A 34-year-old woman comes to the office due to excessive urination at night. For the past 2 weeks, the patient has been getting up at least 3 times at night to urinate. She has a history of hypothyroidism treated with levothyroxine and bipolar disorder treated with lithium carbonate. Blood pressure is 134/78 mm Hg and pulse is 88/min. BMI is 27 kg/m². Physical examination shows decreased skin turgor and dry mucous membranes. Laboratory results after overnight fasting are as follows: This patient's symptoms are most likely caused by a defect in which of the following sites?

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Explanation: 11ec25c8_d139_dd6d_bc81_ff9e5dada309_MD0003_00 This patient with nocturia and persistently dilute urine (urine osmolality <300 mOsmol/kg) with overnight fasting likely has lithium-induced nephrogenic diabetes insipidus (DI). Normally, antidiuretic hormone (ADH) stimulates renal water reabsorption when serum osmolality is high (eg, following water deprivation). ADH resistance or deficiency causes DI, which presents with dilute urine (low urine osmolality) and polyuria (often worse at night). Nephrogenic DI is caused by renal ADH resistance. One of the most common causes in adults is lithium, which accumulates in renal collecting ducts and blocks responsiveness to ADH. After water deprivation (eg, overnight fasting), serum osmolality rises (eg, >295 mOsmol/kg, often with hypernatremia) and ADH increases appropriately; however, urine osmolality remains low. Central DI can occur following hypothalamic or posterior pituitary damage (eg, trauma, infection) and leads to deficient ADH secretion. After water deprivation, serum osmolality rises but ADH remains low; therefore, urine osmolality remains low. Lithium use is only rarely associated with central DI (Choice C). A desmopressin challenge can differentiate central from nephrogenic DI (as desmopressin causes increased urine osmolality only in central DI). (Choice A) Psychogenic polydipsia is classically associated with psychiatric conditions or disorders affecting thirst. Polyuria and dilute urine are seen; however, in contrast to DI, they represent appropriate responses to excessive water intake, and both ADH sensitivity and production are intact. Therefore, following water deprivation, ADH rises and urine becomes concentrated (ie, urine osmolality increases >300 mOsmol/kg). This patient's dilute urine following water deprivation makes psychogenic polydipsia unlikely. (Choice B) Pancreatic cell destruction causes type 1 diabetes mellitus; severe hyperglycemia (eg, diabetic ketoacidosis) can precipitate glucosuria and associated osmotic diuresis. However, osmotic diuresis is associated with high, rather than low, urine osmolality, and this patient's fasting blood sugar is only mildly elevated. (Choice D) Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are diabetic medications that act on the proximal tubule of the kidney, leading to increased excretion of glucose and associated osmotic diuresis. This patient has no history of SGLT-2 inhibitor use, and her low urine osmolality makes osmotic diuresis unlikely. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (Choice F) This patient's elevated TSH suggests suboptimally treated hypothyroidism (possibly from chronic lithium therapy). However, hypothyroidism is not associated with nocturia or persistently dilute urine. Educational objective: Chronic lithium therapy is commonly associated with nephrogenic diabetes insipidus (DI), presenting with polyuria and persistently dilute urine. Lithium-induced nephrogenic DI results from lithium accumulation in the renal collecting ducts, which leads to antidiuretic hormone resistance and impaired renal water reabsorption. References: Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. (http://www.ncbi.nlm.nih.gov/pubmed/26077742)

A 34-Year-Old Woman Comes to the Office Due to Excessive