Introduction: The diagnosis of Cushings syndrome (CS) might be challenging especially in ACTH-dependent CS when it comes to detect the origin of ACTH secretion.
Materials and methods: We retrospectively recorded data about 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two Endocrinology Units. We focused especially on the performance of 3 dynamic tests: the dexamethasone 8 mg overnight challenging (HDDST), the CRH and the desmopressin (DDAVP) test.
Results: Patients with EAS were slightly older and had higher 0800 h. ACTH levels, 0800 h. and after 1 mg dexamethasone cortisol levels, and UFC than patients with CD (P<0.01). On the contrary CD patients had a greater ACTH and cortisol response after CRH injection (P<0.0001) and also a more pronounced decreased of cortisol after HDDST (P<0.0001). A threshold for ACTH increase after CRH stimulation of 72% was able to identify CD with a sensitivity (SE) of 93% (95% CI: 6883%) and a specificity (SP) of 82% (95% CI: 83100%). Regarding HDDST, a cortisol reduction >53% suggested a pituitary origin with SE of 88% (95% CI: 8193%) and SP of 90% (95% CI: 6899%); the latter could be increased to 100% by moving the cut-off to 75% of decrease. The AUC of CRH test and HDDST was 0.93 (95% CI: 0.890.97) in both cases (P=ns). There were no EAS with both positive responses to these 2 tests. ACTH and cortisol increases after DDAVP test were also higher in CD than in EAS (P<0.01), but they added very little to the power of the other dynamic tests.
Conclusions: Patients with CD showed an increased response to both HDSST and CRH; the cut-offs found had good SE and SP in discriminating patients with CD from those with EAS. Lack of response of both tests was highly suggesting of EAS. On the contrary when both tests gave positive responses it indicated CD. We also confirmed the limited role of DDAVP test in this diagnostic phase. In conclusion, dynamic tests may play an important tool in the differential diagnosis of ACTH-dependent CS.