European Journal of Endocrinology最新文献

Pituitary apoplexy (PA) is a rare but potentially life-threatening endocrine emergency caused by sudden hemorrhage or infarction usually within a pituitary tumor. Clinical presentation is highly variable, ranging from isolated headache to severe visual loss or altered consciousness. Prompt recognition, multidisciplinary evaluation, and timely management are essential to improve outcomes. Recent prospective and real-world studies have challenged the traditional view that urgent surgery is always required. Conservative management has been proposed to be a safe and effective option, although comparisons with the outcomes after surgical intervention are limited by differences in the severity of the clinical picture at presentation of the PA. Clinical decisions remain complex and must consider tumor size, symptom progression, radiological features, and individual comorbidities. The Pituitary Apoplexy Score helps guide management but has limitations, as it does not capture key variables such as persistent headache or evolving visual symptoms. Immediate management focuses on hemodynamic stabilization, stress-dose glucocorticoid administration, and neuro-ophthalmological monitoring. Surgical decompression should be considered in patients with progressive visual deterioration or altered consciousness. Follow-up must include hormonal reassessment, ophthalmological evaluation, and imaging surveillance. Although rare, recurrence of PA and tumor regrowth may occur, requiring long-term monitoring. This review provides an updated and pragmatic approach for the diagnosis, acute care, and long-term follow-up of PA, summarizing current evidence and highlighting ongoing controversies, including surgical timing and predictors of conservative treatment failure.

Objective: To synthesize current evidence on genetic testing yield in children with short stature and to identify phenotypic and methodological factors influencing outcomes. The review served as a basis for the development of a consensus guideline on genetic evaluation of short stature.

Design: Systematic review.

Methods: Diagnostic yields were calculated by testing modality and clinical characteristics of study cohorts. Results were compared across time periods and recalculated excluding variants of uncertain significance (VUS). Phenotypic features associated with higher yields and the most frequently implicated genes were also analyzed.

Results: Out of 1163 records, 134 studies were included. The overall diagnostic yield was 4.7% for candidate gene testing (n = 78), 16.3% for chromosomal microarray (n = 8), 21.6% for gene panels (n = 14), and 33.3% for exome sequencing (ES) (n = 39). After exclusion of VUS, the reestimated yields were lower for all approaches. ES approaches yielded higher diagnostic rates in syndromic short stature (50.8%, n = 15) compared to isolated short stature (15.1%, n = 13). Among 45 studies evaluating predictive factors, facial dysmorphism (68.2%) and skeletal abnormalities (61.1%) were most strongly associated with increased diagnostic yield. Recurrently identified genes included PTPN11, NF1, COL2A1, ACAN, and FGFR3.

Conclusions: Genetic testing substantially improves the diagnostic process in children with isolated and syndromic short stature. Diagnostic yield varies by testing modality and phenotype, with higher rates observed using comprehensive genomic methods and in individuals with dysmorphic or syndromic features. Frequently implicated genes highlight common biological pathways involved in growth regulation, underscoring the utility of genetic evaluation in this population.

Objective: Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of congenital adrenal hyperplasia caused by impaired electron transfer to multiple microsomal enzymes. Hypertension in PORD has been attributed to mineralocorticoid excess; however, experimental evidence suggests that POR may also regulate endothelial vasodilatory pathways. The vascular effects of PORD in humans remain poorly defined. We evaluated blood pressure regulation, microvascular structure, and serum vasoactive mediators in patients with PORD.

Design: Observational, cross-sectional study.

Methods: Ten patients with genetically confirmed PORD (4 females, 6 males; age range 8-27 years) and 41 age- and sex-matched healthy controls were evaluated. Office and 24-hour ambulatory blood pressure monitoring (ABPM) were performed. Microvascular structure was assessed using nailfold capillaroscopy (NFC). Serum levels of thromboxane B₂ (TXB₂), prostaglandin E₂ (PGE₂), and nitric oxide (NO) were measured.

Results: Hypertension was present in 80% of patients with PORD compared with 7.3% of controls (P < .001). Office and ambulatory systolic and diastolic pressures were significantly higher in PORD. NFC revealed shorter capillary length (P = .001), more frequent crossed capillaries (P < .001), and avascular areas (P = .039). Serum TXB₂ levels were higher in PORD (P = .007), whereas PGE₂ and NO did not differ between groups.

Conclusions: PORD is associated with an increased prevalence of hypertension, microvascular capillary abnormalities, and elevated TXB₂, consistent with enhanced cyclooxygenase-mediated vasoconstrictor tone and endothelial dysfunction. These findings suggest that cyclooxygenase-dependent mechanisms may contribute to the vascular alterations observed in PORD.

Context: Pheochromocytomas and paragangliomas (PPGL) are rare endocrine tumors with high heritability. Carriers of pathogenic variants (PVs) in susceptibility genes face a lifelong risk of recurrence or metastatic disease. Quality of life (QoL) in patients with PPGL, a history of PPGL and PV carriers, remains insufficiently studied.

Methods: We assessed patient-reported QoL in patients with PPGL before and after surgery and in carriers of susceptibility PVs for the development of PPGLs within the prospective ProsPheo study. QoL was evaluated using standardized questionnaires (SF-12, PHQ-D, and GAD-7).

Results: A total of 202 participants were analyzed. SF-12 physical component summary scores (PCS) differed significantly across subgroups (P = .006), with the lowest PCS scores in patients with metastatic PPGL (40.3) and unresected head and neck paragangliomas (HNPGL) (40.0), compared with PV carriers after curative PPGL resection (50.2). Within metastatic disease, hormonally active tumors showed lower PCS scores than inactive tumors (36.9 vs 46.2; P = .03). Perceived physical health in carriers of a PV without history of a PPGL was significantly lower compared to the age-matched general population. Mental health was not significantly impaired across all subgroups. Clinically relevant anxiety was reported in 15.2% of PV carriers and 21.7% of patients with unresected HNPGLs, compared with about 5.9% in the general population.

Conclusions: Patient-reported physical health was reduced in patients with metastatic PPGLs, unresected HNPGLs, and PV carriers without prior PPGL, whereas patients after curative PPGL resection reported QoL comparable to the general population, regardless of PV status, suggesting that annual follow-up has minimal impact on QoL.

Objective: Primary aldosteronism (PA) adversely affects cardiovascular and renal health and has been linked to increased urinary calcium excretion, elevated parathyroid hormone (PTH) levels, and reduced bone mineral density. Although adrenalectomy and mineralocorticoid receptor antagonists (MRAs) are established treatments, their differential effects on calcium dynamics across PA subtypes remain unclear.

Design: We conducted a retrospective observational study, analyzing a large, well-characterized cohort on calcium metabolism in PA. A total of 352 patients with PA and 57 controls were evaluated.

Methods: Clinical and biochemical parameters, including intact PTH (iPTH) and urinary electrolyte levels, were retrospectively assessed. Comparative analyses were performed before and after treatment in 43 patients with unilateral PA (UPA) and 131 patients with bilateral PA (BPA), with a direct comparison of adrenalectomy and MRAs in UPA.

Results: Patients with PA had higher urinary fractional excretion of calcium (FECa) (1.28% vs 1.04%, P < .001) and iPTH (60.0 vs 57.0 pg/mL, P = .047) than controls, with more pronounced abnormalities in UPA (FECa, 1.50%, iPTH 73.1 pg/mL). Both treatments reduced FECa and iPTH levels, but adrenalectomy resulted in greater improvement than MRAs in the UPA (FECa, 0.68% post-MRA vs 0.36% post-adrenalectomy). In the BPA group, MRAs decreased FECa, irrespective of disease severity.

Conclusion: Adrenalectomy was associated with greater improvements in calcium abnormalities than MRAs in patients with UPA, consistent with its cardiovascular benefits. These findings underscore the importance of subtype-specific strategies and suggest that adrenalectomy may offer additional benefits beyond cardiovascular outcomes.

Objective: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are associated with immune-related adverse events (irAEs), including pituitary dysfunction. Combination immunotherapy with PD-1 and CTLA-4 inhibitors increases the risk of pituitary irAEs compared to PD-1 monotherapy; however, their detailed characteristics remain unclear. We aimed to clarify the clinical features of pituitary irAEs induced by combination immunotherapy.

Design: In this retrospective cohort study, we compared patients treated with combination therapy of nivolumab and ipilimumab (Nivo/Ipi) to those receiving nivolumab monotherapy (Nivo). We analyzed clinical data including presenting symptoms, laboratory findings, pituitary MRI results, and coexisting irAEs.

Results: Pituitary irAEs were more frequent in the Nivo/Ipi group (17.4%) than in the Nivo group (2.7%) and developed earlier (median onset: 63 vs 153 days, respectively). All 15 patients in the Nivo group presented with isolated ACTH deficiency (IAD), whereas the Nivo/Ipi group included 8 cases of IAD and 8 cases of combined pituitary hormone deficiency (CPHD). In the Nivo/Ipi group, CPHD occurred significantly earlier than IAD (median onset: 40 vs 84 days) and was associated with a higher incidence of headache and pituitary swelling on MRI. Furthermore, 75% of patients with CPHD also experienced non-endocrine irAEs. Two CPHD patients experienced worsening of symptoms and pituitary dysfunction following re-administration of Nivo/Ipi.

Conclusion: Pituitary irAEs are more frequent and develop earlier in patients receiving Nivo/Ipi. CPHD and IAD, induced by this combination immunotherapy, exhibit distinct clinical courses. Recognizing these differences is crucial for the optimal management of pituitary irAEs during combination immunotherapy.

The European Reference Network on Rare Endocrine Conditions (Endo-ERN) needs to take a cautious and evidence-based position regarding needs for genital surgery in individuals with differences in sex development (DSD). Given the multi-ERN coverage of DSD, the focus of our network is on rare endocrine care concerns in such surgeries and ensuring Endo-ERN's position aligns with the broader European emphasis on human rights, ethical medical practices, and patient-centered care. This discussion paper addresses the ethical, medical, and legal considerations surrounding genital surgery in individuals with DSD conditions in Europe. It advocates for a shift toward patient-centered care that prioritizes the rights and well-being of individuals with DSD conditions, particularly infants and children. The recommendations emphasize deferring nonurgent surgeries with irreversible effects until the individual can provide informed consent whenever possible, strengthening support systems for families, and promoting a standardized European framework that respects human rights, with clearly defined quality indicators and multidisciplinary care.

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 5-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%), 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.