A 71 year old man was admitted for stabilisation of severe paroxysms of hypertension, tachycardia and constipationdue to catecholamine excess secondary to malignant phaeochromocytoma despite previous treatments with alpha blockade, surgical resections, and peptide receptor radionuclide therapy (PRRT). Investigations showed escalating catecholamines and Chromogranin-A levels (Normetanephrine 19,395pmol/L (RR <900), 3-Methoxytyramine 390pmol/L (RR <110), Chromogranin-A 23,330ug/L (RR <85)) and ongoing Somatostatin Receptor (SSR) positivity on 68Ga-DOTA-TATE PET/CT.
He was trialed on treatment with Metyrosine, a drug that inhibits Tyrosine Hydroxylase, a rate-limiting enzyme in the synthesis of catecholamines. Use is limited in Australia due to cost, difficulty accessing the drug and side effect profile (Green et al, 1982). Metyrosine treatment resulted in a clinical response with stabilization of cardiovascular status and resolution of constipation. A reduction in catecholamines was noted with 3-Methoxytyramine now normal range at 100pmol/L (RR <110) and Normetanephrine reduced to 5567pmol/L (RR <900) (Graph 1), the lowest values in 3 years and a response not seen following previous PRRT. He went on to have a further dose of PRRT with Chromogranin-A levels reduced comparatively to previous cycles of PRRT.
Malignant phaeochromocytomas are rare neuroendocrine tumours (NETs) (Baudin et al, 2014). The 5-year survival for patients is 40-77% with 30% of deaths in this cohort due to catecholamine excess (Baudin et al, 2014). Retrospective studies of these patients demonstrate improved haemodynamic stability when treated with Metyrosine (Wachtel et al, 2015). Differentiated NETs express SSRs and treatment with PRRT takes advantage of this phenomenon (Kwekkeboom et al, 2016), with both clinical and radiological responses seen in these patients who receive Lutetium-DOTA-Octreotate (LuTATE) PRRT (Kong et al, 2014).
This case highlights the effectiveness of PRRT systemic therapy to control tumour progression of malignant Phaeochromocytoma and illustrates a marked clinical and biochemical response to treatment with Metyrosine in patients with refractory catecholamine-excess associated symptoms.