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A 45-year-old woman is evaluated for progressive weight gain, proximal muscle weakness, and easy bruising. Physical examination reveals facial plethora, supraclavicular fat pads, and wide, purplish abdominal striae. A 24-hour urine free cortisol test and a low-dose dexamethasone suppression test both confirm the presence of endogenous hypercortisolism. Her plasma adrenocorticotropic hormone (ACTH) level is 145 pg/mL (normal: 10-60 pg/mL), establishing a diagnosis of ACTH-dependent Cushing syndrome.

Assuming that each consecutive test in the localization workup yields an equivocal or non-diagnostic result, arrange the following radiologic and imaging procedures in the most appropriate chronological sequence according to current evidence-based guidelines.

  1. 1Magnetic resonance imaging (MRI) of the pituitary gland with intravenous gadolinium
  2. 2Bilateral inferior petrosal sinus sampling (IPSS) with corticotropin-releasing hormone (CRH) stimulation
  3. 3Computed tomography (CT) of the chest, abdomen, and pelvis with intravenous contrast
  4. 4Gallium-68 DOTATATE positron emission tomography (PET/CT) scan

Cevap

The correct chronological sequence for localizing the source is: Magnetic resonance imaging (MRI) of the pituitary gland, followed by Bilateral inferior petrosal sinus sampling (IPSS), then Computed tomography (CT) of the chest, abdomen, and pelvis, and finally Gallium-68 DOTATATE PET/CT.
The evidence-based diagnostic pathway for ACTH-dependent Cushing syndrome requires systematically identifying the source of excess ACTH. Because pituitary adenomas are the most common cause, a pituitary MRI is ordered first. If the MRI does not show a definitive adenoma (≥6 mm), IPSS is required to rule in or rule out a central source, as pituitary incidentalomas can mislead the diagnosis. If IPSS proves the source is ectopic, a CT of the chest, abdomen, and pelvis is ordered to find the tumor. Only if this standard CT fails is a specialized functional scan like a Ga-68 DOTATATE PET/CT utilized.

Adım Adım Çözüm

1
Identify the most likely etiology and initial imaging test for ACTH-dependent hypercortisolism.
MRI of the pituitary gland is the mandatory first test because pituitary adenomas (Cushing disease) account for up to 80% of cases.
It is non-invasive and highly sensitive for larger adenomas. Proceeding to other tests without a pituitary MRI violates standard protocols.
2
Determine the next step when the initial pituitary MRI is equivocal (e.g., normal or showing a lesion <6 mm).
Bilateral inferior petrosal sinus sampling (IPSS) must be performed next.
Pituitary incidentalomas are common in the general population. IPSS definitively differentiates a true central pituitary source from an ectopic ACTH-secreting tumor by measuring the central-to-peripheral ACTH gradient.
3
Select the appropriate imaging modality if IPSS confirms an ectopic source (no central-to-peripheral gradient).
CT of the chest, abdomen, and pelvis is placed third in the sequence.
Once an ectopic source is biochemically confirmed, standard high-resolution cross-sectional imaging is the first-line method to locate common tumors such as small cell lung cancer or bronchial/thymic carcinoids.
4
Choose the salvage diagnostic test if standard cross-sectional imaging is unrevealing.
Gallium-68 DOTATATE PET/CT (or alternative somatostatin receptor scintigraphy) is placed last.
This functional imaging modality specifically targets somatostatin receptors commonly expressed on neuroendocrine tumors and is reserved for localizing occult ectopic sources.

Anahtar Kavram

In ACTH-dependent Cushing syndrome, the diagnostic localization sequence must strictly proceed from non-invasive pituitary imaging to invasive pituitary testing, followed by cross-sectional body imaging if an ectopic source is confirmed, and functional body imaging as a last resort.

Alternatif Yöntem

While IPSS is the gold standard for differentiating central from ectopic ACTH secretion, some institutions may utilize high-dose dexamethasone suppression testing or CRH stimulation testing first; however, these biochemical tests lack the definitive accuracy of IPSS, and current surgical guidelines prioritize IPSS when MRI is equivocal.
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