Cushing Syndrome

Cushing Syndrome: Imaging Features and Clinical Essentials

Cushing syndrome is a disorder caused by prolonged exposure to excessive cortisol levels, either from endogenous overproduction or exogenous corticosteroid use. It presents with a constellation of symptoms including central obesity, moon facies, and skin changes. Imaging is crucial for identifying the source of cortisol excess, differentiating between pituitary, adrenal, or ectopic causes, and guiding treatment strategies.

Overview

Cushing syndrome results from chronic exposure to excess cortisol, either due to endogenous overproduction or exogenous corticosteroid intake. It typically affects adults aged 30-50, with women being more commonly affected. Key clinical manifestations include central obesity, moon facies, buffalo hump, skin striae, and muscle weakness. Imaging plays a vital role in localizing the source of cortisol excess, differentiating between pituitary adenomas, adrenal tumors, or ectopic ACTH production, and informing surgical or medical management.

Key Imaging Features

• CT of the abdomen demonstrates adrenal gland morphology; bilateral adrenal hyperplasia suggests pituitary adenoma (Cushing disease) or ectopic ACTH, while a unilateral adrenal adenoma or carcinoma points to primary adrenal overproduction.

• MRI of the pituitary is the modality of choice for detecting pituitary adenomas causing Cushing disease, with thin-slice sequences and gadolinium contrast enhancement being essential for visualizing lesions, often less than 10 mm.

• MRI findings in Cushing disease include microadenomas (typically <10 mm) that may show avid, homogeneous enhancement with delayed washout compared to normal pituitary tissue.

• Adrenal adenomas causing Cushing syndrome are often hyperattenuating on non-contrast CT ( > 20 Hounsfield Units) and show rapid contrast washout within 10 minutes, distinguishing them from non-functional adenomas.

• Ectopic ACTH-producing tumors, commonly in the lung (small cell carcinoma) or pancreas, may be identified on chest or abdominal CT/MRI, though they can be small and difficult to localize.

• In cases of suspected ectopic ACTH syndrome with negative initial imaging, bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation can help lateralize the source by comparing ACTH gradients between the petrosal sinuses and peripheral blood.

• Early adrenal adenomas may appear similar to normal adrenal glands on non-contrast CT, necessitating dynamic contrast-enhanced imaging for detection.

• Adrenocortical carcinomas are typically larger (>4 cm), heterogeneous, and may show calcifications or invasion on CT, with higher attenuation values and slower washout than adenomas.

Pathophysiology

• Pituitary adenomas (Cushing disease) lead to excessive ACTH secretion, stimulating bilateral adrenal hyperplasia and subsequent cortisol overproduction, which is visualized as enlarged adrenal glands on CT/MRI.

• Adrenal adenomas or carcinomas autonomously produce excess cortisol, leading to suppression of ACTH and often unilateral adrenal enlargement, with carcinomas being larger and more aggressive.

• Ectopic ACTH-producing tumors (e.g., small cell lung cancer, carcinoid tumors) secrete ACTH independently, causing bilateral adrenal hyperplasia similar to Cushing disease, but without a pituitary source.

• Chronic high cortisol levels lead to characteristic phenotypic changes (obesity, moon facies, striae) and can cause complications like osteoporosis and hypertension, which may be indirectly visualized on imaging (e.g., vertebral compression fractures).

Differential Diagnosis

• Exogenous Cushing Syndrome (Steroid Use): Clinical features are identical; diagnosis relies on history of glucocorticoid medication use and normal or low ACTH levels.

• Adrenal Incidentaloma with Subclinical Hypercortisolism: Imaging may show a non-functional adrenal mass, but biochemical testing reveals cortisol excess without overt clinical signs; differentiation from true Cushing syndrome requires careful biochemical assessment.

• Metabolic Syndrome/Obesity: Overlap in symptoms like central obesity and hypertension; Cushing syndrome typically has more pronounced skin changes (striae, bruising) and muscle weakness.

• Polycystic Ovary Syndrome (PCOS): Can present with hirsutism and menstrual irregularities, mimicking some aspects of Cushing syndrome; absence of central obesity and characteristic skin changes helps differentiate.

• Pseudo-Cushing Syndrome (e.g., Depression, Alcoholism): Biochemical tests may show elevated cortisol, but dexamethasone suppression tests are often less suppressed than in true Cushing syndrome, and imaging is typically normal.

• Ectopic ACTH Syndrome vs. Cushing Disease: Differentiating requires biochemical tests like BIPSS; ectopic sources are often smaller and may be missed on initial imaging, while pituitary adenomas are typically visualized on dedicated pituitary MRI.

Imaging Protocols and Techniques

• First-line imaging for suspected adrenal tumors is non-contrast CT of the abdomen, followed by contrast-enhanced CT if needed, to assess size, attenuation, and washout characteristics.

• For suspected Cushing disease, high-resolution MRI of the pituitary with thin slices (2-3 mm) and dynamic contrast enhancement is the preferred modality.

• If ectopic ACTH syndrome is suspected and initial imaging is negative, consider dedicated lung CT or MRI, and potentially somatostatin receptor scintigraphy or peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors.

• Bilateral inferior petrosal sinus sampling (BIPSS) is indicated when biochemical testing suggests ACTH-dependent Cushing syndrome but pituitary imaging is negative or equivocal, to differentiate pituitary from ectopic sources.

• A technical pitfall is inadequate pituitary MRI protocols, leading to missed microadenomas; ensure thin slices, appropriate contrast timing, and coronal/sagittal views.

• Follow-up imaging after surgical resection of pituitary adenomas typically involves a postoperative pituitary MRI within 1-3 months to confirm complete resection; surveillance imaging frequency depends on recurrence risk and clinical status.

 

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