Introduction: Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors with high heritability. While most are benign, approximately 25% are malignant, defined by distant metastases. Molecular classification has identified three clusters, with Cluster 3 (Wnt-signaling) being exclusively somatic and associated with aggressive behavior. We report a rare case of metastatic malignant pheochromocytoma driven by a somatic DNMT3A mutation, highlighting its unique imaging characteristics and rapid clinical progression. Case: A 55-year-old female presented with paroxysmal hypertension, headache, and a 10-kg weight loss. Biochemical workup revealed markedly elevated 24-hour urine metanephrines (163 × ULN) and normetanephrines (47 × ULN). Imaging confirmed a 15-cm left adrenal mass with liver and widespread skeletal metastases. Functional imaging demonstrated a striking mixed avidity: liver metastases were predominantly fluorodeoxyglucoseavid (SUVmax 7.0), skeletal lesions showed high Ga-68 DOTATATE avidity (SUVmax 6.9), and the primary tumor exhibited the strongest avidity on 131 I-MIBG scan. Whole Exome Sequencing identified a rare pathogenic somatic variant in the DNMT3A gene (c.2645G>A) with no other germline or somatic mutations in known susceptibility genes. Despite adequate alpha-blockade and supportive care, the patient developed acute liver failure and coagulopathy, rendering her unfit for any form of invasive intervention and finally succumbing to the disease within 3 months of presentation. Conclusion This case underscores the aggressive nature of Cluster 3 PPGLs associated with DNMT3A mutations, which likely promote tumorigenesis via Wnt-pathway activation and epigenetic dysregulation. The discordant functional imaging reflects significant tumor heterogeneity, which may complicate diagnostic and therapeutic strategies. Given the rarity of DNMT3A-mutated PPGL (<1% of cases), this case report emphasizes the necessity of comprehensive molecular profiling in advanced disease to refine risk stratification and guide the development of precisionbased palliative management in rapidly progressive cases.

Introduction: Hypernatremia is a common yet high-mortality electrolyte disorder. The hypothalamus maintains water homeostasis via thirst sensation and arginine vasopressin (AVP) secretion. Hypothalamic tumors, such as gliomas, can progressively destroy these osmoregulatory centres, leading to “malignant” hypernatremia (>180 mmol/L). We report a case of life-threatening hypernatremia in a patient with a progressive hypothalamic glioma, exploring its complex pathophysiology. Case: A 41-year-old female with a progressive high-grade hypothalamic glioma and persistent hydrocephalus presented with generalized weakness, reduced oral intake, and dehydration. Her initial Glasgow Coma Scale was E4V3M6. Laboratory investigations revealed malignant hypernatremia (serum sodium 209 mmol/L) and a serum osmolarity of 441 mOsm/kg. Despite life-threatening dehydration (urea 26.2 mmol/L, creatinine 343 umol/L), she was still able to deceptively produce urine output of 400 mL/day with a concentrated urine osmolarity of 890 mOsm/kg. A 1 mcg IV desmopressin trial reduced urine output to 60 mL/day and serum sodium by 10 mmol/L within 14 hours, confirming relative AVP deficiency. The patient’s malignant hypernatremia was gradually corrected to 168 mmol/L over 1 week (8–12 mmol/L/day) using controlled intravenous hydration. However, her condition deteriorated due to hospital-acquired infection, and she succumbed 10 days after admission. Conclusion This case underscores several critical learning points for managing hypothalamic emergencies. First, hypothalamic tumors can reset the osmostat or destroy osmoregulatory centres, causing adipsic AVP deficiency. Second, clinicians must be alert to “masked polyuria” where severe hypovolemia reduces the glomerular filtration rate, causing urine output to appear “normal” despite underlying AVP deficiency. This state of “relative polyuria” is a hallmark of hypothalamic hypernatremia, thus indicating that a normal urine output does not rule out AVP deficiency. While desmopressin is indicated, its use in adipsic patients demands strict fluid titration to prevent iatrogenic hyponatremia. Rapid hypotonic correction carries a proven risk of cerebral oedema, and sodium measurement accuracy varies significantly across laboratory methods in extreme ranges.
Hypernatremia ; Hypothalamic Neoplasms

Objective: This study was conducted to assess the effects of Methadone Maintenance Therapy (MMT) and buprenorphine-naloxone Maintenance Therapy (BNX) on the Quality of life (QoL) of opiate abusers. Methods: The QoL status of opioid-dependent patients was assessed using the WHOQOL-BREF questionnaire. It is a cross-sectional study involving a total of 108 patients who received MMT or BNX therapy in Malaysia from May 2011 to September 2011. Results: A statistically significant difference in the overall QoL and psychological aspect among patients on MMT was observed. On the contrary, the scores of overall QoL and quality of social relationship for BNX group were higher in patients with lower dosage. Conclusion: The comparison between patients on high dose MMT and high dose BNX exhibited significant difference in the overall QoL especially in psychological, social relationship and environment domains, with the high dose MMT group having better mean score.