Is diagnosis of Cushing's disease moving beyond Bilateral inferior petrosal sinus sampling?

Bilateral inferior petrosal sinus sampling (BIPSS) is the gold standard for distinguishing Cushing's Disease (CD) from Ectopic ACTH syndrome (EAS). It is however rarely evaluated in an intention-to diagnose-analysis, even though final diagnosis remains inconclusive in 7 to 39% of patients in published series. It has been suggested that BIPSS use may be reduced in patients explored by modern imaging and hormonal testing. We tested this hypothesis.

Evolution of BIPSS use and diagnostic outcomes over time in a single-center retrospective study of 229 consecutive patients with ACTH-dependent-Cushing's syndrome (ACTH-CS) without evident endocrine tumors, explored from 1992 to 2021 with hormonal testing (n = 229); pituitary MRI (n = 226) or CT (n = 3); chest/abdominal CT scan (n = 114) and BIPSS (n = 113).In an intention-to-diagnose analysis, we classified outcomes as confirmed CD (cCD) or EAS (cEAS) if there was post-therapeutic evidence of an ACTH-secreting tumor, and suspected CD (sCD) or EAS (sEAS) if not, resulting in 196 cCD (86%), 24 sCD (10%), 5 cEAS (2%), 4 sEAS (2%).

Comparing the 3 decades 1992-2001; 2002-2011; 2012-2021, the use of BIPSS decreased from 68% to 49% and 26%, while the frequency of a typical adenoma image at MRI increased from 40% to 58% and 69%. The proportion of patients with cCD (83%; 81%; 93%) remained stable.

Our study demonstrates a decrease over time in the use of BIPSS without loss of efficacy in diagnosis of CD, suggesting that advances in imaging allow for a safe reduction in the indications for BIPSS.