The Limited Ability Of Inferior Petrosal Sinus Sampling With Corticotropin-Releasing Hormone To Distinguish Cushing Disease From Pseudo-Cushing States or Normal Physiology

摘要

To determine whether or not petrosal sinus sampling is useful to distinguish patients with mild or intermittent Cushing disease from normal subjects and from individuals with pseudo-Cushing states, we performed bilateral inferior petrosal sinus sampling for adrenocorticotropin (ACTH) before and after the administration of corticotropin-releasing hormone (CRH) in 7 eucortisolemic volunteers, 8 hypercortisolemic patients with pseudo-Cushing states, and 40 patients with ACTH-dependent Cushing disease whose urine free cortisol excretion was within the range found in patients having pseudo-Cushing states (<1000nmol/d [<360 μg/d]). The ACTH level, the ratio of the inferior petrosal sinus ACTH to the peripheral vein ACTH concentration (the IPS:P ratio) and the greater ratio of the right to left, or left to right, petrosal sinuses (the R:L ratio) were compared in patients with and without Cushing disease.Maximal petrosal ACTH values were significantly elevated in patients with Cushing disease compared to patients with pseudo-Cushing states before administration of CRH (p<0.001), but not after CRH. Maximal petrosal plasma ACTH values after the administration of CRH as high as 808 pmol/L (3670 pg/mL) and 469 pmol/L (2130 pg/mL) were found in patients with pseudo-Cushing states and in normal volunteers, respectively, whereas maximal petrosal ACTH levels as low as 10 pmol/L (46 pg/mL) were observed in patients with surgically-proven Cushing disease. Maximal IPS:P ratio and minimal IPS:P ratio were significantly greater in patients with Cushing disease than in subjects without Cushing disease before, but not after, CRH. R:L ratios did not differ among groups either before, or after, CRH. All of the subjects without Cushing disease showed large R:L gradients, consistent with the notion of one dominant petrosal sinus containing a greater percentage of pituitary effluent. The ACTH concentrations, the IPS:P ratios, and the R:L ratios exhibited great overlap between those with and without Cushing disease, which resulted in a diagnostic accuracy of 81% at best for the diagnosis of Cushing disease.We conclude that petrosal sinus sampling is of limited usefulness in distinguishing either normal individuals or patients with pseudo-Cushing states from those with mild Cushing disease. This limited usefulness must be recognized when interpreting the results of petrosal sinus sampling in patients with mild or intermittent hypercortisolism who may have a pseudo-Cushing state. Because of these limitations, petrosal sinus sampling should be reserved for patients with clear clinical and biochemical evidence of Cushing syndrome.