European Journal of Endocrinology最新文献

Objective: Recurrence is a key outcome measure of treatment for differentiated thyroid carcinoma (DTC). In international guidelines and current literature, a consistent definition is lacking, which hinders comparison of treatment-related oncological outcomes. Therefore, the aim of this study was to reach international consensus among experts from all medical specialties involved in the care of patients with DTC on the essential elements minimally required for a universal definition of recurrence-serving as a first step toward developing a new, universally accepted definition of DTC recurrence.

Design: We conducted an international Delphi study.

Methods: A steering committee provided advice on the study protocol and Delphi rounds. Experts were identified through various scientific associations, international guidelines, ClinicalTrials.gov, our systematic review on definitions of DTC recurrence, and suggestions from the steering committee. A 3-round Delphi process was conducted to reach consensus on the minimally essential components of the definition of DTC recurrence. The initial list of components was derived from our systematic review.

Results: In total, 127 experts from all medical specialties involved in the diagnosis and treatment of DTC, representing 35 countries across 4 continents, completed 3 Delphi rounds. Thirteen key components critical for defining complete remission and recurrence of DTC were identified, following treatment with total thyroidectomy and postoperative radioiodine therapy (RIT), total thyroidectomy without RIT, and less-than-total thyroidectomy.

Conclusions: The components identified through this international Delphi consensus can serve as the foundation for the further development of universal definitions of DTC recurrence.

Adipose tissue (AT) closely interacts with the adrenal glands to regulate metabolism, energy balance, and stress responses. While the adrenal cortex secretes glucocorticoids and mineralocorticoids that influence AT distribution, lipid storage, and browning, the adrenal medulla releases catecholamines that acutely activate thermogenesis in brown and beige adipocytes. Under physiological conditions, this bidirectional crosstalk maintains energy homeostasis and cardiovascular stability. However, in adrenal diseases such as Cushing syndrome, primary aldosteronism, adrenocortical carcinoma, or pheochromocytoma, excess hormone secretion disrupts this balance, leading to AT dysfunction, altered adipokine secretion, and adverse metabolic profiles, including insulin resistance, visceral adiposity, and hypertension. Emerging evidence suggests that peri-adrenal AT may modulate adrenal tumor biology through endocrine and paracrine signals, and immune cell infiltration, with potential effects on disease progression and clinical presentation. Uncovering cellular and molecular mechanisms underlying the crosstalk between adrenal gland and AT may reveal new therapeutic targets for the reduction of cardiometabolic complications in patients with adrenal disorders. Here, we discuss how 2 endocrine organs-adrenal gland and AT-interact with each other under physiological and pathophysiological conditions and examine whether these interactions influence the progression of adrenal tumors and how this affects systemic metabolic health.

Hyponatremia is one of the most common electrolyte disorders encountering both in hospitalized and in outpatients. Across the past decades, several cross-sectional and observational studies have shown a strong association between low serum sodium levels and adverse bone outcomes such as osteoporosis, falls, and fractures, suggesting a potential direct link between serum sodium disturbances and bone health. However, association does not necessarily imply causality. Data from preclinical studies have shown a possible causative relationship between hyponatremia and activation of osteoclasts with consequent bone resorption, whereas clinical studies so far have shown mostly an association with increased bone formation rather than affection of bone resorption. In this narrative review, we provide an overview of the current evidence on the relationship between serum sodium disorders and bone health, starting with preclinical findings, followed by cross-sectional and association data and concluding with insights from prospective and interventional studies.

Objective: Chronically elevated circulating lipocalin-2 (LCN2) levels are implicated in poor energy regulation, increased cardio-metabolic disease risk, and poor physical function. Exercise is known to improve these factors, but whether LCN2 is modifiable by exercise is not clear. We examined the effect of acute and chronic exercise on LCN2 levels and whether this relates to glucose regulation, body composition, and physical function.

Design and methods: Thirty-three middle-aged and older adults (45-84 years, median body mass index 26.21 kg/m2) completed an acute high-intensity interval exercise session (HIIE). Participants were randomized to 4 weeks of high-intensity interval training (HIIT) or control. Lipocalin-2, insulin, glucose, and homeostatic model assessment for insulin resistance (HOMA-IR) were analysed in serum at baseline and immediately, 1 and 3 h post-HIIE, and post-4 weeks of HIIT. Urinary LCN2 was assessed pre and post 4 weeks of HIIT.

Results: A main effect for time for serum LCN2, insulin, glucose, and HOMA-IR was detected after acute-HIIE (P < .001). Circulating serum LCN2 levels increased significantly immediately post-HIIE compared to baseline (P < .001) and returned to levels similar to baseline by 60 and 180 min post-HIIE. Four weeks of HIIT improved VO2peak, yet had no significant effect on LCN2 levels or physical function.

Conclusions: Acute-HIIE, but not 4 weeks of HIIT, transiently increased circulating LCN2 and improved insulin sensitivity in middle-aged and older adults. It remains unclear if LCN2 is modifiable by chronic exercise training longer than 4 weeks or in people with poor glycaemic control.

Clinical trial registration: Australia New Zealand Clinical Trials Registry: ACTRN12622000337774.

Background: Idiopathic male infertility, characterized by impaired spermatogenesis without identifiable etiology, lacks targeted therapeutic strategies. Empirical hormonal treatments such as aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs), and follicle-stimulating hormone (FSH) are commonly employed, despite limited high-quality evidence.

Objective: To compare the efficacy of AIs, SERMs, and FSH in improving semen parameters among men with idiopathic oligozoospermia and/or asthenozoospermia, using a network meta-analysis (NMA) approach.

Methods: This systematic review and NMA included 24 controlled studies (n = 1676 men). Eligible trials compared FSH, SERMs, or AIs (eg, clomiphene, tamoxifen) to placebo or active comparators. Outcomes included post-treatment sperm concentration, total sperm number, and progressive motility. A frequentist random-effects model was used. Treatments were ranked using P-scores, with inconsistency assessed via node-splitting.

Results: Clomiphene citrate (CC) 25 mg every other day showed the greatest improvement in sperm concentration (mean difference [MD] = 22.00; 95% CI: 14.75-29.25; P-score = 99%). FSH 300 IU every other day also significantly improved sperm concentration (MD = 9.34; 95% CI: 5.14-13.53). For total sperm number, CC 25 mg every other day again ranked highest (MD = 66.70; 95% CI: 27.53-105.87). No intervention showed a significant effect on progressive motility in the NMA. A dose-response trend was observed for FSH (direct relationship) and SERMs (inverse relationship).

Conclusions: Both SERMs and FSH improve sperm concentration and count compared to placebo. Clomiphene at low doses and high-dose FSH may offer the greatest benefit. These findings support a personalized empirical treatment approach and emphasize the need for future trials stratified by clinical phenotype, such as the recently proposed APHRODITE criteria.

Introduction/objective: Bone can contribute to systemic and extra-skeletal processes through bone-derived hormones. The osteoblast-specific protein osteocalcin (OCN) has been reported to positively regulate male fertility, by directly favoring testicular testosterone biosynthesis. We previously demonstrated that aberrant hypoxia-inducible factor (HIF) signaling in osteoprogenitors drastically changes bone properties associated with suppressed OCN expression. This led us to question whether hypoxia signaling in bone could be an upstream determinant of male fertility, by indirectly impacting testosterone production and testicular function through bone-derived OCN.

Design/methods: To investigate the impact of hypoxia pathway activation in osteoprogenitors and/or osteoblasts on male fertility, we genetically deleted the negative HIF-regulator von Hippel-Lindau (VHL) in mice using two independent osteolineage-targeted Cre lines. In these Vhl conditional knockout (cKO) strains, we investigated OCN production, testosterone biosynthesis, testicular morphology, and male fertility, including functional evaluation of reproductive capacity.

Results: Our data demonstrate that loss of VHL in osteolineage cells consistently and strongly reduces the production of OCN in bone, leading to very low circulating levels of both carboxylated and undercarboxylated OCN. Testicular expression of selected enzymes of the testosterone biosynthesis pathway was decreased in Vhl cKO mice. However, our data did not show significant deficiencies in testosterone levels, reproductive organ weights, Leydig cell mass, sperm count, or breeding efficiency in the two strains of skeletal Vhl cKO mice.

Conclusions: These findings indicate that aberrant hypoxia signaling in bone suppresses OCN production without compromising male fertility, possibly reflecting a role for the broader physiological context as critical modulator of OCN's endocrine activity.

Objective: Epidemiology of prolactin-secreting pituitary neuroendocrine tumours (PRL-PitNETs) remains scarce and inconsistent. It is a heterogeneous disease regarding age at onset, sex, and tumour characteristics. We aimed to assess temporal epidemiological trends in PRL-PitNETs.

Design: Cohort study, systematic review, and meta-analysis.

Methods: The cohort study comprised all PRL-PitNET patients in the North Denmark Region (2017-2022; N = 594 634), identified via ICD-10 coding (E22.1) or dopamine agonist treatment. Data included sex, age at diagnosis, adenoma size, and prolactin levels. For the systematic review, PubMed and Embase were searched (May 2025) for studies reporting ≥20 PRL-PitNETs. Extracted data comprised prevalence, incidence, age, and sex distributions. A random-effects meta-analysis was applied.

Results: The cohort included 245 patients: 167 microprolactinomas, 78 macroprolactinomas, and 20 incidentalomas. From 2017 to 2022, prevalence increased by 41% (95% CI: 25%-60%, +61 cases) overall, 42% (95% CI: 19%-68%, +39 cases) for microprolactinomas, 41% (95% CI: 19%-67%, +22 cases) for macroprolactinomas, and 57% (95% CI: 6%-132%, +7 cases) for incidentalomas. Overall incidence was 2.8 (95% CI: 2.2-3.5) per 100 000 person-years. The systematic review and meta-analysis (15 studies, 16 000 PRL-PitNET cases) showed an increasing PRL-PitNET prevalence and incidence, reaching 41 (95% PI: 12-89) per 100 000 persons and 2.3 (95% PI: 1.2-4.3) per 100 000 person-years, respectively; with a phenotypical shift towards more men (from 10%-20% to 20%-30%), macroprolactinomas (∼25 to ∼30%) and incidentalomas (∼6% to ∼10%) over the last two decades.

Conclusion: PRL-PitNETs are increasingly prevalent, partly driven by a rising incidence of men and incidentalomas, suggesting a phenotypic shift and associated increase in clinical and healthcare burden.

The present report from the ESE Educational Program on Parathyroid Disorders (PARAT Program) presents recent developments and novelties in the clinical care of parathyroid disorders in a question-and-answer format, based on a satellite workshop held in relation to the European Congress of Endocrinology in Stockholm, May 2024. The workshop focused on clinical aspects of 3 main themes: primary hyperparathyroidism (PHPT), chronic hypoparathyroidism (HypoPT) in adults, and parathyroid disorders in pregnancy, with an emphasis on advances since the 2022 PARAT consensus report. The first section focuses on the long-term complications-including fractures, renal impairment, mental health, and quality of life-in patients with asymptomatic or mild forms of PHPT and on treatment strategies for syndromic PHPT (multiple endocrine neoplasia 1-4). In the latter, we explore appropriate surgical and non-surgical approaches, imaging techniques for gland localization, and preservation strategies in cases of multiglandular involvement. The second section addresses transient and partial forms of HypoPT in comparison to chronic and complete parathyroid hormone deficiency. It highlights the potential skeletal consequences of chronic HypoPT, the underlying etiologies, and discusses treatment modifications in light of the evolving therapeutic landscape. The final section, dedicated to the specific considerations of parathyroid disorders during pregnancy and lactation, focuses on pregnancy planning in patients with hereditary syndromic forms of PHPT, the differentiation between parathyroid-related and unrelated causes of hypercalcemia, and the associated risks for both mother and fetus. Additionally, it addresses the practical aspects of managing pregnant women with HypoPT, aiming to provide practical guidance for clinicians. Clinical vignettes featuring 3 cases illustrate common clinical situations.