Hormones-International Journal of Endocrinology and Metabolism最新文献

Purpose: In addition to chromosomal abnormalities, several genes have been implicated as causes of disorders of sex development (DSD). The NR5A1 gene expresses SF1, a transcription factor that plays a role in steroidogenesis by controlling multiple stages of adrenal and gonadal development, its mutations having been reported in cases of DSD.

Case presentation: A 15-year-old teenager was admitted to the Children's ICU of a tertiary center due to acute encephalitis. On physical examination, labia majora and minora, open vaginal opening, and a 4.8 cm phallus (stretched length) in the anatomical position of the clitoris were identified. The patient also presented with hirsutism, breast development was Tanner stage I, and pubic hair was Tanner V. Medical history revealed primary amenorrhea. Imaging studies revealed oval formations primarily compatible with testicular parenchyma in the anatomical location of the inguinal ducts. The karyotype identified a 46,XY individual, while whole exome sequencing (WES) revealed the presence of a heterozygous pathogenic splice site variant of the NR5A1 gene (NM_004959.5), c.990G > C, p.Glu330Asp, which, on further genetic testing of the parents, was proven to be de novo. According to psychiatric assessment, the patient self-identifies as a female. Laparoscopic exploration showed no residual Mullerian ducts or the presence of testicular tissue. A gonadectomy was performed and hormone replacement therapy with estrogens was initiated.

Conclusion: We describe a rare case of 46,XY DSD in an phenotypically female adolescent carrying the novel de novo p.Glu330Asp variant of the NR5A1 gene. We also highlight the frequent delay in diagnosis of ambiguous external genitalia.

Objective: Endogenous cortisol excess is known to affect body fat distribution. Ectopic fat is the accumulation of triglycerides in non-adipose tissue regions that normally contain little fat. The aim of study was to investigate the amount of ectopic fat in aortic perivascular and renal sinus fat of patients with endogenous cortisol excess and its relationship with their comorbitidies and laboratory findings.

Design: A total of 119 patients, including 16 patients with pituitary Cushing's disease (CD), 21 patients with adrenal Cushing's syndrome (CS), 34 patients with mild autonomous cortisol secretion (MACS), and 48 patients with nonfunctioning adrenal adenomas were enrolled in this retrospective study. Aortic perivascular fat and renal sinus fat were evaluated with magnetic resonance imaging.

Results: It was determined that the amount of aortic perivascular fat was increased in patients with CD (P = 0.01). The linear regression analysis showed that the amount of perivascular fat was associated with triglyceride levels and cortisol levels after the 1 mg dexamethasone suppression test as well as with gender (P < 0.01). Renal sinus fat measurements were similar in the groups (P > 0.05). After adjusting for age, sex, and BMI, perivascular fat was found to be higher in pituitary the CD than in the MACS and the nonfunctioning adenoma groups, and renal sinus fat was seen to be higher in pituitary the CD than in the MACS groups (P < 0.05). Patients with diabetes mellitus had an increased amount of renal sinus fat (P = 0.008).

Conclusion: The amount of perivascular and renal sinus fat may increase in patients with CD. Further studies are needed to elucidate ectopic fat distribution in patients with endogenous cortisol excess.

Purpose: Primary aldosteronism (PA), which is the commonest cause of secondary hypertension, can be cured by unilateral adrenalectomy. We report the short-and long-term outcomes after adrenalectomy performed at a single UK center over a period of 24 years.

Methods: Retrospective analysis of biochemical (potassium, aldosterone, renin, and ARR) radiological (CT/MRI, AVS, and nuclear scans), and clinical (surgical complications, blood pressure, and number of antihypertensive medications) short-and long-terms outcomes in patients who underwent adrenalectomy for PA between 1998 and 2021. Standardized PASO and Clavien-Dindo criteria to assess biochemical, clinical, and surgical outcomes were used.

Results: A total of 82 patients were treated via adrenalectomy for PA over a 24-year period. Short-term follow-up data (within 3 months after surgery) was available for all 82 patients (M45, F37, mean age 51.7 years): 24 of them were followed up for at least 60 months (range 60 to 72 months) and 77 (93.9%) patients had laparoscopic surgery (one conversion). Seven patients had postoperative complications classified as Clavien-Dindo II (4), IIIa(1) and IVa(2). Median LOS was 2.5 days (1-12). Complete and partial clinical success was achieved in 29 and 58.3% and 41.7 and 45.8% of patients in the short and the long term, respectively. Clinical benefit was observed in 88% of patients. Complete biochemical success was achieved in 95.8% of patients in the short and the long term.

Conclusion: Unilateral adrenalectomy in patients with PA showed clinical benefit in 88% and achieved biochemical cure in almost all of them. Our data suggest that these benefits persisted for at least 5 years.

Purpose: Data on the prevalence of obesity among hospitalized patients are limited. Our objective was to capture the rates of overweight and obesity among people admitted to an internal medicine department and to explore a potential association between body mass index (BMI) and causes of hospitalization.

Methods: Demographic and anthropometric parameters and cause of admission were recorded in all patients admitted to our department over a 30-day period.

Results: One hundred and eighteen patients with a mean age of 71.84 years and a mean BMI of 26.85 kg/m² were included in the analysis. Among study participants, 53.25% were living with overweight and obesity. Patients admitted for hepatobiliary disease had a higher BMI compared to those admitted for other diseases of the gastrointestinal tract (P < 0.001).

Conclusions: More than half of patients admitted to an internal medicine department live with obesity or overweight, the specific reasons for admission being associated with a higher BMI.

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.

Subacute thyroiditis (also known as granulomatous thyroiditis, giant cell thyroiditis, de Quervain's disease, or SAT) is an inflammatory disease of the thyroid gland, usually spontaneously remitting, that lasts for weeks to months. However, recurrent forms sometimes occur which may have a genetic basis. In our paper, we have focused on the pathogenetics, symptoms, and treatment of SAT. We have described the 17-month disease course of a woman with persistent recurrent steroid-resistant SAT. SAT was well established and the patient's symptoms were not only recurrent neck pain with fever, but also recurrent chronic urticaria, which are symptoms that fulfil the criteria for the diagnosis of Schnitzler syndrome. Schnitzler syndrome occurred after vaccination with COVID-19 in the mechanism of ASIA syndrome. In our patient, Schnitzler syndrome involved the thyroid gland, causing persistent subacute thyroiditis, and the pituitary gland, causing transient swelling of the pituitary, which, to our knowledge, is the first reported case in the literature. Also unprecedented, as far as we know, is the fact that we performed thyroidectomy in the above patient, which reduced systemic inflammation and caused SAT to resolve, although only the inclusion of anakinra treatment resulted in resolution of the underlying condition.