A 70-year-old man with stage IV (extensive-stage) small cell lung carcinoma presented with progressive respiratory symptoms, refractory hypophosphataemia and hyponatraemia. The diagnostic evaluation revealed paraneoplastic arginine vasopressin-mediated syndrome of inappropriate diuresis and fibroblast growth factor 23-mediated renal phosphate wasting, consistent with tumour-induced osteomalacia. This report highlights the diagnostic complexity and reasoning required to identify dual paraneoplastic syndromes in an advanced malignancy, with emphasis on biochemical interpretation and integration of laboratory data.

BACKGROUND Carotid-cavernous fistulas (CCFs) are abnormal arteriovenous communications between the carotid artery and cavernous sinus. They may be direct or indirect and commonly present with both ocular and neurovascular symptoms. Endovascular embolization is the main treatment, with high rates of fistula obliteration and clinical improvement. Although generally safe, complications can occur, including cranial nerve dysfunction and vascular injury. Endocrine complications following carotid-cavernous fistula embolization are exceedingly rare. To our knowledge, only 1 case of syndrome of inappropriate antidiuresis (SIAD) after Onyx embolization has been reported in the literature. CASE REPORT A 72-year-old woman developed severe symptomatic SIAD 9 days after transarterial Onyx embolization of an indirect CCF. The procedure was successful but associated with worsening of preexisting left abducens nerve paresis. She subsequently re-presented with dizziness, truncal ataxia, and confusion, which resulted in a fall involving wrist fracture but no head strike. Investigations demonstrated profound hypotonic euvolemic hyponatremia with elevated urine osmolality and urine sodium, suggestive of SIAD. The absence of hypovolemia, polyuria, and a negative fluid balance argued against cerebral salt wasting. Adrenal insufficiency, hypothyroidism, and other causes were excluded. Treatment with hypertonic saline and fluid restriction resulted in gradual sodium correction and complete neurological recovery. CONCLUSIONS Transient hypothalamic-pituitary dysfunction related to Onyx-associated local mass effect and hemodynamic changes may represent a plausible mechanism. This case highlights delayed-onset SIAD as a rare but clinically significant complication temporally associated with CCF embolization. The findings support consideration of both early and delayed electrolyte monitoring, particularly within the first 1 to 2 weeks after the procedure.

Chronic hyponatremia is associated with cognitive deficits, yet the underlying mechanisms remain elusive. A cerebral growth factor which is crucial for cognition and memory is brain-derived neurotrophic factor (BDNF), but its role in hyponatremia has never been investigated. We here examined the influence of hyponatremia correction on serum BDNF levels. This study represents a secondary post hoc analysis of a prospective randomized, double-blind, crossover, placebo-controlled trial. Nine patients with syndrome of inappropriate antidiuresis (SIAD) completed 4 weeks treatments with empagliflozin 25 mg/day versus placebo. Serum sodium, BDNF levels, and Montreal Cognitive Assessment (MoCA) were assessed at baseline and after treatment cycles. Median baseline sodium was 131 mmol/L [130-133], which increased to 134 mmol/L ([131-136], p = .04) after empagliflozin treatment and remained stable after placebo phase (130 mmol/L [126-132], p = .9). Sodium increase was significantly associated with BDNF increase, also after adjusting for treatment arm, sex, age, baseline sodium, and antidepressant treatment (per 1 mmol/L sodium increase: estimate = 0.70 ng/mL, p = .048). This association was stronger upon empagliflozin treatment as shown by the interaction analysis (p = .03). In a subgroup of patients reaching normonatremia after empagliflozin treatment, BDNF increase was slightly higher compared to patients with persistent hyponatremia. MoCA scores did not differ between empagliflozin and placebo phase. Sodium increase was significantly associated with an increase in neurocognitive biomarker BDNF. Further research is needed to clarify BDNF's role in cognitive impairment in hyponatremia and its response to different treatment approaches. Trial registration: ClinicalTrials.gov (NCT03202667).

Prostate adenocarcinoma commonly metastasises to the axial skeleton, but skull base deposits with acute cranial nerve palsies as the first clinical sign are unusual. We report a 68-year-old man admitted with one month history of dyspnoea and weakness, who was found to have severe microcytic anaemia (haemoglobin 6.5 g/dL) with stool positive for occult blood; upper gastrointestinal endoscopy showed only mild antral gastritis. During the first week he developed left-sided ptosis, progressing over three days to complete ophthalmoplegia with binocular diplopia. Gadolinium-enhanced MRI of the brain showed a destructive clival deposit with heterogeneous enhancement extending into the left cavernous sinus. On directed questioning the patient admitted to a five-month history of lower urinary tract symptoms (LUTS) dismissed as age-related. Serum prostate-specific antigen was 754 ng/mL. Cross-sectional imaging and multiparametric prostate MRI confirmed a Prostate Imaging Reporting and Data System (PIRADS) 5 lesion with widespread pulmonary, mediastinal nodal, pelvic nodal and skeletal metastases. The hospital course was complicated by severe hyponatraemia with a high urine sodium (43 mEq/L), supporting the syndrome of inappropriate antidiuresis. Transrectal ultrasound-guided biopsy confirmed prostatic adenocarcinoma. The case is a reminder that cranial nerve palsies in an elderly man can be the first visible sign of silent disseminated prostate cancer, and that asking directly about urinary symptoms at every clinical encounter matter, even though such symptoms are not themselves a reliable indicator of early disease.

Autoimmune small-vessel cerebral vasculitis is an uncommon but potentially reversible cause of rapidly progressive cognitive and neurological decline. Its presentation can be heterogeneous, often mimicking vascular, infectious or degenerative processes. Hyponatraemia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) may occur as a secondary manifestation of hypothalamic involvement or systemic inflammation, compounding neurological dysfunction and complicating management. We describe a middle-aged woman who developed acute cognitive deterioration, emotional lability and gait disturbance secondary to newly diagnosed autoimmune small-vessel vasculitis with serological evidence of systemic autoimmunity, on a background of prior polyautoimmune diseases (type 1 diabetes mellitus and hypothyroidism). Despite resolution of inflammatory activity following high-dose corticosteroid therapy, profound hyponatraemia (serum sodium 110-120 mmol/L) persisted despite conventional measures (fluid restriction, salt supplementation and urea) and despite improvement in inflammatory activity following immunotherapy, consistent with refractory SIADH. Initiation of tolvaptan, a selective vasopressin V2-receptor antagonist, successfully resulted in gradual and sustained correction of serum sodium levels without over-rapid correction, osmotic demyelination or hepatic toxicity. Alongside longer-term immunosuppression with steroids and cyclophosphamide, this led to stabilisation of neurological and cognitive deficits. This case highlights the complexities of managing patients with cognitive and neuropsychiatric sequelae from autoimmune small-vessel central nervous system (CNS) vasculitis and the importance of evaluation and treatment of potential organic causes of cognitive impairment. To our knowledge, there are no prior published reports describing refractory SIADH in autoimmune small-vessel CNS vasculitis requiring V2-receptor antagonism. Awareness of this disease association and this effective therapeutic option allows earlier recognition and improved patient outcomes in similar cases.

A man in his early 60 s developed persistent hyponatremia following lumbar spine surgery complicated by traumatic brain injury with subarachnoid hemorrhage. Initial evaluation demonstrated hypotonic hyponatremia with inappropriately concentrated urine, consistent with the syndrome of inappropriate antidiuretic hormone secretio. Standard therapy including hypertonic saline and oral sodium supplementation resulted in only transient improvement. Given a history of secondary adrenal insufficiency due to long-term topical corticosteroid use, adrenal function was reassessed. An adrenocorticotropic hormone stimulation test confirmed secondary adrenal insufficiency. Initiation of hydrocortisone therapy led to sustained normalization of serum sodium. This case highlights the diagnostic difficulty of post-TBI hyponatremia and underscores the importance of considering adrenal insufficiency, even years after apparent recovery from steroid-induced hypothalamic-pituitary-adrenal axis suppression.

Paraneoplastic endocrine syndromes (PESs) are hormonal disturbances associated with malignancies that result from tumor-related production of hormone-like substances, immune-mediated mechanisms, or dysregulated signaling pathways. While they are well recognized in lung and neuroendocrine cancers, their relevance in gastrointestinal tumors remains less clearly defined. This narrative review synthesizes current knowledge on paraneoplastic endocrine manifestations in gastrointestinal malignancies, based on a structured search of the literature in major databases, including PubMed, Scopus, and Web of Science. The analysis focuses on clinically relevant syndromes such as hypercalcemia, Cushing-like manifestations, disorders of water balance, hypoglycemia, and acromegaly, with emphasis on underlying mechanisms, associated tumor types, diagnostic approaches, and therapeutic considerations. Available evidence indicates that gastrointestinal tumors can produce a range of biologically active substances, leading to diverse endocrine manifestations that may precede tumor detection and influence disease course. Among these, hypercalcemia and Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) are among the most frequently reported, while other syndromes, such as ectopic Cushing syndrome or tumor-related hypoglycemia, are less common but often associated with more severe clinical outcomes. Recognition of these manifestations has direct clinical implications, as they may support earlier diagnosis, contribute to prognostic assessment, and guide therapeutic management. Improved awareness and a multidisciplinary approach remain essential for optimizing outcomes in patients with gastrointestinal malignancies.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and central fever are rare and underrecognized manifestations of multiple system atrophy (MSA). Here, we report a 66-year-old woman who presented with a progressively evolving combination of parkinsonian features and pronounced autonomic dysfunction, fulfilling the diagnostic criteria for clinically probable MSA. Notably, she also developed two uncommon comorbidities: euvolemic hypotonic hyponatremia fulfilling the diagnostic criteria for SIADH, alongside episodic fever refractory to antipyretics in the absence of infection, but responsive to environmental cooling, consistent with central fever. These uncommon comorbidities underscore the involvement of hypothalamic and neuroendocrine regulatory pathways in MSA. This case broadens the well-recognized non-motor clinical spectrum of MSA and emphasizes the importance of considering central mechanisms when evaluating unexplained hyponatremia or fever in MSA. Awareness of these atypical manifestations may facilitate early recognition, guide targeted homeostatic management, and ultimately improve the quality of clinical care in MSA.

Hyponatremia is a relatively frequent finding in multiple myeloma (MM) and may result from either pseudohyponatremia, due to marked hyperproteinemia, or true hyponatremia from genuine sodium-water imbalance. Differentiating between these two entities is essential, as they differ in pathogenesis, clinical relevance, and management. Pseudohyponatremia, observed in approximately 15-20% of MM patients, is a measurement artifact occurring with indirect ion-selective electrode techniques when plasma water fraction is reduced by high M protein levels. Serum osmolality remains normal, and no sodium correction is required. True hyponatremia (<135 mEq/L with hypo-osmolality) is less common but clinically significant, often associated with worse prognosis. Mechanisms include renal impairment (cast nephropathy, Fanconi syndrome, light chain deposition), hypervolemia from advanced renal failure, hypovolemia from gastrointestinal losses or diuretics, drug-induced effects (notably bortezomib, cyclophosphamide), and paraneoplastic SIADH. Alterations in electroneutrality and strong ion difference (SID) from highly cationic M protein may further lower sodium, usually mildly. Pseudohyponatremia is managed by controlling the underlying myeloma and reducing paraproteinemia. True hyponatremia treatment is etiology-specific: isotonic saline for hypovolemia, fluid restriction ± solute supplementation for SIADH, careful diuretic adjustment for hypervolemia, and withdrawal of causative drugs when possible. Optimal control of the plasma cell clone, through modern triplet or quadruplet regimens prevents recurrence. A structured diagnostic approach integrating volume status, laboratory evaluation, and medication review is critical to distinguish pseudo from true hyponatremia, prevent inappropriate interventions, and address the underlying disease.