A 3-month-old boy is brought to the office due to fussiness, poor weight gain, and polyuria. Urine volume is 700-800 mL/day. The patient's maternal grandfather has polydipsia and polyuria. Serum sodium is 151 mEq/L. Genetic testing reveals a vasopressin-2 receptor mutation. Which of the following additional findings is most likely to be seen in this patient?

Question

A 3-month-old boy is brought to the office due to fussiness, poor weight gain, and polyuria. Urine volume is 700-800 mL/day. The patient's maternal grandfather has polydipsia and polyuria. Serum sodium is 151 mEq/L. Genetic testing reveals a vasopressin-2 receptor mutation. Which of the following additional findings is most likely to be seen in this patient?
A 3-month-old boy is brought to the office due to fussiness, poor weight gain, and polyuria. Urine volume is 700-800 mL/day. The patient's maternal grandfather has polydipsia and polyuria. Serum sodium is 151 mEq/L. Genetic testing reveals a vasopressin-2 receptor mutation. Which of the following additional findings is most likely to be seen in this patient? A) A B) B C) C D) D E) E F) F

Quizplus · Accepted Answer

11ec160b_3a30_f19e_9249_47e6b40670eb_MD0001_00 This patient with a vasopressin-2 (V2) receptor mutation has polyuria and hypernatremia, findings which are consistent with congenital nephrogenic diabetes insipidus (DI). V2 receptors are located in the renal cortical collecting ducts. When serum osmolality rises (eg, water deprivation, dehydration), there is increased release of antidiuretic hormone (ADH, vasopressin) which activates V2 receptors to reabsorb water into the systemic circulation. Water reabsorption leads to concentrated urine (low urinary volume, high urine osmolality) and lower serum osmolality. Mutations that impair normal V2 receptor function result in nephrogenic DI (ADH resistance). Following water deprivation, the collecting ducts are unable to reabsorb water despite high circulating ADH levels, leading to ongoing urinary water losses. Therefore, nephrogenic DI manifests with large volumes of abnormally dilute urine (ie, polyuria with low urine osmolality), high serum osmolality (ie, hypernatremia), and dehydration. High serum osmolality, polyuria, and dilute urine also occur in central DI, which is caused by deficient ADH production by the hypothalamus. As with nephrogenic DI, urine remains abnormally dilute after water deprivation. However, challenge with desmopressin (an analogue of ADH) can differentiate between central and nephrogenic DI: (Choice B) High baseline serum osmolality and high urine osmolality can be seen in states of marked hyperglycemia with glucosuria (ie, solute diuresis). Although polyuria can occur, the ADH response remains intact, so urine osmolality will be high with water deprivation. (Choice D) Primary polydipsia can also result in polyuria with dilute urine. However, unlike DI, serum osmolality and sodium are low (due to excess water intake), and dilute urine represents an appropriate physiologic response. ADH response is intact, so urine osmolality is appropriately high following water deprivation. No additional change is seen with desmopressin because maximum ADH levels are reached with water deprivation. (Choices E and F) This patient has visible signs of dehydration and hypernatremia; because sodium is a major determinant of serum osmolality, a high serum osmolality is expected. Educational objective: Vasopressin-2 receptor mutations are a cause of congenital nephrogenic diabetes insipidus, a condition in which renal resistance to antidiuretic hormone results in excessive urinary water losses. Expected findings include high baseline serum osmolality (typically with hypernatremia), persistently dilute urine after water deprivation (low urine osmolality), and lack of response to desmopressin.

A 3-Month-Old Boy Is Brought to the Office Due to Fussiness