Metyrosine-associated endocrinological changes in pheochromocytoma and paraganglioma

Abstract

Objective: Metyrosine (alpha-methyl-para-tyrosine) effectively reduces catecholamine levels in patients with pheochromocytoma/paraganglioma. However, improvements in physiological and metabolic parameters and changes in endocrine function associated with metyrosine administration should be validated in comparison to surgery. This study was performed to confirm the effects of metyrosine on the physiological, metabolic, and endocrinological functions of patients with pheochromocytoma/paraganglioma in the perioperative period.

Design: This retrospective cohort study was performed at a single university hospital.

Methods: We included ten patients with pheochromocytoma/paraganglioma who received oral metyrosine after α-blocker therapy and consecutive surgeries. Urinary catecholamine metabolite levels and other clinical parameters were evaluated before and after metyrosine administration, and 1 week after surgery.

Results: The mean age was 53.1 ± 16.1 years. Of the ten participants (four men and six women), nine had pheochromocytoma and one had paraganglioma. The median maximum metyrosine dose was 750 mg/day. Urinary catecholamine metabolite levels significantly decreased in a dose-dependent manner after metyrosine administration. Both systolic and diastolic blood pressure significantly decreased after metyrosine and surgical treatment. Metyrosine administration significantly improved insulin sensitivity, although surgery improved the the basal insulin secretion. Additionally, serum prolactin and thyroid-stimulatory hormone levels were significantly increased by metyrosine treatment, whereas plasma renin activity was decreased.

Conclusions: Metyrosine significantly reduced catecholamines in patients with pheochromocytoma/paraganglioma and ensured the safety of the surgery. Adjustment of metyrosine administration may make surgical pretreatment more effective in achieving stabilized blood pressure and improving glucose metabolism. Endocrine parameters may manifest as the systemic effects of metyrosine administration.

Keywords: diabetes mellitus; dopamine; paraganglioma; pheochromocytoma; prolactin.

Figure 1

Flowchart of this study. The duration of metyrosine administration (26.7 ± 14.2 days) is indicated by a gray bar.

Figure 2

Changes in MN+NMN, MN, and NMN levels after αMPT administration and after surgery. (A) Differences between urinary catecholamine (CA) metabolite levels at baseline and after αMPT administration. (B) Differences between CA metabolite levels after αMPT administration and after surgical treatment. Changes in catecholamine metabolite levels between baseline and after αMPT administration are presented, comparing those between baseline and after surgical treatment as follows: CA metabolite levels (baseline − after αMPT administration)/CA metabolite levels (baseline – after surgery)) × 100%. †MN levels were not normally distributed and the median (IQR) was 42.6 (14.3–71.5). ‡Differences between baseline urinary MN levels at and MN levels after αMPT administration and after surgery are not presented because there was no postoperative decrease in MN levels. The urinary MN levels at baseline, after MPT administration, and after surgery were all low, with median levels of 0.08 mg/day, 0.06 mg/day, and 0.09 mg/day, respectively. For each participant, the MN + NMN, MN, and NMN levels are shown as gray, open, and closed bars, respectively. The error bars indicate the standard deviations. Correlations between the dose of αMPT and each catecholamine level are presented; (C) MN + NMN, (D) MN, and (E) NMN. Abbreviations: αMPT, α-methyl-para-tyrosine (metyrosine); CA, catecholamine; IQR, interquartile range; MN, metanephrine; NA, not applicable; NMN, normetanephrine.

Figure 3

Changes in physiological and metabolic parameters after metyrosine (αMPT) administration and after surgical treatment. Normally distributed variables are presented as mean ± s.d. Non-normally distributed variables are presented as median (IQR (open box) and range (bars)). When normally and non-normally distributed variables were compared, they were presented as medians (IQR (open box) and range (bar)). †Data were analyzed using paired t-test. ‡Data were analyzed using Wilcoxon’s signed-rank test. P < 0.05 were considered significant and are presented in bold font. αMPT, α-methyl-para-tyrosine (metyrosine); bpm, beats per min; HOMA-β, homeostasis model assessment of β-cell function; HOMA-R, homeostasis model assessment of insulin resistance; NA, not applicable.