Endocrine Connections最新文献

Aim: To describe the epidemiological, clinical, and healthcare profiles of treated hypoparathyroidism in Italy and to evaluate healthcare resource utilization and direct costs.

Methods: Patients with hypoparathyroidism between 2016 and 2022 were identified from the ReS administrative database (∼5.5 million Italian citizens of various regions) through an algorithm based on exemption codes, pharmaceutical consumption, hospital diagnosis/procedures, and emergency department (ED) access. The disease prevalence was determined. Demography, clinical characteristics, 1-year healthcare resource utilization (pharmaceuticals, hospitalizations, ED accesses, and outpatient services), and direct costs were analyzed for the cohort of treated patients and for a sub-cohort with higher treatment intensity (HTI) (i.e. with high-dose of calcium/calcitriol).

Results: Hypoparathyroidism's annual prevalence ranged from 25.5 to 27.6 per 100,000, with a higher prevalence among middle-aged females. The treated patient cohort (n = 2,791) and the sub-cohort with HTI (n = 662) were identified. Among treated patients, 75.2% had at least one comorbidity and 22.2% had three or more; these percentages were higher in the sub-cohort. A widespread consumption of calcium and/or vitamin D was observed in both cohorts, whereas other treatments were scarcely used. Hospitalization and ED access rates were 24.2 and 24.7%, respectively, for the main cohort and 37.8 and 32.5%, respectively, for the sub-cohort. Mean annual per-patient costs were €2,885 for the main cohort and €3,791 for the sub-cohort.

Conclusion: Hypoparathyroidism, due to its chronicity and complex comorbidity profile, represents a substantial and long-term source of healthcare expenditure. These findings highlight an unmet need, particularly for HTI patients, requiring more specific therapies to improve outcomes.

The childhood and adolescent obesity epidemic remains one of the most important and challenging health issues of the 21st century. Excess body weight affects the immediate health of children and adolescents, being associated with a higher and earlier risk of several non-communicable diseases (NCDs), such as type 2 diabetes and cardiovascular diseases, in addition to adverse psychosocial consequences and impacts on pubertal timing. Evidence dating back to the past century points to a secular trend of earlier puberty in boys and girls in various parts of the world, and this earlier onset has been attributed, at least in part, to obesity, especially in girls. In boys, this relationship is not as linear. Moreover, despite some contradictory results, most recent evidence points to earlier puberty also being associated with an excess of body weight in boys. Several mechanisms have been suggested to explain this possible relationship between puberty onset and obesity. However, the most promising link in this connection is leptin and its interaction with the kisspeptin system, in addition to an important contribution from insulin, which is frequently increased in obesity. The gut microbiota is implicated in the pathophysiology of obesity, which, in turn, is commonly associated with insulin resistance and the development of central precocious puberty, particularly in females. This review summarizes current knowledge on the relationship between obesity and the onset and progression of puberty in both sexes, as well as the pathways potentially involved in the pathophysiology of this association.

Background: The prognostic value of Pituitary Adenoma Nomenclature 3 (PANOMEN-3) for incident or persistent hypopituitarism remains uncertain. This study aimed to assess whether baseline PANOMEN-3 grade and its components predict secondary adrenal insufficiency or secondary hypothyroidism in surgically and nonoperatively managed patients.

Methods: We conducted a retrospective cohort study of adults with newly diagnosed pituitary adenoma at Rambam Health Care Campus, a tertiary referral center in Haifa, Israel, between 2010 and 2023. Follow-up was censored on August 31, 2025. Patients were stratified by management (surgical or nonoperative). PANOMEN-3 grades were assigned at the index visit, defined as the initial endocrinology consultation. The primary outcome was the incidence of the composite of secondary adrenal insufficiency or secondary hypothyroidism at follow-up.

Results: The study included 208 adults with pituitary adenomas: 118 underwent transsphenoidal surgery and 90 were managed nonoperatively. In the surgical group, the incidence of secondary adrenal insufficiency or secondary hypothyroidism at a median follow-up of 17.4 months (IQR: 5.0-47.7) was 32.2% and increased with higher baseline PANOMEN-3 grade (0% in grade 0 to 61.1% in grade 3; P = 0.01). In the nonoperative group, the incidence was 11.1% at a median follow-up of 15.5 months (IQR: 5.7-35.8) and was likewise associated with higher baseline grade (0% in grade 0 to 20.0% in grade 3; P = 0.02). Across both groups, baseline hypopituitarism and larger adenoma size were associated with secondary adrenal insufficiency or secondary hypothyroidism (surgical: P < 0.001 and P = 0.04; nonoperative: P < 0.001 and P = 0.03).

Conclusion: PANOMEN-3 grading effectively stratifies the risk of secondary adrenal and thyroid dysfunction in both surgical and nonoperative settings.

Background: Despite adequate conventional therapy, patients with chronic post-surgical hypoparathyroidism (HypoPT) frequently report persistent physical, emotional, and cognitive symptoms that affect quality of life, despite no overt cognitive impairment. The neurophysiological mechanisms underlying these complaints remain unclear.

Purpose: To assess cortical excitability and plasticity in HypoPT patients using transcranial magnetic stimulation (TMS) and to explore the effects of parathyroid hormone (PTH) therapy on these parameters.

Methods: We conducted a cross-sectional study including 32 HypoPT patients on stable conventional treatment without significant cognitive impairment and 16 age-matched healthy controls. In a prospective observational phase, a subgroup of six HypoPT patients (3-palopegteriparatide and 3-teriparatide) was reassessed after 48 months of PTH therapy. All participants underwent TMS evaluation, including motor evoked potentials (MEPs), short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), and assessment of plasticity using intermittent theta burst stimulation (iTBS). The primary outcome was the change in MEP amplitude after iTBS as an index of cortical plasticity.

Results: MEP changes following iTBS differed significantly between HypoPT patients and controls (-0.02 vs 0.4 mV; P = 0.003; corrected P = 0.042), indicating reduced cortical plasticity in HypoPT. In contrast, HypoPT patients receiving long-term PTH therapy showed a significant increase in MEP amplitude, comparable to healthy controls. No other TMS measures differed significantly.

Conclusion: This pilot study provides preliminary evidence of impaired cortical plasticity in HypoPT in the absence of overt cognitive impairment. Although limited by small sample size, the findings suggest that PTH therapy may modulate cortical plasticity. Further research is needed to clarify the clinical relevance and potential central nervous system effects of PTH in HypoPT.

Introduction: Estradiol may influence sleep-wake rhythms via modulation of the circadian timing system, but evidence is limited and often based on small samples. This study examined associations between serum estradiol levels and sleep parameters in men and in pre- and postmenopausal women from the general population.

Methods: This cross-sectional analysis used baseline data from the Netherlands Epidemiology of Obesity (NEO) study. Estradiol was measured in fasting serum using LC-MS/MS. Sleep quality and timing were assessed with the Pittsburgh Sleep Quality Index (PSQI). Associations were evaluated using multivariable weighted linear regression.

Results: In the 4,754 participants (51% men; mean age 56 years), serum estradiol levels were not associated with sleep quality or timing. Participants in the highest 10th percentile of estradiol showed marginally better sleep quality compared with those in the middle range (difference in PSQI = -0.74; 95% CI: -1.11 to -0.36).

Discussion: These findings suggest that, under physiological conditions, estradiol levels are not clearly linked to sleep quality or timing.

Objective: This study investigates the utilisation of modern glucocorticoid medications (Acecort®, Alkindi®, Efmody®, and Plenadren®) for congenital adrenal hyperplasia due to 21-hydroxylase deficiency, examining prescribing patterns, barriers to adoption, and geographical and temporal trends.

Methods: A two-part study was conducted: a retrospective analysis of treatment regimens from the International Congenital Adrenal Hyperplasia Registry across 46 centres in 20 countries (2017-2023) and a qualitative survey of 39 centres regarding barriers to prescribing modern medications. Patients included both paediatric and adult populations. Data analysed included regional prescription trends, timing of modern glucocorticoid adoption, and identified barriers.

Results: From 2017 to 2023, 44 of 790 (5%) patients transitioned from traditional to modern glucocorticoid therapy, with the highest adoption in high-income Western European countries. Alkindi® was exclusively prescribed to patients under 8 years, while 97% of Efmody® users were 7 years or older. By 2023, modern glucocorticoid availability varied among centres: Alkindi® (54%), Efmody® (46%), Plenadren® (33%), and Acecort® (15%).

Conclusion: Adoption of modern glucocorticoid medications for congenital adrenal hyperplasia remains limited, with only approximately 5% of patients transitioning from traditional therapies. Significant barriers include legislative approval, supply chain challenges, and elevated costs.

Plain language summary: This international study looked at how new medications for congenital adrenal hyperplasia are used globally. We found that despite increasing availability of new medications during the study time period, only a small number of patients (5%) switched to these newer treatments. This limited use is mainly due to high costs, problems with getting legal approval, and supply issues, highlighting unequal access to care worldwide.

Graphical abstract: Longitudinal arterial sampling combined with LC-MS/MS profiling was used to define the temporal organization of circulating steroid hormones in adult male mice. Adrenal steroids (corticosterone and deoxycorticosterone) exhibited coordinated diurnal rhythmicity, whereas testosterone secretion was highly variable and episodic, showing no consistent diurnal pattern. In contrast, progesterone remained comparatively stable and was weakly coupled to both adrenal and gonadal steroid dynamics. Created with Biorender.

Abstract: Steroid hormones exhibit temporal fluctuations that influence physiology, yet these dynamics remain incompletely characterized in male mice, a cornerstone model in endocrine research. Using serial arterial sampling and high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS/MS), we performed the first longitudinal, multi-analyte quantification of steroid hormones (testosterone, progesterone, corticosterone, and deoxycorticosterone (DOC)), within the same mice across consecutive days and diurnal periods. Adult male C57BL/6J mice (n = 13) were sampled daily for 5 days and again at 7 AM and 5:30 PM on non-consecutive days (days 1, 3, and 5). Corticosterone and its adrenal precursor - DOC - exhibited coordinated diurnal patterns, with corticosterone showing consistent AM-PM increases across all sampling days and DOC reaching significance only on day 5. These findings confirm a circadian pattern of adrenal steroidogenesis dominated by corticosterone, with its faster-turnover intermediate displaying less stable rhythmicity. In contrast, testosterone fluctuated irregularly and without a consistent AM-PM pattern, varying up to 100-fold within individual mice. Progesterone showed minimal day-to-day or diurnal variation. Correlation analyses revealed tight coupling among corticosterone and DOC (r = 0.99, P < 0.001), but no association between adrenal steroids and testosterone, indicating independent regulation of adrenal and gonadal axes. These results define the natural temporal organization of steroid hormones in male mice, distinguishing coordinated adrenal rhythmicity from pulsatile gonadal variability, and provide a physiologic framework for experimental design and data interpretation in murine endocrine research.

In the SELECT cardiovascular (CV) outcomes trial, semaglutide 2.4 mg significantly reduced all-cause mortality or non-fatal CV events versus placebo in patients with CV disease (CVD) and overweight/obesity, but without type 2 diabetes (T2D). By applying results from SELECT to a UK real-world population, this present cohort study evaluated the impact of semaglutide on life expectancy and CV event-free life-years. Included were individuals from the Discover electronic health record database who met SELECT eligibility criteria (≥45 years old; body mass index: ≥27 kg/m2; established CVD; no T2D). The Discover database comprises linked primary and secondary care data covering people residing in North West London, UK. Cohort entry was the first date between 2004 and 2019 when all inclusion criteria were met. Effect estimates from SELECT were applied using actuarial life tables, estimating the effect of semaglutide on life expectancy overall and by age group. Life expectancy gains and CV event-free life expectancy were estimated using the Arriaga and Sullivan methods, respectively. In total, 19,117 individuals aged ≥45 years were included in the main analysis (63% men; mean age: 65.4 years). The estimated gain in life expectancy with semaglutide treatment was 1.9 years. A CV event-free life-year gain of 2.0 years was predicted with semaglutide. Life-year gains were observed across all age groups but were higher for younger age groups. Based on SELECT data, semaglutide is predicted to increase life expectancy and CV event-free life-years in a real-world population with overweight/obesity and CVD, particularly in younger people.

Background: Currently, there is very limited information on referral patterns, diagnostic workup, and management of adrenal tumours (ATs) across secondary and tertiary endocrine centres in the UK.

Objective: To evaluate current practices in assessing and managing ATs across the UK, including diagnostic pathways and adherence to international guidelines on screening of patients with newly diagnosed ATs.

Methods: A 12-item web-based survey was distributed to members of the Society for Endocrinology, UK (approximately 1,600 contacts), capturing centre characteristics, number of patients with ATs, and diagnostic strategies.

Results: In total, 85 responses representing 80 centres were analysed. Over 45% of respondents, mainly from tertiary centres, reported more than 100 annual referrals. Malignancy rates were <5% in 89.5% of centres. Nearly all centres (99.8%) reported full or partial adherence to 2023 ESE-ENSAT guidelines. However, only 55% held regular adrenal-specific multidisciplinary meetings and 24% reported referral-to-diagnosis times exceeding 6 months. Steroid profiling (urinary or serum) was incorporated into diagnostic workup by 71.8% of centres.

Conclusions: This survey provides the first national overview of AT management pathways in the UK. Findings highlight strong guideline adherence but variability in multidisciplinary practice and diagnostic timelines. These data offer a foundation for policy development and future research, particularly as increasing incidental detections from cross-sectional imaging place growing demands on NHS resources.

Background: Patients with congenital hypogonadotropic hypogonadism (CHH) are geographically dispersed and have unmet health and informational needs. Patients often rely on the internet to learn about CHH, find expert care, and connect with other patients.

Aims: We partnered with patients to co-design a website (virtual empowerment toolkit) and conducted an online evaluation of the website.

Methods: Healthcare providers, patients, and a design team engaged in an iterative 'design thinking' process (i.e., empathize, define, ideate, prototype, refine, test) to co-design the website. Subsequently, patients with CHH were recruited and evaluated the site using the 'gold standard' Patient Education Materials Assessment Tool for audio/visual materials (PEMAT-A/V). Scores ≥80% on PEMAT-A/V domains are considered 'high-quality'. Content analysis was used to group qualitative feedback into salient themes.

Results: Patients were involved from the outset and in all stages of the design thinking process. Iterative patient focus groups and online surveys were used to prioritize content and refine prototypes. In total, 58 participants (48.5±14.4 yrs.) completed the online evaluation. All PEMAT-A/V domains scored >88% (i.e., 'high-quality'). Participants (47/55, 86%) rated the site 'easy to navigate' and 52/55 (95%) would recommend the site to another patient. Qualitative feedback was largely positive and expressed appreciation for the online resource.

Conclusions: Partnering with patients to co-design the virtual patient empowerment toolkit produced an understandable, actionable website that was responsive to patient priorities. This work supports the utility of co-creation and co-design for empowering patients with CHH and may serve as a roadmap for other rare diseases.