Catecholamine and Metanephrine Levels in Breast Milk Before and After Paraganglioma Resection

Introduction

Catecholamine-secreting paraganglioma or pheochromocytoma is a rare condition in the parturient and resection may occur simultaneously or sequentially with respect to delivery. ¹ When the patient presents for delayed resection, the exposure of the infant to catecholamines and medications in breast milk must be weighed against the well-established benefits of breastfeeding. The placental transfer of catecholamines and doxazosin as well as the breast milk concentrations of doxazosin have previously been described, ² but the transfer of catecholamines and metanephrines into breast milk has not been previously reported in the literature.

We describe the case of a 35-year-old woman G2P2 who was diagnosed with a catecholamine-secreting paraganglioma in the 27th week of her pregnancy. At the time of diagnosis her free plasma normetanephrine level measured 20.1 nmol/mL (normal limit <0.81 nmol/mL). She was treated with phenoxybenzamine and propranolol. Her infant was delivered by cesarean section at 36 weeks 2 days gestation under spinal anesthesia. She presented for open paraganglioma resection 5 weeks later, with phenoxybenzamine, propranolol, and nifedipine continued in the interim. She reported a successful breastfeeding relationship with the infant and planned to continue expressing breast milk and breastfeeding when possible during her hospitalization.

We hypothesized that there would be high levels of catecholamines and metanephrines present in the breast milk before the removal of the paraganglioma and that these levels would begin to fall by the following day. Because the tumor was primarily secreting norepinephrine in the preoperative evaluation, we focused our investigation and reporting on norepinephrine and normetanephrine. The patient agreed to provide a small aliquot of her expressed breast milk on the morning of surgery and the first and second postoperative morning.

Materials and Methods

This investigation was deemed exempt by the Mayo Clinic IRB. Written consent was obtained from the patient for the laboratory tests and for inclusion of the results in this publication. The patient collected breast milk with a hospital-grade pump and three morning samples (preoperative day 0, postoperative day 1, and postoperative day 2) were frozen at −80°C and sent to the Mayo Clinic mass spectroscopy laboratory for analysis. The values are reported in absolute concentration (Table 1). Because of the potential instability of catecholamines, we measured normetanephrine levels as well.

Results

The breast milk concentrations of normetanephrine were 42 nmol/L (operative day 0), 1.64 nmol/L (postoperative day 1), and 1.85 nmol/L (postoperative day 2) and are shown in Table 1. The breast milk concentration of norepinephrine was 41 pg/mL (operative day 0) and undetectable (postoperative days 1 and 2). In addition, free plasma normetanephrine was drawn on the morning of postoperative day 1 and measured 1.4 nmol/L (normal limit <0.9 nmol/L).

Discussion

This report is the first description of the levels of catecholamine and metanephrine levels in breast milk in the setting of paraganglioma. Although pheochromocytoma and paraganglioma in the parturient is a rare condition, this may add to the knowledge about their management. The elevated preoperative levels are consistent with the secreting activity of the paraganglioma. As we predicted they rapidly returned to normal levels the following day.

The infant was likely exposed to elevated levels of catecholamines in breast milk during the interim postpartum period. However, the bioavailability of oral catecholamines is very low ³ and this likely represents a lower overall exposure than in utero. This information may be useful to clinicians and patients as they make decisions about breastfeeding postpartum but preresection. For those who have combined delivery and tumor resection, our results indicate that the breast milk likely returns to near-normal concentrations very shortly after resection.

As the interest in supporting breastfeeding mothers through surgical and medical conditions increases, it is important to continue to study how those conditions and medications used to treat them might impact the breastfeeding infant. Limitations of this investigation include that it is a single case and that catecholamine levels may be underestimated due to their instability and need for specific preservative conditions.