Associations of four surrogate insulin resistance indexes with non-alcoholic steatohepatitis in Chinese patients with obesity: a cross-sectional study.

OBJECTIVES: This study was designed to evaluate the association of four surrogate indexes of IR with NASH in patients with obesity. METHODS: A total of 270 patients who underwent bariatric surgery, were included in this cross-sectional study. NASH was diagnosed based on liver biopsies. Binary logistics regression analyses were performed to assess the associations of four surrogate indexes of IR (HOMA-IR, Matsuda index, TyG, and TG/HDL-C) with NASH in patients with obesity. The restricted cubic spline was used to assess the dose-response associations of surrogate indexes of IR with NASH after adjusting for confounding factors. RESULTS: NASH was diagnosed in 136 patients, with a prevalence of 50.37%. Compared with tertile 1, the fully adjusted ORs (95% CIs) of NASH for tertile 3 were 2.711(1.113-6.608) and 0.297 (0.152-0.579) for TyG and Matsuda index. Consistently, per SD increment of TyG were still significantly associated with 64% increased risks of NASH, and per SD increment of Matsuda index were still significantly associated with 38% decreased risks of NASH. In contrast, no significant associations were found between HOMA-IR and TG/HDL-C and the risk of NASH in patients with obesity (all P > 0.05). After adjusting covariates in restricted cubic splines, the risk of NASH decreased with the increment of Matsuda Index levels (P-nonlinear = 0.442, P-overall = 0.007) and with the decrement of TyG levels (P-nonlinear = 0.004, P-overall = 0.001). CONCLUSIONS: In patients with obesity, TyG and Matsuda index were independently related to the risk of NASH after adjustment for traditional risk factors. In addition, compared with HOMA-IR and TG/HDL-C, the Matsuda index and TyG may be more suitable for NASH prediction in patients with obesity.

Central hyperthyroidism due to an ectopic TSH-secreting pituitary tumor: a case report and literature review.

Ectopic thyroid-stimulating hormone (TSH)-secreting tumors are extremely rare, with only 15 reported cases in the literature. Herein, we described a 60-year-old female patient with thyrotoxicosis and elevated or unsuppressed levels of TSH. Family history and laboratory and genetic tests did not support a diagnosis of resistance to thyroid hormone (RTH). Given the unsuppressed TSH, TSH-secreting tumor was suspected, and magnetic resonance imaging (MRI) of the pituitary gland was performed. Surprisingly, the MRI scans revealed a nodule in the nasopharynx rather than a pituitary tumor in the sella region. Further evaluation using Gallium-68 DOTATATE positron emission tomography/computed tomography (68Ga-DOTATATE PET/CT) demonstrated increased DOTATATE uptake in the nasopharyngeal nodule. Additionally, an octreotide suppression test (OST) revealed an obvious reduction in TSH levels, further supporting the suspicion of the nasopharyngeal mass as the cause of inappropriate TSH secretion. To prepare for surgery, the patient received preoperative administration of octreotide, resulting in the normalization of TSH and thyroid hormone levels. The patient subsequently underwent successful surgical removal of the nasopharyngeal mass. Following the procedure, the patient experienced complete resolution of hyperthyroidism symptoms, with TSH declined and thyroid hormone levels returned to normal. Histochemistry analysis of the tumor revealed positive staining for TSH, growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), and somatostatin receptor 2 (SSTR2). We discussed differential diagnosis of hyperthyroidism due to inappropriate TSH secretion, with a particular emphasis on the importance of 68Ga-DOTATATE PET/CT in combination with OST for identifying ectopic pituitary tumors.

Development, Validation, and Application of a Scoring Model for Non-alcoholic Steatohepatitis.

PURPOSE: The aim of this study was to explore risk factors of NASH and then develop a non-invasive scoring model in Chinese patients with obesity. A scoring system was then applied to assess the effect of sleeve gastrectomy on NASH. METHODS: A total of 243 patients with obesity were included and divided into NASH group and non-NASH group according to the pathological results of liver biopsy. Logistic regression was used to determine risk factors of NASH. A scoring model was derived by risk factors of NASH. Then, postoperative follow-up was performed in 70 patients. RESULTS: Among the 243 patients, 118 (48.56%) patients showed NASH. Multivariate logistic regression identified aspartate aminotransferase (AST) (>21.50 IU/L), high-density lipoprotein cholesterol (HDL-C) (<1.155mmol/L), and homeostasis model assessment (HOMA-IR) (>9.368) as independent risk factors of NASH. The model included above risk factors showed a negative predictive value (NPV) of 70.38% in the low-risk category and a positive predictive value (PPV) of 85.71% in the high-risk category, with the area under the receiver operator curve (AUROC) of 0.737. Bariatric surgery resulted in a sharp decline in AST and HOMA-IR and a significant increase of HDL-C. The points of scoring model were improved at 6 months after surgery. CONCLUSION: A non-invasive scoring model was derived by the risk factors of NASH included AST, HDL-C, and HOMA-IR and applied to the postoperative follow-up. After sleeve gastrectomy, the above risk factors and points of scoring model were significantly improved.

Insulin Resistance, but Not Obstructive Sleep Apnea Is Associated with Hepatic Steatosis in Chinese Patients with Severe Obesity.

INTRODUCTION: Severe obesity is often present with non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA). Emerging researches suggest OSA plays an important role in NAFLD development and progression while the relationship between OSA and NAFLD is still conflicting. The interaction of OSA and NAFLD should be further evaluated as obesity surges. The purpose of this study was to assess the prevalence of OSA and NAFLD in patients with obesity undergoing bariatric surgery and evaluate the association between OSA and severity of NAFLD. METHODS: 141 patients with severe obesity undergoing preoperative polysomnography and intraoperative liver biopsy during bariatric surgery were investigated. Clinical, anthropometric variables, liver enzymes, fasting blood glucose, fasting serum insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. The severity of NAFLD was assessed by degree of steatosis, ballooning, intralobular inflammation, and NAFLD activity score. The diagnosis and severity assessment of OSA was based on an apnea/hypopnea index (AHI). RESULTS: OSA was diagnosed in 127 (90.07%), NAFLD in 124 (87.94%), and non-alcoholic steatohepatitis in 72 (51.06%) patients. There was a statistical difference in BMI, waist circumstance, neck circumstance, high-density lipoprotein cholesterol, fasting insulin, and HOMA-IR among the three groups divided by the severity of AHI. In addition, the distribution of hepatic steatosis grades among the three groups was statistically different (p = 0.025). AHI was significantly associated with HOMA-IR and hepatic steatosis when assessing the association between OSA parameters and liver histology in NAFLD (p < 0.05). Patients with steatosis of grades 1-3 had significantly elevated aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, triglycerides, fasting insulin, fasting glucose, HOMA-IR, and AHI compared with the patients with steatosis of grade 0. In a multivariable logistic analysis, the positive association between AHI and hepatic steatosis attenuated after adjusting for HOMA-IR. CONCLUSION: Prevalence of OSA and NAFLD was high in patients with obesity eligible for bariatric procedures. HOMA-IR, but not AHI, was an independent risk factor for hepatic steatosis in this population.

Associations among FT4 level, FT3/FT4 ratio, and non-alcoholic fatty liver disease in Chinese patients with hypopituitarism.

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic metabolic disorder. Thyroid function is associated with NAFLD in different populations; however, little attention has been paid in patients with hypopituitarism. To analyze the association between thyroid function and NAFLD, we included 134 patients with hypopituitarism admitted to the Tianjin Medical University General Hospital between June 2013 and May 2019. Participants were divided into the NAFLD(-) and NAFLD(+) groups based on abdominal ultrasonography findings. We evaluated 68 male and 66 female patients with hypopituitarism. The prevalence of NAFLD was 52.24%. The NAFLD(+) group had a significantly higher free triiodothyronine/free thyroxine (FT3/FT4) ratio than the NAFLD(-) group (p = 0.003). The NAFLD(+) group showed significantly lower levels of FT4 and the growth hormone (GH) than the NAFLD(-) group (p = 0.003 and 0.016, respectively). We observed an association of the FT4 level and FT3/FT4 ratio with NAFLD in the univariate model, which was non-significant after adjustment for metabolic parameters (BMI, HDL-C, triglycerides, serum uric acid, blood pressure, fasting glucose). To better understand the role of each metabolic parameters, we performed additional models for each of those predictors individually after adjustment for age and gender, the association between FT4 level and FT3/FT4 ratio lost significance after adjustment for HDL-C and TG, but not for other predictors. Our findings suggest that thyroid dysfunction may be crucially involved in NAFLD by regulating whole-body metabolism, especially lipid utilization. Therefore, sufficient thyroid hormone replacement therapy for patients with hypopituitarism is recommended from the early stage.

Liraglutide Ameliorates Lipotoxicity-Induced Oxidative Stress by Activating the NRF2 Pathway in HepG2 Cells.

Although glucagon-like peptide-1 (GLP-1) analogue has been reported to suppress oxidative stress in non-alcoholic fatty liver disease (NAFLD), an effective therapeutic agent for NAFLD is currently unavailable. Therefore, in this study, we aimed to investigate the protective effects of the GLP-1 analogue liraglutide against lipotoxicity-induced oxidative stress in HepG2 cells and to elucidate the underlying mechanisms. HepG2 cells were cultured for 48 hours and treated with a free fatty acid (FFA) mixture: FFA mixture and liraglutide or FFA mixture, liraglutide, and exendin (9-39). Lipid accumulation was examined by oil red O staining. Oxidative stress was assessed by measuring the levels of intracellular reactive oxygen species using 2',7'-dichlorofluorescein diacetate and thiobarbituric acid-reactive substances, whereas antioxidant capacity was assessed by measuring the activity of superoxide dismutase and catalase. Expression of the nuclear factor erythroid-2-related factor 2 (NRF2) gene and the genes encoding antioxidant enzymes was analyzed using quantitative RT-PCR. Cellular and nuclear NRF2 expression levels were assessed using immunofluorescence cell staining and western blotting. Liraglutide treatment reduced high fat-induced lipid formation and the levels of oxidative stress markers and increased antioxidant enzyme activity in HepG2 cells. Liraglutide treatment increased the mRNA expression of NRF2 target genes, induced NRF2 nuclear translocation, and increased nuclear NRF2 levels without altering NRF2 mRNA expression. Collectively, these results indicate that liraglutide exhibits a protective effect against lipotoxicity-induced oxidative stress, possibly via modulation of NRF2 and expression of antioxidant enzymes in liver cells.

Effect of hypercortisolism on bone mineral density and bone metabolism: A potential protective effect of adrenocorticotropic hormone in patients with Cushing's disease.

Objective To investigate the effects of Cushing's disease (CD) and adrenal-dependent Cushing's syndrome (ACS) on bone mineral density (BMD) and bone metabolism. Methods Data were retrospectively collected for 55 patients with hypercortisolism (CD, n = 34; ACS n = 21) from January 1997 to June 2014. BMD was examined in all patients, and bone turnover markers were tested in some patients. Healthy controls (n = 18) were also recruited. Results The lumbar spine and femoral neck BMD were significantly lower in the ACS and CD groups than in the control group. Lumbar BMD was significantly lower in the ACS than CD group. The collagen breakdown product (CTX) concentrations were significantly higher while the osteocalcin and procollagen type I N-terminal propeptide (PINP) concentrations were significantly lower in the ACS and CD groups than in the control group. The PINP concentration was significantly lower while the CTX concentration was significantly higher in the ACS than CD group. In the CD group only, lumbar BMD and serum adrenocorticotropic hormone had a significant positive correlation. Conclusions Bone turnover markers indicated suppressed osteoblast and enhanced osteoclast activities. PINP and CTX changes might indicate bone mass deterioration. Adrenocorticotropic hormone might be protective for lumbar BMD in patients with CD.

A case report of syndrome of inappropriate antidiuretic hormone secretion with Castleman's disease and lymphoma.

BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia in hospitalized patients and is often described in patients with small-cell carcinoma of the lung. In this report, we described both Castleman's disease and lymphoma coexisting in one patient with SIADH. CASE PRESENTATION: A 70-year-old Chinese woman with a history of diabetes mellitus and insulin therapy had severe hyponatremia and gastrointestinal symptoms. Through a series of examinations, common causes such as pulmonary carcinoma were excluded. An abdominal mass was detected by computed tomography. Although the peripheral lymph node biopsy showed the pathological result as Castleman's disease, the pathology of the abdominal lymph node revealed diffuse large B-cell lymphoma. After chemotherapy, the hyponatremia was treated during a period of follow-up. CONCLUSION: This patient presented with the rare clinical condition of inappropriate antidiuretic hormone secretion alongside Castleman's disease and lymphoma. Asymptomatic hyponatremia may persist for some time suggesting that clinical physicians should pay attention to the mild cases of hyponatremia. We also hypothesized that Castleman's disease is a condition of pre-lymphoma with both having the ability to cause SIADH. The possibility of lymphoma as well as Castleman's disease triggering the development of SIADH should also be taken into consideration for conducting recurrent biopsies.