Endocrine Abstracts

JOINT1582

Introduction: Arginine vasopressin resistance (AVR) is an orphan disease clinically characterized by severe polydipsia and the excretion of large volumes of dilute urine. Hereditary AVR is linked to mutations in the vasopressin receptor gene predominantly in 90% of cases, which is expressed in the renal collecting ducts (AVPR2). We present a clinical case of AVR in a patient with a mutation in AVPR2 (hemizygous mutation c.587T>C p.Phe196Ser), which has not been previously described in the literature.

Clinical Case: Patient K., a 29-year-old male, presented to the Endocrinology Research Centre (ERC) with complaints of thirst, polyuria up to 15 liters per day, and nocturia. The diagnosis of arginine vasopressin disorder (AVD) was confirmed at age 3 against a water deprivation test. Desmopressin therapy was initiated without clinical effect. Magnetic resonance imaging (MRI) did not reveal any structural abnormalities of subcortical brain structures. At the ERC a desmopressin test was conducted, which showed no increase in urine osmolality. Genetic sequencing of the AVPR2 revealed a hemizygous transition, resulting in a substitution of cytosine for thymine in exon 2 at position 587 (c.587T>C), leading to the amino acid substitution of phenylalanine (Phe) for serine (Ser) at position 196 of the receptor protein (p.Phe196Ser). This mutation has not been documented in medical literature. The patient was prescribed hydrochlorothiazide at a dose of 25 mg twice daily along with potassium supplements, while being monitored for diuresis and electrolyte levels. After two weeks, the patient reported a reduction in thirst, and urine volume significantly decreased. However, due to discomfort and "tingling" sensations behind the sternum, accompanied by hypokalemia, the patient independently discontinued medication, after which potassium levels normalized and the uncomfortable sensations subsided. AVR symptoms recurred. Given the development of hypokalemia despite potassium supplementation while on hydrochlorothiazide, therapy with non-steroidal anti-inflammatory drugs (NSAIDs) was initiated without significant clinical improvement. It was decided to resume hydrochlorothiazide treatment at a reduced daily dose (25 mg) alongside potassium supplements, while a potassium-sparing diuretic (amiloride) was also introduced at a dose of 5 mg daily. Patient monitoring continues.

Conclusions: AVR is a rare disease with social significance. Timely and accurate diagnosis not only prevents severe complications and initiates adequate treatment but also significantly enhances the patient’s quality of life. The vigilance of primary care physicians in the presence of polydipsia-polyuria syndrome, competent patient routing, and an interdisciplinary approach are crucial in diagnosing and managing patients with AVR.