A 65-year-old man is brought to the emergency department by his daughter due to progressiv… — USMLE Step 3

A 65-year-old man is brought to the emergency department by his daughter due to progressive confusion, lethargy, and anorexia over the past week. He has a history of hypertension, type 2 diabetes mellitus, and major depressive disorder. Four weeks ago, fluoxetine was added to his regimen for worsening depression. His other medications include lisinopril and metformin. Vital signs are temperature 37.0°C (98.6°F), blood pressure 128/78 mm Hg, pulse 76/min, and respirations 14/min. Physical examination reveals moist mucous membranes, normal skin turgor, clear lungs, and no jugular venous distention or peripheral edema. Neurologic examination shows disorientation to time and place but no focal deficits.

Laboratory results are as follows:

Laboratory Test	Result	Reference Range
Serum sodium	118 mEq/L	136-145 mEq/L
Serum potassium	4.1 mEq/L	3.5-5.0 mEq/L
Blood urea nitrogen (BUN)	8 mg/dL	7-18 mg/dL
Serum creatinine	0.7 mg/dL	0.6-1.2 mg/dL
Serum glucose	115 mg/dL	70-110 mg/dL
Serum osmolality	252 mOsm/kg H₂O	275-295 mOsm/kg H₂O
Urine osmolality	450 mOsm/kg H₂O	50-1200 mOsm/kg H₂O
Urine sodium	48 mEq/L	20-40 mEq/L

Thyroid-stimulating hormone (TSH) and morning serum cortisol levels are within normal limits.

Based on the clinical presentation and laboratory results, which of the following is the most likely underlying cause of this patient's condition?

Adverse effect of fluoxetineAnswer
B
Osmotic fluid shifts from hyperglycemia
C
Volume depletion from inadequate oral intake
D
Psychogenic primary polydipsia
E
Adverse effect of lisinopril

Answer

The most likely underlying cause of this patient's condition is an adverse effect of fluoxetine, which has triggered the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

The correct answer identifies an adverse effect of fluoxetine. This patient's laboratory workup shows hypotonic hyponatremia (serum sodium

118 \text{ mEq/L}

, serum osmolality

252 \text{ mOsm/kg H}_2\text{O}

). In the setting of clinical euvolemia, the diagnostic next step is evaluating urine studies. A normal physiological response to hypotonicity is complete suppression of antidiuretic hormone (ADH), which would result in maximally dilute urine (

< 100 \text{ mOsm/kg H}_2\text{O}

). This patient's inappropriately concentrated urine (

450 \text{ mOsm/kg H}_2\text{O}

) signifies excess ADH activity. Coupled with an elevated urine sodium (

48 \text{ mEq/L}

) reflecting appropriate sodium handling by the kidneys and normal thyroid/adrenal tests, this profile definitively points to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine are notorious for causing SIADH, particularly in elderly patients.

Step-by-Step Solution

Evaluate the serum osmolality to classify the hyponatremia.

The patient's measured serum osmolality is

252 \text{ mOsm/kg H}_2\text{O}

, confirming true (hypotonic) hyponatremia.

This step distinguishes true hypotonic hyponatremia from pseudohyponatremia (isotonic) and translocational hyponatremia (hypertonic, such as in severe hyperglycemia).

Assess the patient's clinical and biochemical volume status.

The physical examination shows moist mucous membranes and no edema, while the blood urea nitrogen (BUN) is appropriately low-normal (

8 \text{ mg/dL}

). Both indicate a euvolemic state.

Categorizing volume status as hypovolemic, euvolemic, or hypervolemic narrows the differential diagnosis considerably.

Analyze urine osmolality and urine sodium concentrations.

The urine is inappropriately concentrated (

450 \text{ mOsm/kg H}_2\text{O}

) in the face of hypotonicity, and the urine sodium is elevated (

48 \text{ mEq/L}

A urine osmolality

> 100 \text{ mOsm/kg H}_2\text{O}

indicates failure to suppress ADH. A urine sodium

> 40 \text{ mEq/L}

confirms appropriate renal sodium excretion in a volume-expanded (but clinically euvolemic) state, distinguishing SIADH from volume-depleted states.

Synthesize the laboratory data with the patient's history to identify the etiology.

The laboratory pattern is perfectly consistent with SIADH. The recent initiation of fluoxetine, an SSRI known to cause SIADH in older adults, is the definitive trigger.

Connecting the diagnostic pattern of SIADH to the medication list is crucial for determining the underlying cause and guiding management.

Key Concept

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) typically presents as euvolemic, hypotonic hyponatremia with inappropriately concentrated urine (typically

> 100 \text{ mOsm/kg H}_2\text{O}

) and elevated urine sodium (

> 40 \text{ mEq/L}

). Selective serotonin reuptake inhibitors (SSRIs) are a classic pharmacological trigger for SIADH, particularly in older adults.

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