Examkin

Question

Difficulty: MediumOrdering Laboratory Tests

A 35-year-old woman presents to the clinic with a 6-month history of progressive weight gain, proximal muscle weakness, and easy bruising. Physical examination reveals a blood pressure of 155/95 mmHg, facial plethora, central adiposity with violaceous striae, and prominent supraclavicular fat pads. The physician suspects an endogenous hypercortisolism syndrome. Assuming each subsequent test result confirms the need for further diagnostic workup, arrange the following laboratory investigations in the most appropriate chronological order to establish the precise etiology of this patient's condition.

  1. 1Late-night salivary cortisol assay
  2. 2Plasma adrenocorticotropic hormone (ACTH) level
  3. 3High-dose (8-mg) dexamethasone suppression test
  4. 4Bilateral inferior petrosal sinus sampling (IPSS)

Answer

The correct chronological sequence for evaluating suspected Cushing syndrome is: Late-night salivary cortisol assay, followed by Plasma ACTH level, then High-dose dexamethasone suppression test, and finally Bilateral inferior petrosal sinus sampling.
The sequence follows the standard diagnostic algorithm for Cushing syndrome: 1) Confirm hypercortisolism (Late-night salivary cortisol), 2) Establish ACTH dependency (Plasma ACTH), 3) Non-invasive localization of ACTH-dependent disease (High-dose dexamethasone test), and 4) Invasive localization if non-invasive tests are equivocal (IPSS).

Step-by-Step Solution

1
Screen for pathological hypercortisolism.
Perform a late-night salivary cortisol assay (or 24-hour urine free cortisol, or low-dose dexamethasone suppression test).
The diagnosis of hypercortisolism must be definitively established before attempting to localize the source of the excess cortisol.
2
Determine if the hypercortisolism is ACTH-dependent or ACTH-independent.
Measure plasma ACTH levels.
A suppressed ACTH level indicates an adrenal source (independent), whereas a normal or elevated ACTH level indicates a pituitary or ectopic source (dependent).
3
Differentiate between pituitary and ectopic sources of ACTH using non-invasive methods.
Perform a high-dose (8-mg) dexamethasone suppression test.
Pituitary adenomas typically retain some negative feedback mechanisms and will suppress cortisol production at high doses, while ectopic tumors (e.g., small cell lung cancer) typically do not.
4
Confirm the ACTH source if non-invasive tests or imaging are inconclusive.
Perform bilateral inferior petrosal sinus sampling (IPSS).
This is the most accurate, invasive method to definitively differentiate pituitary from ectopic ACTH production by comparing central (petrosal) to peripheral ACTH concentration ratios.

Key Concept

The diagnostic algorithm for Cushing syndrome proceeds in a strict sequential order: establish the presence of hypercortisolism, determine ACTH dependence, and subsequently localize the ACTH source via non-invasive and then invasive testing if needed.
Estimated Time:1m 30s
Rate this question

Topics

Ordering Laboratory Tests

More questions from this topic