Cyclic Cushing's syndrome

While physiological cortisol secretion follows a regulated circadian rhythm, pathological excess as in endogenous Cushing's syndrome is characterised by increased and dysregulated cortisol concentrations. While subtle fluctuations occur in virtually all patients with Cushing's syndrome, cyclic Cushing's syndrome (cCS) represents a sub-entity defined by alternating periods of biochemical hypercortisolism ("peaks") and spontaneous intervals of physiological or even suppressed cortisol concentrations ("troughs"). These oscillations may occur over days to years and are usually unpredictable in frequency or amplitude. CCS is one of the most diagnostically challenging variants of hypercortisolism, which frequently leads to discordant biochemical test results, misclassifications, and prolonged diagnostic latency. Furthermore, diagnostic procedures performed during eucortisolaemic phases may yield false results, occasionally resulting in unnecessary investigations or inappropriate surgical interventions. Recognition of cyclicity is therefore essential in patients presenting with recurrent or fluctuating Cushingoid features and inconsistent biochemical findings. Establishing the diagnosis requires serial hormonal profiling combined with careful clinical correlation. Once confirmed, management should follow established principles for the underlying aetiology, while accounting for the temporal variability in cortisol excess that complicates timing of invasive diagnostic procedures, such as bilateral petrosal sinus sampling, and medical therapy. This chapter provides a concise, clinically oriented review of the epidemiology, etiology, diagnostic approach, and management strategies of cCS, aiming to support clinicians in recognising and effectively managing this complex and often underdiagnosed disorder.