11β-hydroxylase deficiency (11β-OHD) is the second most common form of congenital adrenal hyperplasia (CAH), characterized by androgen excess, mineralocorticoid-driven hypertension, and hypokalemia. We report a 35-year-old individual with a 46,XX karyotype, registered and raised male since birth, in whom a disorder of sexual development (DSD) had remained unrecognized. Abdominal MRI performed for nonspecific abdominal pain revealed bilateral giant adrenal myelolipomas on macronodular adrenal hyperplasia and a retro-vesical uterus-like structure. On examination, external genitalia showed complete masculinization (Prader stage 5); dedicated pelvic MRI further demonstrated a markedly enlarged uterus with diffuse adenomyosis, in a patient who had never menstruated. Hormonal findings were consistent with classical 11β-OHD (DOC ∼140× the upper limit of normal, ACTH 12× normal, elevated adrenal androgens, suppressed gonadotropins, and absent AMH); CYP11B1 genetic testing, which would provide molecular confirmation, was not available. Glucocorticoid replacement normalized potassium and improved blood pressure, with ongoing multidisciplinary follow-up. This case highlights the radiological phenotype of neglected CAH in adulthood and the role of imaging in characterizing complex DSD when clinical signs alone are insufficient to reach a diagnostic conclusion.

Introduction Manual therapy (MT) is widely recommended for musculoskeletal disorders, yet its biological mechanisms remain poorly synthesized, with existing evidence often aggregating distinct techniques and outcome domains. This systematic review and meta-analysis evaluates the neurophysiological and metabolic effects of MT, exploring differences between technique characteristics (high-velocity low-amplitude [HVLA] vs. non-HVLA) and anatomical regions. Methods Registered prospectively (PROSPERO CRD42024497251), five databases (MEDLINE, CINAHL, Web of Science, Scopus and CENTRAL) were searched through 14 July 2025. Randomized controlled trials and controlled clinical trials evaluating neurophysiological or metabolic outcomes following MT in adults, with or without musculoskeletal pain, were included. Risk of bias was assessed using Cochrane RoB 2.0. Meta-analyses used random-effects models; certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Fifty studies (2,147 participants) were included. Meta-analyses showed that joint mobilization significantly increased skin conductance (sympathetic marker) versus sham in healthy cohorts. Conversely, non-HVLA MT, particularly soft tissue techniques, was associated with reduced heart rate and increased RMSSD (parasympathetic marker). No consistent effects were observed for blood pressure, skin temperature, or frequency-domain HRV. Narrative synthesis indicated that HVLA manipulation may attenuate somatosensory evoked potentials and increase muscle conduction velocity, while soft tissue approaches were linked to increased oxytocin and reduced adrenocorticotropic hormone levels. Overall, certainty of evidence ranged from low to moderate due to methodological heterogeneity and imprecision. Conclusion Manual therapy is associated with short-term modulation of neurophysiological regulation, characterized by technique-specific response profiles. Joint mobilization primarily induces sympathetic-driven responses, whereas soft tissue techniques are more frequently associated with parasympathetic-driven markers. The overall pattern of findings suggests that MT interacts with regulatory systems in a technique-dependent manner rather than producing uniform systemic physiological effects.

Amino acids stimulate pituitary hormone secretion, but whether somatostatin-sensitive pathways differentially regulate activation of the corticotropic and somatotropic axes during amino acid infusion remains unclear. We investigated whether somatostatin signaling constrains growth hormone secretion following amino acid infusion differently from ACTH and cortisol responses in humans.

Ectopic Cushing's syndrome (ECS) is a rare but important cause of ACTH-dependent Cushing's syndrome. Metyrapone, a steroidogenesis inhibitor targeting 11-β hydroxylase, has shown effectiveness in controlling hypercortisolism. However, little is known about the practical aspects of its initiation, use, and effectiveness in ECS. We present three cases of severe hypercortisolism secondary to ECS managed with metyrapone and report our experience. Case 1: a 56-year-old male with high-grade neuroendocrine carcinoma. Case 2: a 67-year-old man with a history of stage IIB non-small cell lung cancer (NSCLC) with metastatic neuroendocrine carcinoma. Case 3: a 64-year-old man with metastatic prostate cancer. Biochemical control was achieved with rapid titration of low doses of daily metyrapone in all three cases. Based on our experience, we recommend an initial dose of 1000-1500 mg of metyrapone daily, in divided doses, with physiologic glucocorticoid replacement to mitigate the risk of adrenal insufficiency. Despite improvements in cortisol levels and stabilization of metabolic derangements, all three patients ultimately transitioned to comfort-focused care. Given the rarity, heterogeneity, and aggressiveness of this condition, rapid diagnosis and standardized pharmacologic approach are difficult to achieve. More data are needed to guide optimal therapy selection, dosing, and titration in ECS.

Depression is a global public health issue with unclear pathogenesis and limited conventional treatments. Polysaccharides derived from traditional Chinese medicines have garnered attention for their safety and multitarget effects. This study aimed to evaluate the antidepressant efficacy of Corni Fructus polysaccharide (CFP) and explored its underlying mechanisms associated with oxidative stress, inflammation, and gut microbiota using a chronic unpredictable mild stress (CUMS) mouse model. Behavioral tests (sucrose preference, tail suspension, and open field), hematoxylin-eosin (H&E) staining, GC-MS, 16S rRNA gene sequencing, reverse transcription-quantitative PCR (RT-qPCR) and western blotting (WB) were adopted. CFP treatment significantly alleviated CUMS-induced depressive-like behaviors. It lowered the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and stress hormones (CRH, ACTH, CORT), decreased the accumulation of lipid peroxidation product (MDA), enhanced the activities of antioxidant enzymes CAT and SOD, increased the synthesis of brain-derived neurotrophic factor (BDNF) and monoamine neurotransmitters (5-HT, NE, DA), and alleviated neuronal damage in the hippocampus. Such benefits were associated with CFP-mediated modulation of gut microbiota composition, specifically a reduction in the proportion of Bacillota, an enrichment of beneficial bacteria, and increased levels of colonic and serum short-chain fatty acids (SCFAs), particularly butyric acid. These SCFAs may enter the central nervous system via the bloodstream, suppress the hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, regulate the NF-κB/Nrf2 pathway, promote BDNF and monoamine production, thereby alleviating CUMS-induced depressive-like behaviors. Collectively, these findings provide a solid theoretical basis for considering CFP as a potential multitarget antidepressant candidate.

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a central feature of stress-related affective disorders, and corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) initiate neuroendocrine stress responses. Although the α7 nicotinic acetylcholine receptor (α7 nAChR) has been implicated in emotional regulation, its role in PVN CREB/CRH signaling and anxiety- and depressive-like behaviors remains unclear. Here, using male C57BL/6 mice, we found that pharmacological activation of α7 nAChR with PNU282987 induced anxiety- and depressive-like behaviors under control conditions and further exacerbated behavioral abnormalities following chronic restraint stress (CRS), without significantly affecting locomotor activity. PNU282987 also increased CREB phosphorylation and CRH expression in the PVN and elevated serum CRH, adrenocorticotropic hormone (ACTH), and corticosterone (CORT) levels. Conversely, in CRS mice, the α7 nAChR-preferring antagonist methyllycaconitine (MLA) increased sucrose preference, OFT center exploration, and EPM open-arm time while reducing TST immobility. These behavioral effects were accompanied by reduced PVN CREB phosphorylation and CRH expression and decreased serum CRH, ACTH, and CORT levels. Notably, α7 nAChR protein abundance in the PVN was not significantly altered by CRS or drug treatment, suggesting that functional receptor activation rather than receptor upregulation may drive downstream signaling. Moreover, the CREB-mediated transcription inhibitor 666-15 attenuated PNU282987-induced behavioral abnormalities, serum CRH elevation, and PVN CRH upregulation. These findings indicate that α7 nAChR activation promotes anxiety- and depressive-like behaviors associated with enhanced PVN CREB phosphorylation, CRH upregulation, and HPA axis hyperactivity. CREB-associated CRH signaling may therefore represent a neuroendocrine mechanism linking α7 nAChR activation to stress-related affective disturbances.