Endocrine Practice最新文献

Objective: We aimed to assess the levothyroxine (LT4) dosage needed to achieve a target thyrotropin (TSH) ≤2.5 μIU/mL in LT4 tablet and nontablet users during the first half of pregnancy.

Methods: We conducted a retrospective analysis on pregnant women with hypothyroidism on LT4 at our university hospital over a period of 4 years. Inclusion criteria were (1) 0.5 μIU/mL < TSH < 4.0 μIU/mL after the first visit; availability of serum TSH every 30 to 40 days until midpregnancy; correct LT4 intake and compliance. Predictors of achieving TSH ≤2.5 μIU/mL were explored using a multivariable probit regression model. P value lower than .05 was considered statistically significant.

Results: We included 212 pregnant women (185 with non-post-thyroidectomy hypothyroidism and 27 with post-thyroidectomy hypothyroidism) on LT4 (tablet in 132 women [62.3%], whereas nontablet in 80 women [37.7%]). In non-post-thyroidectomy hypothyroidism, the adjusted analysis, accounting for confounders (ie, maternal weight, thyroid volume, and type of hypothyroidism), revealed that both LT4 dose (P = .001) and formulation (P = .036) were independent and significant predictors of achieving the TSH target. In non-post-thyroidectomy hypothyroidism, the required dose to achieve a 90% probability of success (TSH ≤2.5 μIU/mL) was lower for the nontablet group (1.5 μg/kg/d; 95% CI: 0.47-2.62) than for the tablet group (2.4 μg/kg/d; 95% CI: 1.8-5.6).

Conclusion: In pregnant women with non-post-thyroidectomy hypothyroidism lower LT4 dosages may be necessary to achieve TSH between 0.5 μIU/mL < TSH ≤ 2.5 μIU/mL with LT4 nontablet compared with tablet formulations (therapeutic superiority).

Objective: We aimed to summarize the tumor spectrum and clinical features of multiple endocrine neoplasia type 5 (MEN5) caused by heterozygous inactivating germline MYC-associated factor X (MAX) mutations.

Methods: Articles were retrieved from PubMed and EMBASE from inception to June 2025 using search terms related to "MAX gene" and "MEN5". Additional cases were identified from a targeted Google Scholar search and supporting references of MAX variants reported in the ClinVar database. Eligible articles included those reporting patient-level data on individuals with germline MAX mutations. Data from all reported patients were extracted to generate a dataset containing phenotype information for descriptive analysis.

Results: Of 621 records screened, 45 studies comprising 127 patients with germline MAX mutations met the eligibility criteria. The median age at first tumor diagnosis was 29 years (23.0 - 39.0) and 37.0% were women. The most frequent tumors were pheochromocytoma (PCC, N = 112), pituitary adenoma (N = 11), and paraganglioma (N = 10), with median ages at diagnosis of 31.0, 33.0, and 43.0 years, respectively. Evidence implicating MAX loss in tumorigenesis included paraganglioma, pituitary adenoma, ganglioneuroma, neuroblastoma, pancreatic neuroendocrine tumor, renal oncocytoma, myelolipoma, and liver sarcoma. The causal association between primary hyperparathyroidism and MAX loss remains uncertain. Among PCCs, 38.3% were unilateral, 27.6% were metastatic, and most were norepinephrine-secreting.

Conclusion: Our systematic review characterized the tumor spectrum and clinical features of MEN5. While these findings outline the emerging clinical phenotype, further studies are needed to define the epidemiology, penetrance and genotype-phenotype associations of this newly recognized entity.

Objective: The complex clinical picture of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) includes orthostatic intolerance with symptoms and signs suggesting abnormal water homeostasis and hypovolemia. Since many ME/CFS patients report polyuria-polydipsia, we conducted an observational study based on series of plasma and urine osmolality (P-Osm and U-Osm) as well as plasma levels of vasopressin (P-VP) or copeptin in consecutive patients diagnosed with ME/CFS according to the International Consensus Criteria.

Methods: P-VP as well as P-Osm and U-Osm were measured in 111 patients after 10 h overnight fasting and fluid deprivation. Additional 13 patients were assessed for copeptin, when P-VP measurements were no longer available. The clinical routine also included brain MRI and blood chemistry.

Results: P-Osm was abnormally high (>292 mOsm/kg) in 71 of 124 (57.3%) and U-Osm below the reference interval (<750 mOsm/kg) in 82 of 124 (66.1%) patients. P-VP was below the level of detection (<1.6 pg/mL) in 91 of 111 (82.0%) patients. A normal P-VP level compared with their P-Osm was found in 11 of 111 (9.9%) patients. Copeptin levels were all within the given reference range, albeit in the lower end in most patients. No indication of relevant pathology in either hypothalamus or hypophysis was present.

Conclusions: Our findings suggest that chronic down-regulation of VP mimicking central diabetes insipidus is an important measurable part of the disease mechanism that potentially contributes to criterial symptoms of ME/CFS.

Objective: To quantify drug-specific associations with thyroid dysfunction (TD) using data from FDA Adverse Event Reporting System and to identify agents with significant disproportionality signals.

Methods: Using data from FDA Adverse Event Reporting System (Q1 2004 to Q1 2025), disproportionality analysis (reporting odds ratio; Bayesian confidence propagation neural network) was employed to assess signals of drug-induced TD. Univariate analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate logistic regression were applied to identify independent risk factors. Time-to-onset analysis was used to evaluate the timing of TD following drug initiation.

Results: A total of 44 317 reports associated with TD were identified, with a higher proportion involving female patients (60.3%). The median patient age was 59 years (interquartile range [IQR]: 45-69 years). Signal detection identified 172 suspect drugs significantly associated with TD. Following disproportionality screening, drug candidates with a reporting odds ratio whose 95% confidence interval lower bound exceeded 1, cell count a > 100, and P-adjust < 0.01 were advanced to LASSO regression. LASSO identified 43 drugs associated with TD. In the multivariable logistic regression model, female sex, the 45-59-year age group, and the 43 drugs were independent risk factors for drug-associated TD. Furthermore, the median time-to-onset for drug-induced TD was 34 days (IQR: 7-105 days), with approximately 75% of cases occurring within the first 100 days of drug initiation.

Conclusion: This study identified multiple drugs significantly associated with TD and highlighted sex, age, and specific medications as independent risk factors. These findings support improved pharmacovigilance and clinical awareness of drug-induced TD.

Objective: Cushing disease (CD) is characterized by impaired glucocorticoid negative feedback. In rare cases, patients exhibit glucocorticoid-induced positive feedback (GIPF), which may represent a distinct corticotroph adenoma phenotype. We aimed to investigate the prevalence, clinical and biochemical features, and surgical outcomes of GIPF in a large multicenter cohort.

Methods: A retrospective cohort study from the SPAIN-CUSHING registry. We included 139 patients with CD who had a complete overnight 1-mg dexamethasone suppression test. GIPF was defined as higher serum cortisol after dexamethasone compared with baseline. Clinical, biochemical, and radiological characteristics, as well as surgical outcomes, were compared between groups. Recurrence was evaluated in patients undergoing transsphenoidal surgery, with recurrence-free survival assessed by Kaplan-Meier analysis.

Results: Thirteen patients (9.3%) showed GIPF. These patients had lower body mass index (26.4 vs 29.8 kg/m², P = .032), higher urinary free cortisol expressed as the upper limit of normal ratio (4.7 vs 2.8 upper limit of normal, P = .047), and a markedly greater adrenocorticotropin response to desmopressin (525.0 vs 63.1 pg/mL, P = .022). Tumor size, proportion of macroadenomas, and cavernous sinus invasion did not differ. Despite this, after surgery remission was significantly lower in GIPF (28.6% vs 70.2%, P = .036), and Kaplan-Meier analysis showed reduced recurrence-free survival in GIPF patients (log-rank P = .04). Clinical phenotypes and comorbidities were otherwise similar.

Conclusion: GIPF occurs in up to 9% of patients with CD and is associated with poorer surgical outcomes and lower remission rates. This phenotype likely represents a distinct subtype of corticotroph adenoma, highlighting the need for closer follow-up and molecular characterization.

Objective: Primary hyperparathyroidism significantly impacts bone health leading to decreased bone mineral density (BMD). We assessed changes in BMD following parathyroidectomy in patients with biochemically mild primary hyperparathyroidism.

Methods: A retrospective chart review of 93 patients with primary hyperparathyroidism who underwent parathyroidectomy between 2000 and 2022 was conducted. Dual-energy x-ray absorptiometry (DXA) scans were done at the same site pre- and postparathyroidectomy at varying time points. Statistical analyses were performed using ANOVA as the homogeneity of variance was > 0.05. A P-value of <0.05 was considered statistically significant.

Results: No statistically significant differences in DXA measurements were observed based on age, timing of DXA after parathyroidectomy, number and total weight of removed parathyroid glands, preoperative vitamin D levels, or preoperative 24-hour urinary calcium levels. In site-specific analysis based on T-scores at individual skeletal regions, only the femoral neck showed a significant postoperative BMD improvement in osteoporotic patients compared to those with osteopenia (P = .018) and normal bone density (P = .019), while the lumbar spine and total hip did not. When patients were grouped by overall osteoporosis status-defined as having osteoporosis at any site-significant BMD improvements were observed at the femoral neck and total hip compared to those with osteopenia (P = .031 and P = .015, respectively).

Conclusion: These findings underscore the potential for tailored interventions in managing bone health in patients with mild primary hyperparathyroidism, emphasizing the need for personalized approaches to optimize outcomes.

Objective: Thyroid dysfunction produces characteristic changes in weight and body composition, but treatment often results in progressive weight gain.

Methods: This review examines underlying mechanisms, predictors, and implications for patient management.

Results: There are significant changes in weight, appetite, and body composition associated with underproduction and overproduction of thyroid hormone. The disease states of hypothyroidism and hyperthyroidism can be studied in order to document and understand the significant changes in body weight that ensue with these conditions. In addition, treatment of these conditions is associated with further alterations in body weight. As will be discussed, hypothyroidism is associated with mild to modest increases in body weight and accompanying changes in body composition, with partial reversal of these alterations with its treatment with thyroid hormone. Ongoing treatment of hypothyroidism tends to be associated with ongoing weight gains. In contrast, hyperthyroidism can be accompanied by profound weight loss, with a decrease in fat mass, muscle mass, and bone mass, with reversal of the weight loss with restoration of euthyroidism. Specifically, the transition to euthyroidism with treatment of hyperthyroidism is accompanied by an increase in fat mass, muscle mass, and bone mass. However, resolution of hyperthyroidism typically is associated over time with a net increase in body weight that significantly exceeds the nadir seen during hyperthyroidism.

Conclusion: Understanding these patterns of weight changes described above is critical for clinicians to appreciate so that prior to treatment patients can be counseled about what to expect, and then after treatment strategies can be developed to prevent or minimize long-term weight gain after restoration of euthyroidism.

Currently, the total 25-hydroxyvitamin D (25(OH)D) is recognized as the indicator of vitamin D status that is used to define vitamin D sufficiency. Vitamin D binding protein (DBP) is the major carrier for circulating vitamin D and plays an important role in regulating circulating total and free vitamin D metabolites. Since the concentration of DBP and its affinity to vitamin D varies by different physiologic and clinical conditions, measuring total 25(OH)D may not accurately reflect functional vitamin D status. In addition, DBP is a potential prognostic indicator of clinical outcomes since it has other important functions beyond that as vitamin D carrier, including its role in actin scavenging after tissue injury and inflammation and immune modulation. It has been proposed that circulating DBP is altered in some clinical conditions, which affects the levels of total and free vitamin D metabolites and can explain clinical outcomes. Furthermore, in some clinical situations, total 25(OH)D levels are altered and knowing whether DBP is also changed may have diagnostic and therapeutic implications. The goal of this review is to assess clinical conditions altering DBP concentrations and then total 25(OH)D levels and their effects on prognosis. We suggest using the free 25(OH)D level as a better marker for vitamin D status in certain clinical conditions.

Objectives: Diabetic ketoacidosis (DKA)-related hospitalizations significantly burden the healthcare system. Recurrent DKA prolongs hospitalization and worsens outcome. In this study, we compared patient characteristics, clinical outcomes, and health care cost between patients with DKA who successfully transitioned from intravenous to subcutaneous insulin and those who did not.

Methods: This retrospective cohort study included 493 patients, aged ≥18 years, admitted with DKA. Divided into 2 groups: successful transition (ST) and failed transition (FT) from intravenous to subcutaneous insulin. Clinical characteristics, length of intensive care unit stay, in-hospital mortality, and healthcare costs were compared. Independent-sample t-tests and chi-square tests were used to analyze the data.

Results: Of 493 participants, 84.6% successfully transitioned, while 15.4% failed transition. Compared with the ST group, the FT group had higher mean body mass index (BMI), more comorbidities, longer intensive care unit stay (6.9 ± 7.7 vs2.3 ± 4.5 days; P < .001), and higher in-hospital mortality (9.2% vs1.0%; P < .001). The FT group incurred greater healthcare costs, with mean hospital charge of $224,362 ± 317 628 compared to $75 226 ± 128 042 in the ST group (P < .001). Multivariable logistic regression identified higher BMI (odds ratio [OR]: 1.05; P = .029), the presence of comorbidities (OR: 2.53; P = .034), lower bicarbonate during transition (OR: 0.88; P = .004), and higher anion gap (OR: 1.11; P = .049) as significant predictors of transition failure.

Conclusions: The FT group had worse clinical outcomes and utilized more health care resources than the ST group. Key factors such as higher BMI, more comorbidities, higher post-transition glucose and lower bicarbonate levels are associated with transition failure.

Objective: To investigate the prognostic value of the B-type Raf kinase (BRAF) V600E mutation in papillary thyroid carcinoma.

Methods: A comprehensive search of PubMed/MEDLINE, Scopus, and Web of Science up to August 31, 2025 identified 46 eligible studies including 20,570 patients, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Quality Assessment of Diagnostic Accuracy Studies version 2 quality assessment. Random-effects models were applied to evaluate associations between BRAF status and major oncological outcomes.

Results: BRAF V600E mutation was significantly associated with lymph node metastasis (odds ratios [OR] = 1.38; 95% confidence interval [CI], 1.17-1.61) and showed a borderline association with recurrence risk (OR = 1.56; 95% CI, 1.00-2.41). In contrast, no significant associations were observed for distant metastases (OR = 0.75; 95% CI, 0.48-1.17) or cancer-related mortality (OR = 0.97; 95% CI, 0.64-1.49). Sensitivity analyses confirmed the robustness of all pooled estimates. Meta-regressions revealed an inverse relationship between BRAF mutation prevalence and its prognostic impact, suggesting that the higher the mutation prevalence in a population, the lower its discriminative prognostic power. Funnel plot inspection and Egger's tests indicated no major publication bias.

Conclusion: Overall, these findings confirm that BRAF V600E mutation is associated with an increased risk of nodal metastasis and recurrence in papillary thyroid carcinoma. However, its lack of impact on distant metastases and disease-specific mortality limits its role as an independent prognostic marker in clinical decision-making.