The lateralization accuracy of inferior petrosal sinus sampling in 501 patients with Cushing's disease.

It is often difficult to find an adenoma in patients with Cushing's disease (CD) whose preoperative magnetic resonance imaging (MRI) is normal. Better localizing modalities are needed. The aim of this study was to determine the accuracy of inferior petrosal sinus sampling (IPSS) in predicting adenoma lateralization. We conducted a prospective observational study at a tertiary care clinical research center. A total of 501 consecutive patients (363 female) with confirmed ACTH adenomas and IPSS were included. We measured the accuracy of IPSS to predict the intrasellar location of an adenoma. IPSS confirmed a pituitary source of ACTH secretion in 491 patients (98%). All 10 patients with false-negative results had peak IPSS ACTH concentrations (before or after CRH) of < 400 pg/ml. Interpetrosal (side-to-side) ratios were ≥ 1.4 in 491 patients (98%). This ratio correctly predicted lateralization in 273 of 396 patients (positive predictive value = 69%) with a lateral adenoma. Left-sided IPSS lateralization (P = .008) and consistent lateralization before and after CRH administration (P = .02) were associated with enhanced accuracy. When positive, preoperative MRI correlated with adenoma location in 171 of 201 patients (positive predictive value = 86%). Potential false-negative results, the most common type of diagnostic error with IPSS for the differential diagnosis of CS, can be identified by peak IPSS ACTH values < 400 pg/ml. When MRI is normal, IPSS can be used to guide surgical exploration in patients with negative preoperative imaging. However, because of the limited accuracy of lateralization, thorough exploration of the pituitary gland is required when an adenoma is not readily discovered based on predicted location.