Hormones-International Journal of Endocrinology and Metabolism最新文献

Menarche, the first menstrual period marking the onset of female reproduction, is a milestone of female puberty. The timing of menarche determines the timing of later phases of pubertal maturation in girls and has major implications for health later in life, including behavioral and psychosocial disorders during adolescence and fertility problems and increased risk for certain diseases in adulthood. Over the last few decades, a continuous decline in age at menarche has been noted, with environmental factors contributing to this change in the timing of menarche. However, a genetic component of age at menarche and pubertal onset has been strongly suggested by studies in families and twins wherein up to approximately 80% of the variance in puberty onset can be explained by heritability. Gene association studies have revealed several genetic loci involved in age at menarche, among which LIN28B has emerged as a key regulator of female growth and puberty. LIN28B, a human homolog of Lin28 of C. elegans, is a known RNA-binding protein that regulates let-7 microRNA biogenesis. Genome-wide association studies have identified the association of polymorphisms in the LIN28B gene with age at menarche in several population cohorts worldwide. In this paper, we review the genetic factors contributing to age of menarche, with particular focus on the identified polymorphisms in LIN28B gene.

The prevalence of diabetic foot ulcers (DFUs) is 4 to 10% among people with diabetes mellitus. DFUs are associated with increased morbidity and mortality as well as reduced quality of life and have a significant impact on overall healthcare expenditure. The main predisposing factors for DFU are diabetic neuropathy, peripheral arterial disease, and trauma. The fact that a range of tests can be used to identify patients at risk for DFU often causes confusion among practitioners regarding which screening tests should be implemented in clinical practice. Herein we sought to determine whether tests of somatic nerve function, such as pinprick sensation, thermal (cold/hot) test, ankle reflexes, vibration perception, 10-g monofilament, Ipswich touch test, neuropathy disability score, and nerve conduction studies, predict the development of DFUs. In addition, we examined whether sudomotor function screening tests, such as Neuropad, sympathetic skin response, and other tests, such as elevated plantar pressure or temperature measurements, can be used for DFU screening. If not treated properly, DFUs can have serious consequences, including amputation, early detection and treatment are vital for patient outcomes.

The incidence of thyroid cancer has increased over recent years due to the fact that several diagnostic tools, such as neck ultrasound and fine-needle aspiration, are being ever more widely adopted. Lately, another modality which might provide significant information preoperatively on the aggressiveness of a thyroid tumor, its prognosis, and its recurrence rate is molecular testing. We reviewed the literature with regard to the role of preoperative molecular testing in patients with Bethesda V and Bethesda VI thyroid nodules and its impact on choice of the optimal treatment strategy. Several molecular mutations and alterations are associated with thyroid cancer and its biological behavior, such as BRAF-V600E, RET, and TERT promoter. Although the value of preoperative molecular testing for indeterminate nodules (Bethesda III and Bethesda IV) have been analyzed in numerous studies, the impact of preoperative molecular testing on Bethesda V and Bethesda VI thyroid nodules is not adequately described in the current literature. The preoperative recognition of specific molecular mutations, such as BRAFV600E and TERT promoter mutation, might provide more individualized management for thyroid cancer patients by altering the surgical approach and the extent of surgery for patients diagnosed with a more aggressive or iodine-resistant subtype of thyroid cancer.Thyroid cancer is characterized by multiple genetic mutations and alterations and, as a result, preoperative molecular testing of malignant nodules could be a very useful tool for surgeons, enabling them to decide on the most appropriate surgical approach for each patient.

Purpose: To examine the determinants of health-related quality of life (HRQoL) of patients with type 2 diabetes (PwD) and multimorbidity (MM) (at least one co-occurring condition besides T2D) among sociodemographic, disease-related, and MM variables and the association of MM with therapeutic targets.

Methods: A total of 179 PwD attending primary care (PC) in Greece answered the 15 dimension HRQoL (15D) questionnaire between August 2019 and October 2020. Sociodemographic, disease-related, and MM characteristics were recorded. MM was categorized as concordant or discordant based on whether or not it was related to the pathophysiology of T2D. Independent predictors of the 15D score were examined in stepwise regression models among sociodemographic, disease-related, and MM variables and the association of MM with glycated hemoglobin (A1C) and low-density lipoprotein cholesterol (LDL-C) was assessed.

Results: The mean 15D score was 0.85 ± 0.11 and the mean MM count was 4.3 ± 1.8. Significant predictors of a higher 15D score were male gender, married state, higher monthly income, and more physical activity. Significant predictors of a lower 15D score were employment, depression, musculoskeletal disease, coronary artery disease, neuropathy, and MM count, but discordant had a stronger effect than concordant MM. Increasing MM count was not significantly correlated with A1C and was correlated with lower LDL-C.

Conclusion: Non-medical (physical activity and sociodemographic) rather than disease-related characteristics and discordant more than concordant co-occurring conditions affected HRQoL of multimorbid PwD who did not have worse (A1C) or achieved better (LDL-C) therapeutic targets. A generalist approach to the non-medical needs and overall health conditions of PwD could be promoted in PC within the social determinants of health and MM.

Silver-Russell syndrome 5 (SRS5) is characterized by asymmetric intrauterine growth restriction (IUGR), poor postnatal growth, macrocephaly at birth, and feeding difficulties. Other possible features include triangular shaped face, prominent forehead, hypertelorism, epicanthus, micrognathia, brachydactyly, clinodactyly of the 5th finger, and syndactyly of the 2nd and 3rd toes. Pathogenic variants of the HMGA2 (high mobility group AT-hook 2) gene, on chromosome 12q14, which regulates the transcription of growth factor IGF2, have recently been associated with this syndrome. Herein, we present a 2.5-year-old boy with growth delay, SRS-like phenotype, and a variant of uncertain significance in the HMGA2 gene, which has not, to the best of our knowledge, been described to date in the medical literature. So far, 28 pathogenic variants of the HMGA2 gene in patients with clinical SRS phenotype have recently been reported. Therefore, HMGA2 gene testing should always be done in SRS patients who are found to be negative for the typical 11p15 (epi)mutations and matUPD7, while the mutations should also be added to growth retardation disorder panels.

Purpose: Corticotropin-releasing hormone (CRH) plays an important role in relief of pain by releasing analgesia-associated molecules in several inflammatory states. During inflammation, peripheral CRH acts on cells of the immune system to stimulate the local expression of proopiomelanocortin (POMC) and the production of β-endorphin, which in turn binds to opioid receptors on sensory neurons to produce antinociception. In the present study, we further investigated the role of endogenous CRH in inflammatory pain by determining the effects of Crh-deficiency on this process.

Methods: For this purpose, we used Crh-deficient (Crh-/-) mice and their wildtype (Crh + / +) littermates in the CFA (Complete Freund's Adjuvant)-induced inflammatory pain model. Pain thresholds were evaluated with the Hargreaves apparatus.

Results: Our experiments showed that Crh deficiency led to increased pain response, which was associated with decreased POMC mRNA levels in locally inflamed paws of these mice. Furthermore, Crh-/- mice had higher paw edema than Crh + / + mice. Histological evaluation of inflamed paw tissues revealed increased inflammatory response in Crh-/- mice. Protein levels of proinflammatory cytokines, such as IL-6, TNF-α, and IL-1β, were higher in inflamed tissue of Crh-/- mice compared to wildtype mice. Corticosterone replacement increased the pain threshold of Crh-/- mice, restored their paw volume to the levels of wildtype mice, and significantly reduced their proinflammatory cytokine levels. Furthermore, glucocorticoid administration significantly increased POMC mRNA expression in the inflamed paw.

Conclusion: Our data suggest that genetic deficiency of CRH is associated with increased pain. This effect is likely attributable to the accompanying glucocorticoid insufficiency and is in part mediated by opioids expressed locally.

Background: The cardiometabolic index (CMI) is a new type of obesity index that is based on a combination of lipid levels and abdominal obesity indicators. It is closely correlated with the occurrence of diabetes mellitus, atherosclerosis, hypertension, and other diseases, thus playing an important role in the screening of metabolic diseases. This is coupled with hepatic steatosis and fibrosis which are characterized by excessive liver fat deposition. The aim of this study was to investigate the possible association between CMI and hepatic steatosis and liver fibrosis.

Methods: A cross-sectional investigation was conducted using the 2017-2020 National Health and Nutrition Examination Survey (NHANES) dataset to probe the relationship between CMI and hepatic steatosis and liver fibrosis, while multiple linear regression models were used to test the linear association between CMI and controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Smooth-fit curves and threshold effects analysis were used to describe the nonlinear relationships. Subgroup analyses were performed according to gender, age, body mass index (BMI), hypertension, diabetes, cardiovascular disease, and smoking status.

Results: A total of 3084 adults aged 18-80 years were included in this analysis, and after controlling for a variety of variables, there was a significant positive correlation between CMI and CAP [20.38 (16.27,24.49)]. When subgroups were analyzed, this positive correlation was found to be stronger in the female population than in the male (P for interaction = 0.0303). Furthermore, the association between CMI and CAP was nonlinear. Using multiple regression analysis, it was shown that the linear relationship between CMI and liver fibrosis was not significant [-0.09 (-0.47,0.29)].

Conclusions: The findings suggest that elevated CMI levels are associated with hepatic steatosis, but that CMI is not linked to liver fibrosis. Larger prospective investigations are needed to confirm our findings.

Introduction: Hepatocyte nuclear factor-1 beta (HNF1B) encodes a homeodomain-containing transcription factor, which is expressed early in embryogenesis and is involved in the development of multiple tissues and organs. HNF1B mutations cause complex multisystem disorders, with renal developmental disease and maturity onset diabetes of the young (HNF1B MODY), a rare cause of diabetes mellitus, being representative features.

Methods: We present two adolescent boys from different socioeconomic backgrounds who were diagnosed with genetically confirmed HNF1B MODY following hospitalization for diabetic ketoacidosis in the first case and after diagnostic work-up due to impaired glucose tolerance in the second case. Multisystem manifestations, including pancreatic hypoplasia and early-onset diabetes mellitus (DM), renal cysts, hypomagnesemia, hyperuricemia, liver and biliary impairment, genital tract malformations, and primary hyperparathyroidism were also present, strongly suggesting HNF1B MODY.

Results: The first patient was treated with subcutaneous insulin but was lost to follow-up due to social reasons. Conversely, early diagnosis in the second patient allowed the management of multisystem defects by a multidisciplinary team of experts. Moreover, manifestation of HNF1B MODY in the form of diabetic ketoacidosis was prevented and a structured diabetes training program has proven successful in regulating glycemic control, postponing the necessity for insulin treatment.

Conclusion: Early genetic work-up of patients with dysglycemia associated with a specific phenotype suggestive of HNF1B MODY is extremely important in the care of children and adolescents with diabetes since it ensures that early and optimal management is initiated, thereby preventing the onset of life-threatening diabetic ketoacidosis and other multisystem complications and/or comorbidities.