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Zorluk: OrtaDiagnostic Workup and Test Sequencing

A 38-year-old woman is evaluated in the ambulatory setting for recent, unexplained weight gain and new-onset hypertension. Over the past eight months, she has gained 1414 kg despite no changes to her diet or physical activity level. She also reports increasing difficulty climbing stairs and easy bruising on her extremities. Blood pressure is 158/96158/96 mmHg. Physical examination reveals facial plethora, prominent dorsocervical and supraclavicular fat pads, and broad violaceous striae across the lower abdomen. Initial screening for hypercortisolism is performed using a 11-mg overnight dexamethasone suppression test. Her serum cortisol level at 8:00 AM the following morning is 14μg/dL14 \mu\text{g/dL} (normal: <1.8μg/dL<1.8 \mu\text{g/dL}). Which of the following is the most appropriate next step in the diagnostic evaluation of this patient?

  1. Measurement of plasma adrenocorticotropic hormone (ACTH)Cevap
  2. B
    Magnetic resonance imaging (MRI) of the brain
  3. C
    High-dose (8-mg) dexamethasone suppression test
  4. D
    Computed tomography (CT) scan of the adrenal glands
  5. E
    Bilateral inferior petrosal sinus sampling

Cevap

Measurement of plasma adrenocorticotropic hormone (ACTH) is the most appropriate next step to classify the etiology of the hypercortisolism.
The patient's clinical signs and the failure to suppress morning cortisol after a low-dose dexamethasone test confirm endogenous hypercortisolism (Cushing syndrome). The crucial next step in the diagnostic sequence is to determine whether the excess cortisol is ACTH-dependent (e.g., Cushing disease, ectopic ACTH secretion) or ACTH-independent (e.g., adrenal adenoma, adrenal carcinoma). Measuring plasma ACTH accomplishes this. If ACTH is suppressed, the source is adrenal, and an adrenal CT is warranted. If ACTH is normal or elevated, the source is ACTH-dependent, and an MRI of the pituitary (and potentially a high-dose dexamethasone test) is the appropriate subsequent step.

Adım Adım Çözüm

1
Interpret the initial clinical presentation and laboratory results.
The patient has clinical features of Cushing syndrome and a positive 1-mg overnight dexamethasone suppression test, confirming endogenous hypercortisolism.
Establishing the presence of hypercortisolism is the first required step in the diagnostic algorithm.
2
Determine the next necessary diagnostic phase.
The evaluation must move from confirming hypercortisolism to localizing its source.
Cushing syndrome can be driven by primary adrenal pathology (ACTH-independent) or central/ectopic pathology (ACTH-dependent).
3
Select the appropriate biochemical test for localization before imaging.
Plasma ACTH measurement is selected.
Biochemical localization must precede anatomical imaging to avoid finding and treating incidentalomas.

Anahtar Kavram

In the evaluation of Cushing syndrome, after hypercortisolism is confirmed with initial screening tests (e.g., low-dose dexamethasone suppression test, 24-hour urine free cortisol), the immediate next step is to measure plasma ACTH to differentiate between ACTH-dependent and ACTH-independent etiologies.
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