SAT-007 - When Water Is The Medicine: Unmasking Adipsic AVP Deficiency

Adipsic arginine vasopressin deficiency (AAVPD) is a rare, life-threatening disorder caused by hypothalamic osmoreceptor destruction that impairs thirst and AVP secretion. Unlike classic AVP deficiency, absent thirst eliminates compensatory polydipsia that typically prompts diagnosis. In hypovolemic states, however, intact baroreceptor-mediated (non-osmotic) AVP release can concentrate urine, masking the underlying osmoregulatory defect.

Case: A 26-year-old male with prior pineal germinoma treated with chemotherapy, whole ventricular radiation, and ventriculoperitoneal shunting with bilateral catheters, underwent elective shunt removal 3 years following placement. He presented on postop day 7 with progressive weakness and lethargy in the setting of severe hypernatremia (Na 177 mmol/L), concentrated serum osmolality (378 mOsm/kg), acute kidney injury (creatinine 1.40 mg/dL; baseline 0.62 mg/dL), and concentrated urine osmolality (1058 mOsm/kg).Taken together, data suggested preserved baroreceptor-driven AVP secretion in hypovolemia. Absence of polyuria delayed recognition of AAVPD. Given the history of adipsia and recent neurosurgical manipulation of catheters in contact with the hypothalamus bilaterally, concern for AAVPD remained. Anterior pituitary evaluation revealed low IGF-1 (Z-score −2.3) with otherwise intact axes. Following IV fluid resuscitation, urine osmolality reduced to 248 mOsm/kg despite persistent hypernatremia (Na 150 mmol/L), unmasking AAVPD. Desmopressin 0.25 mcg subcutaneously produced a prompt urine concentration response (Uosm 571 mOsm/kg), confirming AVP deficiency. Oral desmopressin 0.1 mg twice daily with scheduled fluid intake of 1.5 L/day normalized serum sodium to 141 mmol/L at discharge. Over 3-week follow-up, sodium remained stable (137–151 mmol/L) after increasing intake to 2 L/day.

Discussion: AAVPD results from hypothalamic osmoreceptor injury, impairing thirst and osmotic AVP regulation, causing chronic dehydration and hyperosmolality. Brainstem-hypothalamus afferent pathways remain intact, allowing AVP release from magnocellular neurons in response to non-osmotic stimuli such as hypovolemia, hypotension, and nausea. In this case, hypovolemia drove baroreceptor-mediated AVP release, producing concentrated urine and mimicking intact osmoregulation. Fluid resuscitation removed this stimulus, revealing the osmosensory defect. High suspicion is warranted in patients with hypothalamic injury following ventricular radiation for pineal tumors.

Conclusion: Long-term management of AAVPD requires scheduled desmopressin and fixed daily fluid intake, as patients cannot rely on thirst, and remain vulnerable to both hypernatremia and desmopressin-induced hyponatremia. This case highlights fluid resuscitation as a key maneuver to unmask AAVPD when urine appears paradoxically concentrated.

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