Phaeochromocytoma is an uncommon cause of hypertension, accounting for between 1 in 1000-1 in 2500 cases [1,2]. Hypertension associated with pregnancy is not uncommon, but the association with phaeochromocytoma is rare. Nonetheless, a high index of suspicion must be maintained and early, appropriate investigations and management instigated as both foetal and maternal outcome is considerably improved. The following case report serves to emphasize this point.
A 25-year-old woman booked at 9-weeks gestation as a primigravida. She was well, but hypertensive at 160/110 mmHg. The following past medical history was elicited. At the age of 2 years she was investigated for recurrent urinary tract infections. An intravenous (i.v.) pyelogram at that time was normal except for some scarring of the lateral aspect of her left kidney. A micturating cystogram was also normal with no evidence of vesico-ureteric reflux. She was commenced on sulphonamide prophylaxis and followed up for the next 7 years. Blood pressure, urea and electrolytes and urine cultures were repeatedly normal and 2 yearly i.v. pyelograms showed good growth of both kidneys. She was discharged from follow up on no medication with normal blood pressure and renal function. At the age of 19 years she presented to the Family Planning Clinic for oral contraception and was found to be hypertensive at 160/110 mmHg. Her general practitioner confirmed the hypertension and, in view of her history, referred her for further investigations. A renal ultrasound and urea and electrolytes were normal, therefore she was discharged back to the care of her general practitioner, who monitored her 'labile' blood pressure, but did not commence treatment.
One week after her initial booking visit she was admitted from the antenatal clinic with hyperemesis gravidarum. During this admission she was also noted to be hypertensive and complained of episodes of paroxysmal palpitations lasting 15 min. In the ward her blood pressures were between 100/70 and 220/140 mmHg. Other complaints were of sweating, headaches and paraesthesia in both arms. She was commenced on labetalol 300 mg daily with some improvement in her symptoms. Urine was collected for catecholamine metabolites (Table 1). An ultrasound scan showed a 7 cm × 8 cm mass in the left renal region.
A magnetic resonance imaging (MRI) scan of the abdomen confirmed a 9 cm × 8 cm × 7 cm mass in the left para aortic region in close proximity to the renal vessels (Figs 1 and 2). Plasma noradrenaline was grossly elevated at 71.8 nmol L−1 (normal range <4.0 nmol L−1), while plasma adrenaline was normal at 0.3 nmol L−1 (normal range <0.4 nmol L−1). The patient was alpha-blocked with phenoxybenzamine 20 mg b.d. and then beta-blocked with propranolol 20 mg t.i.d. in preparation for surgery.
Resection of the phaeochromocytoma was scheduled for 16-weeks gestation. A premedication of temazepam 20 mg was given. Two large bore peripheral canulae and invasive arterial pressure monitoring were established prior to induction. Central venous access was established prior to surgery. Induction of anaesthesia was achieved with etomidate 6 mg, midazolam 6 mg and alfentanil 5 mg. Vecuronium was used for muscle relaxation. Arterial pressure was controlled with a sodium nitroprusside infusion (50 mg in 250 mL), the maximum infusion rate being 45 mL h−1. Boluses of phentolamine(5 mg total) and labetolol (60 mg total) were also given.
Laparotomy revealed that the mass was anterior to the upper pole of the left kidney and aorta. At its medial aspect the tumour extended posteriorly to encircle the renal vein and artery necessitating removal of the left kidney and adrenal with the tumour. The tumour weighed 180 gm. Histology showed the typical appearance of a paraganglioma with some pleomorphism, occasional mitoses and focal necrosis. Some tumour cells contained hyaline globules. The lesion appeared completely excised. The adrenal medulla was normal.
Shortly after the tumour was resected it was possible to discontinue the sodium nitroprusside. Measured intra-operatove blood loss was 2250 mL. Intra-operative fluids amounted to 2000 mL crystalloid, 1000 mL colloid and 4 units packed cells. Total operating time was four and a half hours.
Post-operatively the patient was transferred to the intensive care unit (ICU) for further monitoring. During the first 12 post-operative hours fluids were administered as required to maintain systolic blood pressure, a 2000 mL positive fluid balance being recorded. Recovery was otherwise uneventful. Plasma catecholamines after surgery were (noradrenaline 2.16 nmol L−1, adrenaline 0.14 nmol L−1). No anti-hypertensive medication was required. Regular follow up at the antenatal clinic showed a normal ongoing pregnancy with normal blood pressure and ultrasound scans showing normal foetal growth. At 38-weeks gestation, an elective Caesarean section was performed and a healthy 3040 g male infant was born.
The management of these complex cases requires a multi-disciplinary team approach. There must be close co-operation between endocrinologists, surgeons, anaesthetists, intensive care staff, pathologists and obstetricians. The largest recent series of reports of phaeochromocytoma in pregnancy was by Harper et al. in 1989 . They report five cases plus a review of 42 cases from the literature occurring in Northern Ireland between 1980 and 1987. Antenatal diagnosis was made in only 53% and resulted in reduced maternal mortality from 17% to 0% and foetal mortality from 26% to 15% when compared with cases undiagnosed antenatally. It is suggested that if phaeochromocytoma is diagnosed prior to 23-weeks gestation surgery should proceed after adrenergic blockade has been established and that after 23-weeks gestation the size of the gravid uterus makes access for surgery too difficult . Medical therapy should then continue until Caesarean section at 38 weeks. As in this case, diagnosis was made before 23 weeks in 11 of the 47 cases and mother and baby survived in 9 following antenatal surgery.
Antenatal diagnosis is confirmed by standard methods, including urinary and/or plasma catecholamines and tumour imaging. While there have been no reports of adverse effects of antenatal computed tomograph(CT) scanning, MRI has the benefit of not employing ionizing radiation and is at least as accurate as CT scanning in detection of phaeochromocytomas . The grossly elevated urinary and plasma noradrenaline with normal adrenaline in this case is in keeping with the histological diagnosis of a large extra-adrenal paraganglioma. Extra-adrenal tumours do not possess the enzyme phenylethanolamine N-methyl transferase(PNMT) which is responsible for conversion of noradrenaline to adrenaline. The explanation for this is not clear, but glucocorticoids stimulate production of PNMT . It may be that adrenal phaeochromocytomas possess PNMT activity by virtue of their close proximity to the adrenal cortex.
In this case surgery was anticipated to be complicated not only by the 16-week gravid uterus, but also by the large size of the tumour and involvement of renal vessels and perhaps also the aorta. Despite this, and despite having to remove the left kidney, the operation was relatively uncomplicated apart from a blood loss of 2250 mL.
The use of phenoxybenzamine in pregnancy associated with phaeochromocytoma has been previously reported with no adverse foetal effects [6,7]. Propranol has also been used with a good foetal outcome in most cases . The use of sodium nitroprusside in resection of phaeochromocytoma is well recognized; however, its use during pregnancy has seldom been reported. Joffe et al. report on the use of sodium nitroprusside in a combined Caesarean section and resection of phaeochromocytoma in a patient with Von Hippel Lindau disease. This was at term not at 16-weeks gestation as in this case.
Malignancy in phaeochromocytoma/paraganglioma is rare and this patient had no evidence of local invasion or metastases. Histological assessment of malignant potential is difficult. Multifactorial analysis suggests that four features may be important: extraadrenal site, coarse nodularity, confluent tumour necrosis and absence of hyaline globules . Because this tumour was extra-adrenal and showed some necrosis, a careful follow-up is planned. The absence of adrenal medullary hyperplasia would indicate that the tumour is sporadic.
While rare, phaeochromocytomas in pregnancy must be considered particularly in hypertension with associated headache, sweating or palpitations, or hypertension in the first trimester, or where a positive family history or neurofibromatosis is present.
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