Endocrinology and Metabolism最新文献

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants.

Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines.

Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040).

Conclusion: The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) accurately measures plasma aldosterone concentration (PAC), but its correlation with radioimmunoassay (RIA), equivalent RIA levels, and optimal cutoff for PAC and aldosterone-to-renin ratio (ARR) in primary aldosteronism (PA) screening have not been determined in a Korean population. Our study of 127 patients who underwent diagnostic testing for PA showed that the LC-MS/MS and RIA methods have good correlation, with a mean bias of 29.3% for PAC. An LC-MS/MS PAC level of 11.7 ng/dL was equivalent to an RIA PAC level of 15 ng/dL. Receiver operating characteristic curve analysis showed that an LC-MS/MS PAC level of 10.3 ng/dL and LC-MS/MS ARR level of 20.0 provided sensitivity of 73.1% with a specificity of 57.3% and sensitivity of 92.3% with a specificity of 14.7%, respectively. When the LC-MS/MS method is used for PA screening, an adjustment of cutoff values is necessary.

Background: The Controlling Nutritional Status (CONUT) score is an immunonutritional test tool based on serum albumin, total cholesterol, and lymphocyte counts. It has been studied as a simple prognostic predictor for various carcinomas. This study aimed to investigate the association between preoperative CONUT scores and the clinicopathological characteristics in papillary thyroid carcinoma (PTC) patients.

Methods: This study included 2,403 PTC patients who underwent total thyroidectomy between 2012 and 2016 at a single tertiary medical center. The CONUT scores were calculated based on preoperative blood tests. The clinicopathological characteristics were retrospectively reviewed. The patients were categorized by the CONUT score (relatively low, 0-2; relatively high, 3-5).

Results: Among the 2,997 PTC patients who underwent total thyroidectomy at Pusan National University Hospital between 2012 and 2016, those without preoperative blood test were excluded (n=149). Finally 2,403 patients were analyzed after excluding 439 patients taking lipid-lowering drugs and six patients without available T stage data after surgery. Based on the CONUT score, the relatively high score group had a lower body mass index (23.7±3.3 kg/m2 vs. 21.9±2.9 kg/m2, P<0.001), more advanced T stage (T stage 3/4, 5.9% vs. 11.4%, P=0.045), and higher extrathyroidal extension (2.1% vs. 7.6%, P=0.005).

Conclusion: Patients included in this large, single-center study all had a preoperative CONUT score of 0-5, but this study demonstrated that higher preoperative CONUT scores were significantly associated with advanced T stage and extrathyroidal extension. The CONUT score, which can be easily used in clinical practice, is thought to be helpful in predicting the aggressiveness of PTC.

Background: This study investigated the risk of frailty in older adults with differentiated thyroid cancer (DTC) and the effect of thyroid- stimulating hormone (TSH) levels on frailty.

Methods: This single-center, cross-sectional study included 70 DTC patients aged ≥60 years with stable TSH levels during the previous year while receiving levothyroxine. Frailty was assessed using the fried frailty phenotype (FFP). Anterior thigh muscle thickness was measured by ultrasound, and the sonographic thigh adjustment ratio (STAR) index was calculated. Muscle strength was measured using a hand dynamometer. Physical activity was determined by the physical activity scale for the elderly (PASE).

Results: The median (interquartile range) age and follow-up time were 65 years (62 to 71) and 11 years (7.0 to 14.2), respectively. The median TSH level was 1.10 μIU/mL (0.49 to 1.62), and 58.6% of patients were prefrail/frail. Muscle mass and strength were reduced in 35.7% and 17.2% of patients, respectively. TSH levels were lower in those with prefrailty/frailty (P=0.002), low muscle mass (P=0.014), and low strength (P=0.037) than in their normal counterparts. TSH levels correlated negatively with FFP (P= 0.001) and positively with the STAR index (P=0.034). TSH below 1.325 μIU/mL was associated with an increased frailty risk (area under the curve=0.719; P=0.001). Low TSH, female sex, low handgrip strength, and low PASE leisure time scores emerged as independent predictors of frailty (P<0.05).

Conclusion: Older adults with lower TSH levels due to DTC are at high frailty risk and have low muscle mass and strength. Therefore, TSH targets should be set based on a comprehensive evaluation with consideration of the risk-benefit ratio.

Background: Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction.

Methods: In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days.

Results: In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson's trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery.

Conclusion: Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.

Background: We evaluated the influence of subclinical hypothyroidism (SCH) on insulin resistance (IR), cardiometabolic risk, and obesity in childbearing-age women without diabetes.

Methods: This cross-sectional investigation included 282 women, aged 18 to 35 years, from rural and suburban Sri Lanka. Anthropometric and biochemical parameters, including IR and lipid/thyroid profiles, were recorded. Data were compared between SCH and euthyroidism (EU) for controls (normal weight) and cases (overweight/obese).

Results: The overall rates of SCH, EU, IR, and metabolic syndrome (MetS) were 40.42%, 59.57%, 73.40%, and 24.46%, respectively. Both controls and cases included individuals with SCH; overall, 168 participants (59.57%) had EU, while 114 (40.42%) exhibited SCH. IR was significantly associated with SCH in both weight groups (P<0.05). Among those with SCH, the odds ratios (ORs) for IR were >2 (95% confidence interval [CI], 0.45 to 3.87) in controls and >6 (95% CI, 3.52 to 8.41) in cases. Similarly, the ORs for MetS were >1 (95% CI, 0.38 to 4.16) in controls and >11 (95% CI, 8.73 to 15.01) in cases. Dyslipidemia and hypertriglyceridemia were significantly more prevalent in the SCH group (P<0.05). Women with SCH exhibited higher mean values for all obesity indices compared to their EU counterparts, surpassing normal thresholds (P<0.05). Among obesity measures, visceral adiposity index (VAI) demonstrated the highest area under the curve and sensitivity for assessing SCH and cardiovascular disease (CVD) risk.

Conclusion: SCH must be identified and managed in young women to help prevent diabetes and cardiometabolic disorders. VAI may aid in precisely detecting SCH and CVD.

Background: Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors.

Methods: Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed.

Results: The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980-2009 and 2010-2020 (P=0.995); however, the 1980-2009 group had significantly lower RFS rates (P=0.031). The 2010-2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group.

Conclusion: Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.

Background: Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty-a condition that best reflects biological age-has not been thoroughly investigated.

Methods: We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.

Results: After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).

Conclusion: These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.