The importance of standardisation of measurement and reference intervals for detection of phaeochromocytoma and paraganglioma (PPGL)

A 51-year-old male presented 25 years ago with excessive sweating and haematuria. Blood pressure was labile. CT abdomen showed a large right-sided adrenal mass. Two 24-h urine collections showed elevated urinary catecholamines. Right adrenal resection was performed; a phaeochromocytoma (PC) was confirmed histologically. Two decades later, the patient represented with excessive sweating and measured variable blood pressure readings. Measurement of plasma metanephrines (PMets) showed elevated normetanephrine (NMN) [50,250 (R.I. 0-1180) pmol/L] and metanephrine (MN) [1030 (R.I. 0-510) pmol/L] values. CT abdomen showed a 100 × 90 × 63 mm enhancing mass in the right retroperitoneum. Curative resection was undertaken confirming recurrent PC. Follow-up post-resection, plasma NMN was discordant, 1314 pmol/L (above decision threshold) at 30 min and 911 pmol/L (below decision threshold) at 40 min. Acute clinical awareness of persistent disease mandated the performance of a metaiodobenzylguanidine (MIBG) scan and CT abdomen. These confirmed residual disease in the upper right side of the retroperitoneum. Persistent disease following redo surgery could have been missed if only seated-sampling upper reference limits were applied to PMets collected at 40 min. Our experience with this patient triggered a review of our PMets sampling strategy. There was no statistically significant difference in PMets sampled at 30 and at 40 min seated-rest. Optimum diagnostic test accuracy was achieved using a supine-sampling strategy at a single time point (30 min). Our case highlights the importance of maintaining a high index of clinical suspicion for residual/recurrent disease in the face of inconclusive biochemistry, followed by appropriate targeted radiology using MIBG or PET-CT in patients with PPGL.