Abstract
Inferior petrosal sinus sampling (IPSS) is considered the gold standard test to distinguish between Cushing's disease (CD) and ectopic ACTH syndrome (EAS). Anomalous venous drainage, abnormal venous anatomy, and lack of expertise can lead to false-negative IPSS results and thereby misclassification of patients with ACTH-dependent Cushing's syndrome. Prolactin measurement during IPSS can improve diagnostic accuracy and decrease false negative results. A baseline prolactin inferior petrosal sinus to peripheral (IPS/P) ratio (ipsilateral to the dominant post-CRH ACTH IPS/P ratio) of 1.8 or more suggests successful catheterization during IPSS. Prolactin-normalized ACTH IPS/P ratios can then be used to differentiate between a pituitary and ectopic source of ACTH. Values ≤ 0.7 are suggestive of EAS and those ≥ 1.3 are indicative of CD, but the implication of values between 0.7 and 1.3 remains unclear and needs further investigation. Larger prospective studies are also needed for further evaluation of the role of contralateral prolactin IPS/P ratios, post- CRH prolactin values, and prolactin-adjusted ACTH inter-sinus ratios for tumor localization in CD.