The adrenal glands each have two zones: the cortex and the medulla. Adenomas and carcinomas are tumours arising from cortex whereas pheochromocytomas and neuroblastomas arise from medulla. Hypoplasia, hyperplasia, cytomegaly, cysts, nodules and accessory tissue are some of the Non-neoplastic lesions of adrenal gland. Adrenal Incidentaloma (AI) or adrenal lesion discovered radiologically is very rare. We report a case of AI with the evidence of pheochromocytoma in 22-year-old female who presented with atypical symptom of left flank pain and constipation with a negative history for sweating, hypertension, chest pain, weight gain, excess hair growth on the body, acne, menstrual irregularity and normal Blood Pressure (BP) finding throughout the course of illness. Biochemical parameters for adrenal hormone were within normal limits. The mass was excised and sent for histopathological examination. The diagnosis of pheochromocytoma was made which was confirmed on immunohistochemistry. PASS scoring was done. IHC was strongly positive for synaptophysin and chromogranin and negative for calretinin and inhibin. Though pheochromocytoma has variable clinical manifestation and diagnosis is usually established by strong clinical suspicion, measurement of catecholamines and its metabolites along with radiographic localisation and histopathological confirmation of excised mass. Malignant potential of pheochromocytoma is only established by metastasis, long-term follow-up in patients after resection is necessary. Our case presents as a diagnostic challenge because of normal biochemical investigation and rare presentation. Surgery is recommended irrespective of size and normal biochemical study to prevent complication.

The effect of dehydroepiandrosterone on the vascular system: role of H2S/NO pathways.

Doege-Potter syndrome is a rare paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia (NICTH) caused by the excessive production of insulin-like growth factor-II (IGF-II), which occurs in less than 5% of solitary fibrous tumors (SFT). SFTs most commonly arise from the pleura, whereas primary omental origins are exceedingly rare. We report a case of Doege-Potter syndrome in an 83-year-old woman who presented with recurrent hypoglycemic episodes caused by a large primary omental SFT. Low serum insulin levels during hypoglycemia and normal adrenocortical hormone levels excluded common causes, such as insulinoma and adrenal insufficiency, and imaging findings raised the suspicion of SFT. Open surgical resection was performed, and the hypoglycemic symptoms resolved immediately postoperatively. Histopathological examination confirmed the diagnosis of high-risk SFTs. Western blot analysis of preoperative and postoperative serum samples demonstrated a postoperative reduction in tumor-derived high-molecular-weight IGF-II (big IGF-II), confirming its role as the cause of hypoglycemia. At 6 months postoperatively, no tumor or hypoglycemia recurrence was observed. This case highlights the importance of considering Doege-Potter syndrome in the differential diagnosis of intra-abdominal tumors that present with hypoglycemic episodes.

The endocannabinoid system (ECS) plays a major role in the central stress response. However, its role in the sympathetic nervous system remains poorly understood. Knowledge about the spatial distribution and function of endocannabinoids (eCBs) in adrenals is lacking. Here, we analysed lipid eCBs and alpha-hemoglobin-derived peptide endocannabinoids (pepcans) across distinct zones of the bovine adrenal gland and investigated the effects of RVD-hemopressin (pepcan-12) and anandamide (AEA) on steroidogenesis. To challenge the hypothesis that pepcans are produced in the adrenal medulla, bovine chromaffin granules (CGs) were isolated and pepcans, eCBs, amino acids and neurotransmitters quantified by targeted metabolomics. To label CGs for flow cytometry, we synthesized the novel vesicular monoamine transporter 2 (VMAT2)-targeting probe CV-28 which specifically stained large dense-core vesicles. While the classical eCBs were present in CGs, pepcans were absent, indicating that these peptides are not released via CGs from chromaffin cells. Interestingly, besides neurotransmitters also N-linoleoylethanolamine (LEA) and L-leucine were markedly enriched in CGs. Overall, N-acylethanolamines including AEA, RVD-hemopressin and its precursor pepcan-23 were predominant in the cortex while 2-arachidonoylglycerol (2-AG) was found in the medulla. This intriguing distribution was supported by the differential expression of serine hydrolases visualized by activity-based protein profiling (ABPP). In NCI-H295R cells, AEA and RVD-hemopressin increase progesterone and reduce testosterone secretion. In basal state, the effect of AEA on increased progesterone secretion was potentiated by RVD-hemopressin. Overall, this study illuminates the CG metabolome and gives impetus to the further investigation of ECS-mediated regulation of adrenal hormone production and adrenal physiology.

Catecholamines are classically viewed as neuronal transmitters and adrenal hormones; however, accumulating evidence demonstrates that sources other than nerve fibres and adrenal medulla play a fundamental role in local organ regulation. Physiological paradoxes, such as preserved organ function after denervation or transplantation, challenge a purely autonomic paradigm and point to intrinsic, tissue-based catecholaminergic control mechanisms. This review critically examines and integrates the emerging concept of endothelium- and epithelium-derived catecholamines, with a particular emphasis on the cardiovascular, genitourinary and respiratory systems. Experimental evidence supporting the biosynthesis, release, metabolism and functional roles of novel endogenous catecholamines, including 6-nitrodopamine (6-ND) and 6-cyanodopamine (6-CYD), is discussed. Endothelium-derived 6-ND and 6-CYD emerges as highly potent and long-lasting modulators of cardiovascular function, exerting positive chronotropic and inotropic effects, whilst uniquely potentiating the actions of classical catecholamines. In vascular tissues, including corpus cavernosum, 6-ND selectively antagonises dopamine-induced contractile responses and promotes smooth muscle relaxation through mechanisms largely independent of the canonical sGC-cGMP pathway. Notably, agarose-coupled 6-ND identified cyclase-associated proteins (CAPs) in cardiomyocyte membranes, linking 6-ND signalling to adenylyl cyclase regulation. In parallel, epithelium-derived catecholamines, including 6-ND and 6-CYD, have been identified throughout the genitourinary and respiratory systems, where they modulate smooth muscle tone. This review proposes a revised framework of autonomic regulation in which neural signalling is integrated with locally produced catecholamines acting in a paracrine and autocrine manner, underscoring their relevance as endogenous regulators and potential therapeutic targets.

The Rice’s whale (Balaenoptera ricei) is a recently described species of baleen whale found in the Gulf of Mexico. With fewer than 50 adults remaining, the Rice’s whale is the most endangered baleen whale species. Analyses of reproductive and adrenal hormones promote the understanding of reproductive cycles and stress physiology in this rare and poorly understood species. Baleen plates contain steroid hormones stored throughout the period of baleen growth and have been used for continuous, multi-year retrospective assessment of the reproductive and glucocorticoid history of individual whales. We measured progesterone, testosterone, cortisol, and corticosterone in baleen plates of seven individual Rice’s whales (four males — one of which was the holotype — and three females), including two individuals believed to have died from starvation and one known to have been killed by ship strike. Baleen powder was obtained by drilling every 1 cm (~15–30 day intervals) from the base of the plates to the distal end. Hormones were quantified with enzyme immunoassay kits, and presence of the specific hormones was further confirmed with analytical chemistry. All assays passed validation assays for Rice’s whale baleen extract. In the two individuals that likely died of starvation, all four steroid hormones show increases in the most recently grown baleen, a pattern observed in other baleen whales in cases of prolonged illness or injury before death. A female with a known recent pregnancy had a sustained elevation of progesterone spanning the majority of her plate, indicating that baleen analysis in this species can detect recent pregnancies. No evidence of annual testosterone cycles was noted in three adult males, suggesting that this subtropical species might not have strong seasonal reproduction, which is atypical for baleen whales. Thus, we conclude that baleen hormone analysis can be used to clarify life history patterns in this critically endangered species.

Relationship between systolic blood pressure (SBP) and adrenocortical hormones in 10 normotensive (NT) control dogs and 84 ill dogs with clinical features of hypercortisolism but normal post-adrenocorticotropic hormone (ACTH) cortisol was studied. Doppler blood pressure classified dogs as NT (<140 mm Hg), prehypertensive (PHT; 140-159 mm Hg), or hypertensive (HT; ≥160 mm Hg). Serum cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, and aldosterone were measured before and 1-hr after intramuscular (IM) ACTH (250 μg/dog). Ill dogs (40 NT, 29 PHT, and 15 HT) were significantly (P ≤ .04) older, smaller, and received higher ACTH dose/kg versus controls. ACTH dose/kg was not significantly associated with post-ACTH hormone concentrations. Compared to controls, baseline hormones were significantly (P ≤ .05) higher in ill dogs, except progesterone and 17-hydroxyprogesterone in HT and aldosterone in PHT dogs; significantly higher post-ACTH 17-hydroxyprogesterone and androstenedione (P ≤ .01) in NT and PHT dogs, and aldosterone (P = .03) in HT dogs occurred. No significant differences in baseline or post-ACTH hormones existed between SBP groups. Only 3/10 controls had all hormones within reference limits. Findings suggest risk for PHT and HT in ill dogs with increased noncortisol adrenocortical hormones, and show inexplicably increased adrenocortical sex hormones in NT healthy dogs.

Sex and adrenal hormone alteration in Ecuadorian adolescents with home and school proximity to floriculture crop area.

Background: Adrenal insufficiency (AI) is a potentially life-threatening condition characterized by deficient production of adrenal hormones. While global guidelines for AI management are well-established, the epidemiology, etiology, diagnostic landscape, and outcomes of AI in the Kingdom of Saudi Arabia (KSA) remain poorly characterized due to the absence of national data and the region's unique genetic, environmental, and healthcare context. Objective: This comprehensive review aims to synthesize and critically evaluate the available literature on the prevalence, etiology, diagnostic challenges, management strategies, and long-term outcomes of AI in the Saudi population, with the goal of identifying knowledge gaps and charting a path toward national evidence-based guidelines. Methods: A narrative review approach was employed, synthesizing data from international literature and available regional studies, including case series, single-center retrospective analyses, and expert opinion from the Saudi endocrine community. Results: The available evidence reveals a distinct profile of AI in Saudi Arabia. The prevalence remains unknown due to the lack of a national registry, but it is likely underestimated. The etiological spectrum is uniquely shaped by a high rate of consanguinity, resulting in a significant burden of genetic forms such as congenital adrenal hyperplasia (CAH) and rare monogenic disorders. Tuberculous Addison's disease persists as a relevant cause, while autoimmune adrenalitis is increasingly recognized but likely underdiagnosed. Diagnostic pathways are hampered by a lack of Saudi-specific reference ranges for cortisol assays, inconsistent access to dynamic testing (ACTH stimulation tests), and significant disparities in healthcare infrastructure between urban and rural regions. Management practices are highly variable, with no standardized national protocols for glucocorticoid selection, dosing, or patient education. Consequently, preventable adrenal crises remain a significant threat, compounded by the unique environmental challenge of extreme heat and the demands of religious practices such as Hajj and Ramadan fasting. Long-term outcomes are compromised by a high prevalence of metabolic complications (obesity, diabetes), osteoporosis, and impaired quality of life. Major knowledge gaps persist in all domains, from basic epidemiology to the effectiveness of culturally tailored interventions. Conclusion: The management of AI in Saudi Arabia is at a critical juncture. The current reliance on extrapolated international data is inadequate for the nation's unique population. There is an urgent and compelling need for a coordinated national strategy. The establishment of a multi-center patient registry is the foundational priority. This must be followed by targeted research to establish local diagnostic standards, characterize the full etiological spectrum using advanced genetic and autoantibody testing, and evaluate long-term outcomes. The ultimate goal is the development and dissemination of evidence-based, Saudi-specific national clinical practice guidelines, developed under the auspices of the Saudi Society of Endocrinology and Metabolism, to standardize and elevate the quality of care, reduce the burden of adrenal crises, and improve the long-term health and quality of life for all patients living with adrenal insufficiency in the Kingdom.

The adrenal gland plays a pivotal role in blood pressure regulation through the secretion of corticosteroids and catecholamines. While its contribution to secondary hypertension is well recognized, its role in essential hypertension remains incompletely understood. This study aimed to investigate whether structural and functional adrenal alterations precede or accompany the development of hypertension and to define the temporal relationship between adrenal remodeling and blood pressure elevation. We systematically examined adrenal morphology, hormone secretion, enzyme expression, ultrastructure, and mitochondrial function in spontaneously hypertensive rats and normotensive Wistar-Kyoto controls across key developmental stages from ages 4 to 24 weeks. Spontaneously hypertensive rats developed progressive hypertension beginning at age 8 weeks, accompanied by disrupted circadian blood pressure rhythms. Notably, levels of aldosterone, corticosterone, and catecholamines were elevated in spontaneously hypertensive rats as early as 4 weeks, before overt hypertension. These hormonal changes were associated with zona glomerulosa thickening, increased Ki-67-positive proliferative activity, and upregulation of steroidogenic and catecholaminergic enzymes (aldosterone synthase, 11β-hydroxylase, and tyrosine hydroxylase). Ultrastructural remodeling included dense-core granule accumulation, smooth endoplasmic reticulum expansion, mitochondrial swelling, and cristae disruption. Functionally, adrenal ATP production and mitochondrial membrane potential were reduced, while oxidative stress intensified, as shown by decreased superoxide dismutase and glutathione and increased malondialdehyde levels. These findings suggest that adrenal hyperfunction and structural remodeling preceded and contributed to the onset and progression of hypertension in spontaneously hypertensive rats. This study highlights the adrenal gland as a dynamic and early modulator in essential hypertension and a promising target for therapeutic intervention.

ABSTRACTIntroductionEctopic adrenocortical adenomas that produce adrenal hormones and mimic renal cell carcinoma are extremely rare.Case PresentationA 49‐year‐old woman underwent partial nephrectomy of the upper pole of the kidney following a clinical diagnosis of renal cell carcinoma. The tumor, initially suspected to be renal cell carcinoma, was definitively diagnosed as an ectopic adrenocortical adenoma producing adrenocortical hormones, which was removed surgically. Postoperatively, she developed tertiary adrenal insufficiency. After hydrocortisone therapy, the patient's symptoms gradually improved, and laboratory results also showed improvement. Retrospectively, the patient exhibited signs of Cushing's syndrome.ConclusionIf the patient's body habitus suggests Cushing's syndrome, it is important to conduct an endocrinological evaluation before surgery. Additionally, early postoperative monitoring and glucocorticoid supplementation should be performed if necessary.

A considerable proportion of life-time depression and anxiety emerges during childhood and adolescence. Some research has shown that pubertal maturity is associated with depression and anxiety. While most research has focused on gonadarche, the earlier phase of adrenarche remains less explored and understood. We aimed to examine the effects of timing and tempo of adrenarche on incidence and chronicity of depression and anxiety during adolescence. Data were from the Child to Adult Transition Study (CATS), a longitudinal population-based cohort from Melbourne, Australia. CATS recruited Grade 3 students in 2012, who were followed up annually across adolescence. Adrenarchal timing was modelled as the level of adrenal hormones (DHEA, DHEAS, and testosterone) relative to peers at age 9 and tempo as the adrenal hormone progression rate relative to peers between 9 and 12. Incidence and chronicity of common mental disorders were defined using self-reported depressive and anxiety symptoms collected annually from age 12-18. G-computation was used to adjust for confounding. Missing data were handled via multiple imputation using chained equations. The study comprised 667 females and 572 males. Depression incidence (76 % females, 44 % males) and chronicity (34 % females, 7 % males) and anxiety incidence (69 % females, 36 % males) and chronicity (29 % females, 7 % males) were more common in female adolescents than males. Regardless of using DHEA, DHEAS, or testosterone as the index for adrenarche, the risk ratios for the association between timing and tempo of adrenarche and the incidence and chronicity of depression or anxiety were close to null and 95 % confidence intervals were inconclusive. This study did not identify a meaningful effect of adrenarchal timing and tempo on depression and anxiety in adolescents, suggesting that individual differences in adrenarche may not influence risk for later significant mental health difficulties.

Congenital Adrenal Hyperplasia (CAH) is a group of disorders characterized by impaired adrenal steroid hormone synthesis, with a wide spectrum of clinical manifestations. The prognosis of CAH depends on factors, such as clinical phenotype, treatment and management. To analyze the factors influencing the quality of life in children with CAH. This retrospective study included 30 CAH patients divided into good prognosis (n=13) and poor prognosis (n=17) groups. Clinical characteristics, genetic mutations, treatment compliance, medication regimens and complications were analyzed by t-tests and logistic regression. The good prognosis group presented better compliance (92.31% vs. 47.06%, P=0.017) and hormonal control (84.62% vs. 35.29%, P=0.01). The prevalence of the salt-wasting (SW) type of CAH was higher in the poor prognosis group (70.59% vs. 23.08%, P=0.038), while the simple virilizing (SV) type was higher in the good prognosis group (53.85% vs. 17.65%). The poor prognosis group received a higher hydrocortisone dose (16±3mg/m2/day) compared to the good prognosis group (12±4mg/m2/day, P=0.025). Complications such as hypertension (P=0.017), hyperpigmentation (P=0.026) and urinary incontinence (P=0.017) were more prevalent in the poor prognosis group. In children with CAH, the quality of life is significantly affected by treatment compliance, hormonal control, and the presence of complications.

PurposeFentanyl is a synthetic opioid analgesic widely used in perioperative medicine due to its high analgesic potency and short duration of action. Previous studies suggest that the analgesic and anesthetic effects of fentanyl may be associated with endogenous catecholamine levels. This study aimed to evaluate the relationship between fentanyl’s analgesic potency and anesthesia duration and endogenous levels of adrenaline (ADR) and noradrenaline (NDR) in rats, as well as changes in oxidative stress and inflammation markers including malondialdehyde (MDA), total glutathione (tGSH), and interleukin-6 (IL-6).Patients and MethodsThree groups of six rats each were formed: an intact group receiving fentanyl, an intact group treated with metyrosine, and an adrenalectomized group receiving fentanyl. Fentanyl was administered at doses of 2, 15, 30, and 75 µg/kg, and anesthesia duration was recorded following intraperitoneal injection. Analgesic activity was assessed by measuring pain threshold using the paw pressure method, and immobility in the supine position was evaluated as an observational parameter. ADR, NDR, MDA, tGSH, and IL-6 levels were biochemically measured in blood and tissue samples.ResultsFentanyl produced analgesic effects in all experimental groups. However, no distinct anesthetic effect sufficient for surgical procedures was observed. Although the durations of immobility in the supine position were recorded, these observations were not evaluated as a direct measure of anesthetic duration. Different doses of fentanyl did not lead to significant alterations in oxidative stress parameters, antioxidant capacity, or anti-inflammatory cytokine levels across the groups.ConclusionIn conclusion, although the analgesic effect of fentanyl increased in a dose-dependent manner, it was found to be independent of serum ADR and NDR levels. High-dose fentanyl (75 µg/kg) did not induce anesthesia and did not significantly affect oxidative stress markers (MDA, tGSH) or IL-6 levels. The increase in MDA and the decrease in tGSH observed in the absence of adrenal hormones support their indirect antioxidant role. Overall, the findings indicate that fentanyl modulates catecholamine responses depending on dose and hormonal status, while its analgesic effect appears to be primarily mediated through µ-opioid receptor activation.

This prospective observational study was carried out to evaluate the response of adrenocortical hormones (cortisol and aldosterone) to head-up tilt (HUT)-induced vasovagal syncope in relation to hemodynamic changes. Blood samples from 79 patients (48 women and 31 men, age 19-73years) who underwent the HUT test were analyzed for serum aldosterone and cortisol. On the basis of their response, patients were categorized into two groups: 50 HUT-positive (HUT+) and 29 HUT-negative (HUT-) patients. HUT+ patients exhibited significantly lower baseline aldosterone levels compared with HUT- patients (203.1 ± 78.8 versus 266.2 ± 76.3pg/ml, p = 0.0009). Similarly, aldosterone levels after the HUT test were lower in the HUT+ as compared with the HUT- group (249.5 ± 101.3 versus 351.4 ± 98.11pg/ml, p < 0.0001). However, serum cortisol showed no significant differences between groups. Aldosterone increased in response to HUT in both groups. Aldosterone positively correlated with systolic and diastolic blood pressure, as well as heart rate. Integration of aldosterone with clinical assessment and additional laboratory tests may improve diagnostic accuracy and risk stratification. The results demonstrate significantly lower serum aldosterone concentrations in HUT+ patients at baseline and after HUT test in comparison with HUT- patients. Moreover, aldosterone levels positively correlated with systolic and diastolic blood pressure (BP). However, serum cortisol levels did not discriminate HUT+ from HUT- patients.

Adrenal insufficiency (AI) is an uncommon but potentially fatal endocrine disorder caused by inadequate secretion of adrenal hormones. Because the presenting symptoms are often vague, diagnosis may be delayed, especially in developing countries. This study aimed to analyze the clinical characteristics, etiological factors, and laboratory findings of patients diagnosed with adrenal insufficiency at a tertiary care center. A retrospective review of 22 confirmed cases was conducted over a period of two years. Diagnosis was established based on early morning serum cortisol levels below 3 mcg/dL or levels between 3-15 mcg/dL with an inadequate response to the cosyntropin stimulation test. The gender distribution was equal among the study participants. Primary adrenal insufficiency accounted for approximately 41% of cases and was observed predominantly among female patients. Autoimmune disease represented the most common cause of primary adrenal insufficiency, whereas tuberculosis contributed significantly to both primary and secondary adrenal insufficiency. The most frequent presenting manifestations included fatigue, dizziness, vomiting, and postural hypotension. Early identification through clinical suspicion and electrolyte screening may improve outcomes and prevent adrenal crisis.

BACKGROUND: Advanced stages of cardiovascular-kidney-metabolic syndrome (CKMs) are associated with a markedly increased risk of mortality. However, the individual and combined effects of cortisol (COR) and aldosterone (ALD) on CKMs remain unclear. We aimed to investigate their separate and joint associations with CKMs stages and major components. METHOD: This cross-sectional study included 8,781 participants to investigate the separate and joint associations of COR and ALD with CKMs and its components, using linear regression, logistic regression, restricted cubic spline analyses (RCS), interaction analyses, and stratified analyses. RESULT: Beyond associations with CKMs staging-related continuous indicators and key components, higher quartiles of COR (Q4 vs. Q1, OR = 1.56, 95%CI, 1.26–1.95) and ALD (Q4 vs. Q1, OR = 1.33, 95%CI, 1.07–1.64) were independently associated with higher odds of advanced CKMs. RCS revealed significant nonlinear associations between log-transformed COR and ALD levels and advanced CKMs. A significant additive interaction was observed between COR and ALD on advanced CKMs (RERI = 0.94, 95%CI, 0.35–1.52; AP = 0.41, 95%CI, 0.30–0.52; S = 3.75, 95%CI, 1.84–7.63). Co-exposure analyses showed a 46% higher odds of advanced CKMs in the “High COR, High ALD” group (OR = 1.46, 95%CI, 1.19–1.80, P < 0.001) compared to the “Low COR, Low ALD” group, with consistent trends across most subgroups. CONCLUSION: Both COR and ALD show significant associations with advanced CKMs. The joint assessment of COR and ALD improves the identification of high-risk individuals, underscoring the value of adrenal hormone profiling in CKMs risk stratification.

Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18-45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs <15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P <0.001 for seven hormones; P =0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35-45-yr (3.05 nmol/L) and 25-34-yr (3.09 nmol/L) age groups than in the 18-24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35-45-yr and 25-34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Cushing's disease and autoimmune thyroid disorders in women: Impacts on fertility, pregnancy, and menopause.

Endocrine-disrupting chemicals have traditionally been conceptualized as organic compounds such as bisphenols, phthalates, and persistent organic pollutants. However, a growing body of experimental, epidemiological, and mechanistic evidence demonstrates that metal ions represent a distinct and underappreciated class of endocrine disruptors. Unlike classical endocrine disruptors that primarily act through receptor agonism or antagonism, metals interfere with endocrine regulation through redox imbalance, displacement of essential cofactors, modulation of hormone synthesis and metabolism, epigenetic remodeling, and disruption of hormone receptor signaling cascades. Metals such as cadmium, arsenic, lead, mercury, chromium, nickel, manganese, cobalt, and vanadium have been shown to alter thyroid, reproductive, adrenal, pancreatic, and steroid hormone systems at environmentally relevant concentrations. Their endocrine effects are often nonlinear, sex-specific, developmentally sensitive, and potentiated by oxidative stress and inflammation. Importantly, metals may act as endocrine disruptors even when systemic concentrations fall below traditional toxicity thresholds, reflecting their capacity to target hormone-sensitive tissues and signaling networks. This review synthesizes current journal evidence on metal-induced endocrine disruption, emphasizing molecular mechanisms, tissue-specific vulnerabilities, redox-endocrine crosstalk, developmental programming, and disease outcomes. We also examine challenges in exposure assessment, the importance of metal speciation and bioavailability, and emerging biomarkers of endocrine disruption. Finally, we discuss regulatory and public health implications, arguing for a paradigm shift that integrates metal chemistry into endocrine risk assessment frameworks.