diabetes and Hashimoto's thyroiditis: a population-based twin study
  • 2022
  • In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 186:6, s. 677-685
  • Journal article (peer-reviewed)abstract
    • Objective: Type 1 diabetes and Hashimoto's thyroiditis frequently cluster in individuals and in families, indicating shared origins. The objective of this study was to investigate familial co-aggregation of these diseases and to quantify shared genetic and environmental factors. Design: This study is a twin cohort study. Methods: National health registers were used to identify cases among 110 814 Swedish twins. Co-aggregation was calculated as risk ratios for type 1 diabetes among co-twins of individuals with Hashimoto's thyroiditis, and vice-versa. Variance explained by genetics (i.e. heritability), and the proportions thereof shared between the diseases, was estimated by contrasting associations in monozygotic and dizygotic twins using structural equation models. Results: Individuals with one disease were at a high risk for the other disease (adjusted risk ratio: 11.4 (95% CI: 8.5-15.3)). Co-aggregation was more common in monozygotic than in dizygotic pairs, with adjusted risk ratios of 7.0 (95% CI: 3.2-15.1) and 1.7 (95% CI: 0.7-4.1), respectively. Genetic effects shared across diseases accounted for 11% of the variance for type 1 diabetes and 9% of the variance for Hashimoto's thyroiditis, while environmental factors unique to individual twins, but shared across diseases, accounted for 10% of the variance for type 1 diabetes and 18% of the variance for Hashimoto's thyroiditis. Conclusions: Both genes and environment unique to individual twins contribute to considerable etiologic overlap between type 1 diabetes and Hashimoto's thyroiditis. These findings add to the current knowledge on the mechanisms behind autoimmune disease clustering and could guide future research aimed at identifying pathophysiological mechanisms and intervention targets.
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31.
  • Stomby, Andreas, et al. (author)
  • Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus
  • 2020
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 182:4, s. 447-457
  • Journal article (peer-reviewed)abstract
    • Context: Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes.Objective: Test the effects of a diet intervention with added exercise on glucocorticoid metabolism.Design: Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX).Setting: Umea University Hospital.Participants: Men and women with type 2 diabetes treated with lifestyle modification +/- metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism.Main outcome measures: Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD1181 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy.Results: Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5 alpha-THF + 5 beta-THF/THE in urine increased in both groups.Conclusions: These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.
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32.
  • Sundin, Anders, 1954- (author)
  • Commentary on Adrenal wash-out CT : moderate diagnostic value in distinguishing benign from malignant masses
  • 2022
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 186:6, s. C9-C12
  • Journal article (peer-reviewed)abstract
    • The increasing use of cross-sectional imaging, mainly CT, results in an accelerating number of incidental findings, for instance of adrenal tumours. Although most 'adrenal incidentalomas' are benign, it is important to identify the malignant and the hormone producing (functional) tumours. For a small fraction of adrenal incidentalomas, the diagnosis is apparent on imaging, but the large majority requires radiological characterisation. To this end, a previous joint European Society of Endocrinology and European Network for the Study of Adrenal Tumours publication in this jounal, recommends CT measurements of the native (non-contrast) tumour attenuation <= 10 Hounsfield units, consistent with a lipid-rich benign adrenocortical adenoma, and imaging at least 6 months apart, on which unchanged tumour size implies a benign tumour. Because of weak evidence, calculation of CT contrast medium washout was not recommended as a means for tumour characterisation, but this technique has nevertheless still been applied in several countries. The recent article by Schloetelburg et al. in this journal is important because, in the largest study to date, the authors confirm that calculation of CT contrast medium washout with established thresholds is insufficient to reliably characterise adrenal tumours. Their results are therefore expected to impact the management of these patients.
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33.
  • Taskinen, M. R., et al. (author)
  • Role of endogenous incretins in the regulation of postprandial lipoprotein metabolism
  • 2022
  • In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 187:1, s. 75-84
  • Journal article (peer-reviewed)abstract
    • Objective: Incretins are known to influence lipid metabolism in the intestine when administered as pharmacologic agents. The aggregate influence of endogenous incretins on chylomicron production and clearance is less clear, particularly in light of opposing effects of co-secreted hormones. Here, we tested the hypothesis that physiological levels of incretins may impact on production or clearances rates of chylomicrons and VLDL. Design and methods: A group of 22 overweight/obese men was studied to determine associations between plasma levels of glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) after a fat-rich meal and the production and clearance rates of apoB48- and apoB100-containing triglyceride-rich lipoproteins. Subjects were stratified by above- and below-median incretin response (area under the curve). Results: Stratification yielded subgroups that differed about two-fold in incretin response. There were neither differences in apoB48 production rates in chylomicrons or VLDL fractions nor in apoB100 or triglyceride kinetics in VLDL between men with above- vs below-median incretin responses. The men with above-median GLP-1 and GLP-2 responses exhibited higher postprandial plasma and chylomicron triglyceride levels, but this could not be related to altered kinetic parameters. No differences were found between incretin response subgroups and particle clearance rates. Conclusion: We found no evidence for a regulatory effect of endogenous incretins on contemporaneous chylomicron or VLDL metabolism following a standardised fat-rich meal. The actions of incretins at pharmacological doses may not be reflected at physiological levels of these hormones.
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34.
  • Teede, Helena J., et al. (author)
  • Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome
  • 2023
  • In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 189
  • Journal article (peer-reviewed)abstract
    • Study question: What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary answer: International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. What is known already: The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from 6 continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low-to low-quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus-based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, the evidence quality was low, and evidence-practice gaps persist. Study design, size, and duration: The 2023 International Evidence-based Guideline update re-engaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation, and ultimately recommendation strength, and diversity and inclusion were considered throughout. Participants/materials, setting, and methods: This summary should be read in conjunction with the full guideline for detailed participants and methods. Governance included a 6-continent international advisory and management committee, 5 guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health, and other experts, alongside consumers, project management, evidence synthesis, statisticians, and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and 5 face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across 5 guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council. Main results and the role of chance: The evidence in the assessment and management of PCOS has generally improved in the past 5 years but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpin 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include the following: (1) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm, and inclusion of anti-Müllerian hormone levels as an alternative to ultrasound in adults only; (2) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnoea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; (3) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care, and shared decision-making to improve patient experience, alongside greater research; (4) maintained emphasis on healthy lifestyle, emotional well-being, and quality of life, with awareness and consideration of weight stigma; and (5) emphasizing evidence-based medical therapy and cheaper and safer fertility management. Limitations and reasons for caution: Overall, recommendations are strengthened and evidence is improved but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. Wider implications of the findings: The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input, and consumer preferences. Research recommendations have been generated, and a comprehensive multifaceted dissemination and translation programme supports the guideline with an integrated evaluation programme.
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35.
  • Traskila, E, et al. (author)
  • Pubertal development and hypogonadism in males with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy: a retrospective study
  • 2023
  • In: European journal of endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 188:4, s. K17-K23
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to describe the course of puberty and hypogonadism in males with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in the Finnish APECED cohort followed 1970-2020. Anthropometry, testicular volumes, and FSH, LH, and testosterone concentrations were analysed retrospectively. Forty-three males were followed until the median age of 42.5 years (range, 16.2–74.8). All subjects fulfilled the clinical criteria of APECED. The median age at the onset of spontaneous puberty was 13.3 years (10.8–14.8). Testosterone medication was used to promote pubertal development from the median age of 14.9 years (13.5–15.7), for 0.7–3.3 years in eight patients. The median adult height was 173.0 cm and differed from the mid-parental target height on average -1.3 SDS (P &lt; 0.001). Hypogonadism was treated in six patients (14%). Azoospermia was found in three patients. Further studies are required to explore the role of AIRE in sperm production and testicular insufficiency.
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36.
  • Trouillas, Jacqueline, et al. (author)
  • Initial pathology in aggressive pituitary tumours and carcinomas : 2b or not 2b?-that is the question
  • 2023
  • In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 188:4, s. 5-8
  • Journal article (peer-reviewed)abstract
    • From a cohort of 171 patients comprising 121 aggressive pituitary tumours (APT) and 50 pituitary carcinomas (PC), the clinicopathological or five-tiered classification based on tumour invasion and proliferation evaluated by at least 2 proliferative markers over the cut-offs (Ki-67 ≥3% or ≥10%, p53 positive or expressed in %, mitotic count >2%), could be applied on 43 tumours: 20 PC and 23 APT. At the initial surgery, 29/43 tumours (67.4%) were grade 2b (invasive and proliferative) of which 44.8% developed metastases during follow-up (PC, grade 3). Out of these 29 tumours, 55.1% had a Ki-67 ≥10%, and were classified grade 2b* (invasive and highly proliferative). There was one tumour grade 1b* (non-invasive and highly proliferative) which metastazed. Out of the 43 tumours, 30.2 % were grade 2a (invasive and non-proliferative). The sensitivity and the specificity of grade 2b for the diagnosis of APT at the initial surgery, were 68% and 90% respectively. The comparison of the high percentage (67.4%) of grade 2b tumours in this selected cohort of APT/PC with the low percentage (8.8%) in a surgical cohort of unselected tumours shows that the initial pathological diagnosis of grade 2b tumour may be considered, in the clinic, as representing a diagnosis of APT. In addition, a significant subgroup of tumours, which will develop metastases supports the proposal that an aggressive grade 2b tumour is “a tumour with malignant potential” or “a malignant tumour without metastases”. So, the clinician may take into account the pathological diagnosis, at the initial surgery, to propose a strict follow-up and to consider earlier use of radiotherapy and/or of temozolomide in the presence of tumours with aggressive behaviour.
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37.
  • Träskilä, E, et al. (author)
  • Pubertal development and hypogonadism in males with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy: a retrospective study
  • 2023
  • In: European journal of endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 188:4, s. K17-K23
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to describe the course of puberty and hypogonadism in males with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in the Finnish APECED cohort followed 1970-2020. Anthropometry, testicular volumes, and FSH, LH, and testosterone concentrations were analysed retrospectively. Forty-three males were followed until the median age of 42.5 years (range, 16.2–74.8). All subjects fulfilled the clinical criteria of APECED. The median age at the onset of spontaneous puberty was 13.3 years (10.8–14.8). Testosterone medication was used to promote pubertal development from the median age of 14.9 years (13.5–15.7), for 0.7–3.3 years in eight patients. The median adult height was 173.0 cm and differed from the mid-parental target height on average -1.3 SDS (P &lt; 0.001). Hypogonadism was treated in six patients (14%). Azoospermia was found in three patients. Further studies are required to explore the role of AIRE in sperm production and testicular insufficiency.
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38.
  • Vouzouneraki, Konstantina, et al. (author)
  • Carpal tunnel syndrome in acromegaly: a nationwide study.
  • 2021
  • In: European journal of endocrinology. - : Bioscientifica. - 1479-683X .- 0804-4643. ; 184:2, s. 209-216
  • Journal article (peer-reviewed)abstract
    • Carpal tunnel syndrome (CTS) is common in patients with acromegaly, with a reported prevalence of 19-64%. We studied CTS in a large national cohort of patients with acromegaly and the temporal relationship between the two diagnoses.Retrospective, nationwide, cohort study including patients diagnosed with acromegaly in Sweden, 2005-2017, identified in the Swedish Healthcare Registries.CTS (diagnosis and surgery in specialised healthcare) was analysed from 8.5 years before the diagnosis of acromegaly until death or end of the study. Standardised incidence ratios (SIRs) with 95% confidence intervals were calculated for CTS with the Swedish population as reference.The analysis included 556 patients with acromegaly (50% women) diagnosed at mean (SD) age 50.1 (15.0) years. During the study period, 48 patients were diagnosed with CTS and 41 patients underwent at least one CTS surgery. Among the latter group, 35 (85%) were operated for CTS before the acromegaly diagnosis; mean interval (range) 2.2 (0.3-8.5) years and the SIR for having CTS surgery before the diagnosis of acromegaly was 6.6 (4.8-8.9). Women with acromegaly had a higher risk for CTS than men (hazard ratio 2.5, 95% CI 1.3-4.7).Patients with acromegaly had a 6-fold higher incidence for CTS surgery before the diagnosis of acromegaly compared with the general population. The majority of patients with both diagnoses were diagnosed with CTS prior to acromegaly. Increased awareness of signs of acromegaly in patients with CTS might help to shorten the diagnostic delay in acromegaly, especially in women.
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39.
  • Öster, Sara, et al. (author)
  • Self-management and hospitalization in 615 Swedish patients with Addison's disease during the COVID-19 pandemic : a retrospective study
  • 2023
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 188:2
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Autoimmune Addison's disease (AAD) entails a chronic adrenal insufficiency and is associated with an increased risk of severe infections. It is, however, unknown how patients with AAD were affected by the coronavirus disease 2019 (COVID-19) pandemic of 2020-2021. The aim of this study was to investigate the incidence of COVID-19 in patients with AAD in Sweden, the self-adjustment of medications during the disease, impact on social aspects and treatment during hospitalization. Additionally, we investigated if there were any possible risk factors for infection and hospitalization.DESIGN AND METHODS: Questionnaires were sent out from April to October 2021 to 813 adult patients with AAD in the Swedish Addison registry. The questionnaires included 55 questions inquiring about COVID-19 sickness, hospital care, medications, and co-morbidities, focusing on the pre-vaccine phase.RESULTS: Among the 615 included patients with AAD, COVID-19 was reported by 17% of which 8.5% required hospital care. Glucocorticoid treatment in hospitalized patients varied. For outpatients 85% increased their glucocorticoid dosage during sickness. Older age (p=0.002) and hypertension (p=0.014) were associated with an increased risk of hospital care while younger age (p<0.001) and less worry about infection (p=0.030) correlated with a higher risk of COVID-19.CONCLUSIONS: In the largest study to date examining AAD during the COVID-19 pandemic, we observed that although one fifth of the cohort contracted COVID-19 few patients required hospital care. A majority of the patients applied general recommended sick-rules despite reporting limited communication with healthcare during the pandemic.
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40.
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41.
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42.
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43.
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44.
  • Chantzichristos, Dimitrios, 1976, et al. (author)
  • MANAGEMENT OF ENDOCRINE DISEASE: Disease burden and treatment challenges in patients with both Addison's disease and type 1 diabetes mellitus.
  • 2020
  • In: European journal of endocrinology. - 1479-683X. ; 183:1
  • Research review (peer-reviewed)abstract
    • Concurrent type 1 diabetes (T1D) and Addison's disease (AD) is a rare combination of diseases and, in approximately one third of these patients, it is also combined with an autoimmune thyroid disease. Recently, it was shown that patients with both T1D and AD have a higher risk of premature death compared to patients with T1D alone, the most common causes of death being due to diabetic complications and cardiovascular disease. These patients receiving replacement therapies with both insulin and glucocorticoids face an increased risk of hypo- and hyperglycemia, and diabetic ketoacidosis, and have a higher risk of adrenal crisis than patients with AD alone. Treatment challenges include the opposing effects of insulin and glucocorticoids on glucose homeostasis, and the need to balance and synchronize these two treatments. The rarity of this disease combination may explain the paucity of data on outcome and specific treatment strategies in this patient group. Based on this review, we suggest management strategies for their insulin and glucocorticoid replacement therapies and indicate future areas of research.
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45.
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46.
  • Elenkov, Angel, et al. (author)
  • Testosterone replacement therapy in men who conceived with intracytoplasmic sperm injection: nationwide register study
  • 2020
  • In: European Journal of Endocrinology. - 1479-683X.
  • Journal article (peer-reviewed)abstract
    • Objectives Male hypogonadism is associated with higher risk of co-morbidity and premature mortality. It is, therefore, of utmost importance to identify young men who are at the highest risk of testosterone deficiency and who may benefit from preventive measures. In this context, infertile men constitute a high-risk group. The extent of testosterone replacement therapy (TRT) among infertile men, defined as men who have to undergo assisted reproduction for fatherhood, is currently unknown. Therefore, we evaluated the pattern of prescription of TRT in the years following child conception among men who have fathered children with the help of intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF). Design By sourcing data from national population registries, hazard ratio (HR) for subsequent TRT was assessed for IVF and ICSI-treated men and compared to those who conceived spontaneously with age Cox regression analysis adjusted for age, educational level and previous intake of medicines for metabolic diseases. Results ICSI and IVF fathers had increased incidence of newly prescribed TRT compared to fathers conceiving spontaneously (ICSI: HR = 3.81, 95% CI = 3.09–4.69, P < 0.001; IVF: HR = 1.54, 95% CI = 1.15–2.05, P = 0.003). After adjustment for prescription of medication for one or more components of the MetS prior to TRT, the risk estimates attenuated but remained robust both for ICSI-treated (HR = 3.17 (95% CI: 2.56–3.9) and IVF-treated men (HR = 1.06 (95% CI: 1.05–1.07). Conclusion Men who have to utilise powerful techniques, such as ICSI for fathering children, may be at risk for testosterone deficiency. Routine endocrine evaluation of men seeking fertility treatment is hence warranted.
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47.
  • Esposito, Daniela, et al. (author)
  • Prolonged Diagnostic Delay in Acromegaly is Associated with Increased Morbidity and Mortality.
  • 2020
  • In: European journal of endocrinology. - 1479-683X. ; 182:6
  • Journal article (peer-reviewed)abstract
    • Clinical features of acromegaly develop insidiously. Its diagnosis may therefore be delayed.Our aim was to study diagnostic delay and its impact on morbidity and mortality in a nationwide cohort of patients with acromegaly.Adult patients diagnosed with acromegaly between 2001 and 2013 were identified in the Swedish National Patient Registry. Diagnostic codes for predefined comorbidities associated with acromegaly were recorded between 1987 and 2013. Diagnostic delay was calculated as the time between the first registered comorbidity and the diagnosis of acromegaly.A total of 603 patients (280 men, 323 women) with acromegaly were included. Mean (SD) diagnostic delay was 5.5 (6.2) years [median (minimum, maximum) 3.3 (0.0-25.9)]. Diagnostic delay was 1-<5 years in 23% patients; 5-<10 years in 17%; and ≥10 years in 24%. No delay was recorded in 36% of patients. Overall, mean (SD) number of comorbidities was 4.1 (2.5) and was higher in patients with longer diagnostic delay (P < 0.0001). Overall, observed number of deaths was 61 (expected 42.2), resulting in a standardized mortality ratio (SMR) of 1.45 (95% CI: 1.11-1.86). Increased mortality was only found in patients with the longest diagnostic delay (1.76, 95% CI: 1.12-2.65). In the other groups, no statistically significant increase in mortality was recorded, with the numerically lowest SMR observed in patients without diagnostic delay (1.18; 95% CI: 0.68-1.92).The diagnosis of acromegaly is delayed in most patients. Prolonged diagnostic delay is associated with increased morbidity and mortality.
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48.
  • Forslund, Maria, 1978, et al. (author)
  • Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis.
  • 2023
  • In: European journal of endocrinology. - 1479-683X. ; 189:1
  • Journal article (peer-reviewed)abstract
    • To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS).A systematic review and meta-analysis was performed, Prospero CRD42022345640.MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials.A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included.Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17kg/m2 [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism.Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38nmol/L {95% CI 0.33-0.43}]) and BMI (MD 0.62kg/m2 [95% CI 0.05-1.20]) compared with conventional COCPs.There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified.With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS.The protocol for the systematic review was registered prospectively in Prospero, CRD42022345640.
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49.
  • Fuchtbauer, Laila, et al. (author)
  • Increased Number of Retinal Vessels in Acromegaly.
  • 2020
  • In: European journal of endocrinology. - 1479-683X. ; 182:3, s. 293-302
  • Journal article (peer-reviewed)abstract
    • Excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as in acromegaly, is associated with an increased risk of diabetes, but whether retinal vessels are altered is unknown. The aim of this study was to evaluate retinal vessel morphology in patients with acromegaly at diagnosis and after treatment and to describe the prevalence of diabetic retinopathy in patients with long-standing acromegaly and diabetes.Two independent observational studies, one being prospective and the other retrospective and cross-sectional.Retinal vessel morphology of 26 patients with acromegaly was examined at diagnosis and 1 year after treatment and compared to 13 healthy controls. Cross-sectional evaluation of 39 patients with long-standing acromegaly and diabetes was performed. Fundus photographs were digitally analyzed for vessel morphology.Patients with acromegaly had a median (interquartile range) of 34.3 (30.0-39.0) vessel branching points compared to 27.0 (24.0-29.0) for healthy controls (P < 0.001). Tortuosity of arterioles and venules remained unchanged. Vessel morphology did not change significantly after treatment. Patients with acromegaly and diabetes for a median of 14 years also had a high number of branching points [34.2 (32.5-35.6)], but the prevalence of diabetic retinopathy was not higher than expected in diabetic patients without acromegaly.Patients with acromegaly have an increased number of vascular branching points in the retina without an alteration of macroscopic vessel morphology. This is consistent with an angiogenic effect of GH/IGF-1 in humans. The prevalence of diabetic retinopathy was not increased in patients with acromegaly and diabetes.
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