A 38-year-old woman is evaluated in the outpatient clinic for progressive weight gain, per… — USMLE Step 3

A 38-year-old woman is evaluated in the outpatient clinic for progressive weight gain, persistent fatigue, and easy bruising over the past six months. She has also noted irregular, infrequent menstrual cycles. Her blood pressure is $156/94$ mmHg, heart rate is $82$ /min, and BMI is $32 \text{ kg/m}^2$ . Physical examination reveals facial plethora, accumulation of dorsocervical and supraclavicular fat, and wide, violaceous striae across her lower abdomen. She takes no medications and has no history of exogenous glucocorticoid use. The physician suspects an endocrine abnormality and plans to initiate a diagnostic workup. Which of the following diagnostic tests are the most appropriate initial screening steps to establish the diagnosis in this patient? (Select exactly 2 tests)

$24$ -hour urine free cortisolAnswer
Low-dose ( $1$ -mg) overnight dexamethasone suppression testAnswer
C
Plasma adrenocorticotropic hormone (ACTH) level
D
Magnetic resonance imaging (MRI) of the pituitary gland
E
Random early morning serum cortisol

Answer

The correct tests are the

24

-hour urine free cortisol and the low-dose (

1

-mg) overnight dexamethasone suppression test.

The patient's clinical presentation strongly suggests Cushing syndrome. The standard diagnostic workup for Cushing syndrome requires a strict sequential approach to prevent misdiagnosis. The first step is to definitively prove the presence of hypercortisolism. Endocrine guidelines recommend using at least two of three established first-line screening modalities: a

24

-hour urine free cortisol, a low-dose (

1

-mg) overnight dexamethasone suppression test, or late-night salivary cortisol. Only after two of these tests are abnormal does the diagnostic algorithm proceed to the next step.

Step-by-Step Solution

Identify the suspected clinical diagnosis.

The patient's presentation of weight gain, facial plethora, supraclavicular fat pads, and wide violaceous striae is highly suspicious for endogenous Cushing syndrome.

Recognizing the classic clinical stigmata is necessary to determine the appropriate diagnostic pathway.

Determine the proper sequencing for the suspected diagnosis.

The first step is to establish the presence of endogenous hypercortisolism using highly sensitive biochemical screening tests.

You must confirm excess cortisol production biochemically before attempting to localize the source.

Select the correct first-line tests according to guidelines.

Guidelines recommend ordering at least two of the following three tests:

24

-hour urine free cortisol, low-dose (

1

-mg) overnight dexamethasone suppression test, or late-night salivary cortisol.

These specific tests reliably demonstrate the loss of normal diurnal cortisol variation or the lack of negative feedback, which are the hallmarks of Cushing syndrome.

Key Concept

The diagnostic sequencing for Cushing syndrome requires initial biochemical confirmation of hypercortisolism (using

24

-hour urine free cortisol, low-dose dexamethasone suppression test, or late-night salivary cortisol) before proceeding to ACTH measurement or anatomical imaging.

Estimated Time:1m 15s

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