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

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From the Guidelines

Cushing's disease is a distinct medical condition caused by a pituitary adenoma that produces excess adrenocorticotropic hormone (ACTH), whereas Cushing's syndrome is a broader term encompassing all causes of excess cortisol, including Cushing's disease. The key difference between the two conditions lies in their etiology, with Cushing's disease being a subset of Cushing's syndrome. According to the most recent guideline update 1, Cushing's disease is caused by an ACTH-secreting pituitary tumor, which leads to excess cortisol production. In contrast, Cushing's syndrome can result from various causes, including adrenal tumors, ectopic ACTH production, and long-term use of glucocorticoid medications.

Key Characteristics of Cushing's Disease and Syndrome

  • Both conditions share similar symptoms, such as weight gain, purple stretch marks, thin skin, easy bruising, muscle weakness, high blood pressure, and high blood sugar.
  • Treatment approaches differ depending on the underlying cause, with surgical removal of the pituitary tumor being the first-line treatment for Cushing's disease, as recommended by a recent consensus guideline 1.
  • For other forms of Cushing's syndrome, treatment varies based on the specific cause, ranging from surgery to medication management to withdrawal of exogenous steroids when appropriate.

Treatment Considerations

  • Surgical removal of the pituitary tumor is the recommended first-line treatment for Cushing's disease 1, with selective adenomectomy being the treatment of choice.
  • Repeat surgery may be considered for persistent or recurrent disease, although the evidence for this approach is moderate at best 1.
  • Lifelong follow-up is essential for individuals treated for Cushing's disease, as recurrence can occur even after apparent surgical cure 1.

From the Research

Definition and Causes

  • Cushing's disease (CD) is a specific form of Cushing's syndrome (CS) caused by a pituitary tumor secreting corticotropin (ACTH), leading to cortisol excess 2.
  • Cushing's syndrome, on the other hand, is a broader term that refers to a group of disorders caused by excess cortisol in the body, which can be due to various reasons, including pituitary tumors, adrenal tumors, or familial Cushing's syndrome.
  • Patients with CD comprise approximately 70% of patients with endogenous Cushing's syndrome (CS) 2.

Diagnosis and Treatment

  • The diagnosis of CD is complex and includes two separate steps: establishing the presence of pathologic hypercortisolism and identifying the underlying cause 2.
  • Transsphenoidal pituitary surgery (TSS) is the primary form of therapy for CD, and pituitary surgery by experienced surgeons leads to remission of CD in 70-90% of patients 2.
  • Recurrence of CD may occur in up to 25% of patients on long-term follow-up, and patients with recurrent CD may be treated with repeat TSS, radiation therapy, or bilateral adrenalectomy 2.

Comparison of Cushing's Disease and Cushing's Syndrome

  • Cushing's disease is a specific form of Cushing's syndrome caused by a pituitary tumor, whereas Cushing's syndrome is a broader term that encompasses various disorders caused by excess cortisol.
  • The treatment and management of CD and CS differ, with TSS being the primary treatment for CD, and other treatments such as medication, radiation therapy, or adrenalectomy being used for CS.
  • The prognosis and outcome of CD and CS also differ, with CD having a higher remission rate after TSS, but also a higher risk of recurrence 2, 3.

Predicting Outcome

  • Several factors can predict the outcome of transsphenoidal pituitary surgery in patients with CD, including operative findings, radiological and histological findings, and early postoperative serum cortisol and urine free cortisol estimates 4.
  • Patients with CD who undergo TSS can achieve remission, but may require lifelong follow-up due to the risk of late relapse 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cushing's disease.

Handbook of clinical neurology, 2014

Research

Persistent Cushing's Disease after Transsphenoidal Surgery: Challenges and Solutions.

Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2021

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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