Endocrine journal最新文献

Twin studies offer a powerful approach for disentangling genetic and environmental influences on human traits. By comparing monozygotic twins with identical genetic makeup, researchers can more accurately identify the environmental contributions to phenotypic variation. Structural equation modeling provides a theoretical framework for estimating the relative contributions of additive genetic effects, shared environmental factors, and unique environmental influences. This model allows researchers to determine the most suitable parameters for explaining the observed data in twin populations. In addition, bioinformatic tools enable in-depth analyses of phenotypically discordant monozygotic twin pairs, helping to uncover both environmental sensitivities and genetic predispositions. This review examines the advantages and limitations of twin study methodologies in research on endocrine disorders, lipid metabolism, and thyroid function. Findings from twin cohorts have enhanced our understanding of heritability, environmental modifiers, and epigenetic factors, offering valuable insights into gene-environment interactions. Overall, twin studies remain critical tools in genetics, endocrinology, and obesity research. In the future, genetic information may enable the development of optimal personalized environments, ultimately providing valuable insights that contribute to physical, mental, and social well-being throughout the lifespan.

Hypercalcemia is an oncologic metabolic emergency in cancer patients, primarily caused by local osteolytic hypercalcemia and humoral hypercalcemia of malignancy. Hormones associated with oncologic metabolic emergency include parathyroid hormone and parathyroid hormone-related peptide (PTHrP), but 1,25-dihydroxyvitamin D (1,25(OH)₂D) is rarely the cause. We report the case of an 87-year-old man with hypercalcemic crisis owing to 1,25(OH)₂D overproduction from a high-grade intranasal non-intestinal-type adenocarcinoma. 1,25(OH)₂D and corrected Ca levels normalized after tumor resection and did not re-elevate subsequently. Serum PTH was suppressed and PTHrP not detected, suggesting the hypercalcemia was not due to the PTH pathway. Immunohistochemistry for CYP27B1, a key enzyme that converts 25-hydroxyvitamin D (25(OH)D) to 1,25(OH)₂D, showed positivity in the cytosol of about 20% of tumor cells, but only about 1% of the macrophages. On the other hand, CYP24A1, a 1,25(OH)₂D-degrading enzyme, was diffusely expressed in the cytosol of about 80% of tumor cells. These findings may suggest overproduction of CYP27B1 mRNA. The balance between synthesis and degradation of 1,25(OH)₂D in tumor tissue is thought to be implicated in the development of 1,25(OH)₂D-producing solid tumors. Further case accumulation and studies will be needed to confirm this hypothesis. Nonetheless, in diagnosing 1,25(OH)₂D-producing solid tumors, it is important to evaluate not only CYP27B1 expression but also CYP24A1.

Body mass index (BMI) can be used to define obesity-a global health concern and a risk factor for various complications. However, it does not accurately represent body composition. Furthermore, a correlation between BMI and the frequency of comorbidities in patients with acromegaly, a condition that affects body composition, remains unclear. This study aimed to investigate the association between BMI and frequency of metabolic complications in patients with acromegaly. This single-center, retrospective, cross-sectional study included patients with untreated acromegaly. The patients were divided into two groups: BMI <25 kg/m² and BMI ≥25 kg/m², and the prevalence of metabolic complications was compared between the groups. Of the 66 patients, the BMI <25 kg/m² group included 39 patients (BMI: 22.7 [20.0-24.1], insulin-like growth factor-1 [IGF-1] standard deviation score [SDS]: 6.7 [4.7-7.9]), and the BMI ≥25 kg/m² group included 27 patients (BMI: 27.6 [25.9-29.8], IGF-1 [SDS]: 8.5 [6.0-10.2]). The prevalence of metabolic complications did not differ between the groups, except for a lower incidence of fatty liver in the BMI <25 kg/m² group (8% vs. 29%, p = 0.04). In these patients, BMI was positively correlated with serum IGF-1 levels (r = 0.29, p = 0.01). Our results suggest that BMI is not useful in predicting metabolic complications in individuals with acromegaly, except for fatty liver disease.

Immune cells undergo substantial metabolic rewiring during differentiation and activation to satisfy the energy demands of an appropriate immune response. Lipids serve as energy sources and function as essential components of cellular membranes and signaling molecules. Recent studies have revealed that reprogramming of lipid metabolism, including lipid uptake, de novo synthesis of cholesterol and fatty acids, and fatty acid oxidation, leads to dynamic alterations in the quantity and quality of intracellular lipids. These metabolic changes play crucial roles in shaping immune cell functions, promoting anti-inflammatory responses, and facilitating the resolution of inflammation. Conversely, dysregulation of lipid metabolism can result in immune cell dysfunction, contributing to the onset and progression of chronic inflammatory diseases such as autoimmune diseases and metabolic syndrome. Notably, cholesterol and fatty acid metabolism influence immune responses by modulating membrane lipid composition and downstream inflammatory signaling. Given these insights, targeting lipid metabolism has emerged as a promising therapeutic approach for restoring immune homeostasis and treating chronic inflammatory diseases.

Rising nicotinamide adenine dinucleotide (NAD⁺) levels mitigate the onset and progression of age-related diseases including metabolic disorders. Several studies have demonstrated that NAD⁺ levels can be efficiently replenished via nicotinamide mononucleotide (NMN) intake and thereby prevent metabolic disorders. However, the acute effects of NMN administration on metabolism remain unclear. We observed metabolic dynamics after a single bolus injection of NMN. Sirt1 and Nampt mRNA levels were increased in the liver suggesting that intracellular NAD⁺ increased after injection. During OGTT, glucose tolerance and insulin secretion did not change significantly in response to NMN administration, while during ITT, increased insulin sensitivity was observed in muscle. NMN administration decreased serum non-esterified free fatty acid (NEFA) concentrations, which would presumably be responsible for the increased muscle insulin sensitivity. Furthermore, NMN administration reduced the respiratory quotient, confirming that NMN promotes utilization of lipids as an energy source. Our data demonstrate acute effects of NMN on metabolism and raise the possibility of NMN as a treatment for metabolic disorders.

Hypercalcemia, a common electrolyte imbalance, requires accurate differential diagnosis to guide appropriate management. PTH-dependent hypercalcemia, predominantly caused by primary hyperparathyroidism (PHPT) and rarely by familial hypocalciuric hypercalcemia (FHH)-mainly due to heterozygous loss-of-function mutations in the CASR gene encoding the calcium-sensing receptor (CaSR)-now includes acquired hypocalciuric hypercalcemia (AHH) as an emerging disease entity. Initially identified as analogous to FHH, AHH was characterized by blocking antibodies targeting the CaSR. However, our research has identified unique autoantibodies, termed biased antibodies, that paradoxically regulate signaling by enhancing Gq activity while suppressing Gi activity. Investigating their mechanisms has not only provided insights into specific treatments for AHH but also suggested novel activation mechanisms and binding sites of the CaSR, offering a fresh perspective on the regulation of PTH secretion. In clinical practice, recognizing AHH is crucial. A key diagnostic feature is fluctuating serum calcium levels, making a wait-and-see approach viable for mild hypercalcemia. Conversely, hypercalcemic crises necessitate immediate diagnostic and therapeutic interventions. The most important diagnostic clue to differentiate AHH from PHPT is hypermagnesemia. Additionally, AHH is less likely to involve AVP resistance (i.e., nephrogenic diabetes insipidus) and acute kidney injury (AKI), owing to preserved medullary hyperosmolarity and minimal interference with AVP signaling. Finally, a relatively low PTH level serves as another distinguishing feature. Based on these observations, we propose a novel diagnostic guide for PTH-dependent hypercalcemia. We anticipate that this guide will help identify previously undiagnosed AHH cases in routine practice, enabling timely and effective management of this rare condition.

The hypothalamic-pituitary-gonadal (HPG) axis is primarily regulated by kisspeptin neurons. In addition, activin and inhibin within the central nervous system might contribute to the regulation of the HPG axis because they are expressed near kisspeptin and gonadotropin-releasing hormone (GnRH) neurons. We investigated the effects of inhibin and activin within the hypothalamus in the estradiol (E2)-induced negative feedback mechanism. Inhibin α subunit gene within the posterior hypothalamus in female rats increased after ovariectomy, and this increase was completely suppressed by E2 supplementation. In contrast, inhibin βA subunit decreased after ovariectomy and this reduction was recovered by E2. In ovary-intact rats, E2 reduced inhibin α subunit and increased inhibin βA expression within the hypothalamus. In the rHypoE8 and GT1-7 hypothalamic cell models, E2 stimulation increased inhibin α subunit gene expression. Activin and inhibin A increased Kiss1 gene expression in GT1-7 cells, while inhibin B reduced it. Kisspeptin increased inhibin α subunit expression in rHypoE8 cells, GT1-7 cells, and the mHypoA55 hypothalamic KNDy neuron cell model. Our findings suggest that the expression of inhibin subunits, especially inhibin α, could be increased by E2 in hypothalamic cells and that kisspeptin, inhibin, and activin mutually influence each other under the actions of E2, but their regulation might be controlled mainly by kisspeptin neurons in vivo. Although the effects of activin and inhibin on Kiss1 gene expression varied depending on the hypothalamic cell model examined, intracerebral inhibin and activin might have potential roles in the E2-induced negative feedback mechanism under the influence of kisspeptin neurons.

Sarcopenia is a prevalent condition among elderly individuals and is characterized by the loss of skeletal muscle mass accompanied by physical dysfunction. In older adults, decreased insulin-like growth factor 1 (IGF-1) has been implicated as a contributing factor to the development of sarcopenia. Children with chronic conditions associated with sarcopenia are rarely evaluated. This study aimed to evaluate muscle mass using cross-sectional computed tomography (CT) images in pediatric patients with acute leukemia and patients without chronic diseases, and to examine the relationship between skeletal muscle mass volume and various growth parameters in children with acute leukemia. The study included 44 pediatric patients (age: 1-15 years) with newly diagnosed acute leukemia (B-cell lymphoblastic leukemia, n = 30; T-cell lymphoblastic leukemia, n = 5; other types, n = 9) who underwent abdominal CT before treatment initiation. Among these, 15 underwent abdominal CT after induction therapy. The total psoas muscle area at lumbar vertebrae levels 3-4, body height, weight, and IGF-1 levels were retrospectively analyzed. The total psoas muscle area significantly decreased after induction therapy in all 15 patients. A significant correlation was observed between the rate of change in total psoas muscle area and IGF-1 levels (n = 9; p < 0.05; r = -0.84). However, no correlation was identified between the rate of change in total psoas muscle area and height velocity before and after treatment. In conclusion, skeletal muscle mass decreased following treatment initiation in pediatric patients with acute leukemia. The degree of muscle mass loss was more severe in patients with higher pre-treatment IGF-1 levels.

Iodine is an essential trace element crucial for thyroid hormone synthesis. While iodine deficiency has been recognized as a global health concern due to its association with hypothyroidism, certain regions may face challenges related to excessive iodine intake. The impact of excessive iodine intake during the perinatal period on higher brain functions remains unclear. To address this gap, we conducted a study using an animal model to elucidate the effects of perinatal iodine excess on higher brain functions. Dams received specific drinking water (control, ×20 iodine (KIO₃ 37.4 mg/L), ×200 iodine (KIO₃ 374 mg/L)) from prior to mating until weaning. Pups received the corresponding drinking water until the end of the experiment. Behavior test battery was utilized to investigate the behavioral outcomes associated with perinatal iodine excess. Excessive iodine intake increased learning acquisition in females whereas it decreased exploration of social novelty in males. Conversely, mRNA levels of several genes related to learning and memory in the hippocampus were rarely affected. Overall, the present study highlights the consequences of excessive iodine intake during developmental periods. However, these effects were mild and varied by sex, warranting the further investigation.

Total ankle arthroplasty (TAA) is an effective treatment for end-stage ankle arthritis. However, the procedure is not without risks due to various factors, one of which is diabetes mellitus (DM). Currently, it remains uncertain whether diabetes is a risk factor for increased adverse outcomes and complications following total ankle arthroplasty. Therefore, this study aims to investigate the impact of diabetes on patients undergoing TAA. A systematic search was conducted for relevant studies published before December 2023 in PubMed, Embase, Cochrane Library, and Web of Science. The study assessed demographic data, postoperative complications, and functional outcomes of diabetic and non-diabetic patients following primary TAA. The Newcastle-Ottawa Scale (NOS) was used to evaluate study quality, and meta-analysis was performed using Stata 15.1, with forest plots generated for each variable. This meta-analysis included 14 studies involving 20,557 patients (3,847 with diabetes and 16,710 without). Compared to non-diabetic patients, those with diabetes had higher revision rates, postoperative infection rates, and 30-day readmission rates, longer hospital stays, and significantly different improvements in the SF-36 Physical Component Summary (PCS) score. Diabetic patients undergoing TAA are more likely to require revision surgery, face a higher risk of surgical site infections or periprosthetic joint infections, and experience increased hospital stay and 30-day readmission rates. These findings are crucial for guiding perioperative management of diabetic patients undergoing TAA and for explaining the associated surgical risks to patients.