A 27-year-old woman is brought to the emergency department by her partner due to severe, d… — USMLE Step 3

A 27-year-old woman is brought to the emergency department by her partner due to severe, diffuse abdominal pain and new-onset confusion that began 24 hours ago. The pain is severe, constant, and associated with nausea and non-bilious vomiting. Three days ago, she was evaluated at an urgent care center for a presumed urinary tract infection and was prescribed oral trimethoprim-sulfamethoxazole. She has no other medical history and does not use tobacco, alcohol, or illicit drugs.

Temperature is 37.1°C (98.8°F), blood pressure is 165/100 mmHg, pulse is 118/min, and respirations are 18/min. Physical examination shows an anxious and profusely diaphoretic woman. The abdomen is soft and non-distended with diffuse mild discomfort on deep palpation, but there is no localized tenderness, guarding, or rebound. Bowel sounds are diminished. Neurologic examination reveals symmetric 4/5 weakness in the proximal upper and lower extremities and decreased deep tendon reflexes.

Laboratory studies show:

Laboratory Test	Result	Reference Range
Hemoglobin	$13.8 \text{ g/dL}$	$12.0-16.0 \text{ g/dL}$
Leukocyte count	$8,500/\text{mm}^3$	$4,500-11,000/\text{mm}^3$
Platelet count	$210,000/\text{mm}^3$	$150,000-400,000/\text{mm}^3$
Sodium	$122 \text{ mEq/L}$	$136-145 \text{ mEq/L}$
Potassium	$3.9 \text{ mEq/L}$	$3.5-5.0 \text{ mEq/L}$
Bicarbonate	$24 \text{ mEq/L}$	$22-28 \text{ mEq/L}$
Blood urea nitrogen	$10 \text{ mg/dL}$	$8-20 \text{ mg/dL}$
Creatinine	$0.7 \text{ mg/dL}$	$0.6-1.2 \text{ mg/dL}$
Aspartate aminotransferase (AST)	$45 \text{ U/L}$	$8-40 \text{ U/L}$
Alanine aminotransferase (ALT)	$35 \text{ U/L}$	$7-35 \text{ U/L}$
Lipase	$35 \text{ U/L}$	$10-140 \text{ U/L}$

Serum $\beta$ -hCG is negative. A non-contrast CT scan of the head shows no abnormalities.

Which of the following is the most appropriate next step in laboratory evaluation?

Measurement of spot urine porphobilinogenAnswer
B
24-hour urine collection for fractionated porphyrins
C
CT angiography of the abdomen and pelvis
D
Measurement of whole blood lead level
E
Measurement of serum acetaminophen level

Answer

Measurement of spot urine porphobilinogen is the correct next step in laboratory evaluation.

The correct answer is measurement of spot urine porphobilinogen. This patient's clinical picture of severe abdominal pain with a benign abdominal examination, autonomic hyperactivity (tachycardia, severe hypertension, diaphoresis), profound hyponatremia, and new-onset proximal motor weakness is highly characteristic of an acute attack of acute intermittent porphyria (AIP). AIP is an autosomal dominant disorder of heme biosynthesis caused by a deficiency of the enzyme porphobilinogen deaminase. Acute neurovisceral attacks are classically precipitated by factors that upregulate hepatic cytochrome P450 enzymes—such as certain medications (e.g., sulfonamide antibiotics, antiepileptics), fasting, or alcohol use—leading to the toxic accumulation of porphyrin precursors. The hyponatremia is typically driven by the syndrome of inappropriate antidiuretic hormone secretion (SIADH) resulting from hypothalamic involvement. During an acute attack, the most appropriate, sensitive, and rapid initial laboratory test is a spot urine assay for porphobilinogen (PBG), which will be markedly elevated.

Step-by-Step Solution

Analyze the patient's clinical presentation.

The patient exhibits severe neurovisceral symptoms including abdominal pain without peritoneal signs, autonomic hyperactivity (tachycardia, hypertension, diaphoresis), confusion, and new-onset proximal motor weakness.

Identifying the constellation of neuropathic pain, autonomic instability, and motor deficits helps narrow the differential diagnosis to systemic or metabolic etiologies rather than primary intra-abdominal pathology.

Identify potential triggers and correlate with laboratory findings.

The symptoms began shortly after starting trimethoprim-sulfamethoxazole (a known cytochrome P450 inducer). Laboratory results reveal profound hyponatremia (

122 \text{ mEq/L}

Sulfonamides are classic precipitants of acute intermittent porphyria (AIP) attacks by increasing hepatic heme demand. The severe hyponatremia is consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH), a well-known complication of acute porphyria.

Determine the most appropriate initial laboratory test.

The initial screening test of choice is the measurement of spot urine porphobilinogen (PBG).

During an acute attack of AIP, porphobilinogen deaminase deficiency leads to a rapid, massive accumulation of the upstream precursor PBG. A spot urine test is highly sensitive, rapidly obtainable, and minimally invasive for confirming the diagnosis in the emergency setting.

Key Concept

Diagnosis and acute evaluation of Acute Intermittent Porphyria (AIP)

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