A 33-year-old previously healthy woman, gravida 1, para 0, presented during her first trimester with palpitations and an increase in sweating. Her symptoms began at approximately 10 weeks’ gestation and increased at 12 weeks’ gestation. At this time, she noticed a flushing of her face, headaches and worsening palpitations. She attributed the changes to normal features associated with pregnancy.
On examination, at 12 weeks’ gestation, her blood pressure (BP) was noted to be 130/80 mm Hg; pulse, 102 beats per minute (bpm); and BMI, 24.7. Fetal heart rate was detected at 150 bpm. A urinalysis was obtained, which revealed the absence of proteinuria. She was told to return in 1 week for repeat BP monitoring.
At 13 weeks’ gestation, her BP was elevated at 150/95 mm Hg, and a repeat urinalysis revealed no protein. In the setting of palpitations, headaches and hypertension, a biochemical investigation was performed, which revealed a plasma fractionated total metanephrines level of 3,083 pg/mL (normal, <205 pg/mL), normetanephrines level of 3,020 pg/mL (normal, <148 pg/mL) and metanephrines level of 63 pg/mL (normal, <57 pg/mL). A subsequent 24-hour vanillylmandelic acid level (VMA) was obtained, which was elevated at 18.9 mg/24 hours (normal, <6 mg/24 hours), and a 24-hour urinary metanephrine level was elevated at 7,119 mcg/24 hours (normal, 122-676 mcg/24 hours).
Concern for a pheochromocytoma was increased, and an MRI of the abdomen was obtained at 15 weeks’ gestation, which revealed a well-circumscribed left adrenal mass measuring 3.3 cm x 3.4 cm x 3.5 cm.
The patient was started on an alpha-blocker (phenoxybenzamine) preoperatively with a beta-blocker subsequently added 10 days later in the setting of persistent tachycardia. At 17 weeks’ gestation, a laparoscopic resection of a left adrenal mass was performed with close intraoperative monitoring and no complications. The pathology was consistent with a pheochromocytoma.
Perioperatively, the patient was closely monitored and remained hemodynamically stable. An elective Cesarean section was subsequently performed at 37 weeks’ gestation after concern for fetal bradycardia, with delivery of a healthy baby.
Pheochromocytomas are a rare event and are an even rarer occurrence during pregnancy, with an incidence of approximately 0.007%.1 The diagnosis is particularly important to consider during pregnancy, as an undiagnosed and/or untreated pheochromocytoma has a high maternal and fetal mortality rate, ranging from 15% to 25% in some studies1, 2 to as high as 40% to 50% in others.3 Although pheochromocytoma associated with pregnancy is a rare disease, an increased clinical suspicion must be maintained given the reduction in mortality with medical treatment and surgical resection.3
The most common presenting symptom of a pheochromoctyoma during pregnancy is uncontrolled hypertension, either paroxysmal or sustained. Accompanying symptoms include diaphoresis, palpitations and impaired glucose tolerance.4 In one study of 15 pregnant women presenting with pheochromocytoma during pregnancy, the classic triad of hypertension, headache and sweating was only seen in three women, whereas palpitations, headaches and diaphoresis associated with headaches were noted in five pregnant women.5 Additional, less common presenting symptoms have been reported including dyspnea, chest pain, seizures and postpartum pulmonary edema.6
Hypertension due to a pheochromocytoma during pregnancy is often mistakenly attributed to preeclampsia, particularly in the setting of proteinuria, which can delay the diagnosis. Certain features can help distinguish between the two diseases. For instance, preeclampsia typically manifests in the latter part of pregnancy, whereas pheochromocytomas can present at any time during pregnancy. If not diagnosed intrapartum, the hypertension of pheochromocytoma persists after delivery, whereas preeclampsia resolves.7
Similar to the nonpregnant state, pheochromocytomas are typically unilateral and sporadic, with 10% occurring as bilateral, malignant or familial. Examples of familial disorders associated with pheochromocytoma are multiple endocrine neoplasia II, von Hippel-Lindau syndrome and type 1 neurofibromatosis.2, 1
Establishing the diagnosis in the nonpregnant state is similar to the pregnant state, namely quantifying 24-hour urinary fractionated metanephrines and catecholamines and plasma fractionated metanephrines at least twice the upper limit of the normal range. Under normal circumstances, pregnancy and preeclampsia should not influence catecholamine levels.7
In the setting of a high clinical suspicion for a pheochromocytoma, MRI without gadolinium and/or ultrasound is recommended during pregnancy as an imaging modality. Ultrasound is often limited by the gravid uterus and has limited utility in diagnosing extraadrenal tumors.
There is no clear consensus on the treatment of pheochromocytomas diagnosed during pregnancy, with most data limited to small case studies. Medical therapy is a vital aspect of treatment, regardless of if surgical intervention occurs during pregnancy; alpha-adrenergic blockade is essential and beta-adrenergic blockade may be required 10 to 14 days later. Antihypertensive drugs during pregnancy can cause fetal complications including hypoxia and intrauterine growth retardation, placental ischemia and placental abruption. These risks need to be balanced with the potential maternal complications from uncontrolled hypertension, which include hypertensive crisis, pulmonary edema, and cardiac and cerebral complications.7
Numerous case reports suggest an optimal window for surgical resection during the second trimester. If the diagnosis is made early in pregnancy or mid-pregnancy, surgery is recommended. The use of alpha-receptor blockade medications can decrease BP and control for expansion of blood volume.
In general, phenoxybenzamine is the drug of choice during pregnancy (pregnancy class C). However, the drug crosses the placenta and can result in transient hypotension in the neonate.9 Beta-blockade can be initiated after alpha-blockade to control for tachycardia.
According to case reports in the literature, if diagnosed early in pregnancy, appropriate medical treatment should be initiated until surgery can occur. If diagnosed later in pregnancy, medical treatment should be initiated and surgery deferred until delivery.9
Surgery is the definitive treatment for pheochromocytoma; however, the timing must be coordinated with respect to trimester of pregnancy and fetal status. Patients require postoperative assessment as well as close monitoring due to the possibility of incomplete resection of tumor and recurrence or development of a malignant adrenal mass. In addition, genetic screening is recommended to assess for hereditary causes of pheochromocytoma, including multiple endocrine neoplasia II and von Hippel-Lindau syndrome.8
In summary, the overall management of pheochromocytoma begins with a high clinical suspicion for the condition, appropriate assessment and diagnosis, with medical treatment and surgical resection timed according to the gestational age of the baby.
In early pregnancy, fetal outcome is improved with both medical treatment and tumor resection; after the second trimester, elective Cesarean section is preferred closer to delivery with improved maternal and fetal outcomes.9 With appropriate diagnosis and treatment, there is a significant reduction in maternal and fetal mortality associated with this rare diagnosis.
- Kamoun M, Mnif MF, Charfi N et al. Adrenal diseases during pregnancy: pathophysiology, diagnosis and management strategies. Am J Med Sci. 2014;347(1):64-73.
- Girling J, Martineau M. Thyroid and other endocrine disorders in pregnancy. Obstetrics, Gynaecology and Reproductive Medicine. 2010;20(9):265-271.
- Lenders JW. Pheochromocytoma and pregnancy: a deceptive connection. Eur J Endocrinol. 2012;166(2):143-150.
- Keeley E. Endocrine causes of hypertension in pregnancy: when to start looking for zebras. Semin Perinatol. 1998;22(6):471-484.
- Salazar-Vega JL, Levin G, Sansó G et al. Pheochromocytoma associated with pregnancy: unexpected favourable outcome in patients diagnosed after delivery. J Hypertension.2014; 32(7):1458-1463.
- Kamari Y, Sharabi Y, Leiba A et al. Am J Hypertens. Peripartum hypertension from pheochromocytoma: a rare and challenging entity. 2005;18(10):1306-1312.
- Dong D, Li H. Diagnosis and treatment of pheochromocytoma during pregnancy. J Matern Fetal Neonatal Med. 2014[Epub ahead of print].
- Oliva R, Angelos P, Kaplan E, Bakris G. Pheochromocytoma in pregnancy: a case series and review. Hypertension. 2010;55(3):600-606.
- Ahlawat SK, Jain S, Kumari S, Varma S, Sharma BK. Pheochromocytoma associated with pregnancy: case report and review of the literature. Obstet Gynecol Surv. 1999;54(11):728-737.