Inferior Petrosal Sinus Sampling with DDAVP Stimulation in Adults with Cushing Disease: Coping with a Global CRH Analog Shortage

Introduction: There are various methodologies to diagnose Cushing disease, with the recent gold standard being inferior petrosal sinus sampling (IPSS) after corticotropin-releasing hormone (CRH) analog stimulation. Given recent global supply chain issues, CRH analogs have been widely unavailable in many regions. Desmopressin (DDAVP) is widely available, more cost-effective, and had been proposed previously as an alternative to CRH analogs for IPSS testing purposes. While there is significant literature on the ability of CRH analogs to correctly diagnose Cushing disease and predict tumor lateralization, the literature is lacking in recent descriptions of the similar use of DDAVP. In this study the authors aim to compare the usage of DDAVP to the historical usage of CRH analogs.

Methods: A retrospective single-center chart review from 2017 to 2022 of adults undergoing inferior petrosal sinus sampling (IPSS) for evaluation of Cushing Disease and subsequent endonasal endoscopic tumor resection took place. IPSS was performed after stimulating with either CRH or DDAVP. ACTH and prolactin levels were drawn from the right and left inferior petrosal sinus at 5 time points (−5 minutes, 0 minutes, 3 minutes, 5 minutes, 10 minutes) as well as from the periphery at 6 time points (an additional 30 minute post-stimulation time point). Evaluation and interpretation of IPSS for laterality were recorded. Laterality based on surgeon observation as discussed in operative reports was recorded, as well as pathology reports from the resected lesion. R-studio and descriptive statistics were used for analysis.

Results: A total of 81 patients underwent IPSS for evaluation of Cushing disease from 2017 to 2022 at our single institution. The majority (N = 59, 77%) underwent stimulation with CRH, while the remainder (N = 18, 23%) underwent stimulation with DDAVP. Four patients were excluded due to inability to cannulate 1 or more of the patient's inferior petrosal sinuses, confounding medications, or due to laboratory errors resulting in an incomplete dataset. In the 77 patients who underwent IPSS, 3 were excluded from a diagnosis of Cushing disease, and 3 were diagnosed with an ectopic ACTH-producing neoplasm. Of the 71 patients who had a confirmed diagnosis of Cushing disease, operative records were available for 51 patients who were reviewed and analyzed. Of these 51 patients, 36 were CRH recipients (70%) and 15 (30%) were DDAVP recipients. Overall, IPSS correctly matched tumor laterality noted in the operative note in 88% (N = 45) of the patients. There was no significant difference in accuracy when stimulated with CRH compared with DDAVP (p = 0.47). 86% (N = 31) of those that underwent stimulation with CRH and 93% (N = 14) of those that underwent stimulation with DDAVP had consistent laterality between IPSS interpretation and the operative note from the time of resection.

Conclusions: While there was no significant difference in accuracy when predicting Cushing tumor laterally when undergoing IPSS and stimulating with CRH versus DDAVP. DDAVP was revealed to accurately predict tumor laterality in 93% of cases.

Publication History

Article published online:
01 February 2023