University of Tartu, Tartu, Estonia. Oxford University Hospitals, Oxford, United Kingdom
Cyclical Cushings Syndrome (CS) is a rare and complex disorder, accounting for approximately 14-18% of all CS cases. It is characterized by repeated episodes of cortisol excess in blood, saliva, and/or urine, interspersed with periods of normal or even low cortisol levels, observed on at least 2-3 separate occasions. The duration of each hypercortisolemic episode can vary widely, lasting from days to years, and may occur at regular or irregular intervals. This condition is also referred to by other terms, including variable, periodic, episodic, and intermittent Cushings syndrome. A recent systematic review by Nowak et al. revealed that the most common cause of cyclical CS is a pituitary adenoma (67%), followed by ectopic tumors (17%) and adrenal tumors (11%). Diagnosing cyclical CS is particularly challenging, as patients may present with normal laboratory results if tests are conducted during a quiescent period. This can lead to misdiagnosis or unnecessary pituitary surgeries in patients with ectopic tumors. Careful planning of inferior petrosal sinus sampling (IPSS) during hypercortisolemic states is crucial. Postoperative remission rates are generally lower in patients with cyclical CS, and the time to remission is significantly longer compared to those with non-cyclical Cushings syndrome. Cyclical CS remains a challenging condition, even in highly specialized centers. It should be strongly suspected in patients exhibiting signs and symptoms of hypercortisolism, particularly when diagnostic results are inconclusive. Long-term observation is essential for accurate diagnosis and management.