A 42-year-old woman is evaluated for a 6-month history of progressive weight gain, facial … — USMLE Step 2 CK

A 42-year-old woman is evaluated for a 6-month history of progressive weight gain, facial rounding, and worsening hypertension. She also reports easy bruising, newly developing dark hairs on her chin, and muscle weakness when climbing stairs. She takes amlodipine and lisinopril, but her blood pressure remains poorly controlled at $162/98\text{ mmHg}$ . Physical examination shows central obesity, facial plethora, supraclavicular fat pads, and wide, violaceous abdominal striae.

Laboratory findings:
- Serum potassium: $3.3\text{ mEq/L}$
- 24-hour urine free cortisol: $420\ \mu\text{g}$ (Normal: $< 45\ \mu\text{g}$ )
- Overnight 1-mg dexamethasone suppression test: Serum cortisol is $15\ \mu\text{g/dL}$ (Normal: $< 1.8\ \mu\text{g/dL}$ )
- Plasma ACTH: $110\text{ pg/mL}$ (Normal: $10-60\text{ pg/mL}$ )

An MRI of the brain with contrast reveals a $4\text{ mm}$ focal hypointense lesion in the anterior pituitary gland.

Which of the following is the most appropriate next step in management?

Inferior petrosal sinus samplingAnswer
B
Transsphenoidal surgical resection
C
CT scan of the chest and abdomen
D
Pelvic ultrasonography
E
Adrenal venous sampling

Answer

Inferior petrosal sinus sampling

The patient's clinical presentation and initial laboratory results (elevated 24-hour urine free cortisol, failure to suppress on the 1-mg dexamethasone test) confirm Cushing's syndrome. The elevated ACTH level indicates ACTH-dependent disease, which narrows the etiology to either a pituitary adenoma (Cushing's disease) or an ectopic ACTH-secreting tumor. When the subsequent pituitary MRI shows an adenoma that is less than 6 mm, or is normal, bilateral inferior petrosal sinus sampling (IPSS) is the gold standard next step. Pituitary incidentalomas smaller than 6 mm are found in up to 10% of the general population. Therefore, discovering a 4-mm lesion does not guarantee it is the source of the excess ACTH. IPSS measures ACTH levels in the venous drainage of the pituitary compared to peripheral blood, confirming a central source if a gradient is present, and directing the patient to transsphenoidal surgery.

Step-by-Step Solution

Analyze the clinical presentation and initial laboratory findings.

The patient has classic signs of Cushing's syndrome confirmed by elevated 24-hour urine free cortisol and failure to suppress on the overnight 1-mg dexamethasone suppression test.

This establishes the diagnosis of hypercortisolism.

Determine the etiology based on the ACTH level.

The plasma ACTH is elevated (

110\text{ pg/mL}

), which indicates ACTH-dependent Cushing's syndrome.

This localizes the source to either a pituitary adenoma (Cushing's disease) or an ectopic ACTH-secreting tumor.

Interpret the MRI findings and determine the next step.

The MRI shows a

4\text{ mm}

pituitary lesion. Because it is less than

6\text{ mm}

, inferior petrosal sinus sampling is required.

Pituitary incidentalomas are common. Without IPSS confirmation, there is a risk of missing an ectopic source and performing unnecessary brain surgery.

Key Concept

In patients with ACTH-dependent Cushing's syndrome, if the pituitary MRI is normal or shows an adenoma

< 6\text{ mm}

, inferior petrosal sinus sampling is required to differentiate Cushing's disease from ectopic ACTH syndrome.

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