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Persistently elevated plasma metanephrine levels in a patient with MEN2 – when to diagnose a phaeochromocytoma?

Hannah Cheney Lowe¹, Kate Newbold², Daniel Morganstein^{1, 1}Chelsea and Westminster Hospital, ²Royal Marsden Hospital

Background: MEN2 is a hereditary syndrome caused by mutations in the RET proto-oncogenes; characterised by medullary thyroid cancer in almost all individuals and phaeochromocytomas in 50%. Hyperparathyroidism can also occur. Phaeochromocytomas, catecholamine producing tumours of the adrenal medulla, can be diagnosed by elevated levels of catecholamines or metanephrines in urine or plasma. Surgery is the treatment of choice but requires lateralisation pre-operatively.

Case History: A 51 year old lady with background of medullary thyroid cancer (total thyroidectomy September 2007) and MEN2 (RET mutation L790F) has been under follow up in a specialist MTC clinic. She describes intermittent headaches, ear pain and episodes of ‘electric shock-like’ symptoms, as well as anxiety. Urinary metanephrine collection levels were persistently elevated - September 2015: 1.84, February 2016: 1.81 and August 2016: 1.73 (reference range 0-1.2 micromol/24 hrs). Plasma metanephrine levels were also raised at 1173 (reference range 80-510pmol/L). She was on no medication likely to cause a raised metanephrine level. She proceeded to imaging but CT and MIBG scans have not localised a phaeochromocytoma. CEA and calcitonin remained stable.

Discussion: Urine and plasma metanephrines both have high sensitivity and specificity for the presence of a phaeochromocytoma. Despite this both tests can have false positives, but in the presence of MEN2 the pre-test probability is high¹. Cross sectional and nuclear imaging have not identified a phaeochromocytoma in this patient, but the possibility of a small lesion remains. This therefore leaves the options of bilateral adrenalectomy (with consequent hypoadrenalism in a young patient) vs watchful waiting with alpha blockade (with ongoing small risk of phaeochromocytoma crisis).

References:

1.  van Berkel et al. Diagnosis of Endocrine Disease: Biochemical diagnosis of phaeochromocytoma and paraganglioma. European Journal of Endocrinology. R109–R119. 2014