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Difficulty: MediumDiagnostic Workup and Test Sequencing

A 48-year-old woman comes to the clinic for evaluation of progressive weight gain, fatigue, and easy bruising over the past 8 months. She reports difficulty climbing stairs due to proximal leg weakness. Her medical history is unremarkable, and she takes no medications. Her blood pressure is 162/98 mm Hg, and her pulse is 82/min. Physical examination reveals a plethoric face, prominent supraclavicular fat pads, and broad, violaceous striae over the lower abdomen. Which of the following is the most appropriate next step in the diagnostic evaluation of this patient?

  1. Measurement of late-night salivary cortisol concentrationAnswer
  2. B
    Measurement of serum adrenocorticotropic hormone level
  3. C
    High-dose overnight dexamethasone suppression test
  4. D
    Magnetic resonance imaging of the pituitary gland
  5. E
    Measurement of a random morning serum cortisol

Answer

Measurement of late-night salivary cortisol concentration
The correct answer is the measurement of late-night salivary cortisol concentration. This patient presents with classic clinical features of Cushing syndrome. The diagnostic workup for Cushing syndrome must follow a strict sequence to avoid false-positive localizations. The first mandatory step is to biochemically establish the presence of pathological hypercortisolism. This is achieved by utilizing one of three first-line screening tests: late-night salivary cortisol (assessing the loss of normal diurnal variation), 24-hour urine free cortisol (assessing total daily production), or a low-dose (1-mg) overnight dexamethasone suppression test (assessing the loss of normal negative feedback).

Step-by-Step Solution

1
Identify the clinical syndrome presented by the patient.
The patient exhibits classic signs of Cushing syndrome, including progressive weight gain, proximal muscle weakness, easy bruising, facial plethora, supraclavicular fat pads, broad violaceous striae, and secondary hypertension.
Recognizing the constellation of symptoms dictates the specific diagnostic pathway for hypercortisolism.
2
Determine the first step in the established diagnostic sequence for the suspected condition.
The initial step in evaluating suspected Cushing syndrome is confirming the presence of endogenous hypercortisolism using one of three recommended screening tests.
Biochemical confirmation of the disease state must precede any attempts to localize the source of the hormone excess.
3
Select the appropriate screening test from the available options.
Late-night salivary cortisol is one of the validated initial screening tests. The other options represent tests utilized further down the diagnostic algorithm or inappropriate tests.
Diagnostic test sequencing strictly requires establishing hypercortisolism before measuring ACTH or performing imaging.

Key Concept

The initial evaluation of suspected Cushing syndrome requires confirming hypercortisolism with a 24-hour urine free cortisol, late-night salivary cortisol, or low-dose dexamethasone suppression test before assessing ACTH levels or performing imaging.
Estimated Time:1m 15s
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Diagnostic Workup and Test Sequencing

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