Biochemical and Imaging Workup for Patients Referred for Clonidine Suppression Testing

Objective:
The role of the clonidine suppression test (CST) is contended given advances in other imaging and lab modalities for diagnosing pheochromocytoma/paraganglioma (PPGL). At AACE 2022, we presented data from 2016-2022 that CST only identified 1 PPGL despite high PPGL volume (185 surgically-proven cases) at our center in that time. CST had 17% positive predictive value, and led to hypotension in 23% of patients. Following that study, we sought to examine the clinical circumstances and workup prior to CST to identify patients who would benefit from CST and reduce unnecessary workup. We combine our data, guidelines, and expert opinion to create a recommended pathway for PPGL evaluation.

Methods:
This is a unicenter retrospective cohort study of all patients referred for CST between July 2016 and March 2022. High suspicion for PPGL were defined as a family or personal history of PPGL, genetic syndrome associated with PPGL, or adrenal mass with suspicious features.

Results:
There were 73 patients referred for CST, 65% female, mean age 57 (±12 yrs). The majority 68/73 (93%) were low suspicion at the outset and 5/73 (7%) were high suspicion. PPGL evaluations were done for symptoms in 51/73 (70%), incidental imaging findings in 17/63 (23%), and 5/73 (7%) other. Pre-CST adrenal/abdominal imaging was obtained in 43/73 (59%), of which 20/43 (47%) had an adrenal nodule: 2 had features concerning for malignancy, 18 appeared benign. Nearly all 71/73 (97%) had biochemical evaluation prior to CST: 92% had plasma metanephrines, 48% had plasma catecholamines, 55% had urine metanephrines, and 38% had urine catecholamines. All had a value above the upper limit of normal but 26/73 (36%) had all values within twice the upper limit of normal. Of 65 patients who had CST baseline labs, 16/65 (25%) had all within normal, and 49/65 (75%) had all within twice the upper limit of normal. Applying a twice the upper limit of normal cutoff and repeating the abnormal test under ideal circumstances before ordering CST would reduce further workups by 36% and 75%, respectively. In follow up (range 6 months-6 years) we have not identified any false negative results after applying these new cutoffs in our cohort.

Discussion/Conclusion:
False positive results would be reduced without significant increase in false negative results if initial plasma metanephrine screening were reserved for high suspicion patients, if abnormal labs were repeated under ideal circumstances, and if a cutoff of twice the upper limit were used for catecholamines. These recommendations were integrated into a pathway for the evaluation of PPGL which was presented and accepted by our institution's endocrinology department in September 2022.