Erdheim-Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis with multiorgan involvement. Less than half of patients present with central nervous system (CNS) involvement, usually affecting the hypothalamic-pituitary axis (HPA), meninges, and brain parenchyma. CNS-only involvement is extremely rare and can lead to challenges in both diagnosis and management. Clinical course of the disease is varied, ranging from indolent to disabling and life-threatening forms. We report a case of a 55-year-old woman who presented with panhypopituitarism and central diabetes insipidus (DI) in 2016 and was found to have a rapidly enlarging suprasellar mass with non-specific radiologic features. Transcortical biopsy at the time of presentation was inconclusive, and high-dose corticosteroid therapy with close clinical follow-up was initiated. Over a period of six months, the patient had progressive disease with involvement of the hypothalamus and profound tracking cytotoxic edema. Surgical management in the form of endonasal, extended transsphenoidal resection was performed. Final pathology demonstrated a histiocytic neoplasm positive for BRAF V600E mutation (VE1) by immunohistochemistry, consistent with ECD. This case highlights the diagnostic challenges associated with ECD involving the CNS, particularly in anatomically complex regions where tissue sampling may be limited and histologic findings non-specific. While BRAF-targeted therapies were not routinely available at the time of the patient's presentation, identification of BRAF mutations has significant therapeutic implications, enabling the use of targeted therapies in patients with unresectable or progressive disease. This case underscores the importance of maintaining a high index of suspicion in patients presenting with central DI with indeterminate suprasellar lesions.

Primary adrenal insufficiency (PAI) is a severe and potentially life-threatening condition characterised by the inability of the adrenal cortex to produce enough glucocorticoids and/or mineralocorticoids. The clinical signs of PAI are primarily due to deficient steroid hormone synthesis and include weight loss, orthostatic hypotension secondary to dehydration, hyponatremia, hyperkalaemia, and hypoglycaemia. In the paediatric population, PAI is most commonly associated with inherited monogenic disorders, particularly enzyme deficiencies. X-linked adrenal hypoplasia congenita (AHC) is a rare condition caused by deletions or single-nucleotide variants in the NR0B1 (DAX1) gene, which encodes the DAX1 protein expressed in the adrenal cortex, gonads, hypothalamus and pituitary gland. Although molecular genetics has significantly expanded our understanding of the aetiology of PAI, clinical diagnosis remains challenging when the initial hormonal findings are atypical, often delaying recognition and treatment. Pathogenic variants of DAX1 can lead to a spectrum of phenotypes, ranging from isolated adrenal insufficiency (AI) to complex syndromic presentations combining AI with hypogonadotropic hypogonadism and impaired spermatogenesis. Here, we report a case of a male patient with AI due to a de novo pathogenic variant in the NR0B1 gene. Furthermore, we provide a non-systematic review of the available literature on the diagnostic challenges facing and clinical variability in AHC, with a particular focus on the paediatric population. This case highlights the importance of a stepwise, comprehensive diagnostic approach to suspected PAI, particularly when initial biochemical and genetic testing is inconclusive. Considering rare causes-such as NR0B1 pathogenic variants in men-can be crucial for establishing a definitive diagnosis, with significant implications for the management of patients and their families.

Background and Clinical Significance: Clear cell renal cell carcinoma (ccRCC) is notorious for its aggressiveness and great propensity to metastasize to virtually any organ, with a dismal five-year survival rate. While metastases from ccRCC typically occur in the lungs, lymph nodes, bones and liver, involvement of atypical locations such as the breast, pituitary gland and stomach is extremely rare. These unusual metastases can masquerade as primary tumours at their respective sites, posing significant diagnostic challenges. Case Presentation: Here, we describe three cases of metastatic ccRCC to unusual anatomical sites following nephrectomy: (1) a patient who presented with a suspicious left-sided breast mass and synchronous liver and lung metastases six months following the initial diagnosis of ccRCC; (2) a patient who presented with diplopia, found to have a pituitary lesion four months after nephrectomy; and (3) a patient with known pre-existing lung metastases who developed upper gastrointestinal bleeding one year post-nephrectomy, in whom oesophagogastroduodenoscopy (OGDS) revealed an 8 mm pedunculated gastric polyp. Histopathological examination following biopsies of these lesions showed compact nests and sheets of malignant cells with clear to eosinophilic cytoplasm and distinct membranes. Immunohistochemically, these malignant cells demonstrated CD10 immunopositivity, and were negative for CK7 and CK20, in keeping with the diagnosis of metastatic ccRCC. Conclusions: This case series illustrates the rare metastatic behaviour of ccRCC with its potential to spread to uncommon sites. Awareness of such presentations is crucial, particularly in patients with a known history of ccRCC, as these lesions may clinically and radiologically mimic primary tumours of the affected sites. Careful evaluation of its histomorphological features and judicious use of immunohistochemical panels, together with clinical and radiological correlations, is the key to arriving at an accurate diagnosis.

Background/Objectives: Sleep deprivation (SD) induces the accumulation of reactive oxygen species (ROS) in the intestine, causing inflammation in the intestine, thereby damaging the intestinal epithelial barrier function. As a traditional Chinese medicine, Dendrobium huoshanense (DHS) modulates intestinal flora, maintains the intestinal mucosal barrier, and promotes gastrointestinal motility and digestive secretion. However, the role and mechanism of DHS in improving SD-induced intestinal injury have not been fully studied. Methods: The SD model was established by subjecting rats to complete SD using a specialised SD instrument. Hematoxylin and eosin (HE) staining was performed to evaluate pathological injury in ileal tissues. Enzyme-linked immunosorbent assay (ELISA) and biochemical methods were used to quantify the main inflammatory cytokines, oxidative stress markers, and hypothalamic-pituitary-adrenal (HPA) axis activity. The expression levels of E-cadherin and Occludin proteins in the ileum tissue were analyzed by Western blotting. Additionally, the pH value of ileal mucus, unit secretion, water content, and dry matter weight were measured. Differential metabolites in rat ileum mucus were profiled using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Results: DHS alleviated the pathological injury of the ileum induced by SD. DHS reduced the levels of serotonin (5-HT), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), while increasing interleukin-10 (IL-10) levels, thereby attenuating systemic inflammatory responses. Furthermore, DHS decreased malondialdehyde (MDA) content and elevated glutathione (GSH) and superoxide dismutase (SOD) levels in ileal tissues. DHS also upregulated the protein expression of E-cadherin and Occludin in intestinal tissues. In addition, DHS decreased the pH of ileal mucus, promoted intestinal mucus secretion, and increased dry matter content, facilitating the restoration of the mucus barrier. DHS may alleviate SD-induced ileal injury by modulating steroid hormone biosynthesis. DHS decreased the levels of adrenocorticotropic hormone (ACTH), cortisol (CORT), and corticotropin-releasing hormone (CRH), indicating that DHS suppresses the abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis. Conclusions: In this study, a comprehensive multi-index evaluation showed that DHS could significantly improve the ileal injury caused by SD in rats. The mechanism involved regulating the balance of serum neurotransmitters and inflammatory factors, reducing oxidative stress in tissues, and improving the physicochemical properties of intestinal mucus. Metabolomic analysis further revealed that these protective effects may be mediated via the regulation of steroid hormone biosynthesis pathways and are associated with the inhibition of abnormal HPA axis activation.

The pituitary gland is an uncommon site of tumor metastasis and is predominantly associated with malignancies of the lung and breast. Metastatic involvement of the pituitary gland in lung cancer (LC) typically indicates advanced disease and is associated with poor prognosis and pituitary insufficiency, which often remains underdiagnosed and significantly affects quality of life and survival. We present four cases of pituitary metastasis (PM) originating from LC, characterized by distinct histological subtypes, variable timing from initial diagnosis, and diverse clinical manifestations. Clinical presentation was heterogeneous: two patients had involvement of both pituitary lobes with multiple pituitary hormone deficiencies, one had anterior lobe involvement with anterior pituitary deficiency following immune checkpoint inhibitor-associated hypophysitis, and one remained asymptomatic. Therapeutic approaches included partial surgical resection followed by radiotherapy in two patients and radiotherapy alone in the other two; all patients continued systemic antineoplastic therapy and received hormone replacement as indicated. Mean overall survival was 7.5 months. PM can occur across all histological subtypes of LC and typically signifies advanced disease with poor prognosis. Early identification and appropriate management of hypopituitarism may improve quality of life and clinical outcomes.

Thyroid Hormones (THs) are central regulators of energy metabolism, traditionally viewed as key determinants of Basal Metabolic Rate (BMR) and whole-body energy expenditure. Beyond their classical systemic effects, it is now evident that TH action is critically shaped by tissue-specific mechanisms that regulate intracellular hormone availability and signaling. These processes enable a fine-tuned and physiological state-specific control of metabolic activity. In this review, we synthesize current knowledge on the role of THs in energy homeostasis, with a particular focus on the mechanisms that govern local triiodothyronine (T3) signaling. We discuss how the integration of hormone transport, intracellular activation and inactivation by Deiodinases, and receptor-mediated transcriptional responses determine the intensity and timing of TH action in the target tissues. This spatiotemporal regulation supports metabolic flexibility, enabling coordinated control of substrate utilization, mitochondrial function, and energy expenditure under diverse physiological conditions. We further examine how TH signaling is modulated in response to key metabolic challenges, including physical exercise, changes in body weight and adiposity, and circadian rhythms. During exercise, local activation of TH signaling, particularly through type 2 Deiodinase (D2), facilitates mitochondrial adaptation, muscle remodeling, and improved metabolic efficiency. In the context of obesity, interactions between THs and adipose-derived signals such as leptin influence both central and peripheral pathways controlling energy balance, although these mechanisms may become impaired in leptin-resistant states. In parallel, circadian regulation of the Hypothalamic-Pituitary-Thyroid (HPT) axis and peripheral TH metabolism introduces an additional temporal dimension to metabolic control, allowing local tuning of TH action across the day. By integrating molecular, physiological, and systemic perspectives, this review highlights the concept of THs as context-dependent modulators of metabolic flexibility and underscores their potential as targets for interventions in metabolic disorders.

MLMarker is a machine learning tool that computes continuous tissue similarity scores for proteomics data, addressing the challenge of interpreting complex or sparse datasets. Trained on 34 healthy tissues, its Random Forest model generates probabilistic predictions with SHAP-based protein-level explanations. A penalty factor corrects for missing proteins, improving robustness for low-coverage samples. Across three public datasets, MLMarker revealed brain-like signatures in cerebral melanoma metastases, achieved high accuracy in a pan-cancer cohort, and identified brain and pituitary origins in biofluids. MLMarker provides an interpretable framework for tissue inference and hypothesis generation, available as a Python package and Streamlit app.

Pituitary neuroendocrine tumors (PitNETs) exhibit diverse biological behaviors, yet the metabolic determinants underlying lineage-specific characteristics remain poorly understood. This study characterized intratumoral steroid metabolite profiles in relation to transcription factor (TF)-defined lineages and radiological tumor features in 69 PitNET specimens obtained during transsphenoidal surgery between 2021 and 2023. Tumors were classified according to WHO 2022 TF-based criteria (SF-1, PIT-1, TPIT). Tissue concentrations of 14 steroid metabolites were quantified via liquid chromatography-tandem mass spectrometry, with associations evaluated using multivariable regression and partial least squares discriminant analysis (PLS-DA). Gonadotroph tumors (n=34) exhibited marked pregnenolone (PREG) elevation compared to other lineages (median 104.6 vs 1.2 ng/g, p<0.001, ε2=0.38). Corticotroph tumors (n=9) showed enrichment of glucocorticoid metabolites, particularly 11-deoxycortisol (adjusted p=0.002, ε2=0.30), while PIT-1 tumors (n=23) displayed intermediate levels. PLS-DA corroborated these patterns, with 11-deoxycortisol and pregnenolone emerging as the primary discriminators (68% total variance). Multivariable analysis confirmed SF-1 lineage as independently associated with PREG levels after adjusting for clinical and radiological covariates (adjusted R2=0.56, p<0.001). Inverse associations were observed between deoxycorticosterone/11-deoxycortisol and tumor expansion (r=-0.7 and r=-0.4, both p<0.001), and PREG correlated with cavernous sinus invasion within gonadotroph tumors (p=0.03). During follow-up (median 32-38 months), steroid profiles showed no association with clinical outcomes. TF-defined PitNET lineages exhibit distinct intratumoral steroid profiles reflecting intrinsic metabolic properties of lineage-specific cell populations, revealing a novel metabolic dimension to PitNET biology.

Erdheim-Chester disease is a rare, aggressive non-Langerhans cell histiocytosis characterized by multisystem infiltration of histiocytes. It commonly affects middle-aged men and is driven by acquired mutations in the MAPK signaling pathway. This essential cellular pathway relays extracellular signals to the nucleus and regulates cell proliferation and survival. We report the case of a 39-year-old male who presented with progressive, severe left-sided frontal and temporal headaches. Imaging revealed a symptomatic craniocervical mass, a nonsecreting pituitary lesion, and bilateral perinephric soft tissue infiltration extending throughout the retroperitoneum. Histopathologic evaluation demonstrated foamy histiocytes consistent with Erdheim-Chester disease, and molecular testing identified a BRAF mutation. Notably, no FDG-avid skeletal involvement was identified on available whole-body FDG PET/CT imaging, an uncommon feature in Erdheim-Chester disease. The patient was treated with the BRAF inhibitor vemurafenib, with dose reduction due to dermatologic toxicity, and subsequently tolerated therapy well. He has maintained a stable disease course at one-year follow-up. This report demonstrates the variable clinical manifestations of Erdheim-Chester disease and emphasizes the importance of molecular profiling in directing targeted therapeutic strategies.

A 32-year-old woman with panhypopituitarism following surgical resection, chemotherapy, and radiotherapy for a pituitary germinoma underwent assisted reproductive treatment. Management involved comprehensive hormone replacement therapy, ovulation induction with exogenous gonadotropins, in vitro fertilization (IVF), and thromboprophylaxis with low molecular weight heparin due to a diagnosed thrombophilia. A fresh embryo transfer resulted in a successful singleton pregnancy. The pregnancy progressed uneventfully and reached full term and a healthy neonate was delivered. This case highlights the feasibility of pregnancy in women with complex endocrine and thrombotic conditions and adds to the limited literature supporting IVF in women with significant hypothalamic-pituitary axis compromise.

Giant aneurysms are rare vascular anomalies that can induce symptoms through compression of neural structures. This report describes a case of a giant sellar aneurysm initially manifesting as diabetes insipidus (DI), challenging conventional diagnostic paradigms for sellar mass lesions. Although DI typically arises from antidiuretic hormone (ADH) deficiency, its presentation as the primary symptom of a giant sellar aneurysm is exceedingly uncommon. The distinctiveness of this case lies in the occurrence of DI, likely due to aneurysmal compression of the pituitary gland, underscoring the imperative to include aneurysms in the differential diagnosis of sellar lesions. Giant sellar aneurysms are frequently misdiagnosed as pituitary adenomas, particularly when atypical symptoms are present. Through multidisciplinary collaboration, this case was successfully managed, yielding valuable clinical insights. This report not only advances the understanding of giant sellar aneurysms but also provides a foundation for future research to mitigate misdiagnosis and enhance patient quality of life.

This study aimed to investigate the relationship between indices of thyroid hormone sensitivity and insulin resistance (IR) in euthyroid adults. In this cross-sectional study of 1393 euthyroid individuals from Beijing, participants were stratified into IR (Homeostatic Model Assessment for Insulin Resistance ≥ 2.5) and non-IR groups. We calculated indices of central thyroid hormone sensitivity: Thyroid Feedback Quantile-based Index, Thyrotroph T4 Resistance Index, and Thyroid-Stimulating Hormone Index and the peripheral free triiodothyronine/free thyroxine ratio. Multivariable logistic regression analyses were performed to determine their associations with IR, adjusting for key metabolic confounders including age, sex, body mass index, blood pressure, glycated hemoglobin, and lipids. A significant inverse association was observed between central thyroid hormone resistance and IR. After full adjustment, participants in the highest quartile of Thyroid Feedback Quantile-based Index, Thyrotroph T4 Resistance Index, and Thyroid-Stimulating Hormone Index had approximately 50% lower odds of IR. In contrast, a higher free triiodothyronine/free thyroxine ratio, indicating enhanced peripheral conversion, was positively associated with increased odds of IR. These relationships followed a threshold effect, being most pronounced in the extreme quartiles. Among euthyroid adults, reduced central sensitivity to thyroid hormones is independently associated with lower odds of IR, while increased peripheral conversion is linked to higher odds. This dissociation underscores the critical role of the hypothalamic-pituitary-thyroid axis set-point and peripheral hormone activation in metabolic health, suggesting these indices could be valuable for stratifying metabolic risk.