Cyclic Cushing's syndrome: a clinical challenge

Area of Science:

• Endocrinology
• Internal Medicine

Background:

• Cyclic Cushing's syndrome (CS) presents with intermittent cortisol excess, complicating diagnosis.
• Clinical signs can fluctuate or be absent, and biochemical findings may be discrepant.
• The pathophysiology of cyclic CS remains largely unknown.

Purpose of the Study:

• To review reported cases of cyclic CS and analyze their origins and diagnostic challenges.
• To highlight the importance of recognizing cyclic CS in clinical practice.
• To recommend appropriate diagnostic strategies for suspected cyclic CS.

Main Methods:

• Systematic review of 65 reported cases of cyclic CS.
• Analysis of the origins of cyclic CS (pituitary, ectopic ACTH, adrenal).
• Evaluation of diagnostic methods, including biochemical screening and further testing.

Main Results:

• Cyclic CS originates from pituitary adenomas (54%), ectopic ACTH tumors (26%), and adrenal tumors (11%).
• Diagnosis is difficult due to fluctuating clinical signs and biochemical results.
• Frequent urinary or salivary cortisol measurements are reliable screening tools.

Conclusions:

• Clinicians must actively consider cyclic CS in patients with suspected but biochemically normal or discordant findings.
• Appropriate diagnostic workup, guided by ACTH dependency, is crucial once cyclic CS is confirmed.
• Specific tests for carcinoids or neuroendocrine tumors are needed for suspected ectopic ACTH production.