During a routine follow-up visit, an individual managed for a chronic mood disorder report… — USMLE Step 3

During a routine follow-up visit, an individual managed for a chronic mood disorder reports a bothersome requirement to consume large volumes of water and awaken multiple times nightly to urinate. This symptom pattern has progressively worsened over the last six months. Current daily medications include lithium carbonate and citalopram. Vital signs indicate a blood pressure of 118/76 mmHg and a heart rate of 82/min. Initial laboratory assessment yields the following results:

Laboratory Parameter	Patient Value	Reference Range
Serum sodium	147 mEq/L	136-145 mEq/L
Serum potassium	4.1 mEq/L	3.5-5.0 mEq/L
Serum glucose	95 mg/dL	70-99 mg/dL
Serum calcium	9.2 mg/dL	8.5-10.5 mg/dL
Urine specific gravity	1.003	1.005-1.030
Urine osmolality	145 mOsm/kg	500-800 mOsm/kg

The clinician initiates a water deprivation test. After several hours, the serum osmolality reaches 305 mOsm/kg, while the urine osmolality remains low at 155 mOsm/kg. Following a subcutaneous injection of exogenous desmopressin, a repeat urine osmolality is measured at 165 mOsm/kg.

Based on the diagnostic evaluation, which of the following is the most likely underlying diagnosis?

A
Central diabetes insipidus
B
Primary psychogenic polydipsia
C
Syndrome of inappropriate antidiuretic hormone secretion
Nephrogenic diabetes insipidusAnswer
E
Uncontrolled diabetes mellitus

Answer

Nephrogenic diabetes insipidus

The clinical presentation and laboratory findings are pathognomonic for nephrogenic diabetes insipidus. The patient has polyuria and dilute urine (low specific gravity and osmolality) despite a high-normal/elevated serum sodium, which strongly points toward diabetes insipidus. The water deprivation test confirms this because the urine fails to concentrate even when the serum becomes hyperosmolar. Finally, the administration of desmopressin (an ADH analog) elicits no significant increase in urine osmolality, proving that the renal tubules are resistant to ADH. This ADH resistance is a well-documented and common side effect of chronic lithium therapy, which this patient takes for their mood disorder.

Step-by-Step Solution

Analyze the baseline laboratory profile in the context of polyuria.

The patient has polyuria accompanied by hypernatremia (147 mEq/L) and highly dilute urine (specific gravity 1.003, osmolality 145 mOsm/kg).

This establishes the presence of a primary water diuresis (diabetes insipidus) rather than an osmotic diuresis or primary polydipsia (which typically presents with low or low-normal serum sodium).

Interpret the physiological response to the water deprivation test.

Despite an elevated serum osmolality (305 mOsm/kg) indicating systemic dehydration, the urine remains inappropriately dilute (155 mOsm/kg).

This confirms the diagnosis of diabetes insipidus, as a healthy individual or someone with primary polydipsia would appropriately concentrate their urine under these conditions.

Differentiate the subtype of diabetes insipidus using the desmopressin challenge.

Administration of exogenous desmopressin (an ADH analog) produces only a minimal change in urine osmolality (from 155 to 165 mOsm/kg).

This lack of response demonstrates that the kidneys are resistant to antidiuretic hormone, confirming nephrogenic diabetes insipidus. This is a well-known complication of chronic lithium therapy.

Key Concept

Differential diagnosis of polyuria using baseline sodium levels, the water deprivation test, and desmopressin challenge.

Estimated Time:1m 30s

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