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Cushing's Syndrome

Once a diagnosis has been confirmed, treatment is available.

Standard first- and second-line treatment

As cortisol normalization is the main goal of Cushing’s syndrome (CS) treatment to help reduce comorbidities and improve quality of life, an individualized treatment approach is recommended, with patient values and preferences taken into consideration.1

First-line treatment: surgery, if appropriate1

  • Complete resection of the underlying tumor to normalize cortisol

Second-line treatment: repeat surgery or medication or radiation therapy when surgery is not an option or fails to normalize cortisol levels1

  • Medication therapy has been increasingly used for all types of endogenous CS when surgical therapies have failed or are not feasible 
  • Radiation can be used as additional treatment for patients with endogenous CS who do not achieve remission when surgery is not feasible

Monitoring cortisol levels closely after post-surgical tumor resection

  • Within 48 hours post-surgery, most patients in remissiona develop a glucocorticoid withdrawal syndrome associated with circulating cortisol levels of <2 μg/dL.2

  • Serum cortisol levels <2 μg/dL after surgery are associated with remission and a low recurrence rate of approximately 10% at 10 years.3

aRemission is generally defined as morning serum cortisol values <5 μg/dL (<138 nmol/L) or UFC <28-56 nmol/d (<10-20 μg/d) within 7 days of selective tumor resection.1

Pharmacologic therapy is a potential treatment choice for patients for whom surgery is not an option or has failed to effectively normalize cortisol2

Pharmacologic therapy may be appropriate for:

  • Patients who are ineligible or have refused for surgery4
  • Patients with persistent or recurrent CS4
  • Patients undergoing radiotherapy who require further control in cortisol levels4

Medications lower cortisol in three different ways

cortisol-pathway

Therapeutic targets in cortisol normalization

Target: Pituitary tumor



One class of medications directly targets the pituitary tumor in the brain. This helps to lower levels of adrenocorticotropic hormone, or ACTH levels. Lower ACTH results in lower cortisol levels and may help many of your symptoms.

Pituitary gland:

  • Somatostatin analog
  • Dopamine agonist

Target: Adrenal glands (cortisol production)


Cortisol is made in the adrenal glands located on top of the kidneys. This class of medications target the adrenal glands to stop them from making too much cortisol. By directly lowering cortisol levels, this can reduce the symptoms and comorbidities that are caused by too much cortisol.

Adrenal gland:

  • Steroidogenesis inhibitors
  • Adrenolytic drug

Target: Cortisol receptors

There is another class of medicines that doesn’t actually reduce ACTH or cortisol levels. These medications bind to cortisol receptors found throughout the body. The cortisol that is made in the adrenal glands is then not able to attach to these receptors. This will reduce the symptoms caused by too much cortisol.

Glucocorticoid receptor:

  • Antagonist

Adult patients with CS who cannot undergo pituitary surgery or for whom surgery has been ineffective

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REFERENCES: 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(8):2807-2831. doi:10.1210/jc.2015-1818. 2. Lonser RR, Nieman L, Oldfield EH. Cushing’s disease: pathobiology, diagnosis, and management. J Neurosurg. 2017;126(2):404-417. doi: 10.3171/2016.1.JNS152119. 3. Biller BM, Grossman AB, Stewart PM, et al. Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2008;93(7):2454-2462. doi: 10.1210/jc.2007-2734. 4. 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(12):847-875. doi:10.1016/S2213-8587(21)00235-7. 5. Ritzel K, Fazel J, August L, et al. Biochemical Control in Cushing’s Syndrome: Outcomes of the Treatment in a Large Single Center Cohort. J Clin Endocrinol Metab. 2025;110(4):e1038-e1045. doi: 10.1210/clinem/dgae337