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Review
. 2025 Oct 1;32(5):222-232.
doi: 10.1097/MED.0000000000000920. Epub 2025 Jul 17.

Advances in the medical management of hypercortisolism: current strategies, monitoring, and emerging therapies

Jorge Esteban Mosquera  1 , Leili Rahimi, Oksana Hamidi
Affiliations
Review

Advances in the medical management of hypercortisolism: current strategies, monitoring, and emerging therapies

Jorge Esteban Mosquera et al. Curr Opin Endocrinol Diabetes Obes. .

Abstract

Purpose of review: This review outlines the indications for medical management of hypercortisolism and summarizes available and emerging pharmacologic agents.

Recent findings: Endogenous Cushing syndrome is a complex endocrine disorder resulting from chronic cortisol excess. The underlying etiology of Cushing syndrome is due to either adrenocorticotropic hormone (ACTH)-dependent causes, such as pituitary tumors (Cushing disease) or ectopic ACTH syndrome from nonpituitary neuroendocrine tumors, or ACTH-independent causes, such as autonomous cortisol production by adrenal adenomas, hyperplasia, or carcinomas. Cushing syndrome is associated with increased cardiometabolic morbidity and mortality, infections, thromboembolic events, cognitive and psychiatric disorders, and reduced quality of life. Successful treatment significantly reduces mortality and improves associated clinical and metabolic consequences of chronic hypercortisolism. Management of Cushing syndrome varies depending on the underlying etiology. While surgical resection of the causal lesion remains the first-line treatment for all etiologies of Cushing syndrome, second-line treatments, such as medical management, radiation therapy, and bilateral adrenalectomy, may be needed when surgery is not feasible or has failed.

Summary: We discuss the efficacy of medical therapies for hypercortisolism, combination therapy strategies, special considerations in unique populations, and monitoring protocols. Finally, we explore emerging treatments and potential future directions in the management of this complex condition.

Keywords: Cushing syndrome; block-and-replace; dose titration; targeted therapy.

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References

    1. Reincke M, Fleseriu M. Cushing syndrome: a review. JAMA 2023; 330:170–181.
    1. Fleseriu M, Auchus R, Bancos I, et al. Consensus on diagnosis and management of Cushing's disease: a guideline update. Lancet Diabetes Endocrinol 2021; 9:847–875.
    1. Nieman LK, Biller BM, Findling JW, et al. Treatment of Cushing's syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015; 100:2807–2831.
    1. Melmed S. Pituitary-tumor endocrinopathies. N Engl J Med 2020; 382:937–950.
    1. Dekkers OM, Horváth-Puhó E, J⊘rgensen JOL, et al. Multisystem morbidity and mortality in Cushing's syndrome: a cohort study. J Clin Endocrinol Metab 2013; 98:2277–2284.