Hormones-International Journal of Endocrinology and Metabolism最新文献

Purpose: Variants in the GNB1 gene, which encodes for the beta-1 subunit of G proteins, have been associated with intellectual development disorder (OMIM: 616973), characterized by developmental delay, infantile hypotonia, seizures, and psychiatric problems. GNB1 variants may also cause a multisystem disorder, with symptoms such as hearing and vision impairment, gastrointestinal disorders, genitourinary abnormalities, and growth delay.

Case presentations: We present two pediatric patients with two novel GNB1 variants. The first patient is a 12-year old Caucasian European female with a history of neonatal hypotonia, feeding difficulties, and failure to thrive for the first 2 years of life. Subsequently, she developed grade 3 obesity, hyperphagia, and autoimmune thyroiditis. Whole Exome Sequencing (WES) revealed a novel likely pathogenic variant in the GNB1 gene (NM_002074.5:c.93_94del, p.Gln32AspfsTer46), which is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. The second patient is a 2-year old Roma female with severe failure to thrive during infancy, congenital hypothyroidism, and transient hyperoxaluria. No developmental delay was identified. Genetic testing excluded primary hyperoxaluria and WES revealed to be a novel likely pathogenic variant {NM_002074.5:c.183G > T (NP_002065.1:p.Met61Ile), which is predicted to have a damaging effect on the gene or gene product.

Conclusion: We present two rare pediatric cases with novel GNB1 variants which highlight the phenotypic variability associated with disrupted GNB1 expression. GNB1 may serve as a candidate gene for severe early onset obesity, hyperphagia, neurodevelopmental delay, and other metabolic and endocrine disorders.

Purpose: Anxiety is a common mental health issue during pregnancy. Moreover, women with gestational diabetes mellitus (GDM) seem to have to cope with higher levels of anxiety, being at higher risk for several health and mental complications. Women with GDM are recommended to undertake regular physical exercise to improve metabolic and reproductive outcomes. However, there are no specific guidelines for exercise in women with GDM and data on its relationship with mental health are scarce. The aim of this study was to investigate the effect of exercise on anxiety symptoms in pregnant women with GDM.

Methods: The present non-randomized, open-label clinical trial was a pilot study intended to provide initial data on the effect of exercise on anxiety symptoms of pregnant women with GDM. Forty-three women were assigned to three the following three study groups, (a) Advice Group (n = 17), Walking Group (n = 14), and Mixed Exercise Group (n = 12), from GDM diagnosis to delivery.

Results: Based on the Beck Anxiety Inventory (BAI) scores, all groups showed normal anxiety changes or mild anxiety levels pre- and post-intervention, ranging between 9.00 (1.00-32.00) (pre-intervention) and 7.5 (1.00-26.00) (post-intervention), but none experienced severe anxiety.

Conclusion: In the present study, a trend of self-selected pace walking to reduce the BAI scores was identified since the Walking Groups had lower scores after the intervention. However, this trend did not reach statistical significance. Brisk walking (30-45 min) three times per week may produce positive changes in both the treatment plan and the anxiety state of women with GDM. Moreover, the study confirms that routine medical care, counseling, and support by an interdisciplinary team are protective against anxiety in women with GDM.

Background and objectives: Growing evidence suggests that endogenous sex hormones (ESH) are associated with the risk of eczema or dermatitis. However, the causal relationship is not yet clear. This study aims to examine the potential effects of ESH (sex hormone-binding globulin levels, estradiol levels, total testosterone levels) on the risk of eczema or dermatitis using a two-sample Mendelian randomization (MR) study.

Methods: Genetic instruments from the largest available genome-wide association study (GWAS) for sex hormone-binding globulin levels, estradiol levels, and total testosterone levels were utilized to investigate the relationships between ESH and eczema or dermatitis. A set of complementary approaches was conducted to assess horizontal pleiotropy and potential caveats associated with this MR study.

Results: The MR analysis suggested that higher sex hormone-binding globulin levels are associated with an increased risk of eczema or dermatitis (MR-Egger: odds ratio [OR] = 1.003, 95% confidence interval [CI]:1.001-1.005, P = 0.007; weighted median: OR = 1.003, 95CI%:1.000-1.005, P = 0.023). Additionally, a suggestive association was observed between total testosterone levels and an increased risk of eczema or dermatitis (inverse variance weighted: OR = 1.005, 95CI%: 1.001-1.010, P = 0.024). However, the results showed no causal effects of estradiol levels on eczema or dermatitis. The accuracy and robustness of these findings were confirmed through sensitivity analyses.

Conclusions: This MR study supports a causal effect of SHBG sex hormone-binding globulin and TT levels on the risk of eczema or dermatitis, whereas estradiol appears to have no effect. These findings suggest that endogenous sex hormones may serve as potential biomarkers for eczema or dermatitis, which could be relevant to population groups beyond those of Europe.

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.

Purpose: Neoangiogenesis is necessary for adhesion and invasion of endometriotic lesions. We hypothesize that by blocking angiogenetic pathways we can suppress endometriosis. Oral contraceptive pills (OCs) are routinely used in endometriosis to suppress symptoms of the disease. In the current study, we attempt to evaluate the effects of OCs on various angiogenetic factors in women with endometriosis.

Methods: Sixty women with endometriosis were randomly divided into two groups. Group A consisted of 30 women who received OCs in a cyclical manner for 3 months before surgery and group B of 30 women who did not. Biopsy specimens of ovarian endometrioma were collected. We used qRT-PCR to study the mRNA expression levels of VEGF, TF, PAR-2, SP1, and FGF1.

Results: The levels of mRNA of all angiogenic factors were found to be elevated in women who received OCs compared with women who did not. This difference was statistically significant for VEGF, TF, FGF1, SP1 (p < 0.001), and PAR-2 (p = 0.046).

Conclusion: OC administration does not inhibit neoangiogenesis in endometriotic lesions; on the contrary, angiogenetic pathways might be upregulated.