A 52-year-old man is evaluated for treatment-resistant hypertension. His current blood pre… — USMLE Step 3

A 52-year-old man is evaluated for treatment-resistant hypertension. His current blood pressure is $168/95\text{ mmHg}$ despite adherence to amlodipine, lisinopril, and chlorthalidone. Laboratory studies obtained two weeks ago showed:

- Serum sodium: $144\text{ mEq/L}$
- Serum potassium: $2.9\text{ mEq/L}$
- Plasma aldosterone concentration: $32\text{ ng/dL}$ (Normal: $3-16\text{ ng/dL}$ )
- Plasma renin activity: $0.2\text{ ng/mL/h}$ (Normal: $0.6-4.3\text{ ng/mL/h}$ )

A dedicated adrenal protocol computed tomography (CT) scan demonstrates a $1.8\text{-cm}$ lipid-rich nodule in the right adrenal gland. The left adrenal gland appears normal.

To guide further management, an adrenal venous sampling (AVS) procedure is performed with continuous cosyntropin (ACTH) infusion. The laboratory results from the procedure are shown in the table below:

Cannulation Site	Aldosterone ( $\text{ng/dL}$ )	Cortisol ( $\mu\text{g/dL}$ )
Peripheral vein (IVC)	$30$	$15$
Right adrenal vein	$600$	$150$
Left adrenal vein	$1200$	$300$

Based on these laboratory findings, which of the following is the most accurate interpretation of this patient's underlying condition?

Bilateral idiopathic adrenal hyperplasiaAnswer
B
Right-sided aldosterone-producing adenoma
C
Left-sided aldosterone-producing adenoma
D
Unsuccessful right adrenal vein cannulation
E
Adrenocorticotropic hormone-dependent hypercortisolism

Answer

Bilateral idiopathic adrenal hyperplasia

The correct diagnosis is bilateral idiopathic adrenal hyperplasia. Adrenal venous sampling (AVS) interpretation requires a stepwise calculation. First, successful cannulation is verified by dividing adrenal cortisol by peripheral (IVC) cortisol (Selectivity Index); a ratio

>5

with cosyntropin confirms success. Here, the right SI is

10

(

150/15

) and the left is

20

(

300/15

). Second, because absolute hormone levels are subject to dilutional variance based on exact catheter position and blood flow, aldosterone must be normalized to cortisol. The aldosterone-to-cortisol (A/C) ratio is

4

on the right (

600/150

) and

4

on the left (

1200/300

). Finally, the lateralization index is calculated by dividing the highest A/C ratio by the lowest A/C ratio (

4/4 = 1

). A lateralization index

<3

indicates symmetric, bilateral aldosterone hypersecretion. The right-sided nodule seen on imaging is therefore a non-functioning incidentaloma.

Step-by-Step Solution

Calculate the selectivity index (SI) for both adrenal veins to verify proper catheter placement.

Right SI = 150/15 = 10; Left SI = 300/15 = 20.

An SI > 5 (during cosyntropin infusion) confirms the catheter is properly placed in the adrenal vein, avoiding dilution from peripheral venous blood.

Calculate the aldosterone-to-cortisol (A/C) ratio for each adrenal vein.

Right A/C = 600/150 = 4; Left A/C = 1200/300 = 4.

Absolute aldosterone levels are misleading due to varying blood flow and dilution; cortisol acts as an internal standard to normalize the values.

Calculate the lateralization index (LI) to determine if secretion is unilateral or bilateral.

LI = Dominant A/C divided by Non-dominant A/C = 4 / 4 = 1.

An LI > 4 indicates unilateral autonomous hypersecretion (adenoma), whereas an LI < 3 indicates bilateral symmetric hypersecretion (hyperplasia).

Correlate the biochemical AVS diagnosis with the imaging findings.

The patient has bilateral adrenal hyperplasia, and the right-sided adrenal nodule is a non-functioning incidentaloma.

CT imaging is notoriously misleading in primary aldosteronism due to the high prevalence of non-functioning adrenal incidentalomas; AVS provides the definitive functional diagnosis.

Key Concept

Interpretation of adrenal venous sampling (AVS) using cortisol-normalized aldosterone ratios to distinguish between unilateral adenoma and bilateral hyperplasia.

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