Purpose: The aims of this study were to evaluate the feasibility of time-restricted eating (TRE) in patients with Cushing's disease (CD) and assess its effects on body weight and metabolic parameters. Methods: Twelve CD patients in remission with obesity were enrolled in a TRE program restricting food intake to 10:00-18:00. Anthropometric data, glycemic and lipid profiles, and circadian cortisol secretion were assessed at baseline and post-intervention. Serum cortisol levels were measured at multiple time points to evaluate diurnal patterns. Results: Nine patients completed the study. Over the 12-week period, participants showed a significant reduction in body weight, with median values decreasing from 93.8 kg [83.1-106.5] to 82.6 kg [76.9-100.3] (p = 0.011). Body mass index (BMI) also declined from 37.6 kg/m[2] [34.2-39.7] to 34.4 kg/m[2] [32.6-38.3] (p = 0.012). No statistically significant changes were observed in fasting glucose, HbA1c, or lipid parameters. Notably, 24 h urinary free cortisol levels significantly decreased (p = 0.01), and serum cortisol showed a downward trend at all measured time points, with the most pronounced reductions during mid-day and evening hours. No clinical or biochemical evidence of CD relapse was observed during the 12-month follow-up. Conclusions: Time-restricted eating is a feasible and well-tolerated dietary approach for patients with CD in remission, promoting weight loss and modest improvements in metabolic markers and cortisol rhythmicity.

Objective: ZhiZhu Kuanzhong (ZZKZ) capsule, a Chinese herbal extract, is extensively employed for the clinical management of functional dyspepsia (FD) in China. This study aimed to elucidate the therapeutic efficacy and underlying mechanisms of ZZKZ on the co-morbidity of anxiety and depression of FD. Methods: The FD model was established in Sprague-Dawley rats via neonatal gastric irritation with 0.1% iodoacetamide. Subsequently, FD rats were gavaged with ZZKZ or fluoxetine. Depression-like behaviors were evaluated using the sucrose preference test (SPT) and forced swimming test (FST), while anxiety-like behaviors were assessed via light-dark box (LDB) and open field tests (OFTs). Network pharmacology and molecular docking were conducted to explore the mechanisms of ZZKZ's action. Hippocampal levels of monoamine neurotransmitters and monoaminergic system components were evaluated by HPLC and RT-qPCR, respectively. Serum concentrations of HPA axis hormones were determined by ELISA. Results: ZZKZ administration reversed the deficits in body weight gain and food intake in FD rats. Behaviorally, ZZKZ increased sucrose consumption in SPT and prolonged swimming duration in FST, and it increased duration and entries into the central zone in OFT. According to the prediction of network pharmacology, ZZKZ treatment elevated hippocampal levels of 5-HT/NE/DA, increased expression of TPH2/TH, and decreased expression of MAOA/SERT in FD rats. Molecular docking further confirmed high-affinity binding between core ingredients of ZZKZ and TPH2/TH/MAOA/SERT. Moreover, ZZKZ administration attenuated the stress-induced elevation of serum CRH/ACTH/CORT. Conclusions: ZZKZ effectively ameliorates the disordered gut-brain interaction and mitigates anxiety-like and depression-like behaviors, which might be modulated by the hippocampal monoaminergic system and hypothalamic-pituitary-adrenal axis response.

Bone is a highly dynamic and purposefully organized structure that remodels constantly throughout adult life. Disordered bone remodeling, in which resorption of old bone by osteoclasts exceeds new bone formation by osteoblasts, results in bone loss, which, in turn, is associated with debilitating conditions, including osteoporosis and metastatic bone disease. The past decade has revealed vital new insights into the role of the central nervous system in skeletal regulation. These studies have led to a better understanding of physiologic circuitry, enabled us to revisit disease pathophysiology, and in doing so, prompted the creation of candidate therapeutics. The central neural control of bone is exerted through two arms - an amplitude-modulated (AM) neurohormonal arm that relies on changes in circulating levels of anterior and posterior pituitary hormones, which act on bone directly, and a frequency-modulated (FM) arm that arises from changes in the firing frequency of sympathetic, parasympathetic, and sensory nerves that innervate bone. Here, we review the medical consequences arising from the dysfunction of the AM and FM arms, as well as studies that have unmasked promising therapeutic targets.

To describe a rare case of pituitary metastasis arising from mandibular squamous cell carcinoma (SCC), in which pituitary-related symptoms represented the first clinical evidence of distant metastatic disease. Case report and targeted literature review. A patient with previously treated mandibular SCC presented with new-onset visual disturbance and endocrine dysfunction. Imaging, endocrine evaluation, and histopathologic confirmation were performed. Published reports of pituitary metastases from head and neck SCC were reviewed. Magnetic resonance imaging demonstrated an enhancing sellar mass with suprasellar extension and infundibular thickening concerning for metastatic disease. Endoscopic endonasal biopsy confirmed metastatic keratinizing SCC consistent with the primary mandibular tumor. No other distant metastases were identified on staging imaging. Visual field deficits and partial hypopituitarism were the sole presenting manifestations of metastatic spread. Pituitary metastasis from mandibular SCC is exceptionally rare and may present as the earliest sign of distant disease.

Dual ectopic secretion of adrenocorticotropic hormone (ACTH) and growth hormone-releasing hormone (GHRH) by a single neuroendocrine tumor (NET) is extremely rare. We report a 43-year-old woman presenting with acral enlargement, weight gain, hyperpigmentation, and proximal muscle weakness. Laboratory evaluation revealed elevated cortisol, ACTH, and insulin-like growth factor 1 (IGF-1), consistent with concurrent Cushing syndrome and acromegaly. Imaging demonstrated a left hilar mass, and biopsy confirmed a pulmonary NET with immunohistochemical (IHC) positivity for synaptophysin and chromogranin. Pituitary magnetic resonance imaging (MRI) showed diffuse hyperplasia, suggesting trophic stimulation rather than a primary pituitary adenoma. Surgical resection resulted in normalization of hormone levels, marked clinical improvement, and regression of pituitary enlargement. Although direct histologic confirmation of tumor-derived GHRH was unavailable, the reversible pituitary hyperplasia favors ectopic GHRH-mediated stimulation rather than primary ectopic GH secretion. IHC of the resected tumor demonstrated ACTH positivity, supporting ectopic ACTH secretion. This case highlights the importance of recognizing dual hormone-secreting NETs in patients presenting with overlapping endocrine syndromes, as early detection and complete resection can lead to remission.

Exosomes are increasingly recognized as critical mediators of intercellular communication within the central nervous system and along the brain-periphery axis, with emerging relevance to the pathophysiology of depression. These nanoscale extracellular vesicles transport bioactive cargo-including microRNAs (miRNAs), proteins, lipids, and metabolites-that can modulate neuroinflammatory signaling, synaptic remodeling, hypothalamic-pituitary-adrenal (HPA) axis dynamics, and gut-brain communication. Converging evidence from human and preclinical studies suggests that alterations in circulating and brain-derived exosomal cargo are associated with major depressive disorder (MDD) and secondary depression following neurological insults such as traumatic brain injury (TBI), implicating shared inflammatory and synaptic pathways alongside distinct etiological drivers. Circulating neuron-enriched exosomes carrying miRNAs such as miR-16 and miR-124 have been proposed as minimally invasive biomarkers reflecting brain-relevant molecular alterations. However, most human data remain cross-sectional and associative, with limited longitudinal replication and incomplete validation of cellular origin. Therapeutically, mesenchymal stem cell (MSC)-derived exosomes demonstrate antidepressant-like effects in rodent models through modulation of microglial activation, enhancement of synaptic plasticity, and attenuation of neuroinflammatory cascades. Engineered exosomes further offer a potential platform for targeted delivery of anti-inflammatory or neuroplasticity-enhancing cargo. Induced pluripotent stem cell (iPSC)-derived exosomes represent a potentially scalable and standardizable therapeutic platform. Despite this promise, substantial barriers impede clinical translation. Isolation workflows-including ultracentrifugation, size-exclusion chromatography, and immunoaffinity capture-vary in yield, purity, and reproducibility, complicating cross-cohort comparability. Moreover, definitive attribution of vesicle origin in peripheral biofluids remains technically constrained, and standardized reporting frameworks are inconsistently applied. Advances in multi-omics profiling, high-throughput sequencing, mass spectrometry, and spatially resolved molecular analyses may improve mechanistic resolution and biomarker robustness. Collectively, exosome research in depression resides at an early but rapidly evolving translational stage. Rigorous methodological standardization, longitudinal cohort validation, and mechanistic dissection across primary and injury-related depression will be essential to determine whether exosome-based diagnostics and therapeutics can fulfill their potential within precision psychiatry.

Functional hypogonadism in men is a syndrome characterized by low testosterone levels and clinical signs of hypogonadism without organic disease of the hypothalamus-pituitary-gonadal axis. It is most often caused by obesity, diabetes type 2, exogenous steroid abuse, excessive physical exercise, opioid use, co-occurring diseases, and is most prevalent among middle-aged and older men as so-called late-onset hypogonadism. It seems that the most important epidemiological factor causing functional hypogonadism is excess adipose tissue. Obesity is currently one of the most important public health problems and its prevalence is higher in men than in women. Complications of obesity include not only cardiovascular diseases or type 2 diabetes mellitus, but also lead to decreased testosterone levels, reduced libido and erectile dysfunctions, and impaired fertility in men. These disorders in men with obesity are associated with decreased gonadotropins and testosterone secretion due to hyperinsulinemia, hyperleptinemia, chronic inflammation and oxidative stress. Currently, it seems that an important complication of obesity is the deterioration of semen parameters (sperm concentration, motility, and morphology) and reduced fertility. Theoretically, obesity-related functional hypogonadism in men is reversible, so the basis of initial treatment is primarily lifestyle modification and effective treatment of chronic diseases but primarily reducing body fat mass (physical exercise and low-caloric diet). Unfortunately, lifestyle changes are often insufficient to significantly increase testosterone levels and resolve the clinical symptoms of hypogonadism. Because in men seeking fertility conventional testosterone replacement therapy is contraindicated, alternative pharmacological methods, such antiestrogens (selective estrogen receptor modulators and aromatase inhibitors) are often used.

Pituitary neuroendocrine tumors, formerly referred to as pituitary adenomas, are common intracranial neoplasms. Most are benign and slow-growing. Clinical manifestations typically arise from hormonal hypersecretion or mass effect on adjacent structures. Hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion is an uncommon presentation of pituitary tumors and has been rarely reported. We present the case of a 35-year-old woman with a history of secondary amenorrhea and infertility who exhibited progressive headache and recurrent presyncope episodes. Laboratory tests showed that the patient had severe hyponatremia (sodium {Na}: 121 mmol/L), low serum osmolality (252 mOsm/kg), inappropriately elevated urine osmolality (748 mOsm/kg), elevated urinary sodium (112 mEq/L), hypouricemia (1.9 mg/dL), and a fractional excretion of uric acid of 11.66%, consistent with syndrome of inappropriate antidiuretic hormone secretion. Hormonal assessment indicated hypogonadotropic hypogonadism characterized by diminished levels of follicle-stimulating hormone, luteinizing hormone, and estradiol. Magnetic resonance imaging of the brain showed a sellar mass measuring 19 × 31 × 32 mm with a suprasellar extension and compression of the optic chiasm. Visual field testing corroborated bitemporal hemianopsia. The patient had an endoscopic transsphenoidal resection of the lesion. Histopathological examination identified a plurihormonal mature pituitary neuroendocrine tumor of gonadotroph lineage, exhibiting positive immunohistochemical staining for SF-1 and INSM1, negative expression for Pit-1, and a Ki-67 proliferation index of 10%. This case illustrates an uncommon manifestation of a gonadotroph pituitary neuroendocrine tumor presenting as severe hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion. Identifying this unusual presentation is crucial, as prompt diagnosis and intervention may avert considerable neurological, metabolic, and visual complications.

Clinically non-functioning pituitary neuroendocrine tumors (PitNETs), the most common subtype of pituitary tumors, are frequently detected because of mass effects, such as visual impairment and incidental findings. In the World Health Organization classification in 2022, pituitary adenomas have been termed PitNETs, reflecting their biological diversity. This review summarizes the diagnostic evaluations, surgical indications, pathological characteristics, and surgical techniques for non-functioning PitNETs on endoscopic endonasal transsphenoidal surgery (eTSS). Preoperative assessment requires a meticulous endocrine evaluation and detailed magnetic resonance imaging to define tumor extension and invasion, and its relationship with the surrounding neurovascular structures. Surgery is the first-line treatment for symptomatic tumors. Asymptomatic patients with radiological risk factors were selected. Pathologically, non-functioning PitNETs comprise heterogeneous subtypes defined by transcription factors, including gonadotroph, silent corticotroph, and Pit-1 lineage tumors, with some exhibiting aggressive behavior. Technical aspects of eTSS, including intrasellar and extracapsular tumor removal and extended approaches for suprasellar extension, are discussed, highlighting safe and effective tumor resection. Individualized surgical strategies based on tumor characteristics are essential to achieve optimal outcomes.

Pituitary apoplexy (PA) is an endocrine emergency caused by haemorrhage or infarction of the pituitary gland, often occurring in patients with known tumours. Classical presentation includes headache, visual disturbances, and cranial nerve palsies. We describe a rare presentation of PA with epistaxis in a 71-year-old man with a known non-functioning pituitary macroadenoma. On admission, he had acute confusion, worsening headache, and left-sided epistaxis with signs of Cranial Nerve (CN) III palsy and reduced consciousness. Initial Computerized Tomography (CT) showed a stable macroadenoma without acute changes. Laboratory evaluation showed panhypopituitarism and features of vasopressor deficiency. Rapid clinical deterioration prompted repeat CT and Magnetic Resonance Imaging (MRI), which demonstrated interval enlargement of the adenoma with haemorrhage and mass effect. MRI also revealed a catastrophic left middle cerebral artery infarct secondary to M1 segment thrombosis. Despite intensive care support, the patient failed to recover neurologically and passed away. Our case report describes the rare occurrence of epistaxis in PA, due to tumour extension into the sphenoid sinus and erosion of the sellar floor. We emphasize the importance of an early MRI and endocrinology review for timely diagnosis and management. We underscore the need to consider PA in patients with known adenomas and acute neurological decline, even with atypical symptoms. Our case report adds to the limited literature on epistaxis as a presenting sign of PA and associated high morbidity.

Ectopic Cushing syndrome (ECS) is an exceptionally rare cause of endogenous hypercortisolism in children, accounting for less than 1% of pediatric Cushing syndrome (CS) cases. We report a rare case of ECS in an 8-year-old girl secondary to an adrenocorticotrophic hormone (ACTH)-secreting Wilms tumor. She exhibited classical features of hypercortisolism, including rapid weight gain, hypertension, hyperpigmentation, easy bruisability, and a palpable abdominal mass. Laboratory evaluation revealed markedly elevated serum cortisol and ACTH levels, with absent cortisol suppression following low- and high-dose dexamethasone suppression tests, suggestive of ectopic ACTH secretion. Pituitary and thoracic imaging were unremarkable. Contrast-enhanced abdominal computed tomography identified a large left renal mass. She underwent left radical nephrectomy with perioperative hydrocortisone supplementation. Postoperatively, she showed rapid clinical improvement with a significant decline in ACTH levels. Histopathology confirmed a stage III triphasic Wilms tumor with favorable histology. Although initial ACTH immunostaining was negative, repeat staining demonstrated focal ACTH positivity, suggesting tumor heterogeneity. She was subsequently treated with chemotherapy and radiotherapy. Persistently low cortisol levels postsurgery indicated hypothalamic-pituitary-adrenal axis suppression, requiring continued glucocorticoid replacement. This case underlines the importance of considering ectopic ACTH-producing tumors in pediatric Cushing syndrome and highlights the diagnostic complexities associated with focal hormone expression.