A 34-year-old woman is referred to the endocrinology clinic for evaluation of a 14-kg weig… — USMLE Step 3

A 34-year-old woman is referred to the endocrinology clinic for evaluation of a $14$ -kg weight gain over the past year, accompanied by proximal muscle weakness and new-onset facial hair growth. Her blood pressure is $156/94$ mmHg. Physical examination reveals central adiposity, facial plethora, and wide, violaceous abdominal striae. Laboratory testing confirms hypercortisolism with significantly elevated $24$ -hour urine free cortisol levels on two separate collections and failure to suppress morning serum cortisol following a low-dose ( $1$ -mg) overnight dexamethasone suppression test. Subsequent biochemical evaluation shows a morning plasma adrenocorticotropic hormone (ACTH) level of $95$ pg/mL (normal: $9$ to $52$ pg/mL). Magnetic resonance imaging (MRI) of the sella turcica with gadolinium demonstrates a $3$ -mm hypoenhancing lesion in the right anterior pituitary gland. Which of the following is the most appropriate next step in the diagnostic workup?

Bilateral inferior petrosal sinus samplingAnswer
B
Computed tomography of the chest and abdomen
C
Transsphenoidal pituitary adenomectomy
D
High-dose (8-mg) dexamethasone suppression test
E
Computed tomography of the adrenal glands

Answer

Bilateral inferior petrosal sinus sampling

The correct answer is bilateral inferior petrosal sinus sampling (BIPSS). The patient has confirmed ACTH-dependent Cushing syndrome. The next step is to localize the source of ACTH, which can be central (Cushing disease) or peripheral (ectopic ACTH syndrome). While the MRI shows a 3-mm pituitary lesion, pituitary incidentalomas are present in up to 10-20% of the general population. Endocrine Society guidelines state that a pituitary MRI finding of a lesion less than 6 mm is not definitive evidence of Cushing disease because it could represent a nonfunctioning incidentaloma in a patient with a small, occult ectopic tumor. Therefore, BIPSS is required to measure the central-to-peripheral ACTH gradient. A central-to-peripheral ratio of >2.0 at baseline or >3.0 after corticotropin-releasing hormone (CRH) stimulation confirms Cushing disease.

Step-by-Step Solution

Analyze initial labs to confirm the diagnosis.

Elevated 24-hour urine free cortisol and abnormal 1-mg dexamethasone suppression test confirm Cushing syndrome.

Hypercortisolism must be biochemically established before searching for a cause.

Interpret the plasma ACTH level.

ACTH is elevated at 95 pg/mL.

An elevated ACTH level indicates ACTH-dependent Cushing syndrome, narrowing the differential to a pituitary adenoma (Cushing disease) or an ectopic ACTH-secreting tumor.

Evaluate the pituitary MRI findings in the context of the clinical picture.

The MRI shows a 3-mm lesion. Current guidelines require an adenoma to be at least 6 mm to definitively diagnose Cushing disease without further testing.

Pituitary incidentalomas are very common (10-20% of the population). A small lesion could be an unrelated incidentaloma in a patient who actually has an ectopic ACTH-producing tumor.

Determine the definitive test to differentiate the ACTH source.

Bilateral inferior petrosal sinus sampling (BIPSS) is selected.

BIPSS measures the central-to-peripheral ACTH gradient. A significant central gradient confirms Cushing disease, while no gradient points to ectopic ACTH syndrome, requiring further whole-body imaging.

Key Concept

In patients with ACTH-dependent Cushing syndrome and a pituitary MRI showing a lesion less than 6 mm, bilateral inferior petrosal sinus sampling is required to definitively distinguish between Cushing disease and ectopic ACTH syndrome.

Estimated Time:2m 0s

Question

Answer

Step-by-Step Solution

Key Concept

Common Mistakes

Topics

More questions from this topic