Hormones-International Journal of Endocrinology and Metabolism最新文献

Purpose: To evaluate the prevalence of thyroid dysfunction and its association with possible contributing factors related to diagnosis and treatment in children who received hematopoietic stem cell transplantation (HSCT) in the only national transplant unit in Greece.

Methods: This is an observational, retrospective, single center cohort study that included 194 patients (58.6% boys) who survived for at least 1 year following allogeneic HSCT. Conditioning regimens depended upon diagnosis and protocols active at the time of transplantation. Some patients received irradiation, either central nervous system prophylaxis (n = 20), or total body irradiation (TBI) (n = 8). Thyroid gland evaluation included thyroid-stimulating hormone, free thyroxine, thyroid autoantibodies, and sonogram. Univariate and multivariate logistic models were used to examine the association of the above-mentioned factors with hypothyroidism.

Results: The mean age at diagnosis and at bone marrow transplant (BMT) in years was 7.51 ± 0.46 and 7.58 ± 0.36, respectively. The median follow-up time was 4.83 years. Hypothyroidism was detected in 33 cases (17.7%), four of those patients having received TBI. Factors contributing to hypothyroidism as per the multivariate analysis were male sex, [OR: 3.005, 95% CI (1.145-7.890)], irradiation, [OR: 2.876, 95% CI (1.120-7.386)], and years after HSCT [OR: 1.148, 95% CI (1.042-1.266)], while malignancy was identified only in the univariate analysis. The multivariate model presents a good class separation capacity [AUC = 72%, 95% CI (61.4%-82.4%)], Two patients had papillary thyroid cancer, both among children who had received TBI.

Conclusion: These data highlight the fact that male sex and radiotherapy are two independent factors that lead to increased risk for hypothyroidism. Furthermore, the prevalence of hypothyroidism increases with time post HSCT.

Background: Vitamin D-dependent rickets type 1 A (VDDR1A) is an autosomal recessive disorder due to mutations in the CYP27B1 gene which result in inability to generate 1,25(OH)₂D.

Case presentation: An 18-month-old boy with VDDR1A presented with hypotonia and respiratory distress. He had been diagnosed 2 months earlier, having been evaluated for stunted growth, hypotonia, and delayed developmental milestones. He was stabilized with oxygen and bronchodilators for his bronchiolitis and high doses of alfacalcidol, calcium, and phosphate supplements for his hungry bone syndrome. Of note, the patient sustained upper limb fractures after a fall from his bed during admission. Overall, he had a protracted disease course; however, his bone profile gradually improved and he steadily recovered.

Conclusion: VDDR1A causes failure to thrive, hypotonia, and increased fracture risk and may complicate the clinical course of lower respiratory tract infections. Furthermore, management of hungry bone syndrome requires supraphysiologic doses of vitamin D metabolites and calcium.

The increasing prevalence of type 2 diabetes mellitus (T2DM) and its microvascular and macrovascular complications necessitate an optimal approach to prevention and management. Medical nutrition therapy serves as the cornerstone of diabetes care, reducing reliance on diabetic medications for glycemic control and mitigating cardiovascular risk. The broadening field of research in the effect of low glycemic index (GI) and/or glycemic load (GL) diets on individuals with T2DM has yielded promising results in the existing literature. Adopting low-GI and GL dietary patterns contributes to minimizing fluctuations in blood glucose levels, thus presenting a good strategy for achieving enhanced glycemic control. Furthermore, the above dietary practices may offer a viable alternative and practical approach to weight management in individuals with T2DM. However, clinical practice guidelines for diabetes dietary management show inconsistency regarding the certainty of evidence supporting the implementation of low-GI/GL nutritional patterns. This review aims to thoroughly evaluate the available data on the effectiveness of low-GI and low-GL diets in managing glycemic control and reducing cardiovascular risk factors.

Purpose: Evidence from previous experimental and observational research demonstrates that the gut microbiota is related to circulating adipokine concentrations. Nevertheless, the debate as to whether gut microbiome composition causally influences circulating adipokine concentrations remains unresolved. This study aimed to take an essential step in elucidating this issue.

Methods: We used two-sample Mendelian randomization (MR) to causally analyze genetic variation statistics for gut microbiota and four adipokines (including adiponectin, leptin, soluble leptin receptor [sOB-R], and plasminogen activator inhibitor-1 [PAI-1]) from large-scale genome-wide association studies (GWAS) datasets. A range of sensitivity analyses was also conducted to assess the stability and reliability of the results.

Results: The composite results of the MR and sensitivity analyses revealed 22 significant causal associations. In particular, there is a suggestive causality between the family Clostridiaceae1 (IVW: β = 0.063, P = 0.034), the genus Butyrivibrio (IVW: β = 0.029, P = 0.031), and the family Alcaligenaceae (IVW: β=-0.070, P = 0.014) and adiponectin. Stronger causal effects with leptin were found for the genus Enterorhabdus (IVW: β=-0.073, P = 0.038) and the genus Lachnospiraceae (NK4A136 group) (IVW: β=-0.076, P = 0.01). Eight candidate bacterial groups were found to be associated with sOB-R, with the phylum Firmicutes (IVW: β = 0.235, P = 0.03) and the order Clostridiales (IVW: β = 0.267, P = 0.028) being of more interest. In addition, the genus Roseburia (IVW: β = 0.953, P = 0.022) and the order Lactobacillales (IVW: β=-0.806, P = 0.042) were suggestive of an association with PAI-1.

Conclusion: This study reveals a causal relationship between the gut microbiota and circulating adipokines and may help to offer novel insights into the prevention of abnormal concentrations of circulating adipokines and obesity-related diseases.

Population aging is a global phenomenon driving research focus toward preventing and managing age-related disorders. Functional hypogonadism (FH) has been defined as the combination of low testosterone levels, typically serum total testosterone below 300-350 ng/dL, together with manifestations of hypogonadism, in the absence of an intrinsic pathology of the hypothalamic-pituitary-testicular (HPT) axis. It is usually seen in middle-aged or elderly males as a product of aging and multimorbidity. This age-related decline in testosterone levels has been associated with numerous adverse outcomes. Testosterone therapy (TTh) is the mainstay of treatment for organic hypogonadism with an identifiable intrinsic pathology of the HPT axis. Current guidelines generally make weak recommendations for TTh in patients with FH, mostly in the presence of sexual dysfunction. Concerns about long-term safety have historically limited TTh use in middle-aged and elderly males with FH. However, recent randomized controlled trials and meta-analyses have demonstrated safe long-term outcomes regarding prostatic and cardiovascular health, together with decreases in all-cause mortality and improvements in various domains, including sexual function, body composition, physical strength, bone density, and hematopoiesis. Furthermore, there are numerous insightful studies suggesting additional benefits of TTh, for instance in cardio-renal-metabolic conditions. Specifically, future trials should investigate the role of TTh in improving symptoms and prognosis in various clinical contexts, including sarcopenia, frailty, dyslipidemia, arterial hypertension, diabetes mellitus, fracture risk, heart failure, stable angina, chronic kidney disease, mood disorders, and cognitive dysfunction.

Theodoros Aretaios (1829-1893), having pursued advanced studies at home and abroad and possessing a wide range of competences and interests, was among the first Greek physicians to produce educational treatises for both students and doctors of medicine. Among these is his medical treatise Surgery which deals with thyroid operations and goiter symptoms as well as post-operative lesions which included a record of his extensive experience, learned recommendations, deep insights, and advanced techniques. In this medical archive, which is preserved in the National Library of Greece, there is, for example, the physician's vivid description of a thyroidectomy that he performed which illustrates his expertise as a surgeon as well as the surgical knowledge of his times. Aretaios was not the first to perform this operation in Greece: he was, however, the first to document it, which he did for the benefit of his fellow Greeks and of surgeons worldwide.

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: 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.

Aim: Neuropathy, a common complication of diabetes associated with metabolic issues, lacks clarity regarding its prevalence in metabolically healthy obese versus non-obese individuals. Our study aims to compare neuropathy rates between those with and those without obesity and who are metabolically healthy.

Methods: We included individuals aged 20-50, one group with a body mass index (BMI) ≥ 30 kg/m² (metabolically healthy and obese) and another with a BMI < 30 kg/m² (metabolically healthy and non-obese). Exclusion criteria encompassed diabetes, hypertension, chronic renal disease, vitamin B12 deficiency, anemia, primary amyloidosis, immune system disorders, malignancy, active infection, and paraneoplastic syndromes. Patients underwent assessments using the Neuropathy Symptom Score (NSS) and modified Neuropathy Disability Score (mNDS).

Results: The median scores for NSS and mNDS were higher among metabolically healthy obese individuals than non-obese participants (2 (1-4) vs. 0 (0-1) for NSS; p < 0.001 and 4 (2-5) vs. 2 (1-4) for mNDS; p < 0.001). Individuals with obesity had a 110.09 times higher likelihood of experiencing neuropathy compared to those without obesity. The severity of neuropathy was significantly greater in the metabolically healthy group with obesity. There were no statistically significant differences in anthropometric and laboratory values between participants with and without neuropathy, except for triglyceride levels. Patients with neuropathy exhibited higher triglyceride levels compared to those without neuropathy.

Conclusion: Our study demonstrated a higher prevalence of neuropathy among metabolically healthy obese individuals in comparison to those who were metabolically healthy and non-obese.

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.