What are the causes of hypercortisolism (Cushing's syndrome)?

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From the Guidelines

Hypercortisolism, also known as Cushing's syndrome, is primarily caused by excessive adrenocortical steroid levels, which can be due to pituitary tumors, ectopic tumors, benign or malignant adrenal tumors, or bilateral multinodal hyperplasia. The underlying cause of hypercortisolism can be determined by evaluating the levels of adrenocorticotropic hormone (ACTH) and cortisol in the body 1.

Causes of Hypercortisolism

  • Pituitary tumors, which are usually benign, can cause excessive cortisol secretion by producing high levels of ACTH 1.
  • Ectopic tumors in the lung, thyroid, pancreas, or bowel can also produce ACTH, leading to hypercortisolism 1.
  • Benign adrenal tumors, such as adrenal adenomas, can cause ACTH-independent Cushing's syndrome 1.
  • Malignant adrenal tumors, such as adrenal carcinomas, can also lead to hypercortisolism 1.
  • Bilateral multinodal hyperplasia is a rare cause of ACTH-independent Cushing's syndrome 1.

Diagnosis and Treatment

The diagnosis of hypercortisolism involves evaluating the levels of cortisol and ACTH in the body, as well as imaging studies such as CT or MRI scans to identify any tumors or other abnormalities 1.

  • Treatment for hypercortisolism depends on the underlying cause and may involve surgical removal of tumors, medical management with adrenostatic agents such as ketoconazole, or bilateral adrenalectomy 1.
  • It is essential to address the underlying cause of hypercortisolism to prevent serious health problems, including weight gain, high blood pressure, diabetes, and weakened immune function 1.

From the Research

Causes of Hypercortisolism (Cushing's Syndrome)

The causes of hypercortisolism, also known as Cushing's syndrome, can be categorized into two main types: exogenous and endogenous.

  • Exogenous Cushing's syndrome is caused by the use of steroid medications 2.
  • Endogenous Cushing's syndrome is caused by the overproduction of cortisol in the body, which can be due to various factors, including:
    • Adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (Cushing's disease) 3, 4, 5.
    • Ectopic tumors secreting ACTH or corticotropin-releasing hormone (CRH) 3, 4.
    • Adrenocortical tumors or hyperplasias 3, 4.
    • Aberrant membrane hormone receptors or altered activity of eutopic receptors in cortisol-producing adrenal tumors or bilateral macronodular hyperplasias 3.

Diagnosis and Treatment

Diagnosis of Cushing's syndrome typically involves a combination of tests, including:

  • 24-hour urinary free cortisol test 2, 3, 6.
  • Late-night salivary cortisol test 2.
  • Overnight dexamethasone suppression test 2, 6.
  • Midnight salivary cortisol test 6. Treatment options for Cushing's syndrome depend on the underlying cause and may include:
  • Surgery to remove the source of excess cortisol production 2, 3, 4, 5, 6.
  • Medications to inhibit steroid synthesis or block glucocorticoid receptors 3, 4, 5.
  • Radiation therapy 2, 5.
  • Bilateral adrenalectomy 2, 3, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

New perspectives in the treatment of Cushing's syndrome.

Current drug targets. Immune, endocrine and metabolic disorders, 2004

Research

The Treatment of Cushing's Disease.

Endocrine reviews, 2015

Research

[Endogenous Cushing's syndrome].

Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 2006

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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