Hormones-International Journal of Endocrinology and Metabolism最新文献

Purpose: The immature and developing hypothalamic-pituitary-thyroid axis leads to different levels of thyroid function in twin neonates, including free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) levels. No reference intervals for twins have been established until now. To compensate for this lack, we collected data and established this standard across different gestational ages (GAs) and sexes.

Methods: A total of 273 pairs of neonates admitted to the NICU in Southeast China from 2015 to 2022 were included. Each pair was divided into Neonate A (relatively heavy birth weight (BW)) and Neonate B (relatively light BW). Their thyroid functions were analyzed to establish reference intervals and comparisons were made stratified by GA and sex.

Results: The FT3, FT4, and TSH reference intervals in twin neonates with a GA of 26-36 weeks were as follows: Neonate A and B: 3.59 ± 0.99 and 3.57 ± 1.00 pmol/L; Neonate A and B: 17.03 ± 5.16 and 16.77 ± 5.29 pmol/L; and Neonate A and B: 4.097 ± 3.688 and 4.674 ± 4.850 mlU/L, respectively. There were significant differences between serum FT3 and FT4 reference intervals and GA (p < 0.05). The serum FT3 and FT4 reference intervals for male neonates were lower than those for female neonates in the 29-32-week group (p < 0.05).

Conclusion: This was the first study, to our knowledge, to establish reference intervals for thyroid function in twin neonates from the fifth to seventh day of life, which will be beneficial for the diagnosis and management of congenital hypothyroidism.

Empress Dowager Cixi, the supreme ruler of China's Qing Dynasty, along with Imperial Concubine Jin, may have suffered from goiter. Our suspicions were aroused by two interesting historical photographs. Herein, we provide a medical interpretation of these historical images in an attempt to present the cases of these two historical figures.

Purpose: Leydig cell hypoplasia (LCH) type II is a rare disease with only a few cases reported. Patients presented with hypospadias, micropenis, undescended testes, or infertility. In this study, we report a new patient with compound heterozygous variants in the LHCGR gene and LCH type II phenotype.

Methods: Whole exome sequencing (WES) was performed followed by Sanger sequencing to confirm the detected variants in the patient and his parents.

Results: A novel missense variant (p.Phe444Cys) was identified in a highly conserved site and is verified to be in trans with the signal peptide's 33-bases insertion variant.

Conclusion: Our research provides a more comprehensive clinical and genetic spectrum of Leydig cell hypoplasia type II. It highlighted the importance of WES in the diagnosis of this uncommon genetic disorder as well as the expansion of the genotype of LCH type II.

Objective: Menopausal hormone therapy (MHT) has consistently shown a bone protective effect by reducing the risk of vertebral, non-vertebral, and hip fractures in postmenopausal women regardless of baseline fracture risk. However, the optimal sequential treatment after MHT discontinuation has not been determined. This systematic review aimed to obtain the best evidence regarding the effect of antiresorptive or osteoanabolic treatment on bone mineral density (BMD) and/or fracture risk following MHT.

Methods: A comprehensive search was conducted in the PubMed, Scopus, and Cochrane databases up to October 31, 2023. Randomized-controlled trials (RCTs) and observational studies conducted in postmenopausal women were included.

Results: After the exclusion of duplicates, 717 studies were identified. Two were eligible for qualitative analysis, one RCT and one retrospective cohort study. The RCT showed that alendronate 10 mg/day for 12 months further increased lumbar spine (LS) BMD by 2.3% following MHT and maintained femoral neck (FN) BMD in postmenopausal women (n = 144). It also decreased bone anabolic and resorption markers by 47 and 36%, respectively. In the retrospective study (n = 34), raloxifene 60 mg/day increased both LS and FN BMD at 12 months by 3 and 2.9%, respectively. No fractures were reported.

Conclusions: Antiresorptive therapy with either a bisphosphonate (i.e., alendronate) or raloxifene could be considered a sequential antiosteoporosis therapy after MHT withdrawal since they have been shown in studies to further increase BMD. However, no safe conclusions can be drawn from the existing literature.

Premature ovarian failure (POF) defines the occurrence of ovarian failure prior to the age of 40. It occurs in one out of 100 women but is very rare before age 20 (1:10,000). Maturity-onset diabetes of the young (MODY), caused by mutations in the HNF1A gene, is also a rare disorder; all types of MODY account for 1-2% of adult diabetic cases. These two rare nosologic entities coexisted in an adolescent girl evaluated for delayed puberty. Although this combination could represent a chance association, an interrelation might exist. We examined HNF1A expression in human fetal and adult ovaries by immunohistochemistry using a polyclonal HNF1A antibody. HNF1A protein was expressed in both the fetal and adult human ovaries. Based on these findings, we hypothesize that HNF1A participates in ovarian organogenesis and/or function and that mutations in the HNF1A gene might represent another molecular defect causing POF, possibly in combination with other genetic factors. The study underlines the importance of rare clinical paradigms in leading the way to elucidation of the pathogenetic mechanisms of rare diseases.

Purpose: Treatment guidelines for gender-affirming hormone therapy with estrogen (GAHT-E) recommend specific dosing regimens based on limited data. Well-controlled efficacy trials are essential to tailoring treatment to patient goals as the guidelines recommend. The goal of this study was to take a foundational step toward designing community-centered effectiveness trials for gender-diverse individuals seeking GAHT-E.

Methods: Our team developed a cross-sectional survey based on broad clinical experience and consultation with our community advisory board. The survey included 60 items covering demographics, transition history, goals and priorities for treatment, indicators of treatment success, sexual function goals, and future research priorities. The survey was distributed during the summer of 2021, primarily through social networks designed for gender-expansive individuals seeking treatment with estrogen.

Results: A total of 1270 individuals completed the survey. Overall treatment goals most frequently rated "extremely important" or "very important" were the following: (1) improved satisfaction with life (81%), (2) appearing more feminine (80%), (3) appearing less masculine (77%), (4) improved mental health (76%), and (5) being seen as your true gender by others (75%). The three body characteristics most frequently rated "highest priority" or "high priority" among changes were the following: (1) facial hair (85%), (2) breast shape or size (84%), and (3) body shape (80%). The highest-rated research priority was comparing feminization with different routes of estrogen administration.

Conclusion: The goals and experiences of individuals seeking GAHT-E are diverse. Future clinical trials of GAHT-E should be grounded in the needs and priorities of community stakeholders.

Purpose: The relationship between thyroid hormone sensitivity and albuminuria remains unclear. We aimed to investigate the association between thyroid hormone sensitivity and the risk of albuminuria in a euthyroid population.

Methods: This cross-sectional study included 7634 euthyroid adults collected from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2012. Central sensitivity to thyroid hormones was evaluated using the thyroid-stimulating hormone index (TSHI), the thyrotrophic thyroxine resistance index (TT4RI), and the thyroid feedback quantile-based index (TFQI). Peripheral sensitivity to thyroid hormones was measured using the free triiodothyronine/free thyroxine (FT3/FT4) ratio. Furthermore, the independent relationship between sensitivity to thyroid hormones and albuminuria was assessed.

Results: The proportion of albuminuria increased with a higher interquartile range of TFQI levels (7.31% vs. 7.89% vs. 7.95% vs. 9.89%, P = 0.024). Furthermore, TFQI was found to be independently associated with the risk of albuminuria after adjusting for confounding factors (OR = 1.28, 95% CI 1.01-1.60, P = 0.037). Subgroup analysis revealed a significant relationship between TFQI and albuminuria, especially among individuals over 60.

Conclusions: In euthyroid subjects, impaired central sensitivity to thyroid hormones is associated with albuminuria. TFQI holds significant potential as an epidemiological tool for quantifying the impact of impaired central sensitivity on the risk of albuminuria.

Purpose: The role of endocannabinoids (ECs) in the regulation of the hypothalamic-pituitary-adrenocortical axis has already been studied; however, data are scarce in humans. The aim of our study was to analyze EC [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and cortisol (F) levels in hair samples of patients with adrenal incidentalomas (AIs) in comparison with those found in controls and assess their association with the hormone profile.

Methods: Forty-four patients with AIs [32 with non-functioning AIs (NFAIs) and 12 with possible autonomous secretion (PACS)] and 44 controls were recruited. Basal and post-1 mg overnight dexamethasone suppression test (ODST) F, adrenocorticotropic hormone, dehydroepiandrosterone sulfate, and 24-h urinary free cortisol were analyzed. After hair collection, EC and F levels were measured by liquid chromatography tandem-mass spectrometry.

Results: There was no difference between the groups regarding age, sex, and metabolic status. Significantly decreased hair AEA and 2-AG levels were found in patients with AIs compared to controls (p < 0.001 and p = 0.002, respectively) as well as between NFAI or PACS and controls (p < 0.001 or p = 0.002 and p = 0.038 or p = 0.02, respectively). Among the AI patients, EC levels tended to be lower in the PACS group. AEA hair levels were negatively correlated with F levels post-1 mg ODST (r_s = -0.257, p = 0.033). We found no significant difference comparing hair F between the groups.

Conclusion: Our findings suggest that hair EC measurement could be a potential biomarker in the evaluation of patients with AIs, whereas hair F analysis is not a useful diagnostic test for mild hypercortisolemia.

Purpose: Disorders of sex development (DSD) have complex pathogenesis, and evidence suggests an association between MAMLD1 defects and DSD. MAMLD1 is expressed in gonadal tissues and affected males exhibit hypospadias, steroid hormone abnormalities, or gonadal underdevelopment. We performed genetic testing on a newborn patient with severe hypospadias and an elevation of 17-hydroxyprogesterone (17α-OH) for the diagnosis of DSD.

Methods: Genetic testing of the proband and parents was conducted using whole-exome and Sanger sequencing. The identified variant was transfected into HEK293T cells to assess mutant protein expression using western blot (WB) and into steroidogenic NCI-H295R cells to assess MAMLD1 and CYP17A1 transcript levels using qPCR. Molecular dynamics simulations were performed to construct a structural model and analyze potential biological implications.

Results: A novel heterozygous variant was identified in the proband's MAMLD1, NM_005491.5: c.1619_1637del (p.Gln540Alafs*72), inherited from the mother. In transfected cells, the wild-type and mutant proteins were 86.2 and 68.3 kDa, respectively, indicating the formation of a truncated protein. While MAMLD1 transcription was not affected, CYP17A1 transcription levels decreased with the variant compared to wild-type, suggesting an impact on the transactivation of CYP17A1. The truncated protein exhibited enhanced hydrophobicity, owing to the absence of the C-terminal structural portion, resulting in a looser protein structure.

Conclusion: Severe hypospadias in the proband may be attributed to a novel MAMLD1 variant, whereas the 17α-OH elevation might be related to interference with CYP17A1 transcriptional activation. This study expands the spectrum of MAMLD1 variants and underscores the critical role of genetic testing in the diagnosis of DSD.