De moeilijke diagnostiek van een cyclisch cushingsyndroom

The difficult diagnosis of cyclical Cushing’s syndrome Cyclic Cushing Syndrome (CCS) is a condition characterized episodes of normo- or hypocortisolism and episodes of hypercortisolism. The clinical presentation and complications are similar to non-cyclic CS. However, diagnosis is even more challenging than in non-cyclic Cushing's; various diagnostic modalities can yield both false positive and false negative results when testing is performed during an episode without hypercortisolism. Diagnostic tests for CS include 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC), and the dexamethasone suppression test (DST). Unlike non-cyclic CS, DST can result in a paradoxical reaction. Repeated tests are needed when CCS is suspected, with testing conducted during periods of hypercortisolism. A new, promising technique for detecting CCS involves hair cortisol measurement, where cortisol levels can be determined over an extended period of time. However, there are currently no standardized reference values available. The underlying etiology of CCS is similar to that of classic CS, including ACTH-dependent hypercortisolism due to a pituitary adenoma or ectopic ACTH- or CRH production, and ACTH independent hypercortisolism. Further differentiation is based on various tests: dynamic testing (CRH, desmopressin, high-dose DST), bilateral inferior petrosal sinus sampling (BIPSS), and imaging (pituitary MRI, FDG-PET, somatostatin analogs PET-CT). The main difference from non-cyclic CS is that testing with desmopressin and BIPSS is unreliable when performed during a trough phase. The high-dose dexamethasone test can result in a paradoxical response. There is no clarity on the ideal sequence of investigations. In some cases, despite extensive investigations, the underlying etiology remains unclear.