Endocrines

Background: Plastic pollution driven by human activities has become a critical global issue for human health. A growing literature demonstrates that micro- and nanoplastics (MNPs) contain endocrine-disrupting chemicals (EDCs) and other harmful compounds that enter the body easily, acting as agonists or antagonists for a wide range of hormonal receptors, and promoting endocrine toxicity. Endocrine disruption induced by MNPs occurs through the aberrant activation/inhibition of different signaling pathways that in addition to directly interfering with hormonal balances, trigger apoptosis, oxidative stress, and inflammation in endocrine cells. However, to date, the molecular mechanisms of these contaminants remain not completely elucidated. Furthermore, given the unanimous consensus on the negative impact of MNPs on human health, several methodologies have been developed to detect MNPs and contaminants not only in the environment but also in biological fluids and human tissues. Results: This review comprehensively summarizes the emerging experimental and clinical evidence explaining the mechanisms underlying the toxicity related to chronic plastic pollution in relation to the endocrine system. In addition, the review illustrates the new methodological approaches to detect MNPs in human biological samples, highlighting that employing complementary methods enables the precise characterization and quantification of MNPs. Conclusions: Future studies employing experimental, epidemiological, epigenetic, and multi-omics approaches are essential for understanding the short and long-term effects of MNPs on endocrine glands and developing effective strategies to mitigate their impact on human health. Full article

Background: Oncocytic adenomas (OAs) of the thyroid, previously referred to as Hürthle cell adenomas, are uncommon tumors, particularly in pediatric populations, where they represent a minority of thyroid nodules. Due to their rarity and the potential difficulty in distinguishing benign from malignant forms on cytology, these adenomas present unique diagnostic and management challenges. Here, we report a pediatric case of a large OA of the thyroid, managed with surgical resection following inconclusive fine-needle aspiration (FNA) results. Case Presentation: A 13-year-old girl presented with an enlarging thyroid nodule. An ultrasound examination showed a large (26 × 16 mm), solid, isoechoic nodule with a hypoechoic halo. The FNA findings were inconclusive, indicating a follicular neoplasm with oncocytic features, classified as Bethesda IV. The patient underwent a hemithyroidectomy, and a histopathological examination confirmed an encapsulated OA without evidence of capsular or vascular invasion. The postoperative recovery was uneventful, and follow-up assessments showed no recurrence. Conclusions: OAs in pediatric patients are rare and may pose diagnostic challenges. This case highlights the importance of a comprehensive approach, including surgical resection, for definitive diagnoses in cases where FNA results are inconclusive. Further studies are warranted to establish guidelines for the management of oncocytic thyroid neoplasms in pediatric patients, as well as to understand their clinical behavior in this population. Full article

Background: Vitamin D is essential for neonatal health, with maternal vitamin D status crucial in fetal development and neonatal outcomes. During pregnancy, vitamin D is transferred to the fetus via the placenta, forming an initial reserve. Postnatally, neonates rely on maternal levels and supplementation due to limited sunlight exposure and immature skin synthesis. Objectives: This review evaluates neonatal vitamin D deficiency’s causes and clinical consequences, emphasizing its impact on newborn and infant health. Results: Maternal vitamin D levels strongly correlate with neonatal 25(OH)D concentrations, influencing birth weight, bone development, and overall health. Supplementation during pregnancy reduces the risk of severe deficiencies and rickets, particularly in exclusively breastfed infants who require daily supplementation of 400 IU. Formula-fed infants typically meet requirements through fortified formulas. Preterm infants are at a higher risk of complications like osteopenia and rickets, with mixed evidence on the effectiveness of higher supplementation doses. Vitamin D is critical in skeletal development, immune function, and protection against respiratory infections such as bronchiolitis and pneumonia. Deficiency is associated with respiratory distress syndrome (RDS), atopic dermatitis, and impaired bone mineralization due to reduced placental calcium transport. Conclusions: Vitamin D deficiency during pregnancy and infancy has significant clinical implications, including impaired skeletal and immune development. Maternal and neonatal supplementations are critical to prevent deficiencies, particularly in high-risk groups such as preterm and breastfed infants. Targeted strategies are essential to improve neonatal health outcomes and prevent complications. Full article

Background/Objectives: Hyperprolinemia is a rare autosomal recessive disorder with two distinct types: I (HPI) and II (HPII). The clinical presentation varies widely, with some individuals remaining asymptomatic and others exhibiting neurological, renal, or auditory defects and seizures. However, it has never been associated with hypoglycemia. The present case report describes a 5-year and 6/12-month-old boy with HPII, with an episode of severe hypoglycemia and Pituitary Stalk Interruption Syndrome (PSIS) with isolated growth hormone (GH) deficiency (GHD). Results: The boy was presented to the Department of Pediatric Endocrinology for routine thyroid function assessment due to hypothyroidism. He was diagnosed with HPII at the age of 2 years old during an investigation for seizure episodes. Clinically, the boy exhibited attention deficit hyperactivity disorder (ADHD) and a reduction in growth velocity (1.6 cm/year). Hematological and biochemical analyses were within the reference range. Hormone profiling revealed lower-than-expected insulin-like growth factor-1 (IGF-1) concentrations, prompting a GH stimulation test, which, in turn, revealed GHD. Brain magnetic resonance imaging (MRI) showed features consistent with PSIS. Noteworthy is the occurrence of severe hypoglycemia during an episode of gastroenteritis, leading to hospitalization, eventually attributed to GHD. Following the exogenous administration of recombinant human GH, the boy exhibited increased growth velocity, with no adverse events over the follow-up period. Conclusions: Hyperprolinemia is a rare condition; in this context, the occurrence of severe hypoglycemia accompanied by a low growth velocity poses a challenge for the clinical pediatrician. Furthermore, the coexistence of hyperprolinemia and PSIS has never been reported in the literature thus far. Full article

This review examines the relationship between cholesterol and bone resorption. It seeks to elucidate the dependence of bone turnover on cholesterol metabolism by highlighting the common inhibitory effect of both statins and nitrogen-containing bisphosphonates on cholesterol biosynthesis and bone resorption as well as on bone density. Moreover, this paper also discusses the epidemiologic studies of the effects of nitrogen-containing bisphosphonates on all-cause and cardiovascular mortality using the latest publications to reinforce the relationship between bone resorption and cardiovascular disease. This review will also discuss the role of lipoproteins in supplying cholesterol to both osteoclasts and osteoblasts and the effects of doing so on both of these bone cells and their precursors. As inflammation is a major factor in both bone resorption and cardiovascular calcification, this article will also discuss the role of cholesterol in triggering inflammatory responses. Finally, this paper will raise questions unanswered to date that bear on the relationship between lipid metabolism, bone resorption, and cardiovascular disease. Full article

Background: This paper briefly reviews the most important endocrine features of primary ovarian insufficiency (POI) and shows their relevance for the diagnosis and treatment of this condition. Introduction: Endocrine disturbances in POI cause problems for both the fertility and general health status of the affected women. Both subfertility and infertility result from the depletion of growing ovarian follicles which, in its turn, is the causative factor of hypoestrogenism; this is responsible for most of the general health problems affecting women. Method: Search of literature. Results and conclusion: A combination of high-serum follicle-stimulating hormone (FSH) and low 17β-estradiol (E2) concentrations is a key feature characterizing POI and is the decisive element for POI diagnosis. However, an in-depth search for possible genetic and non-genetic causes is important for adequate counseling regarding prevention and early intervention. The treatment of general health problems, based on correcting hypoestrogenism through hormone replacement therapy (HRT), is relatively easy. On the other hand, resolving infertility is a much more difficult task, and oocyte donation is the only really efficient instrument. Fertility preservation is a suitable alternative in patients with early POI diagnosis, in whom some viable follicles are still present in the ovaries. In patients who refuse oocyte donation, intraovarian injection of autologous platelet-rich plasma and in vitro activation of dormant follicles may be considered. Other innovative treatments, such as stem cell therapies or nuclear transfer, are currently under investigation. Full article

Background/Objectives: Chronic somatic diseases are significant risk factors for the development of mental disorders. Type 1 diabetes mellitus (T1D) is the most common chronic endocrine pathology in children. Treatment requires nutrition management, physical activity, lifelong insulin therapy, and proper self-monitoring of blood glucose. It is complicated and therefore may result in a variety of psychosocial problems for children, adolescents, and their families. Considering the rapidly growing incidence of type 1 diabetes in the pediatric population of Latvia, it is important to detect and prevent the risks of anxiety and depression in families with children suffering from type 1 diabetes. Methods: This was a quantitative interdisciplinary cross-sectional study to determine the prevalence of anxiety and depression in adolescents with T1D and their parents. Two tools were used to detect the presence of symptoms of anxiety and depression: the Generalized Anxiety Disorder Scale-7 (GAD-7) and the Patient Health Questionnaire 9 (PHQ-9) scale. Results: A total of 812 respondents were eligible for screening. Anxiety and depression symptoms were seen significantly more frequently in the study group than in the control group. The study found negative effects of anxiety and depression on the compensation of diabetes. Conclusions: Adolescents with type 1 diabetes and their parents are more predisposed to anxiety and depression symptoms than somatic healthy children and their parents, thus worsening disease control and prognosis. Full article

Precocious puberty (PP) is characterized by the early onset of secondary sexual characteristics and accelerated growth, which often result in compromised adult height (AH). Central precocious puberty (CPP), a subset of PP, is treated with gonadotropin-releasing hormone analogs (GnRHa) to suppress premature hormonal activation and delay epiphyseal closure, thereby preserving height potential. The present review examined the effects of GnRHa on AH outcomes in girls with idiopathic CPP. Although AH is greater with GnRHa therapy than without it, the treatment does not consistently restore the patient’s genetic potential. The benefits of the treatment are most evident in girls in whom idiopathic CPP is diagnosed before 6 years of age and they achieve a height gain of 4.5–14.1 cm, which is unattainable without treatment. However, the treatment of older children (ages 6–8) shows conflicting results, with the AH outcome varying among previous reports. In particular, slowly progressive CPP is known to have a favorable height prognosis even without treatment. Another factor influencing the AH prognosis is the timing of GnRHa discontinuation; the best time to discontinue GnRHa therapy for the best AH outcome is reportedly the bone age of approximately 12 years. In conclusion, although GnRHa therapy significantly improves the AH, especially in early-onset CPP, its effectiveness is uncertain in borderline or late-onset cases. Further research is required to formulate more precise criteria for patient selection and treatment discontinuation to optimize height outcome in girls with idiopathic CPP. Full article

Background/Objectives: Understanding sex-based differences in both the pathophysiology and clinical presentation of diseases is necessary to improve health care towards precision medicine. The endocrine system is deeply involved in human health, and endocrine diseases may be influenced by steroidal hormone exposure. Thyroid nodular disease and differentiated thyroid cancer, in particular, show a high prevalence in the female sex; however, little is known about sex-related differences in risk factors and clinical presentation. This study aims to assess whether morphological differences, which can be detected by ultrasound examination, can be related to sex in order to refine diagnostic approaches and oncological risk classification. Methods: A retrospective observational study on 1355 ultrasound images of thyroid nodules obtained from 2017 to 2020 at a single university center was conducted. The images were reviewed by a single observer blinded to the patient’s sex and the cytological nature of the nodules. The qualitative description, size, anatomical location and oncological risk classification were assessed. Results: A taller-than-wide shape (anteroposterior/craniocaudal axis ratio > 1) was found to be more frequent in men than in women (6.7% vs. 3.6%, p = 0.027); the nodular volume was significantly larger in males (p << 0.01) than in females. Significant tropism for the upper lobe and isthmus was described in women (26% vs. 16.5%, p = 0.011) and for medium–lower thyroid lobes in men (83.5% vs. 73.8%, p = 0.011). Background thyroiditis was more common in women, while the number of cytological diagnoses of malignant or likely malignant nodules was higher than expected in men (9% vs. 6%, p = 0.01). Conclusions: Thyroid nodules show different distributions, in terms of a larger volume, more frequent taller-than-wide shape and lobular caudal location, in men vs. women. These results should be confirmed by further investigations, and the underlying mechanism should be clarified. However, our explorative research is of interest due to its novelty and possible future clinical implications. Full article

Objectives: This study investigated the effects of the menstrual cycle phases on cortisol levels before and after a maximal incremental exercise test in women with and without premenstrual syndrome (PMS). Methods: Nineteen healthy, active and eumenorrheic women completed five maximal incremental exercise tests; three of those were performed at specific phases of the menstrual cycle (i.e., menses, follicular, and luteal). The participants were allocated into two groups according to the presence of PMS (n = 11) or absence of PMS (NO-PMS, n = 8). Samples of blood were collected before and after each experimental test. A three-way ANOVA was conducted to compare the differences between menstrual cycle phases (i.e., menses, follicular, and luteal), time (before and after) and groups (PMS and NO-PMS). Results: The results demonstrated an alteration of cortisol across the menstrual cycle, with cortisol levels significantly (p < 0.05) higher during the follicular phase (mean = 11.0 µg/dL, CI95% = 9.1, 12.9) compared to the luteal phase (mean = 8.6 µg/dL, CI95% = 7.2, 10.4) in the PMS and NO-PMS groups. There was no difference (p > 0.05) in cortisol levels for groups or time. Conclusions: This study observed significant cortisol fluctuations across the menstrual cycle phases in women with and without PMS. Future studies should consider alternative maximal incremental test protocols and incorporate a more comprehensive hormonal profile to provide a deeper physiological understanding of this population. Full article

Introduction: Early-life neurological and inflammatory disorders significantly affect long-term cognitive, social, and emotional development. The ‘Developmental Origins of Health and Disease’ hypothesis states that an adverse intrauterine environment may predispose offspring to chronic health conditions due to altered growth and development. Factors measured in umbilical cord blood can provide information about the status of the in utero environment during development. Evidence indicates that umbilical cord blood adipokines, namely leptin and adiponectin, may influence fetal programming and could be useful in predicting offspring health outcomes. Leptin and adiponectin are crucial in energy homeostasis, immune response, and placental function, and some studies suggest that altered concentrations may increase the risk of developing inflammatory and neurological disorders in later life. Further, limited studies have demonstrated sex-specific differences in adipokine concentrations and disease risk. Conclusions: Understanding the role of umbilical cord blood adipokines in fetal programming could offer new insights into early risk prediction and intervention strategies, promoting better health outcomes for children at risk of neurological and inflammatory diseases due to an adverse maternal environment during pregnancy. Full article

Background/Objectives: Dienogest 0.5 mg tablets (DNG0.5) taken twice daily (1 mg/day) are more effective than cyclic low-dose estrogen/progestin/combined oral contraceptive (LEP/COC) in ameliorating dysmenorrhea pain and are recommended for dysmenorrhea treatment in Japan. However, their efficacy has not been directly compared with continuous LEP/COC regimens. Here, we evaluated the effectiveness of DNG0.5 compared to Yazflex^® (YZF), a continuous LEP, in treating dysmenorrhea. Methods: The efficacy of DNG0.5 in treating dysmenorrhea was compared retrospectively with that of Yazflex, the longest continuously administered LEP/COC available in Japan. Results: The improvement rates of dysmenorrhea scores at 3 and 6 months post-treatment were 59.1% and 66.4% in the LEP group (n = 113) and 88.1% and 96.4% in the DNG0.5 group (n = 125), respectively. The complete resolution rate of dysmenorrhea at 6 months was 88.0% in the DNG0.5 group and 23.9% in the LEP group. These findings indicate that DNG0.5 was significantly more effective than LEP (p < 0.01). DNG0.5 exerted an early pain-suppressing effect, which continued to increase thereafter. Furthermore, the presence of endometrial polyps, uterine fibroids, or adenomyosis, which are risk factors for irregular genital bleeding, was examined. Among these, endometrial polyps were particularly more likely to cause bleeding and potentially reduce the effect of DNG0.5; however, even with these three risk factors, DNG0.5 was more effective than LEP in reducing pain. Conclusions: Dienogest was more effective than LEP in managing dysmenorrhea, even at a dosage of 0.5 mg twice daily. However, factors affecting irregular vaginal bleeding should be considered when prescribing DNG0.5. Full article

Stress responses enable vertebrates to adapt to environmental challenges while maintaining homeostasis. Zebrafish larvae are a valuable model for studying stress regulation due to their genetic accessibility and rapid development. This review examines the integration of zebrafish larvae with water vortex protocols to investigate hypothalamic–pituitary–interrenal (HPI) axis functionality during early development, advancing stress research while adhering to the 3Rs principle. Key publications are reviewed to discuss the potential of water vortices in zebrafish larvae for studying stress responses. These purely physical stressors exploit the innate positive rheotropism of developing zebrafish, offering precise control over timing and strength while avoiding confounding factors associated with chemical or biological interventions. The approach enables reproducible assessments of stress responses. The reviewed publications show advances in understanding cortisol response dynamics, glucocorticoid feedback, and early-life stress-induced changes in HPI axis function. Key findings include detailed cortisol patterns after acute stress, rapid glucocorticoid receptor-mediated feedback regulating cortisol levels, developmental shifts in HPI axis sensitivity, and reduced cortisol reactivity following early-life challenge (ELC). Vortex-driven ELC affects cortisol regulation, neuropeptide expression in the nucleus preopticus, and stress-related gene transcription. Combining zebrafish larvae and vortex protocols provides a robust and innovative platform for investigating stress biology. This approach leverages active, demanding behaviour to study stress mechanisms under controlled conditions, yielding insights with broad applications across vertebrate models while supporting the 3Rs principle. Future studies can build on these findings to address unresolved questions in stress regulation and enhance our understanding of adaptive physiological mechanisms. Full article

A balanced diet and regular physical activity are essential for maintaining musculoskeletal health. Key nutrients such as calcium, vitamin D, and protein are especially important for preventing falls and fractures. While the benefits of these nutrients are well-established, other dietary components have not been studied as extensively. For instance, vegetables, which are rich in nutrients vital for muscle and bone health, play a crucial role in preventing falls and fractures. Over recent decades, a great emphasis has been given to the combinations of nutrients and foods in dietary patterns that may have synergistic or antagonistic effects. Despite the challenges in researching the impact of nutrition and physical activity on musculoskeletal health due to the extensive heterogeneity of the results, healthcare professionals should continue to promote healthy eating and regular physical activity, and these principles should be emphasized in public health initiatives. Ultimately, a sufficient and balanced diet, abundant in plant-based foods and low in processed or discretionary foods, along with consistent physical activity, remains the most effective strategy for the prevention of musculoskeletal issues. This article aims to review the updated literature of recent years on the links between nutrition and physical activity with bone and skeletal muscle health. Full article

Background/Objectives: In contrast to endochondral bone healing, the process of intramembranous bone regeneration is poorly understood. This limits our ability to repair and regenerate the craniofacial skeleton to either correct deformity or optimally heal tissues following injury. While there are several preclinical models of intramembranous regeneration within the craniofacial skeleton, some are not load bearing and others are technically challenging. The goal of this pilot study is therefore to describe a simple method for induction of cortical defects within the mandible that does not involve compounding injury to the surrounding tissues. Methods: Single cortex defects were generated in the mandible body of 8-week-old male and female mice. The extent of bone regeneration within the defect was characterized at days 0, 3, 14, and 28 following defect generation via micro-computed tomography and histology. Conclusions: Observed healing was predictable and reproducible and resulted in intramembranous bone formation. This model will help aid the understanding of intramembranous bone healing in load bearing bones (e.g., mandible) within the craniofacial skeleton Full article

Background/Objectives: Primary aldosteronism (PA) is associated with a higher cardiovascular disease (CVD) risk than essential hypertension (EH) and is mainly driven by the excess of aldosterone production. Studies suggest a relationship between aldosterone and parathormone (PTH) homeostasis. Excessive PTH levels seem to also be associated with CVD. The impact of PTH levels on CVD in PA patients has not been totally elucidated. We evaluated the associations of PTH levels and hyperparathyroidism with CVD in patients with PA and EH. Methods: A cross-sectional study of a group of 67 patients was carried out, with 35 patients with PA and a control group of 32 patients with EH. We looked at the presence of CVD and data on the factors associated with its presence were collected and analyzed. A binary logistic regression was performed to assess multivariate relationships. Results: PA patients had higher PTH levels compared to the EH group (64 ± 42 vs. 39 ± 13 pg/mL, p = 0.004). Significative differences in PTH levels were observed according to the grade of hypertension in PA patients. Both hyperparathyroidism and CVD were found at higher rates in patients with PA. Patients with CVD exhibited significantly higher PAC values than patients without it (41.4 ± 18 vs. 21.4 ± 12 ng/dL, p < 0.001). Patients with hyperparathyroidism had higher rates of CVD than patients without it (58 vs. 24%, p = 0.018). Patients with PA and hyperparathyroidism manifested a higher rate of CVD than patients without this combination. A logistic regression showed an independent association of PAC and hyperparathyroidism with the presence of CVD in the total cohort. Conclusions: Hyperparathyroidism is associated with a higher probability of CVD both in PA and EH. The presence of hyperparathyroidism in PA seems to exacerbate the risk of CVD, with higher PTH levels associated with higher grades of hypertension in this cohort. Full article

Alex Vermeulen (1927–2023) was a leading Belgian endocrinologist whose name will forever remain linked to testosterone and androgen metabolism. As a dedicated scientist and clinician, he made seminal contributions to endocrinology throughout his career. These included the development of chromatography and radioimmunoassays of steroid hormones. His work also focused on the biological significance and metabolism of corticosteroids and androgens, and he defined key concepts in the role of steroid hormones in the human menstrual cycle, pregnancy, and menopause. His love for math, endocrinology, and problem-solving led to a formula for the estimation of free testosterone in serum, which has not been improved upon to date and is still in use worldwide. He contributed to enhancing our understanding of the role that male sex hormones may play in a variety of clinical problems in endocrinology, including bone health, type 2 diabetes, and, especially, endocrine function in aging males. Alex Vermeulen literally was “a giant in endocrinology”. Beyond his scientific contributions, Vermeulen was a wise and engaging mentor, a Renaissance man, and an aficionado of the finer things in life. He owned an eclectic choice of modern artworks, all of which he bequeathed to the Ghent Museum of Fine Arts, thus significantly enhancing the museum’s art patrimony. Full article

Gestational diabetes mellitus (GDM) is a prevalent condition impacting approximately 14% of pregnancies globally, posing significant health risks to mother and child. This review explores the role of diet, physical activity (PA), and sedentary behavior (SB) in preventing and managing GDM. Consumption of fish, fruits, vegetables, and legumes, and adherence to healthy dietary patterns, like the Mediterranean diet, are linked to lower GDM risk. Higher levels of PA and structured exercise consistently show protective effects against GDM, enhancing glucose metabolism and insulin sensitivity. Conversely, SB is a risk factor for GDM; prolonged sedentary periods detrimentally affect glucose regulation. The review emphasizes the need for a combined approach integrating healthy dietary habits, regular PA, and reduced SB to mitigate GDM risk effectively. Future research should prioritize standardized assessment methods and personalized lifestyle interventions to optimize GDM prevention strategies, ultimately informing public health guidelines and clinical recommendations for healthier pregnancies and better long-term outcomes. Full article

The endocrine system relies on complex cell signaling and epigenetic processes to adjust to the body’s needs. However, stressors such as climate change and heat can disrupt the endocrine system. This study aims to collect and systematically review evidence from publications exploring how climate change impacts endocrine laboratory parameters. The review process included developing research questions, defining inclusion and exclusion criteria, conducting database searches, screening and selecting relevant publications, collecting and analyzing data, interpreting the findings, and drawing conclusions. This review identified multiple endocrine parameters linked to climate change and the mechanisms by which various stressors disrupt endocrine function. Climate change, especially heat stress, affects the production and levels of key hormones. The mechanisms underlying the disruption of key hormones are also explored in this paper. This review provides a clear overview of how climate change influences endocrine parameters and outlines the processes underlying stress-triggered endocrine disruption. Full article