Journal of Endocrinological Investigation最新文献

Purpose: Childhood obesity is a global health problem that may be linked to changes in the gut microbiota. The aim of this pilot study was to link the clinical parameters of children with obesity, who underwent a dietary intervention, with their gut microbiota profiles to better understand the factors associated with weight loss.

Methods: The study focused on 36 male children with obesity (aged 12-15 years) who were referred for treatment of primary obesity. Personal medical history information was collected at enrollment. Body composition was assessed before and after a three-week balanced hypocaloric diet with preserved nutritional value. Bacterial taxa were analyzed by 16S rRNA gene amplicon sequencing. Linear regression models and machine learning algorithms were used to determine how subjects' clinical factors and gut microbiota contribute to weight loss efficacy.

Results: Results showed that higher abundance of Lachnospiraceae members (Blautia and Anaerostipes) prior to the diet intervention, and later introduction of non-dairy food were positively related to weight loss efficacy, while higher abundance of Erysipelotrichaceae UCG-003 and Faecalibacterium in the pre-diet samples was negatively correlated with BMI change. The change in the abundance of Enterobacteriaceae and Bacteroidetes members between the pre- and post-diet samples was negatively associated with delta BMI.

Conclusion: The efficacy of weight loss in male children with obesity under dietary treatment is related to the composition of the gut microbiota and the timing of the introduction of non-dairy food. Promoting beneficial gut bacteria could increase the success of dietary treatment for weight loss and improve long-term health outcomes in children with obesity.

Background: Endothelial dysfunction may contribute to the increased cardiovascular risk associated with thyroid diseases. This systematic review and meta-analysis aimed to assess endothelial function, evaluated by flow-mediated dilation (FMD), in both hypo and hyperthyroidism, and its response to treatment.

Methods: We searched Embase and PubMed (until April 2025) for studies on FMD in hypo- and hyperthyroidism (PROSPERO registration number: CRD42024629806). Risk of bias was assessed using Cochrane criteria. Mean differences (MD) with 95% confidence intervals (CI) were calculated using random-effects models. Statistical heterogeneity was assessed with I² statistics. Analyses were conducted using Review Manager 5.4.1.

Results: Forty-two studies (1,663 subjects with hypothyroidism, 247 with thyrotoxicosis/endogenous hyperthyroidism, and 1520 euthyroid controls) were included. FMD was significantly reduced in subjects with untreated hypothyroidism compared to euthyroid controls (MD -2.99, 95% CI, -3.83, -2.14; I² = 99%), improved with levothyroxine treatment (MD 3.06, 95% CI: 1.94, 4.19; I² = 91%) and reached values similar to controls upon restoration of euthyroidism (MD 0.22, 95% CI: -0.75, 1.18; I² = 75%). A non-statistically significant difference emerged comparing untreated hyperthyroid subjects with controls (MD - 2.55; 95% CI: -5.38, 0.28; I² = 98%), and low risk of bias studies showed reduced FMD in this subset (MD - 6.57; 95% CI: -7.53, - 5.60; I² = 45%). Subclinical hyperthyroidism was associated with FMD impairment (MD - 4.21; 95% CI: -7.07, - 1.35; I² = 97%).

Conclusion: Hypothyroidism is associated with endothelial impairment, reversible after restoration of euthyroidism, highlighting the importance of appropriate management. Hyperthyroidism, especially subclinical, seems associated with FMD reduction, but larger, well-designed studies are needed.

Purpose: Polycystic ovary syndrome (PCOS) is a common endocrinological disorder closely associated with metabolic dysfunction. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a new comprehensive term encompassing metabolic dysregulation and hepatic steatosis. This study aims to evaluate the diagnostic performance of the hepatic steatosis index (HSI), fatty liver index (FLI), and metabolic parameters in detecting MASLD among PCOS patients. It also aims to explore the prevalence of MASLD across PCOS phenotypes to assess phenotype-specific risks.

Methods: A retrospective analysis of 1,192 women aged 18-40 years with PCOS, diagnosed based on the Rotterdam criteria, was conducted. Participants were categorized into two groups: MASLD and non-MASLD. Clinical and metabolic parameters were analyzed, including body mass index (BMI), waist-to-hip ratio, lipid profiles, homeostatic model assessment for insulin resistance (HOMA-IR), and liver enzymes. HSI and FLI scores were calculated, and their diagnostic performance was assessed using ROC analysis. Subgroup analysis evaluated the prevalence of MASLD among PCOS phenotypes (A, B, C, D). Multivariate logistic regression identified independent predictors of MASLD.

Results: MASLD prevalence was 25.8%. HSI (AUC: 0.88) and FLI (AUC: 0.89) demonstrated strong diagnostic performance. MASLD patients had significantly higher BMI, HOMA-IR, and triglyceride levels, and lower high-density lipoprotein levels (p < 0.001). Phenotypes A and B exhibited the highest risk of MASLD, with hyperandrogenism emerging as a key factor (p < 0.004).

Conclusion: HSI, FLI, and metabolic parameters are practical, non-invasive tools for diagnosing MASLD in PCOS patients. Routine screening using these indices may help clinicians detect and manage MASLD early. To reduce MASLD risk, phenotype-specific treatments targeting obesity, insulin resistance, and hyperandrogenism may be recommended.

Background: The diagnostic accuracy of screening and confirmatory tests to differentiate primary aldosteronism (PA) among patients with low-renin hypertension (HTN) is suboptimal. We aimed to assess the role of the postural stimulation test (PST) in differentiating PA from low-renin HTN.

Patients and methods: Clinical and endocrine data in clinostatic position (CP) and orthostatic position (OP) during PST were evaluated in 190 hypertensive patients: 80 with PA and 110 with low-renin HTN. Multivariate techniques were computed: Principal Component Analysis (PCA), Partial Least Square-Discriminant Analysis (PLS-DA) and k-means clustering.

Results: PST response differentiated our cohort: 96% of PA were detected in the 56/190 patients with always suppressed renin levels during PST, 80% of patients with low-renin HTN were identified among 56/190 subjects with de-suppression of renin from CP to OP and 78/190 with always measurable renin. Normal potassium and measurable renin in OP were predictors of low-renin HTN. Cluster analysis distinguished PA from low-renin HTN: Cluster 2 included 104/110 low-renin HTN; Cluster 1 PA patients showed a higher frequency of suppressed renin levels at baseline and during PST (100% in CP and 95% in OP, respectively). Cluster 1 low- renin HTN patients had lower potassium and a higher frequency of suppressed renin levels at diagnosis and during PST, compared to Cluster 2. PLS-DA and PCA confirmed that renin in OP, renin response to PST, and hypokalemia were the most relevant parameters for distinguishing PA from low-renin HTN.

Conclusion: Renin response during PST can be used to differentiate PA from low-renin HTN.

Purpose: This study explored the association between TPOAb levels and the incidence and progression of coronary artery calcification (CAC) among participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Methods: We included individuals with no prior cardiovascular disease who underwent two CAC measurements within the ELSA-Brasil cohort from the São Paulo Research Center. Fasting serum TPOAb levels were analyzed as continuous data, categorized in quartiles, and as detectable and positive levels. Incident CAC was defined as a baseline CAC = 0 followed by a CAC > 0 in the second measurement. CAC progression was assessed using the Hokanson method only for participants with CAC > 0 at baseline. We performed Poisson regression models with robust variance and logistic regression models using the first quartile of TPOAb as the reference.

Results: A total of 3013 individuals were included (57.2% women, age 49.3 ± 8.1 years, 55.2% white). The third (IRR = 1.38, 95% CI = 1.03-1.85) and the fourth (IRR = 1.43, 95% CI = 1.07-1.91) quartiles of TPOAb were associated with a higher risk of CAC incidence, even after adjusting for sociodemographic variables, cardiovascular risk factors, and thyroid function. These associations remained consistent in sensitivity analyses for euthyroid individuals (Q3: IRR = 1.49, 95% CI = 1.07-2.06 and Q4: IRR = 1.60, 95% CI = 1.15-2.22). Sex-stratified analyses revealed a stronger association between the fourth quartile of TPOAb and CAC incidence in men, while the third quartile was significantly associated with CAC incidence in women. There was a statistically significant association between high detectable TPOAb and CAC progression (OR = 1.50, 95% CI = 1.01-2.24).

Conclusion: Our findings indicate that individuals with higher levels of TPOAb were at higher risk of developing CAC over a 5-year follow-up period, suggesting an atherogenic role of TPOAb independent of thyroid function.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by MEN1 gene mutations, typically involving primary hyperparathyroidism (PHPT), pancreatic neuroendocrine tumors (PanNETs), and/or pituitary neuroendocrine tumors (PitNETs). However, 10-30% of patients with MEN1-like features lack identifiable MEN1 mutations and are classified as phenocopies. This retrospective multicenter study, conducted across 10 Italian referral centers, aimed to characterize the main clinical features of phenocopies. Among 240 patients evaluated for suspected MEN1 over five years, 175 (mean age 43.2 ± 19.7; 101 females) had genetically confirmed MEN1, while 65 (27%; mean age 59.9 ± 11.6; 44 females) were identified as phenocopies. Of these, 46 (70.7%) were also negative for CDKN1B mutations, confirming the rarity of MEN4. Phenocopies were diagnosed one to two decades later than MEN1 patients (p < 0.0001). PHPT was the most frequent manifestation in both groups (80% of phenocopies vs. 81% of MEN1), but tumor associations differed significantly between groups (p < 0.001): 41% of MEN1 patients showed the classic triad, compared to only 1% of phenocopies; PHPT with NETs was more common in MEN1 (32%), whereas PHPT with PitNETs occurred more often in phenocopies (54%), reflecting patterns of sporadic tumors. Notably, 11% of phenocopies had a first-degree relative with MEN1-related diseases, and 51% had a personal or family history of cancer. In conclusion, MEN1 phenocopies are relatively common and represent a clinical challenge. Given their distinct features and familial backgrounds, an extended genetic panel should be offered to these patients together with periodical screening of MEN1-related disease.

Purpose: Subtotal parathyroidectomy (STP) is the preferred surgery for MEN1-related primary hyperparathyroidism (PHPT), balancing recurrence and complication risks. MEN1-negative patients show a milder disease course, supporting the hypothesis that post-operative outcomes may also differ between MEN1-positive and MEN1-negative patients.

Methods: We conducted a retrospective study of 101 MEN1 patients undergoing parathyroidectomy to compare PHPT outcomes by genetic status and surgical approach. MEN1-positive patients mainly received total parathyroidectomy (TP) or STP, while MEN1-negative patients underwent less than subtotal parathyroidectomy (LSTP).

Results: No significant differences were found between MEN1-positive and MEN1-negative patients in remission (p = 0.423), recurrence (p = 0.509) or persistence (p = 0.814) rates, regardless of surgical approach. Chronic postsurgical hypoparathyroidism occurred only in MEN1-positive patients (12.7%). In a sub-analysis of LSTP cases, MEN1-negative patients showed significantly better outcomes, with higher remission (47.6% vs. 16.6%, p = 0.01), and lower recurrence and persistence. Among MEN1-positive patients, TP or STP led to better outcomes compared to LSTP, with higher remission (60.5% vs. 16.7%, p = 0.00005), and lower recurrence and persistence. Recurrence occurred earlier after LSTP (84.0 vs. 160.0 months, p = 0.032).

Conclusions: MEN1 genetic status and surgical strategy both shape PHPT outcomes. MEN1-positive patients benefit from more extensive surgery, performed at high-volume centers, whereas MEN1-negative patients have more favorable outcomes with limited resections, though their remission still trails that of sporadic PHPT. These differences underscore the need for individualized surgical planning.