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Difficulty: MediumOrdering Laboratory Tests

A 38-year-old female patient is evaluated in the outpatient clinic for an 8-month history of progressive weight gain, generalized fatigue, and easy bruising. She has also noted the recent onset of facial hair growth and irregular menstrual cycles. She has no significant past medical history and takes no medications. Her blood pressure is 155/95 mmHg155/95 \text{ mmHg}, and her body mass index is 34 kg/m234 \text{ kg/m}^2. Physical examination demonstrates facial plethora, a prominent dorsocervical fat pad, and multiple violaceous striae across the abdomen. Proximal muscle weakness is evident in the bilateral lower extremities. Which of the following is the most appropriate next step in laboratory evaluation?

  1. A
    Plasma adrenocorticotropic hormone (ACTH) concentration
  2. B
    Random morning serum cortisol measurement
  3. Late-night salivary cortisol measurementAnswer
  4. D
    High-dose dexamethasone suppression test
  5. E
    Corticotropin-releasing hormone (CRH) stimulation test

Answer

Late-night salivary cortisol measurement is the most appropriate initial diagnostic laboratory test to confirm hypercortisolism.
This patient's clinical presentation is highly suspicious for Cushing syndrome (hypercortisolism). The diagnostic algorithm for Cushing syndrome strictly dictates that the first step is to definitively confirm the presence of excess cortisol. This is achieved using one of three primary screening tests: late-night salivary cortisol (usually requiring two measurements), 24-hour urine free cortisol, or a low-dose (1-mg) overnight dexamethasone suppression test. Therefore, ordering a late-night salivary cortisol measurement is the most appropriate next step in laboratory evaluation.

Step-by-Step Solution

1
Identify the clinical syndrome described in the patient vignette.
The patient presents with classic signs and symptoms of Cushing syndrome, including central obesity, facial plethora, violaceous striae, easy bruising, proximal muscle weakness, and hypertension.
Recognizing the clinical phenotypic pattern dictates the appropriate subsequent diagnostic laboratory workup.
2
Recall the established diagnostic laboratory algorithm for Cushing syndrome.
The first essential step is to definitively establish the presence of endogenous hypercortisolism before attempting to determine the underlying etiology.
Prematurely testing for the cause (e.g., measuring ACTH) without first confirming hypercortisolism can lead to diagnostic errors due to overlapping reference ranges and normal physiological variations.
3
Identify the appropriate initial screening tests for hypercortisolism.
The three validated first-line screening tests are late-night salivary cortisol, 24-hour urine free cortisol, and the low-dose (1-mg) overnight dexamethasone suppression test.
These specific tests are highly sensitive and take advantage of the loss of diurnal cortisol variation or the failure of negative feedback that characterizes Cushing syndrome.

Key Concept

The initial laboratory evaluation of suspected Cushing syndrome requires definitively confirming hypercortisolism using a late-night salivary cortisol test, a 24-hour urine free cortisol measurement, or a low-dose overnight dexamethasone suppression test prior to evaluating the specific etiology.
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Ordering Laboratory Tests

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