Prolactin correction for adequacy of petrosal sinus cannulation may diminish diagnostic accuracy in Cushing's disease

Objective: Petrosal venous prolactin concentrations have been promoted to improve the diagnostic accuracy of inferior petrosal sinus sampling (IPSS), beyond that achieved with ACTH measurement alone, in diagnosing a pituitary ACTH source and determining corticotrophinoma side (L/R). Our objective was to assess the effect of using prolactin to confirm adequacy of petrosal cannulation in a cohort of patients with ACTH-dependent Cushing's syndrome. Design: Retrospective cohort study. Patients: Thirteen patients with clinical and biochemical Cushing's syndrome who underwent IPSS. Measurements: Serum prolactin and ACTH in peripheral and inferior petrosal sinus blood before and after corticotrophin-releasing hormone (CRH) injection. Results: Thirteen consecutive patients were diagnosed with Cushing's disease using uncorrected ACTH ratios. The side of PRL excess was the same as the side of ACTH excess in all cases. Use of various published prolactin-related equations suggested that the ACTH non-dominant side was not cannulated in four, six or seven patients depending on the equation used. The equations generally decreased the central-to-peripheral gradient on the uncorrected ACTH dominant side, increased the central-to-peripheral gradient on the contralateral side and diminished or even reversed the ACTH intersinus gradient. Conclusions: Consistent co-lateralisation of prolactin and ACTH in IPSS strongly suggests that prolactin cannot act as an independent guide to the diagnosis and lateralisation of Cushing's disease. All patients with Cushing's disease had a prolactin intersinus gradient towards the tumourous side of the pituitary, for likely biological reasons. PRL-corrected ACTH concentrations may threaten the sensitivity and specificity of IPSS in diagnosing Cushing's disease and conceal lateralisation.