Second-line tests in the differential diagnosis of ACTH-dependent Cushing’s syndrome

Abstract

Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.

Diagnostic accuracy of increased urinary cortisol/cortisone ratio to differentiate ACTH‐dependent Cushing's syndrome

“…Dynamic tests, pituitary MRI and BIPSS are the cornerstones in the difficult management of ACTH‐dependent CS (ie, occult EAS or negative pituitary imaging in patients with CD). Regrettably, their diagnostic accuracy is suboptimal, or they are not available worldwide . Surgery remains the first choice in the management of CS, hence the correct diagnosis is crucial .…”

“…The human CRH test and HDSST were performed as previously described . As thresholds for CD we considered those recently proposed: ACTH peak >72% during CRH test and >53% serum cortisol suppression after HDDST …”

“…The differential diagnosis of ACTH‐dependent CS may be a challenge: many strategies have been proposed, but no test reaches 100% of diagnostic accuracy . Dynamic tests have been suggested at first: CRH stimulation test is considered the most accurate to differentiate between pituitary and ectopic ACTH secretion, but it is expensive and not widely available . On the other hand, high‐dose dexamethasone suppression test (HDDST) can be easily performed, but it is slightly less accurate than CRH, while desmopressin test shows low diagnostic performance .…”

“…Dynamic tests have been suggested at first: CRH stimulation test is considered the most accurate to differentiate between pituitary and ectopic ACTH secretion, but it is expensive and not widely available . On the other hand, high‐dose dexamethasone suppression test (HDDST) can be easily performed, but it is slightly less accurate than CRH, while desmopressin test shows low diagnostic performance . In clinical practice, some patients with confirmed CD exhibit equivocal results to dynamic tests, and it is not uncommon that some EAS act like a pituitary corticotropinoma.…”

“…In clinical practice, some patients with confirmed CD exhibit equivocal results to dynamic tests, and it is not uncommon that some EAS act like a pituitary corticotropinoma. In addition, imaging is not always helpful, because gadolinium‐enhanced MRI is able to detect pituitary tumours in roughly 40%‐50% of patients with CD, and furthermore incidental pituitary lesions have been reported in the general population, including a minority of patients with EAS . Bilateral inferior petrous sinus sampling (BIPSS) may provide adjuvant data; however, this invasive procedure requires specific expertise to perform catheterization (to minimize side effects) and to analyse results (to avoid false positives or negatives) .…”