Therapeutic management of different etiologies of cushing syndrome

Objectives: This review summarizes current therapeutic strategies for managing Cushing syndrome, a rare endocrine disorder caused by prolonged exposure to excessive glucocorticoids. The objective is to present treatment approaches tailored to the major etiologies of cortisol excess: exogenous glucocorticoid-induced Cushing syndrome, Cushing disease, ectopic ACTH syndrome, and adrenal causes of hypercortisolism. Methodology: Methods include a structured review of the literature focusing on interventions such as surgery, pharmacologic therapies, and supportive management of metabolic, cardiovascular, and neuropsychiatric complications. The review emphasizes how treatment selection should be individualized according to the underlying cause, the severity of hypercortisolism, and patient-specific factors. Main Findings: Key conclusions are that management must differ based on where cortisol overproduction originates. For exogenous Cushing syndrome, the cornerstone is reducing glucocorticoid exposure while actively treating associated complications. In Cushing disease, transsphenoidal surgery remains the first-line therapy. For ectopic ACTH syndrome, tumor-directed treatment is prioritized when feasible. Adrenal causes of hypercortisolism are primarily managed with adrenalectomy. Pharmacologic options are important for patients with persistent, recurrent, or non-operable disease. Novelty: Overall, the paper highlights the need for a multidisciplinary, personalized approach to achieve biochemical control, minimize complications, and improve outcomes despite common diagnostic delays and the risk of recurrence. The novelty lies in integrating all major etiologies into a single etiology-based framework linking each to first-line and pharmacologic options.