Approach to the Patient With Cyclical Cushing Syndrome

Cyclical Cushing syndrome (CS) is a subentity of CS, characterized by repeated episodes of excess cortisol (peaks) followed by spontaneous periods of normal or low cortisol secretion (troughs). Although considered rare, its prevalence reaches 70 of 514 to 91 of 514 (14%-18%) in patients with CS according to its definition in some reported series and can concern all etiologies of CS. Physicians should be alert to the presence of cyclical CS in patients with fluctuating symptoms or where the results of biochemical investigations indicate eucortisolism or hypocortisolism in patients with clinical CS. Cyclicity leads to difficulties in establishing the diagnosis of CS and discovering its etiology, since patients may have paradoxical/aberrant results in biochemical investigations, including inferior petrosal sinus sampling. Similarly, cyclicity complicates the interpretation of therapeutic outcomes and interferes with medical treatments for CS. Apart from cyclicity, variability of hypercortisolism is a more common phenomenon seen in CS but can cause similar problems. Since the pathophysiology and molecular basis of cyclical CS are largely unknown, a marked variability in cortisol secretion can be considered as representing a milder aspect of cyclicity within the same continuum. In this issue of "Approach to the patient," the characteristics, main diagnostic and therapeutic pitfalls, as well as strategies for diagnosing and managing cyclicity and marked variability in CS, are discussed from the clinician's perspective using 3 clinical cases.