What is the difference between Cushing's syndrome and Addison's disease?

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Last updated: April 25, 2025View editorial policy

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From the Guidelines

Cushing's syndrome and Addison's disease are two distinct adrenal gland disorders that require different management approaches, with Cushing's syndrome typically involving treatment to reduce excess cortisol production and Addison's disease involving lifelong hormone replacement therapy to replace deficient cortisol and aldosterone production. The primary distinction between the two conditions lies in their underlying pathophysiology, with Cushing's syndrome resulting from excess cortisol production and Addison's disease resulting from deficient cortisol and aldosterone production.

Key Differences in Presentation and Treatment

  • Cushing's syndrome presents with symptoms such as weight gain, purple stretch marks, thin skin, easy bruising, muscle weakness, high blood pressure, and high blood sugar, and is typically caused by prolonged steroid medication use, pituitary tumors, or adrenal tumors 1.
  • Addison's disease, on the other hand, presents with symptoms such as fatigue, weight loss, low blood pressure, salt craving, hyperpigmentation, and potentially life-threatening adrenal crisis, and is typically caused by autoimmune destruction of the adrenal glands, infection, or adrenal gland removal 1.
  • Treatment for Cushing's syndrome depends on the underlying cause but may include surgery, radiation, or medications like ketoconazole or metyrapone to reduce cortisol production 1.
  • Treatment for Addison's disease involves lifelong hormone replacement with oral hydrocortisone (typically 15-25 mg daily in divided doses) and fludrocortisone (usually 0.05-0.2 mg daily) to replace cortisol and aldosterone respectively, with dose adjustments based on clinical response and increased steroid dose during illness or stress to prevent adrenal crisis 1.

Management Considerations

  • Patients with either condition require regular monitoring and dose adjustments based on clinical response.
  • Those with Addison's disease need to increase their steroid dose during illness or stress to prevent adrenal crisis.
  • Education on stress dosing, emergency injections, and a medical alert bracelet or necklace is crucial for patients with Addison's disease.
  • Endocrine consultation is recommended for planning before surgery or high-stress treatments, and for management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy 1.

From the Research

Cushing's Syndrome vs Addison's Disease

  • Cushing's syndrome is a condition characterized by excessive production of cortisol, whereas Addison's disease is a condition where the adrenal glands do not produce enough cortisol and aldosterone 2.
  • The symptoms of Cushing's syndrome include weight gain, hypertension, and hyperglycemia, whereas Addison's disease is characterized by fatigue, weight loss, and hypotension.
  • Cushing's syndrome can be caused by a variety of factors, including pituitary tumors, adrenal tumors, and familial Cushing's syndrome, whereas Addison's disease is often caused by autoimmune disorders, infections, and adrenal gland damage.

Treatment Options

  • Treatment for Cushing's syndrome typically involves surgery to remove the source of excess cortisol production, followed by medication to control cortisol levels 3, 4, 2.
  • Medications used to treat Cushing's syndrome include adrenal-blocking agents, such as ketoconazole and metyrapone, as well as glucocorticoid receptor antagonists 3, 5.
  • In contrast, treatment for Addison's disease typically involves replacement therapy with glucocorticoids and mineralocorticoids to replace the deficient hormones.

Medication Side Effects

  • Ketoconazole, a commonly used medication for Cushing's syndrome, can cause hepatotoxicity, as well as increases in liver enzymes 6.
  • Metyrapone, another medication used to treat Cushing's syndrome, can cause increased androgen and mineralocorticoid production, as well as hepatotoxicity 3.
  • Etomidate, a medication used to rapidly reverse cortisol excess in patients with severe Cushing's syndrome, can cause sedative-hypnotic actions and should be used with caution 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pharmacological management of severe Cushing's syndrome: the role of etomidate.

Therapeutic advances in endocrinology and metabolism, 2022

Research

Ketoconazole in Cushing's disease: is it worth a try?

The Journal of clinical endocrinology and metabolism, 2014

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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