Hormones-International Journal of Endocrinology and Metabolism最新文献

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of end-stage liver disease and liver transplantation in the Western world, with an approximate prevalence of 30% worldwide which is continuously rising. It is characterized by intrahepatic fat deposition along with at least one cardiometabolic risk factor, such as diabetes mellitus, obesity, hypertriglyceridemia, and hypertension. MASLD consists of a spectrum of liver diseases ranging from simple liver steatosis to steatohepatitis, liver fibrosis, and cirrhosis. Recently, the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD), and the European Association for the Study of Obesity (EASO) released the latest guidelines regarding the management of patients with MASLD. This article highlights the critical points of these guidelines and emphasizes problematic issues that need further evaluation.

Purpose: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent disease with limited treatment options. The aim of this study was to evaluate the preventive effects of a sodium-glucose co-transporter (SGLT)-2 inhibitor, empagliflozin, on a dietary mouse model of MASLD.

Methods: In total, 24 C57BL/6 J mice of both sexes were randomly allocated to three groups, as follows: the fast food diet (FFD) group (eight mice, receiving a high-fat, high-cholesterol, high-fructose diet, FFD), the EMPA group (eight mice, fed a FFD with 10 mg/kg/d empagliflozin), and the chow diet (eight mice, CD) group. The mice were weighed and blood samples were drawn every 4 weeks; after 25 weeks the mice were euthanized, at which point liver tissues were histologically evaluated.

Results: After 25 weeks, there was no significant difference in body weight between the three groups, whereas liver-to-body weight ratio was greater in the EMPA compared to the CD group (p = 0.002). Hepatic fibrosis was marginally different between the three groups (p = 0.045). Fibrosis stage 1 was present in five mice on FFD (62.5%), in one mouse on EMPA (12.5%), and in one mouse on CD (12.5%). Lipogenic, inflammatory, and fibrogenic genes did not differ between the EMPA and FFD groups. Interestingly, mRNA encoding for SGLT-1 and SGLT-2 was detected in the mouse livers.

Conclusions: Empagliflozin treatment in mice on a FFD did not result in any significant effects on morphological, biochemical, or histological features or on expression of hepatic genes associated with MASLD compared to those fed a FFD without empagliflozin. The observed effects on mild hepatic fibrosis warrant validation, possibly via studies of longer duration.

Purpose: Bilateral inferior petrosal sinus sampling (BIPSS) is the gold standard for localizing ACTH-dependent Cushing's syndrome (CS). While corticotropin-releasing hormone (CRH) was initially used for stimulation, desmopressin has become a common alternative. This research evaluates desmopressin's effectiveness in lateralizing Cushing's disease (CD) during BIPSS compared to CRH stimulation.

Methods: The study included 33 individuals with ACTH-dependent CS who underwent BIPSS and had diagnoses confirmed by endoscopic endonasal transsphenoidal pituitary surgery (EETPS). Fourteen participants underwent BIPSS with CRH and 19 with desmopressin. A comparative analysis was conducted.

Results: BIPSS accurately lateralized 76% of cases, specifically, 71% with CRH and 79% with desmopressin (p = 0.2). For tumors < 6 mm on MRI, overall accuracy was 82%, namely, 75% with CRH and 90% with desmopressin (p = 0.4). IPSS achieved 100% accuracy in the four cases with no lesion on preoperative MRI.

Conclusion: This study demonstrates no significant difference in lateralization accuracy between desmopressin and CRH for IPSS. In challenging cases, especially those with microadenomas or non-lesional CD, desmopressin with IPSS aids in preoperative lateralization.

Background: We present a case of metachronous metastasis of papillary thyroid carcinoma to the parotid gland, this being an extremely rare metastasis, and a literature review.

Case report: A 56-year-old female patient presented with a history of a slowly growing mass on the left side of the neck. The patient reported a medical history of thyroidectomy due to papillary thyroid carcinoma 23 years previously and neck dissection for lymph node metastases 10 years previously, with additional therapy using radioactive iodine in both cases. Computed tomography (CT) of the neck revealed a single nodular solid mass in the tail of the left parotid gland which showed heterogeneous intake of contrast agent. FNA biopsy of the left parotid gland revealed cells typical of papillary thyroid carcinoma with positive immunochemistry for TTF-1. Due to this new metastasis, a total parotidectomy with preservation of the facial nerve was performed and additional therapy with radioactive iodine was administered.

Conclusion: Despite the fact that papillary thyroid carcinoma has a low incidence of regional and distant metastases, there are a few rare cases with distant metastases reported in the literature. Thus, awareness, especially among endocrinologists, and a multidisciplinary approach are crucial to ensure early detection and efficient treatment of these rare cases, distant metastases being the main cause of mortality and of reduction of overall survival rate among these patients.

Graves' disease is the most common form of hyperthyroidism, especially in younger people. Current European guidelines recommend antithyroid drugs as initial treatment for a period limited to 12-18 months. Definitive treatment such as surgery or radioactive iodine is proposed in the case of contraindication to antithyroid drugs or in the case of recurrence after medical treatment. However, more recent studies show that long-term antithyroid treatment is associated with reduced risk of recurrence without an increase in adverse effects. Such data support the option of long-term treatment of Graves' disease with antithyroid drugs and suggest the necessity for a change to long-standing practices in the field. Herein, after reviewing some general knowledge on Graves' disease treatment, we discuss the evidence regarding long-term treatment of Graves' disease with antithyroid drugs for endocrinologists, internists, and other specialists involved in the management of these patients. We consider the main studies in the field, outline their respective strengths and limitations, and, finally, present our opinion on when, in the light of this new evidence, endocrinologists should consider long-term treatment with antithyroid drugs.

The complex communication network between the central nervous system and the hypothalamic-pituitary axis forms the basis of endocrine functional plasticity, which facilitates adaptation to changing internal and external conditions, but also makes it vulnerable to the negative effects of stressful psychological factors. Herein, clinical conditions such as functional hypothalamic amenorrhea, eating disorders, growth faltering, post-traumatic stress disorder, and pubertal disorders that may emerge during childhood or adolescence, their origin possibly including psychological stressors, are analyzed regarding their genetic susceptibility and reversibility of endocrine function. A discussion on the optimization of therapeutic management defined by managing stress and maximizing the degree and rate of reversibility follows.

Introduction: Somatic mutations in ubiquitin-specific protease-8 (USP8), encoding a deubiquinating protein, are found in approximately 30% of corticotroph-derived pituitary adenomas (CPAs). Stratifin, a protein encoded by SFN, inhibits USP8 catalytic activity. USP8 has immunomodulating properties that have been demonstrated in non-tumoral diseases.

Methods: We assessed the influence of USP8 on the immune landscape of CPA and validated this effect and its dependency on stratifin in large cohorts of non-pituitary tumors. We analyzed data of CPA samples (n = 20) and additional non-pituitary tumors from the TCGA database, using transcriptome signature-recognition algorithms. Immune tumor microenvironment (iTME) was compared both by USP8 and SFN expression levels (n = 843) and by USP8 mutation status and SFN expression (n = 12,389).

Results: CPA with activating USP8 mutations was associated with "cold" iTME compared with wild-type USP8 CPA, as reflected by lower fractions of immune cells, including B cells, CD4, regulatory and gamma/delta T cells, natural killer cells, M0 and M1 macrophages, dendritic cells, and eosinophils (p < 0.05 for all comparisons). Pathways altered by the presence of USP8 mutation, based on the most differentially expressed genes (3061 genes), included microglia pathogen phagocytosis and multiple toll-like receptor signaling pathways (p < 0.0001). In a validation analysis based on large cohorts of non-pituitary tumors, high expression of USP8 was associated with a suppressed iTME effect that was augmented by a low SFN expression.

Conclusions: Our data demonstrate for the first time, to our knowledge, a distinct immune landscape of tumors based on USP8 status and expression and the dependency of this immunological effect on SFN expression.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic liver disease closely associated with the epidemics of obesity and type 2 diabetes mellitus (T2DM), but without licensed pharmacological treatment to date. As glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are approved anti-diabetic and anti-obesity medications, they were also considered a potential therapeutic option for NAFLD. Preclinical studies suggest that GLP-1RAs have a beneficial effect on major NAFLD histological outcomes, i.e., hepatic steatosis and inflammation, through multiple intrahepatic mechanisms, including increased fatty acid β-oxidation, activation of autophagy, suppression of inflammation, and oxidative stress. Data on hepatic fibrosis are limited or inconclusive, although some studies reported improvement in indices of fibrosis or prevention of fibrosis initiation or reduction of collagen deposition. Whether the positive impact of GLP-1RAs on hepatic histology is indirect, i.e., through their action on extrahepatic tissues, or whether their action is direct, i.e., through activating GLP-1R on the hepatocytes, is still a controversial issue. Alongside GLP-1RAs, newly emerging peptide polyagonists (i.e., synthetic molecules that combine the amino acid sequences of more than one peptide, thus having the ability to bind more than one receptor) are now being investigated in NAFLD with high expectations. This review summarizes the existing knowledge derived from animal studies on the effects of GLP-1RAs and GLP-1RA related peptide polyagonists on NAFLD in an attempt to illuminate areas of uncertainty and provide the groundwork for future animal and clinical research in the field.

Introduction: Excess growth hormone (GH) secretion in acromegaly has a major impact on mineral balance and serum phosphate levels. However, the clinical utilization of serum phosphate levels as a marker for long-term disease outcomes in acromegaly has not been evaluated.

Methods: This is a retrospective study of patients with acromegaly who were followed in a tertiary center. Data were retrieved on patient characteristics, endocrine and biochemical evaluation, and tumor parameters. Comparisons were performed by measuring baseline phosphate levels and conducting correlation analysis and multivariable logistic regression.

Results: Sixty-one patients were followed for 4.5 years (range 1-21). Patients with hyperphosphatemia (> 4.5 mg/dl) at baseline had larger adenomas (15.0 mm [8.0, 47.0] vs. 10.0 mm [3.0, 24.0], p = 0.001), a rate chance of invasive adenoma (16 [80.0%] vs. 14 [46.7%], p = 0.02), and lower serum cortisol levels (226.0 nmol/l [27.6, 516.0] vs. 294.0 nmol/l [32.0, 610.0], p = 0.02). Baseline serum phosphate levels positively correlated with IGF-1 levels (r = 0.43, p = 0.003) and negatively correlated with morning plasma cortisol levels (r = -0.46, p = 0.002). Regarding long-term impact, baseline phosphate levels correlated with the number of pituitary axes involved 6 months after diagnosis (r-0.34, p = 0.01). In multivariable analysis, baseline plasma phosphate levels were independently associated with risk for disease progression/recurrence (odds ratio [OR] 9.66, 95% confidence interval [CI] 1.5, 105.9, p = 0.03) and for invasive adenoma (OR 6.21, 95% CI 1.6, 28.7, p = 0.01).

Conclusion: Elevated pretreatment serum phosphate levels are associated with a greater risk of disease persistence and recurrence and with altered pituitary function in patients with acromegaly.

Aims: A few studies have evaluated the performance of the American College of Radiology Thyroid Imaging Reporting And Data System (ACR-TIRADS) in pediatric and elderly patients and found differences between the latter two age groups and middle adulthood. Thus, the present study was undertaken to explore the possible variation of ACR-TIRADS performance across different ages of patients.

Methods: A retrospective population undergoing thyroidectomy was selected to use histology as the reference standard. Ultrasound images were reviewed, and alignment of ACR-TIRADS with the corresponding histological diagnosis was made afterwards. Results of the age groups were compared. The ACR-TIRADS diagnostic performance was calculated considering the assessment of nodules across risk categories (i.e., from TR1 to TR5), rate of unnecessary FNAC (UN-FNAC), and rate of necessary but non-performed FNAC (NNP-FNAC).

Results: Overall, 114 patients with a total of 220 nodules (46 carcinomas) were included. The rate of UN-FNAC was 66.3%, being 93.1% in TR3, 82.1% in TR4, and 31.4% in TR5. There were 15 NNP-FNACs. No significant difference was observed between age groups in terms of sample size, nodule, cancer, and FNAC. The nodule assessment according to ACR-TIRADS categories did not vary across ages. Sensitivity and specificity recorded in three age tertiles were not significantly different.

Conclusions: The present study shows that the performance of ACR-TIRADS is not significantly influenced by patient age.