Perinatal/Neonatal Case Presentation

A catecholamine-secreting neuroblastoma leading to hydrops fetalis

Abstract

A case of fetal neuroblastoma of the right adrenal gland, with rapid development of hydrops fetalis due to catecholamine-induced cardiomyopathy, is reported. A fetus with a right suprarenal mass detected during ultrasonography at 32 weeks gestation progressively developed into hydrops fetalis by 35.2 weeks gestation. An emergent cesarean section was performed. At birth, the female neonate was hypertensive, with markedly elevated catecholamine levels; echocardiography showed poor contractility. Morphine, human atrial natriuretic peptide, milrinone, nitroprusside and dobutamine were initiated and her blood pressure was maintained within the normal range and her cardiac contractility improved 2 weeks after birth. Neuroblastoma cells were detected in the placenta, resulting in the right adrenal mass being diagnosed as a neuroblastoma. She was well, and the mass diminished in size within 4 months, without surgery. A fetus with suspected neuroblastoma, indicated by a suprarenal mass, should be managed with appropriate consideration of hydrops.

Introduction

Neuroblastomas constitute 25% of congenital malignancies,1 and some secrete catecholamine, causing hypertension. Catecholamine excess can cause oxygen free radical development, calcium overload in the heart, downregulation of cardiac β-adrenergic receptors and myofibril loss, all of which lead to myocyte injury,2 which is described as ‘catecholamine-induced cardiomyopathy’.

Hydrops fetalis results from fetal cardiac failure owing to various mechanisms, including fetal cardiomyopathy. Excessive catecholamine secretion from a fetal neuroblastoma may lead to fetal cardiomyopathy and results in hydrops fetalis. However, previous reports of this have not been described.

Here we report a neonate who developed hydrops fetalis because of catecholamine-induced cardiomyopathy, secondary to a fetal catecholamine-secreting neuroblastoma.

Case

A 33-year-old, primiparous Japanese woman with an unremarkable personal or family medical history was referred to our hospital because of a fetal, right, suprarenal mass detected during a routine, prenatal ultrasonogram at 32 weeks gestation. A solid, 3-cm diameter mass was detected on the anterior and superior pole of the fetus’ right kidney (Figure 1). Although hydrops was not evident at 34.0 weeks gestation, hydrops fetalis (ascites, pleural effusion and edema) and cardiomegaly (cardiothoracic area ratio, 46%) developed progressively by 35.2 weeks gestation; the fetus was delivered by emergent cesarean section. The blood gas analysis of blood from the umbilical artery revealed a pH of 7.289, a CO2 partial pressure of 47.6 mm Hg, an O2 partial pressure of 16.1 mm Hg, a HCO3− concentration of 22.8 mmol l−1 and a base excess of −3.5 mmol l−1.

Figure 1
figure1

Fetal neuroblastoma of the right adrenal gland. (a) Transverse ultrasonography showing the prenatal appearance of the neuroblastoma on the anterior and superior pole of the right kidney. The neuroblastoma was a solid, 3-cm diameter mass. (b) Coronal T1-weighted magnetic resonance image of the patient showing the right, round, suprarenal mass displacing the right kidney downward. The mass was well defined and heterogenous; the rim of the lesion was isointense and the central portion was of low intensity. (c) Coronal, T2-weighted magnetic resonance image showing the low-intensity rim of the lesion and the high-intensity central portion.

Upon delivery, the female neonate had generalized edema and weighed 3268 g, with 1 and 5 min Apgar scores of 8; she was in respiratory distress, necessitating mechanical ventilation. The baby was hypertensive, with a blood pressure (BP) of 76/47/59 mm Hg (systolic/diastolic/mean). Cardiac arrhythmia was absent, and her hemoglobin level was 11.7 g dl−1. An echocardiography showed normal cardiac structure and a patent ductus arteriosus; her left ventricular ejection fraction was low (46%). Her plasma and urinary catecholamine and metabolite levels were markedly increased, without an elevation in adrenocorticotropic hormone, cortisol, renin activity or aldosterone (Table 1). We speculated that her hypertension and heart failure resulted from sustained fetal catecholamine elevation.

Table 1 Laboratory data

A continuous infusion of morphine was started after birth, and beginning on day 1, human atrial natriuretic peptide, milrinone and nitroprusside were started to treat the patient’s hypertension; dobutamine was added to treat low cardiac function on day 2. The patient’s mean BP began to fluctuate between 20 and 70 mm Hg for 12 h and then gradually normalized (Figure 2). Dobutamine infusion was discontinued on day 3 but episodes of periodic paroxysmal hypertension recurred on days 4 and 5. As the patient’s BP normalized, we discontinued the administration of nitroprusside, morphine and human atrial natriuretic peptide by day 6. Thereafter, the infant’s BP stabilized and her cardiac contractility improved. On day 14, we discontinued milrinone.

Figure 2
figure2

Periodic changes in blood pressure (BP) on day 2. The duration of these changes was 12 h, with a period of 20 min. The mean BP was 20–70 mm Hg.

Scintigraphy, using metaiodobenzylguanidine, showed a cold spot on the right suprarenal mass but no other metastatic spots. Placental histopathology revealed several neuroblastoma cells in a small, angiomatous tissue section of the placenta. The neuroblastoma cells were diagnosed as a poorly differentiated subtype, without N-myc amplification. On the basis of the patient’s biochemical data, clinical course and placental pathology, we speculated that the catecholamine-induced cardiomyopathy resulted from a sustained elevation of catecholamine secreted by the right adrenal neuroblastoma, which led to hydrops fetalis and newborn hypertension.

The patient’s right adrenal mass did not require surgical intervention because her neuron-specific enolase and catecholamine levels were normalizing and the tumor was poorly differentiated, without N-myc amplification. The patient was discharged on day 57; she was well and the tumor had decreased in size by 4 months of age.

Discussion

We believe this is the first report describing a neonate who developed hydrops fetalis because of catecholamine-induced cardiomyopathy secondary to a fetal catecholamine-secreting neuroblastoma. The patient’s suprarenal mass was not histologically evaluated but neuroblastoma was diagnosed through a histological examination of the placenta. A previous report emphasized the importance of placental examinations in cases of congenital tumors because the placenta is readily available at birth and the procedure is noninvasive.3 Furthermore, placental examination enabled our patient to avoid surgery as the histology suggested a good prognosis.

The possible mechanisms of hydrops fetalis with neuroblastoma are (1) invasion of erythropoietic tissue by tumor cells, resulting in severe fetal anemia;4 (2) mechanical compression of the vena cava by the primary tumor or enlarged liver;4, 5 (3) blood flow impedance by tumor cells in the hepatic and placental vasculature;4 (4) intrauterine arrhythmia and ductal arteriosus constriction caused by excessive catecholamine secretion, both leading to fetal heart failure;4, 5 (5) hypersecretion of aldosterone, induced by tumor encroachment or irritation of the fetal adrenal cortex;4 and (6) cardiomyopathy resulting from sustained catecholamine elevation secreted from a fetal neuroblastoma. The present patient did not have severe anemia, a mass effect due to the tumor, liver metastasis or hyperaldosteronism. Furthermore, at birth, the ductal arteriosus was patent and arrhythmia was not detected before or after birth. Placental blood flow was also unlikely to have been interrupted because she did not have significant placental metastasis. Compression of the neuroblastoma during vaginal delivery can induce catecholamine release,6 but the present infant was delivered by cesarean section. We did not detect excessive secretion of catecholamine antenatally, but its presence was indicated by the patient’s highly elevated serum catecholamine levels at birth. Therefore, in this case, hydrops fetalis was apparently caused by intrauterine catecholamine-induced cardiomyopathy.

Many cases of catecholamine-induced cardiomyopathy due to pheochromocytoma have been reported. However, patients with neuroblastomas causing catecholamine-induced cardiomyopathy are rare. This difference is thought to be due to the relatively small serum catecholamine elevations associated with neuroblastomas, compared with pheochromocytomas. The catecholamine storage mechanism in a neuroblastoma is less efficient than that in a pheochromocytoma, leading to increased intracellular breakdown of catecholamines.7 To our knowledge, there are only five reported cases of neuroblastomas possibly causing antenatal development of catecholamine-induced cardiomyopathy. However, none developed hydrops fetalis.6, 8, 9, 10, 11

Our case is unique because the patient experienced repeated BP changes after birth. Pheochromocytomas are the known causes of periodic BP changes, but this observation is rare in cases involving neuroblastomas. Only one case of a neuroblastoma leading to paroxysmal hypertension, after metastasis to the spine, has been reported. In that case, the paroxysmal hypertension was believed to have resulted from disruption of autonomic pathways.12 Our case did not involve the central nervous system, so the mechanism of paroxysmal hypertension may have been due to intermittent secretion of catecholamine from the tumor; this is not clear because we did not find periodic changes in serum catecholamine levels.

In summary, a case of hydrops fetalis resulting from excessive secretion of catecholamine from a fetal neuroblastoma was reported. The presence of a neuroblastoma-like tumor should be a cause for frequent patient monitoring because a catecholamine-secreting neuroblastoma may lead to hydrops fetalis.

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Acknowledgements

We thank Shouichiro Amari, MD, Ikuko Hama, MD, Yukiko Tasaki, MD, Masao Kaneshige, MD, Sae Hanai, MD, Yuka Wada, MD, PhD, Shigehiro Takahashi, MD, Hideshi Fujinaga, MD, Keiko Tsukamoto, MD (Center for Maternal–Fetal and Neonatal Medicine, National Center for Child Health and Development) and Yasushi Misaki, MD (Division of Cardiology, National Center for Child Health and Development) for their helpful clinical suggestions.

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Inoue, T., Ito, Y., Nakamura, T. et al. A catecholamine-secreting neuroblastoma leading to hydrops fetalis. J Perinatol 34, 405–407 (2014). https://doi.org/10.1038/jp.2014.19

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Keywords

  • congenital neuroblastoma
  • catecholamine-induced cardiomyopathy
  • placental metastasis
  • paroxysmal hypertension

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