Endocrine Abstracts

Methods: The diagnosis of Cushing’s Syndrome (CS) was made as per the prevalent endocrine society guidelines. CS patients with serum ACTH>15 pg/ml were considered as ACTH-dependent CS. Baseline ACTH (both inferior petrosal sinuses and peripheral) values were obtained, and since 2014, stimulated ACTH values (5 and 10 minutes post one unit iv vasopressin) were obtained as standard protocol. Prolactin corrected ACTH ratios were additionally being calculated since 2016. The highest central to peripheral ACTH gradient >2 in baseline samples (bC:P), >3 in samples after vasopressin stimulation (sC:P), and >0.8 in PRL-corrected ratios (pC:P) was used as reference value indicative of Cushing’s Disease (CD). An inter-petrosal gradient >1.4 was considered to be suggestive of an adenoma located on the side of the petrosal sinus with the higher ACTH concentration.

Results: Of the 51 patients with ACTH-dependent CS who underwent BIPSS, four patients with incomplete data, one patient with unilateral petrosal sinus catheterization, one patient with Cortisol Resistance Syndrome were excluded from the analysis. Mean age of our cohort was 37.5 years, with 77.8% females. 39 patients had CD, while six had ectopic CS. bC:P>2 (n=45) demonstrated 92.3% sensitivity, 83.3% specificity, 97.3% PPV and 62.5% NPV, while sC:P>3 (n=31) demonstrated 96.3% sensitivity, 100% specificity, 100% PPV and 80% NPV to diagnose CD. pC:P>0.8 (n=20) improved the sensitivity and NPV to 100%, with a 75% specificity and 94.1% PPV. On ROC analysis, cut-point ratio of 2.55 for bC:P value gave a sensitivity of 89.7% and specificity of 100% (AUC=0.964); sC:P ratio of 2.95 had 96.3% sensitivity and 100% specificity (AUC=0.991); 0.93 for pC:P ratio provided a sensitivity of 93.8% and specificity of 100% for diagnosis of CD (AUC=0.984). Maximum-stimulated petrosal sinus ACTH to baseline petrosal sinus ACTH ratio of <1.11 provided a 100% sensitivity, while a ratio >1.75 provided 100% specificity towards diagnosis of CD. 71.4% (10/14) patients with left sided adenoma, and 85% (17/20) patients with right sided adenoma were correctly lateralised on BIPSS. In patients whom adenoma was detected on pituitary MRI, 66.7% (6/9) were correctly lateralised to the left side, and 94.1% (16/17) to the right side.

Conclusions: BIPSS provides high sensitivity and specificity to diagnose CD. Vasopressin stimulation improves the sensitivity and specificity, while prolactin correction improves the sensitivity of BIPSS, as compared to baseline ratios. Maximum-stimulated petrosal sinus ACTH to baseline petrosal sinus ACTH ratio can be additionally used, especially in CD patients suspected of false negative localization.