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Adrenal Cushing's syndrome — Clinical Guidelines

Overview

Cushing's syndrome results from prolonged exposure to excess glucocorticoids, often due to pituitary ACTH hypersecretion or adrenal abnormalities, leading to diverse clinical manifestations including metabolic disturbances, cardiovascular issues, and cognitive impairment 1 2 3 12.

Diagnosis

Clinical Presentation: Assess for characteristic signs such as central obesity, striae, hypertension, and glucose intolerance 1 2 3.

Laboratory Tests: Measure 24-hour urinary free cortisol (UFC) and late-night salivary cortisol levels 1 2.

Suppression Tests: Dexamethasone suppression test and corticotropin-releasing hormone (CRH) stimulation test 1 2 22.

Imaging: CT or MRI of the pituitary and adrenal glands; inferior petrosal sinus sampling for ACTH gradients in ACTH-dependent cases 22.

Differentiating Causes: Evaluate plasma ACTH levels to distinguish between pituitary and ectopic ACTH sources 3 33.

Genetic Considerations: Assess for genetic causes, particularly in familial cases 8.

Management

First-Line Treatments:

- Surgery: Transsphenoidal surgery for pituitary adenomas 1 2 22. - Medical Therapy: - Steroidogenesis Inhibitors: Osilodrostat and metyrapone 5 6 16. - Pasireotide: For ACTH-dependent cases, particularly when surgery is not feasible 4.

Adjunctive Treatments:

- Radiation Therapy: For residual or recurrent pituitary tumors 1 2. - Bilateral Adrenalectomy: For unresectable or refractory cases 55.

Glucose Management: Tight glycemic control with insulin or other antidiabetic agents as needed 19 20.

Special Populations

Pregnancy: Rare occurrence; management focuses on maternal and fetal safety, often requiring multidisciplinary care 40 41.

Pediatrics: Consider genetic causes like McCune-Albright syndrome; tailored surgical and medical interventions 11 38.

Comorbidities: Address comorbidities such as hypertension and infections (e.g., nocardiosis) with targeted therapies 13 28.

Key Recommendations

Screen High-Risk Patients: Routinely screen patients with hypertension, obesity, and unexplained glucose intolerance for Cushing's syndrome (Evidence: Moderate) 1.

Use UFC for Initial Diagnosis: Utilize 24-hour urinary free cortisol levels for initial screening (Evidence: Strong) 1 2.

Consider Genetic Testing: Evaluate for genetic causes, especially in familial cases, to guide management (Evidence: Moderate) 8.

Prioritize Surgical Intervention: For ACTH-dependent Cushing's syndrome, prioritize transsphenoidal surgery when feasible (Evidence: Strong) 1 2 22.

Monitor and Manage Comorbidities: Closely monitor and treat comorbidities such as hypertension and infections (Evidence: Moderate) 13 28.

Tailored Medical Therapy: Select appropriate medical therapy based on etiology, considering steroidogenesis inhibitors like osilodrostat or metyrapone (Evidence: Moderate) 5 6 16.

References

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Adrenal Cushing's syndrome