DISCUSSION
Pheochromocytoma is a rare cause of hypertension during pregnancy occurring only in 1 in 50,000 cases and may be clinically challenging to differentiate from preeclampsia because hypertension and headache occur with both disorders. It is a catecholamine-producing tumor arising from chromaffin cells of medullary region of adrenal gland or sympathetic ganglia. Symptoms specific to pheochromocytoma include paroxysms of generalized sweating, palpitations, tremor, pallor, shortness of breath, generalized weakness, and panic attack-type symptoms. Some women with pheochromocytoma have an elevated blood glucose level (impaired fasting glucose, apparent type 2 diabetes mellitus). Our patient had an atypical presentation which was right flank pain. She also developed seizures which is one of the uncommon presentations of pheochromocytoma. Overall, antenatal diagnosis of the condition is crucial because intrapartum maternal and fetal mortality are high without appropriate treatment5 .
While the diagnosis of preeclampsia may overlap with pheochromocytoma presenting in pregnancy, the distinguishing feature is that preeclampsia usually develops after 20 weeks gestation and is associated either with proteinuria or evidence of end-organ damage whereas pheochromocytoma may present at any time throughout the entire pregnancy and is rarely associated with proteinuria 6 . In this case, the patient presented late in pregnancy, around 35 weeks gestation, her 24-hour urine collection was negative for proteinuria and her investigations did not show any evidence of end-organ damage.
A review of literature has shown that 10% of pheochromocytomas are bilateral, 10% of them are extra-adrenal in origin and 10% are malignant. They may be part of multiple endocrine neoplasia (MEN type IIa) syndrome and, if it is the case, the patient should be screened for medullary cell carcinoma of the thyroid and parathyroid adenomas by measuring serum calcitonin and parathyroid hormone (PTH) levels respectively 7 . Our patient’s tumor was unilateral (right side), adrenal in origin and benign in nature, as per postoperative histopathological examination. MEN syndrome was ruled by taking the patient’s past medical and family histories.
The diagnosis of pheochromocytoma is made by the detection of elevated 24-hour urinary levels of catecholamines (norepinephrine, metanephrines and vanillylmandelic acid) and/or raised plasma catecholamines. Non-specific assays may give false-positive results if the patient is on alpha-methyldopa or labetalol and screening should ideally be performed before antihypertensive therapy is started. Once the diagnosis has been confirmed, CT, ultrasound and MRI offer the best methods for localizing the tumor, although the latter two are preferable in pregnancy. However, MIBG (131I-meta-iodobenzylguanidine) scan to localize norepinephrine uptake is contraindicated in pregnancy 8 .
When pheochromocytoma presents in pregnancy, there is a greatly increased maternal and fetal mortality rate, especially if, as in up to 50% of cases, the diagnosis is not made antenatally, as potentially fatal hypertensive crises may be precipitated by labor, vaginal or abdominal delivery, general anesthesia or opiates. Hypertensive episodes may occur in pregnancy even when patient is in supine position owing to the pressure caused by the gravid uterus on the tumor. The main causes of maternal mortality are arrhythmias, cerebrovascular accidents or pulmonary edema. Its rate may reach up to 17% in undiagnosed cases while it is only about 4% in diagnosed cases. On the other hand, the perinatal mortality rate is about 26% in undiagnosed cases and 11% in diagnosed cases 9 .
The only curative option for pheochromocytoma is surgical removal of the tumor, either open or laparoscopic. The optimal timing for that depends on the gestational age at which the diagnosis is made. There is an increasing vogue to delay tumour resection until the puerperium. If pharmacological blockade, ideally with α-blockade with phenoxybenzamine, prazosin or doxazosin to control hypertension followed by β-blockade, if required, to control tachycardia, has been achieved prior to 23 weeks’ gestation, then resection may be performed in pregnancy especially if the tumor is small. If the pregnancy is more than 24 weeks’ gestation, then surgery becomes more hazardous and should be delayed until fetal maturity, when caesarean section with concurrent or delayed tumour removal is undertaken 10 .
Expert anaesthetic care is necessary in dealing with these cases and both perinatal and maternal mortality rates have improved significantly since the advent of α-blockade, which should be given for at least 3 days prior to the surgery. IV Phenoxybenzamine must be available for caesarean section. In an emergency if IV α-blockade is not available, then IV labetalol is the appropriate alternative11 .