Failure of metyrosine therapy for preoperative management of pheochromocytoma: a case report

Abstract

Purpose Pheochromocytomas (PHEOS) are rare catecholamine-secreting adrenal tumours requiring surgical resection. Preoperative alpha-adrenergic receptor blockade to prevent intraoperative hypertension has traditionally been achieved with phenoxybenzamine. Due to changes in the availability of phenoxybenzamine in Canada, alternate therapies are needed for patients. We report our first experience using metyrosine, a tyrosine hydroxylase inhibitor, for preoperative management in a symptomatic patient with a unilateral PHEO. Clinical features A 50-yr-old male was referred to our centre with a history of symptoms suggestive of a catecholamine-secreting PHEO, including tachycardia, diaphoresis, nervousness, and tremor. Computerized tomography revealed a right adrenal mass, and additional positive imaging and elevated urine epinephrine levels supported a diagnosis of PHEO. The patient was admitted to hospital five days prior to surgery, and metyrosine therapy was initiated and titrated to 4 g daily over four days. Despite adequate blood pressure (BP) control leading up to the resection, the initial BP reading in the operating room was 191/106 mmHg, but it subsequently declined and was well controlled during induction (100-110 mmHg systolic BP). Significant hypertension (up to 201/110 mmHg) developed upon tumour manipulation and resolved with phentolamine administration and surgical isolation of the tumour. The patient's BP remained stable throughout the residual part of the procedure and in the recovery room and step-down unit. Conclusion In the case of this patient's PHEO, the use of metyrosine was unsatisfactory in achieving sufficient inhibition of catecholamine synthesis as evidenced by significant intraoperative hypertension. Metyrosine could have a role in preoperative management of these patients, but it may not be optimal as monotherapy for some patients with actively secreting tumours. RésuméObjectif Les phéochromocytomes sont des tumeurs corticosurrénaliennes rares sécrétrices de catécholamines qui nécessitent une résection chirurgicale. Le blocage préopératoire des récepteurs alpha-adrénergiques est habituellement obtenu avec de la phénoxybenzamine afin de prévenir une hypertension peropératoire. Compte tenu des modifications dans la disponibilité de la phénoxybenzamine au Canada, des traitements de substitution sont nécessaires pour les patients. Nous décrivons notre première expérience d'utilisation de la métyrosine, un inhibiteur de la tyrosine hydroxylase pour la gestion préopératoire d'un patient ayant un phéochromocytome unilatéral symptomatique.Author contributions Kabilan Thanapaalasingham coordinated the project, was responsible for data collection and analysis, drafted the manuscript, and provided critical feedback. André Pollmann assisted in the study conceptualization, coordination, and data collection aspects of the project. He was responsible for submitting the manuscript for publication. Benjamin Schelew conceptualized the study and supervised the data collection and clinical aspects of...

Pheochromocytoma

“…In a study from Japan by Naruse et al (2018), they have concluded that it was well tolerated and relieved symptoms by reducing excess catecholamine in pheos patients under both preoperative and chronic treatment. Death, failure of treatment and variation in intraoperative blood pressure in metyrosine patients were reported (Thanapaalasingham et al 2015;Naruse et al 2018).…”

Preoperative Management of Pheochromocytoma and Paraganglioma

“…Although Butz et al reported that patients treated with metyrosine and pheoxybenzamine had wider range of intraoperative blood pressure variations than phenoxybenzamine-only patients ( 47 ), it has been reported by most studies that the combination of metyrosine and α-AR antagonists lead to better blood pressure control, decreased intraoperative blood loss, and reduced volume replacement during operation compared with the classical method of monotherapy of α-AR blockade ( 45 , 46 , 48 , 49 ). In a case report of a patient with PPGL, the administration of metyrosine alone was unable to satisfactorily control intraoperative blood pressure ( 50 ), which was probably due to the incomplete depletion of CA stores no matter what dose used. Therefore, metyrosine is always used in combination with α-AR antagonists in patients with serious symptoms which cannot be well controlled by other medications, such as those with biochemically active tumors or extensive metastatic tumors ( 8 , 45 ).…”

Approach to the Patient: Perioperative Management of the Patient with Pheochromocytoma or Sympathetic Paraganglioma

“…The initial oral dose is usually 250 mg 3 times a day, which may gradually be increased to a maximum daily dose of 4 g. In general, metyrosine is prescribed in combination with an α-adrenergic receptor blocker, in particular phenoxybenzamine [54][55][56]. A few case reports suggested that monotherapy with metyrosine is less effective (57,58). Similar to phenoxybenzamine, metyrosine is expensive and has a limited availability in several countries.…”