Evaluation of the Utility of Extended Time Points in Inferior Petrosal Sinus Sampling Procedures for Cushing's Disease

Background: Inferior petrosal sinus (IPS) sampling (IPSS) is a diagnostic procedure used to help localize potential corticotropin (ACTH)-secreting pituitary tumors resulting in Cushing's disease. During this procedure, adrenocorticotropic hormone (ACTH) blood levels are measured from the IPS at standardized time points within the first 10 minutes following administration of DDAVP. Peripheral blood is simultaneously drawn at these time points as well as at extended time points, usually up to 60 minutes post-DDAVP, as peripheral vein ACTH measurements greater than 50% above baseline levels are suggestive of pituitary-dependent disease. Obtaining these extended time points for peripheral ACTH levels drastically lengthens the procedure time of IPSS and decreases utilization efficiency of hospital resources by increasing the amount of idle time spent in the procedure room. Furthermore, it is unclear how much additional information is gained from obtaining these extended time points during an IPSS procedure.

Methods: A retrospective review was performed on all cases between 1998 and 2013 involving patients at a single institution who underwent IPS sampling for a histopathology-confirmed pituitary microadenoma. Cases were reviewed for ACTH levels measured in the IPS at the standard time points of -5, -1, 2, 5, and 10 minutes relative to DDAVP administration. Peripheral ACTH levels were also documented at the same time points in addition to the extended time points of 30, 45, and 60 minutes after DDAVP injection. Data from all patients were first pooled and trended over 60 minutes to better understand ACTH trends during IPS sampling. A paired analysis was then conducted to compare the average peripheral ACTH levels at the earlier, standardized time points with the average ACTH levels that included the extended 30-, 45-, and 60-minute time points.

Results: There were 53 cases involving patients with confirmed ACTH-secreting pituitary microadenomas who underwent preoperative IPS and peripheral blood sampling at the standardized time points. Examination of ACTH levels over the course of the IPS sampling procedure revealed that the highest concentrations were observed 30 minutes after DDAVP administration, but that ~85% of peak values were observed by the 10-minute time point ([Fig. 1]). After ACTH levels peak at 30 minutes, a slow decrement is observed until the 60-minute time point. The average peripheral ACTH level measured in patients was 94.7 ± 16.9 at the early time points and 124.1 ± 15.0 when including the extended time points (p = 0.197).

Conclusions: Inspection of ACTH trends over the duration of IPS sampling showed that peripheral concentrations reach ~85% of their peak value by 10 minutes on average with a gradual decline occurring from 30 to 60 minutes, which may be sufficient for demonstrating pituitary-dependent disease during IPSS. Comparison of the measured peripheral ACTH levels at both early and extended time points demonstrated that there was not a statistically significant difference in these measured averages. Together, this suggests that the extended time points in these procedures may offer limited utility while dramatically increasing procedure times from ~10 minutes to over an hour.