Endocrine Abstracts

Introduction: The importance of highly sensitive screening tests for pheochromocytoma/paragnaglioma (PPGL) is clear. However, a low level of specificity may lead to unnecessary biochemical and imaging investigations and even to needless surgical procedures. Therefore, in patients with elevated values of metanephrines, it is essential to establish a rational threshold for performing prompt thorough diagnostic investigations rather than opting for active surveillance.

Objective: This study sought to investigate the positive predictive value (PPV) of different thresholds of elevated urinary fractionated metanephrines (UFM) and to analyze current features of PPGL in a large cohort of community-dwelling patients.

Methods: The study was conducted at a large publicly-funded health maintenance organization (HMO) in Israel insuring approximately two million residents. We reviewed the computerized files of all patients who performed UFM tests in 2012–2017 and their levels of metanephrines and/or normetanephrines were ≥1.5x the upper normal limit (UNL). Clinical, biochemical and imaging data were retrospectively analyzed.

Results: Of the 10164 subjects referred to UFM testing, levels of >1.5xUNL and ≥2xUNL were found in 264 (2.6%) and 143 (1.4%), respectively. Sixty patients were subsequently diagnosed with PPGL (mean age 51.8±14.3, 65% females). Of these, 59 (98.3%) had UFM ≥2×UNL, yielding a positive predictive value (PPV) of 41.3% (59/143) for this threshold. A diagnosis of PPGL was established in only one out of 121 individuals with UFM level of 1.5–2×UNL (PPV=0.8%), in 7 out of 45 individuals with UFM level of 2–2.5×UNL (PPV=15.6%), and in 7 of 28 with UFM of 2.5–3×UNL (PPV=25%). The main reason for UFM screening, in 51.7% (31/60) of PPGL patients, was adrenal incidentaloma. Median metanephrines/normetanephrines levels were 2.9xUNL and 2.5×UNL, respectively (mean: 6.6±9×UNL and 6.1±8.9×UNL, respectively). Extra-adrenal tumor was detected in 6 patients (10%); bilateral masses and malignant PPGL in one patient, each. The classical triad of pheochromocytoma (headaches, sweating, tachycardia) was present in only one patient and 34 (56.7%) had none of these symptoms.

Conclusions: Most PPGL patients are currently diagnosed due to the detection of an adrenal incidentaloma. While in patients with UFM ≥×2UNL the PPV for PGGL justifies a thorough diagnostic assessment, in patients with milder elevations the probability of PPGL diagnosis is very low.