Clinical Endocrinology最新文献

Introduction: Arginine vasopressin deficiency (AVP-D) requires lifelong desmopressin replacement. In March 2025, the national suspension of intranasal desmopressin necessitated urgent transition to oral alternatives. However, optimal conversion ratios and clinical response remain undefined. We evaluated clinical outcomes following this supply-driven transition.

Methods: A retrospective study at a tertiary UK centre (01/01/2025-01/07/2025) identified patients with confirmed AVP-D switched from intranasal to oral desmopressin. Demographic and clinical data were collected. Conversion ratios (intranasal: oral) were calculated before and after titration.

Results: Forty two patients were included (mean age 52.6 ± 2.3; 31% male). 15/42 (35.7%) isolated AVP-D; 11/42 (26.2%) partial hypopituitarism; 16/42 (38.1%) panhypopituitarism. Median intranasal desmopressin dose pre-switch was 10 mcg/day (IQR 10-20 mcg). Initial median oral dose before titration was 200 mcg/day (IQR 100-200 mcg); final median oral dose after titration was 200 mcg/day (IQR 162.5-300 mcg). 23/42 (54.8%) were switched initially using 1:10 ratio (10 mcg intranasal desmopressin to 100 mcg oral tablet). 13/23 (56.5%) reported symptomatic recurrence, warranting further titration. The remaining 19/42 (45.2%) were switched initially using a median ratio of 1:20 (IQR 1:11.8-1:20). 10/19 (52.6%) reported symptomatic recurrence. Overall, switching from intranasal to oral desmopressin resulted in 16 patient calls, 79 additional blood tests and one hospitalisation. Similarly, the findings of The Pituitary Foundation Impact Report demonstrated that the switch led to 121/161 (75.2%) of patients reporting poorer symptomatic control post-switch, and 76/161 (47.2%) requiring additional endocrine input.

Conclusion: 45.2% (19/42) of patients achieved adequate symptom control post-switch with varying conversion ratios, and over half (13/23, 56.5%) of patients switched with an initial 1:10 conversion ratio reported symptomatic recurrence. Although a higher initial conversion ratio closer to 1:15 may reduce symptomatic recurrence in some patients, initiating treatment at a 1:10 ratio with careful up-titration represents a safe and pragmatic approach that minimises the risk of over-replacement and hyponatraemia, although inter-patient variability necessitates tailored titration. In parallel, national patient-reported data from The Pituitary Foundation Impact Report demonstrate the substantial patient and clinical burden of this supply-driven switch, highlighting the need for standardised guidance and prospective studies.

The complexity of transition of pediatric patients to adult care is well recognized, with a multidisciplinary approach widely agreed to be essential. Despite extensive existing literature in this area, practical guidance as to the management of specific medical aspects and how to address these with patients and families is lacking, with little accessible literature to help guide practitioners. Many paediatric endocrine conditions have a genetic or epigenetic aetiology. Both presentation and evolution of their specific health issues may be unfamiliar to adult endocrinologists, few of whom have experience and expertise in both paediatric and adult domains. This paper aims to address these knowledge gaps and provide guidance for the transition of patients with childhood-onset endocrine disorders, delineates management strategies for both the paediatric and adult clinicians, and highlights areas that may be unfamiliar in adult practice.

Background: Hyperthyroxinemia with non-suppressed thyroid-stimulating hormone (TSH) is a complex clinical entity that presents significant diagnostic challenges. Inherited causes include resistance to thyroid hormone beta (RTHβ), characterised by highly variable clinical presentation, and familial dysalbuminemic hyperthyroxinemia (FDH), a form of assay interference caused by pathogenic variants in the ALB gene leading to pseudo elevation of free thyroxine (FT4). This study aimed to characterise the clinical, laboratory, and molecular features of a paediatric cohort presenting with hyperthyroxinemia and non-suppressed TSH, and to identify clinical parameters that may aid in differential diagnosis.

Methods: In this retrospective observational study, 25 children from 19 unrelated families with elevated FT4 and non-suppressed TSH were evaluated. Clinical history, anthropometric data, physical examination findings, vital signs, laboratory results, radiological imaging, and sequencing data of the THRB and/or ALB genes were reviewed.

Results: THRB gene sequencing was performed in 21 children from 18 families, identifying pathogenic or likely pathogenic variants in six patients from six unrelated families, including a novel variant c.997 G > C, p.(Glu333Gln), consistent with a diagnosis of RTHβ in 33.3% of those tested. Among these patients, tachycardia was observed in three cases (50%). ALB gene sequencing was completed in 16 children from 13 families, revealing the hotspot variant c.725 G > A, p.(Arg242His) in 12 patients from six unrelated families, corresponding to FDH in 46.2% of those tested. None of the FDH-confirmed patients exhibited tachycardia or other signs of thyroid dysfunction. FT4 and TSH levels were similar between RTHβ and FDH groups; however, FT3 levels tended to be lower in FDH, although FT3/FT4 ratio did not differ significantly.

Conclusion: Our findings highlight the critical role of molecular testing in accurately diagnosing the underlying cause of elevated FT4 with non-suppressed TSH and in preventing unnecessary interventions. Hotspot analysis of the ALB gene is recommended as a first-line test, particularly in asymptomatic individuals.

Background: 46,XY differences in sex development (DSD) comprise a heterogeneous group of conditions. Molecular diagnosis guides management by giving insights into the pathophysiology of sex development, reproduction, tumour formation and extragenital issues.

Methods: Children with 46,XY DSD from a tertiary hospital in India underwent comprehensive assessment and stepwise genetic testing. Targeted testing for SRD5A2 and AR was performed in cases with suspected 5α-reductase type 2 (5αR2) deficiency/androgen insensitivity syndrome (AIS). For all other patients, and those without variants in SRD5A2 or AR on Sanger sequencing, NGS using a targeted 155-gene panel was performed. Longitudinal clinical data was also collated.

Results: One hundred and forty-seven children with 46,XY DSD with a median (interquartile range) age of 3.8 (1.4, 10.6) years were enrolled. Provisional clinical diagnoses were 5αR2 deficiency/AIS (n = 83, 56.5%), gonadal dysgenesis (n = 31, 21%), testosterone biosynthetic defect (n = 11, 7.5%) and others (n = 22, 15%) based on clinical, biochemical and radiological assessment. Sequential single gene testing for SRD5A2 and AR performed in 75 patients with a clinical diagnosis of 5αR2 deficiency/AIS identified pathogenic/likely pathogenic variants in 44 subjects. NGS in the remaining 103 children revealed pathogenic/likely pathogenic variants in 20 subjects across 12 genes, with NR5A1 being the most frequent (7/103). Four subjects had variants of uncertain significance (VUS) deemed possibly pathogenic due to good genotype-phenotype correlation. Overall, 68/147 (46%) achieved a molecular diagnosis in this cohort.

Conclusion: Sanger sequencing followed by NGS could provide molecular diagnosis in 46% of this Indian cohort with 46,XY DSD. SRD5A2, AR and NR5A1 were the most frequently implicated genes.

Background: Primary aldosteronism (PA) has been linked with reduced health-related quality of life (QoL) and increased prevalence of anxiety and depression. While most studies compared patients with PA to healthy subjects, this study focused on comparison with hypertensive patients without PA to identify PA-specific effects. Furthermore, the impact of targeted therapy on QoL and mental health was evaluated.

Methods: Mental and physical health-related QoL, anxiety and presence of depressive and panic symptoms were assessed using the SF-12, GAD-7 and PHQ questionnaires in 925 patients with arterial hypertension tested for PA in a prospective, multi-center international prospective cohort study. Questionnaires were assessed at baseline as well as 3-6 months after initiation of targeted therapy.

Results: Amongst 833 of 925 patients who completed the necessary diagnostic procedures, 211 were diagnosed with PA. 98 of 116 patients with unilateral PA received unilateral adrenalectomy. At baseline, QoL, anxiety and mental health scores did not differ in patients with PA vs patients with hypertension without PA. At outcome assessment, SF-12 mental and physical component summaries as well as GAD-7 specifically improved in patients with unilateral PA after adrenalectomy (mean Δ = 4.2, p = 0.018, Δ = 3.6, p = 0.038 and Δ = -1.9, p = 0.006, respectively) in contrast to no improvement in patients with PA on MRA treatment.

Conclusions: There was no difference in health-related QoL, anxiety and mental health in patients with hypertension with versus without PA. Unilateral adrenalectomy but not medical therapy improved health-related QoL and decreased anxiety in patients with PA.

Background: Radiofrequency ablation (RFA) has become an established minimally invasive treatment for benign thyroid nodules (BTN), offering excellent safety and efficacy. However, factors predicting treatment success and post-procedural thyroid dysfunction remain incompletely understood. This study aimed to perform a preliminary evaluation of clinical, procedural, and biochemical predictors of RFA outcomes in a real-world consecutive patient cohort.

Study design and methods: A retrospective analysis was conducted on consecutive patients who underwent ultrasound-guided RFA for cytologically benign thyroid nodules between January 2018 and March 2024 at a single tertiary medical centre. Demographic, sonographic, procedural, and biochemical variables, including thyroid-stimulating hormone (TSH), thyroglobulin (Tg), and anti-Tg antibodies, were analysed. The primary endpoint was the Volume Reduction Ratio (VRR), with ≥ 50% defined as procedural success.

Results: Sixty-two patients (mean age 52.6 years; 85.5% female) were included. The median best VRR achieved was 61.9% (IQR 46.6-74.5), with 71% of patients attaining ≥ 50% reduction. Higher pre-treatment Tg levels were significantly associated with reduced VRR (p < 0.001) and remained independently associated with procedural failure in an exploratory multivariable model (OR 0.87 per 10 ng/mL increase, p = 0.011). Pretreatment TSH levels showed a univariate positive trend but did not reach statistical significance on multivariate analysis. Two patients (3.2%) developed hypothyroidism post-RFA, both with positive anti-Tg antibodies (total 13 patients had positive anti Tg Ab). The overall complication rate was 6.5%, with no major adverse events.

Conclusions: Our results suggest that pre-treatment thyroglobulin levels may serve as a potential biochemical predictor of RFA success in benign thyroid nodules, while antibody positivity may suggest susceptibility to post-ablation hypothyroidism. While most existing literature focuses on imaging features (e.g., sonographic features) or surgeon technique, our findings highlight the unique importance of biochemical characteristics. Incorporating biochemical profiling into pre-procedural assessment could refine patient selection and enhance individualised treatment planning. Future prospective studies are warranted to validate Tg as a biomarker of RFA response.

Context: Papillary thyroid carcinoma (PTC) with T4aM0 stage, which involves extrathyroidal extension without distant metastasis, presents challenges in treatment management. While radioactive iodine (RAI) therapy has been shown to benefit certain high-risk thyroid cancer patients, its effect on cancer-specific survival (CSS) in T4aM0 PTC patients remains unclear.

Objective: We aim to evaluate the impact of RAI therapy on CSS in T4aM0 PTC patients following total thyroidectomy.

Methods: 1938 PTC patients with T4aM0 stage who underwent total thyroidectomy in the SEER database were identified. Clinical-pathological and CSS data were systematically collected. Patients were stratified into the RAI-treated group and the non-RAI-treated group. Propensity score matching (PSM) was implemented with 1:1 nearest-neighbour matching to balance baseline covariates. Intergroup comparisons of demographic and clinical characteristics were performed in the entire cohort and PSM cohort. Subset analyses were conducted to indicate the effect of RAI therapy on CSS in different subgroups. Cox proportional hazards regression models were employed to evaluate CSS outcomes.

Results: After PSM, 472 pairs of patients were included in the analysis. In both the entire cohort and the PSM cohort, no significant difference in CSS was observed between RAI-treated and non-RAI-treated patients (HR = 0.797, 95% CI: 0.540-1.175, p = 0.252; HR = 0.709, 95% CI: 0.437-1.151, p = 0.709). Subgroup analysis also showed no survival benefit of RAI across various clinical characteristics.

Conclusion: RAI therapy does not significantly improve cancer-specific survival in T4aM0 PTC patients after total thyroidectomy. These findings suggest that RAI may not be necessary for this subgroup, advocating for more individualised treatment approaches.

Objective: Crooke cell adenomas (CCAs) are considered rare and potentially aggressive variants of corticotroph adenomas. However, data on their clinical behaviour remain limited. This study aimed to compare the clinical, biochemical, radiological, and surgical outcomes of patients with CCAs and non-CCA Cushing's disease (CD).

Material and methods: We retrospectively analyzed patients diagnosed with CD at our tertiary Pituitary Centre. Clinical presentation, baseline biochemical characteristics, tumour size, Ki-67 index, remission rates, recurrence, and presence of residual tumour on follow-up MRI were compared between CCA and non-CCA groups.

Results: At baseline, patients with CCAs (n = 21) and non-CCAs (n = 60) demonstrated comparable biochemical profiles, except for ACTH levels, which were higher in the CCA group compared with the non-CCA group (p = 0.007). Remission and recurrence rates at 3, 6, and 12 months did not differ significantly between the two groups (p > 0.05 for all). However, CCAs tended to present with larger tumour sizes and higher Ki-67 proliferation indices than non-CCAs (p = 0.055 and p = 0.05, respectively). Moreover, residual pituitary lesions were more frequently detected on follow-up MRI among patients with CCA (p = 0.005).

Conclusion: Our findings suggest that CCAs may not be as aggressive as previously assumed with respect to biochemical remission and recurrence rates. Nonetheless, their larger tumour size, higher proliferative index, and increased likelihood of residual disease underscore the importance of careful long-term follow-up. Further multicenter studies are warranted to better characterize the clinical course of CCAs.