European Journal of Endocrinology最新文献

Objective: To examine body image (BI) concerns in women with polycystic ovary syndrome (PCOS) by comparing perceptions with normative data, assessing links with psychological distress, clinical features, disordered eating, and quality of life (QoL), and identifying body image cut-offs that predict psychological risk.

Design: Mixed-methods observational study conducted in the United Kingdom (June 2023-October 2024).

Methods: Women with PCOS (n=171) completed validated questionnaires assessing BI (Multidimensional Body-Self Relations Questionnaire - Appearance Scale), depression, anxiety, disordered eating, and QoL; 41 also participated in semi-structured interviews. Moderation by ethnicity and socioeconomic status (SES) was examined.

Results: Women with PCOS reported greater BI-distress than normative data, driven by elevated body mass index (BMI) and hirsutism. Poorer BI was linked to higher depression, anxiety, disordered eating, and reduced QoL. ROC-analyses identified self-classified weight scores (SW)≥4.25 as the cut-off for depression and overweight preoccupation (OP)≥2.88 for anxiety. In adjusted models, higher SW scores predicted nearly fivefold greater depression risk, while elevated OP scores conferred a fourfold higher anxiety risk and doubled disordered eating risk. Together with BMI, OP and SW predicted most PCOS-QoL domains, with the strongest effects in weight-related QoL. Socioeconomic deprivation amplified OP effects on disordered eating, while ethnicity showed minimal influence. Qualitative findings echoed these results, with weight gain, hirsutism, negative diagnostic experiences, and social withdrawal emerging as key distress drivers.

Conclusion: BI concerns are central to psychological morbidity and reduced QoL in PCOS. Establishing OP and SW cut-offs enables early risk stratification, while acknowledging SES influences may support equitable, patient-centred care.

Background: The Itabaianinha cohort in Brazil carries a homozygous growth hormone-releasing hormone (GHRH) receptor (GHRH-R) gene mutation, causing congenital isolated GH deficiency (GHD). Affected individuals present with severe short stature, central obesity, hypercholesterolemia, and marked reductions in serum GH, IGF-I, and IGFBP 3 concentrations yet show no premature atherosclerosis and maintain a normal lifespan. IGF-I mostly circulates bound to IGFBPs and requires proteolytic cleavage for IGF-I receptor activation. Pregnancy-associated plasma protein A (PAPP-A) is an important IGF-dependent cleavage enzyme, binding to IGFBP 4 and releasing IGF-I. PAPP-A activity is inhibited by stanniocalcin-2 (STC2). The IGFBP 4-STC2-PAPP-A axis (ISPa) has emerged as a key regulator of IGF-I bioactivity.

Methods: We evaluated the ISPa in: (1) GHD subjects with homozygous GHRH-R c.57 + 1G→A mutation, (2) heterozygotes (HTZ), and (3) homozygous wild-type controls (HMZ). Parameters from the ISPa were measured at LMU Klinikum, Munich. Additional biochemical parameters were analyzed at the Federal University of Sergipe, Brazil.

Results: As expected, GHD subjects had markedly low GH, IGF-I, IGF-II, free IGF-I, and IGFBP 3 (P < .001), while HTZ resembled HMZ subjects. STC2, PAPP-A, and PAPP-A-STC2 complex concentrations did not differ between groups. However, PAPP-A2 and intact IGFBP 4 were higher in the GHD subjects (P < .05 and P < .01). Notably, IGF-I and IGFBP 3 positively correlated with IGF-II, whereas intact IGFBP 4 and PAPP-A2 showed inverse correlations with IGF-I and IGF-II.

Conclusion: Our findings suggest altered IGF-I bioavailability regulation via the ISPa in congenital lifetime GHD, leading to increased PAPP-A2 proteolytic activity, reduced PAPP-A enzymatic activity, and reduced sequestration of PAPP-A2 by STC2.

Objective: Glucagon-like peptide-1 (GLP-1) plays an important modulatory role in sodium and water homeostasis. Recent studies demonstrated that long-term treatment with GLP-1 receptor agonists (RAs) reduces fluid intake and urine output. To the best of our knowledge, no direct effect of GLP-1 on vasopressin has been observed. This secondary analysis aimed to investigate changes in copeptin levels in euvolemic participants treated with the GLP-1 RA dulaglutide versus placebo.

Design: Secondary analysis of two randomized, double-blind, placebo-controlled, cross-over trials in 34 patients with primary polydipsia and 20 healthy participants.

Methods: Participants received a 3-week intervention with dulaglutide (Trulicity) 1.5 mg or placebo (.9% sodium chloride) subcutaneously once weekly. Blood for copeptin analysis was collected at 08:00 after each treatment phase. To estimate the treatment effect of dulaglutide, we derived the absolute within-subject differences of copeptin between dulaglutide and placebo and used the Wilcoxon rank test for statistical analysis.

Results: All 54 participants of the two cross-over trials were included. Median age was 27 years [interquartile range (IQR), 24-37.5 years], and 63% were female. Median body mass index (BMI) was 23 kg/m2 (IQR, 20.8-24.8). After 3-week treatment, dulaglutide was associated with a significant suppression of copeptin with a median within-subject difference of -.7 pmol/L (p = .047), corresponding to a 12% reduction compared to placebo. Treatment-induced changes in copeptin were not significantly correlated with GLP-1-mediated reductions in blood pressure, BMI, or incidence of nausea.

Conclusions: Our analysis provides evidence that the GLP-1-RA dulaglutide inhibits the vasopressin system and proposes physiological mechanisms that may explain the role of GLP-1 in sodium and water balance.

Introduction: Brown adipose tissue (BAT) thermogenesis is mediated by sympathetic nervous system activation and enhanced by thyroid hormones via upregulation of uncoupling protein 1. Studying thyroid hormone response to cooling in populations with habitual cold exposure may give new insights to the role of thyroid hormones in non-shivering thermogenesis.

Methods: Twenty-one participants (11 Greenlanders, 10 Danes) underwent a cross-over protocol with experimental sessions of cooling and thermal comfort, followed by [18F]FDG positron emission tomography/computed tomography scans. Serial blood samples were collected to assess thyrotropin (TSH), total triiodothyronine (TT3), total thyroxine (TT4), and thyroglobulin (Tg) before, during, and after cooling.

Results: Cooling induced an increase in TSH (Danes: 0.24 mIU/L, P < .001; Greenlanders: 0.15 mIU/L, P = .009). TT3 also increased in response to cooling (Danes: 0.15 nmol/L, Greenlanders: 0.09 nmol/L, Pboth < .001). Greenlanders had lower TSH and higher TT3 levels compared to Danes (baseline 0.27 nmol/L, P = .009) with an attenuated TT3 response to cooling (-0.07 nmol/L, P  =  .009). The T3/T4 ratio was elevated during cold exposure compared to thermoneutral conditions in both Danes (P < .001) and Greenlanders (P = .022), and Greenlanders had consistently higher T3/T4 ratios compared to Danes (baseline, P = .001; after cooling, P = .023). Finally, Tg levels were higher in participants with low- compared to high-BAT volume (7.27 µg/L, P = .008).

Conclusion: Serial measurements of thyroid hormones and thyroglobulin with gold-standard detection of BAT activity documented distinct thyroid responses to cooling. The findings suggested a physiological preparedness to acute cold exposure in individuals with cold adaptation, irrespective of origin.

Objective: Androgen abuse for performance- and image-enhancement is increasing despite preventive efforts, yet no controlled trials have evaluated harm reduction strategies. This trial assessed whether a harm reduction intervention could reduce androgen abuse in males.

Design: Historically controlled trial.

Methods: This 1-year prospective intervention study included 99 male amateur athletes planning to start an androgen cycle. Outcomes were compared to a historical cohort study (n = 100) from our research group receiving no intervention. The intervention comprised individualized counseling and medical assessments. Primary outcomes included cumulative androgen dose, cycle duration, and weekly dosage. Secondary outcomes included within-participant deviation from planned abuse.

Results: Baseline characteristics were largely comparable, although intervention participants reported slightly more weekly training time and lower intended cumulative cycle dose. Twelve percent refrained from initiating a cycle due to the intervention. The mean cumulative androgen dose was 13 087 (95% CI -16 564 to -9609) mg lower in the intervention group (6323 ± 5229 mg) compared to controls (19 410 ± 16 497 mg). Within-person differences showed an average reduction of 8729 (95% CI -11 297 to -6287) mg in the intervention group compared to controls. Multivariable regression confirmed that the interventions' effect was independent of baseline differences. No significant enabling effect was observed.

Conclusion: This is the first controlled study to demonstrate that a harm reduction intervention can reduce androgen exposure among men planning to abuse androgens. These findings support harm reduction as a promising strategy to mitigate health risks associated with androgen abuse. Future studies should confirm generalizability and monitor for potential enabling effects.

Clinical trial registration number: Registration number P2117, study number NL77191.028.21.

Objective: Endocrine and metabolic diseases are known to be common late effects in childhood cancer survivors (CCS). We assessed the prevalence of these diseases in a large German CCS cohort, and a matched comparison population, using health claims data.

Design: The cohort study was based on record linkage between the nationwide German Childhood Cancer Registry and claims data from 13 major German statutory health insurances.

Methods: The monitored insurance period covered the years 2017-2021. We assessed the frequencies of endocrine and metabolic diseases among 11 863 five-year CCS, diagnosed 1991-2021, with continuous insurance coverage and a matched comparison group of 35 589 insured persons without a history of childhood cancer. We present prevalence and prevalence ratios (PR) with corresponding 95% confidence intervals (95% CI).

Results: At least one endocrine or metabolic disease was recorded in 31.3% of survivors (n = 3716) and in 16.4% of the comparison group (n = 5819, PR = 1.9; 95% CI: 1.8-2.0). The frequency of diseases was higher among females than among males in both groups. The PR was 2.4 (95% CI: 2.3-2.5) for males and 1.6 (95% CI: 1.5-1.7) for females. The frequency of at least one disease increased with increasing attained age. The disease with the highest frequency among CCS was hypothyroidism (15.85%), and the highest PR was estimated for patients with primary thyroid cancer (43.5; 95% CI: 24.2-78.1).

Conclusions: Our study highlights the increased vulnerability of CCS to endocrine and metabolic diseases compared to the general population and underscores the need for risk-adapted surveillance during the whole survivorship trajectory.

Background: Premature pubarche (PP) is characterized by the early onset of pubic or axillary hair, body odor, or mild acne, most commonly reflected by elevated plasma dehydroepiandrosterone-sulfate (DHEA-S) concentrations. However, recent evidence suggests that 11-oxygenated adrenal androgens (11β-hydroxyandrostenedione (11OHA4), 11β-hydroxytestosterone (11OHT)) may better represent true androgenic activity.

Aim: This study aims to evaluate the predictive value of adrenal androgens in determining growth characteristics among girls with PP.

Subjects and methods: A prospective study was conducted to evaluate anthropometric and clinical features and to quantify plasma adrenal androgens-including DHEA, DHEA-S, androstenedione (A4), androsterone, 11OHA4, and 11OHT-using liquid chromatography-mass spectrometry (LC-MS/MS) in 53 girls with isolated PP at presentation and during follow-up. Thirty-six age-matched girls without PP served as the control group.

Results: The height, BMI-SDS, DHEA, DHEA-S, A4, androsterone, and 17OH-pregnenolone concentrations were higher (p<0.0001), whereas no difference in 11OHA4 and 11OHT concentrations was observed in the PP group compared to controls. There was no correlation of adrenal androgen concentrations with height, corrected height, and growth velocity at baseline or during follow-up of 2.7 years. Corrected height SDS was positively correlated with baseline corrected height SDS (r=0.63, p<0.0001), baseline bone age/chronological age ratio (r=0.31, p=0.02), and baseline bone age SDS (r=0.32, p=0.01) but not with hormone concentrations.

Conclusion: Isolated idiopathic premature pubarche appears to be a benign variant of normal development. In this setting, adrenal androgen concentrations are not associated with adverse linear growth outcomes and are unlikely to influence clinical management, supporting a conservative approach after exclusion of pathological causes.

Objective: Management of 21-hydroxylase deficiency (21-OHD) congenital adrenal hyperplasia (CAH) in early infancy is challenging, with extent of variation in management unclear.

Design and methods: Using the I-CAH Registry, we retrospectively reviewed management over the first 90 days of life of 154 infants with 21-OHD born in 2018-2023, across 33 centers in 18 countries.

Results: Of 154 infants (92 female, 62 male), 136 were diagnosed postnatally, with median (10th centile, 90th centile) presentation age of Day 4 (0, 20.8). At initial hospital discharge, median doses of hydrocortisone (HC), fludrocortisone (FC), and salt were 17 (11.4, 39.6) mg/m2/day, 100 (50, 200) mcg/day and 3.5 (1.6, 8.7) mmol/kg/day, and at Day 90 (D90) 14.5 (8.7, 24.1) mg/m2/day, 100 (50, 200) mcg/day, and 2.1 (1.0, 5.2) mmol/kg/day, respectively. Hyponatremia, hyperkalemia, and hypoglycemia were reported in 70.0%, 71.9%, and 13.0% of infants, respectively. At D90, hyponatremia and hyperkalemia were reported in 7.4% and 28.6%, respectively. At D90, BP measurements were recorded in 30.5%, amongst whom 31.9% had hypertension reported. Median total hospitalization duration over 90 days was 9 days (2, 24). Adrenal crises were associated with 40. 6% of hospitalization episodes. Percentages (males:females) of cases seen by a pediatric endocrinologist, psychologist, pediatric endocrine nurse specialist, and surgeon by D90 were 95.9% (58:84), 33.3% (9:35), 42.1% (20:36), and 23.8% (0:35), respectively.

Conclusions: Contemporary management of CAH in early infancy varies considerably. Hypertension and hyperkalemia are frequently reported. Our data may help inform development of quality indicators for benchmarking CAH care in infancy.