Metyrosine Use in Patients with Pheochromocytoma and Paraganglioma: The Mayo Clinic Experience

Presentation Number: SUN 383
Date of Presentation: April 2nd, 2017

Sina Jasim*1, Allison Ducharme-Smith2, Toby Weingarten1, William F Young Jr.1 and Irina Bancos1
1Mayo Clinic, Rochester, MN, 2Mayo Clinic

Abstract

Background: Surgical resection is the optimal treatment for pheochromocytoma and paraganglioma (PPGL). Preoperative alpha-adrenergic blockade has been shown to reduce surgery-related morbidity and mortality. The tyrosine hydroxylase inhibitor, metyrosine, is infrequently used in the preoperative preparation of patients with PPGL because of cost and drug-related side effects.

Objectives: Review the indications for, side effects of, and impact of metyrosine use in patients with PPGL.

Methods: The medical records of patients with PPGL who were treated with metyrosine at Mayo Clinic, Rochester, MN during the years 2000-2015 were retrospectively reviewed for patient and tumor characteristics, medication dose, duration, side-effects, and tolerance.

Results: A total of 120 patients with PPGL were treated with metyrosine during the study timeframe (59 men; median age 47 yrs [range, 4-76)]). Metyrosine therapy was used prior to surgical intervention for patients with large PPGL with an anticipated difficult resection and /or difficult to control of hypertension with standard alpha- and beta-adrenergic blockade (surgical and non-surgical). Surgical procedures included adrenalectomy (N=54), PGL resection (N=53), and others (N=2). Non-surgical procedures included planned ablative therapy (n=12), embolization (n= 9), and chemotherapy (n= 9) in anticipation of tumor lysis. The median cumulative metyrosine dosage was 8000 mg (range, 1000- 18000) for median duration of 4 days (range, 1-10). All patients were pre-treated with alpha-adrenergic blockade (phenoxybenzamine in 85% ;dose range, 10 - 100 mg per day), 87 % with beta-adrenergic-blockers, and 35% with calcium channel blockers prior to surgery. Metyrosine associated side-effects included: fatigue (25%), sleepiness (37%), drowsiness (10%), and others (tremor, weakness, decrease appetite, and depression) in 11%. One patient had to discontinue the metyrosine because of myalgias and tremors.

Surgery was completed by the laparoscopic approach in 36 patients and open approach in 73. The pre-operative median systolic blood pressure (SBP) and heart rate (HR) were 116 mmHg and 75 bpm respectively. Intraoperative hemodynamics: median nadir SBP was 77 mm Hg (range, 32-117), median peak intra-operative SBP of 173 mm Hg (range, 110 – 276). The median estimated blood loss was 200 mL. Intraoperative resuscitation measures: mean crystalloid 3969 mL; RBC transfusion (31%); temporary vasopressors (70%); and, intravenous antihypertensive medication use (68%). Median hospital stay was 5 days (range, 1-29).

Conclusion: Preoperative use of metyrosine was well tolerated by most patients. This agent has an important role in patients with large PPGLs where it is anticipated that the resection will be difficult or when ablative therapy is planned or when it is difficult to control hypertension with standard alpha- and beta-adrenergic blockade.

 

Disclosure: IB: Advisory Group Member, Diurnal. Nothing to Disclose: SJ, AD, TW, WFY Jr.