Endocrine Abstracts

Introduction: In patients with ACTH-dependent Cushing Syndrome, differentiating between pituitary and ectopic sources can be challenging. Noninvasive testing can be performed, but bilateral inferior petrosal sinus sampling (BIPSS) remains the gold standard. In the last years however, novel imaging modalities, namely 3T-MRI with 3-dimensional spoiled gradient-echo sequence and 68Ga-tagged CRH combined with positron emission tomography, have been proposed as alternatives.

Aim: To evaluate the accuracy of BIPSS performed in a single tertiary hospital in differentiating between hypophyseal and ectopic causes of ACTH-dependent Cushing syndrome. A secondary aim was to compare BIPSS and traditional non-invasive test results (MRI, high-dose dexamethasone suppression test and CRH stimulation test).

Methods: Forty patients with ACTH-dependent Cushing syndrome underwent BIPSS from 2006 to 2022 in a tertiary hospital. Fourteen patients were excluded due to lack of documented hypercortisolism at the time of BIPSS, lack of a definitive diagnosis, or sample loss (hemolysis). Clinical files were reviewed for patient demographics, biochemical, histological and imaging findings. Cushing’s disease was confirmed in case of cure after transsphenoidal surgery or histology indicative of an ACTH positive pituitary adenoma. Similarly, ectopic Cushing syndrome was confirmed in case of cure after surgery or histology indicative of ACTH-positive neuroendocrine tumor (surgery or biopsy).

Results: Twenty-six participants were evaluated (76.92% female, median age 43.31±2.36 years). Cushing’s disease was confirmed in 19 patients, and BIPSS was compatible with this diagnosis in 13 patients. Ectopic Cushing syndrome was confirmed in 5 patients, and BIPSS was compatible with this diagnosis in 4 patients. The fifth patient had results suggestive of ectopic Cushing syndrome before CRH stimulation, and Cushing’s disease after. BIPSS sensitivity was 71.43%, and specificity was 100.00% and 80.00%, before and after CRH stimulation. Accounting for an estimated prevalence of Cushing’s disease of 80% among patients with ACTH-dependent Cushing’s syndrome, accuracy was 77.14% and 70.74%, before and after CRH stimulation. MRI (n=26) sensitivity was 66.67% and specificity was 60.00%. High dose dexamethasone suppression test (n=14) sensitivity was 80.00% and specificity was 25.00%. CRH stimulation test’s (n=8) sensitivity was 100.0% and specificity was 0.00%.

Conclusion: BIPSS had overall lower sensitivity and higher specificity compared with non-invasive testing. Specificity was higher before CRH stimulation. Novel non-invasive diagnostic tools with higher accuracy in differentiating the cause of ACTH-dependent Cushing syndrome could possibly replace invasive testing in the future.