Endocrine Abstracts

JOINT923

Introduction: Arginine vasopressin resistance (AVR) is a rare disorder with both congenital and acquired causes. Primary AVR is linked to mutations in the AVPR2 and AQP2 genes, while secondary AVR can result from conditions such as ureteral obstruction, a rare yet potentially reversible cause that remains under-researched. We present two clinical cases of primary and secondary AVR. Despite differing etiologies, both patients exhibited similar symptoms from an early age.

Clinical Case 1: Patient P., a 24-year-old male, has had AVR since birth. Bilateral hydronephrosis was diagnosed in utero at 32 weeks of gestation. By age 7, urine output had reached 5 liters per day. His clinical diagnosis included bilateral megaureter, meatal stenosis, a posterior urethral valve, and secondary pyelonephritis. He underwent a meatotomy and endoscopic resection of the posterior urethral valve. At age 7, AVR was confirmed via a water deprivation test and desmopressin challenge. Despite treatment with hydrochlorothiazide and desmopressin, he continued to experience persistent polyuria, nocturia, fatigue, and difficulty concentrating. At 22 years, he was diagnosed with chronic kidney disease (CKD) stage 4. Due to progressive renal decline, renal replacement therapy and placement on the kidney transplant waiting list were recommended.

Clinical Case 2: Patient G., a 37-year-old male, was first hospitalized in the neuroendocrinology department at age 23 with severe thirst, nocturia, and polyuria of up to 16 liters per day. His symptoms had begun in childhood, with urine output reaching 20 liters daily by age 7. Despite prior desmopressin therapy, his condition remained unresponsive. AVR was confirmed through a water deprivation test and desmopressin challenge. Genetic testing identified a hemizygous AVPR2 mutation (c.539delA p.R180fsX211), confirming the diagnosis. Treatment with thiazide diuretics and potassium supplements led to a significant reduction in thirst and urine output, stabilizing at 4–5 liters per day.

Conclusions: AVR in childhood is rare, with often nonspecific clinical manifestations. Regardless of etiology, timely and accurate diagnosis is crucial, as affected patients are at risk for hypernatremic dehydration and developmental delays. Increasing awareness among healthcare providers, particularly pediatricians, is essential to ensure proper evaluation of polyuria-polydipsia syndrome and a systematic approach to diagnosing arginine vasopressin disorders.