A diagnosis not to miss: Pheochromocytoma during pregnancy

Abstract

Sirs: Pheochromocytoma during pregnancy is a life-threatening situation for both mother and fetus. Its diagnosis is too often missed [1, 2], mainly due to three reasons. Firstly, pheochromocytoma is extremely rare with an estimated prevalence in full-term pregnancies of 1 in 54,000 [3]; secondly, it has the ability to mimic a huge number of acute, insidious clinical syndromes and the tumor has been correctly termed the “Great Masquerader” [1]; thirdly, pheochromocytoma can be asymptomatic until delivery. Classic attacks include acute hypertension, headache, sweating and tachycardia. However, patients can be completely free of manifestations between attacks. Thus, diagnosis of pheochromocytoma during pregnancy remains a great challenge, but is essential to prevent disastrous complications for both mother and fetus [2, 4]. Although a few recent reports exist in the obstetric and anesthetic literature on this condition, curiously, to our knowledge there are no reports in recent neurological literature. A 30-year previously healthy woman in the 26th week of her first pregnancy was referred from her gynecologist because of new-onset headache. Symptoms had started six weeks earlier with pain in the neck, lightheadedness, nausea and vomiting after prolonged sunbathing. While all symptoms vanished with bed rest, a stabbing neck pain persisted, which during the next two weeks evolved into a daily occipital squeezing headache of mild intensity, intermingled with periodic pulsating neck pain. Subsequently, she developed episodic frontal throbbing headaches of moderate to severe intensity, accompanied by nausea, vomiting and hyperventilation. Episodes occurred up to five times daily and lasted from a few minutes to one hour. On two occasions the patient had noted a scintillating scotoma in the left visual field. She had no history of migraine. Since proteinuria and edema were absent, preeclampsia had been ruled out by her gynecologist prior to referral. Neurological examination, including fundoscopy, was unremarkable. The patient had no fever and blood pressure was 130/85 mmHg in both arms. Routine laboratory testing revealed mild leucocytosis and trombocytosis, slightly increased C-reactive protein and liver enzymes, but normal thyroid function and blood glucose. While the initial symptoms were consistent with aseptic meningitis secondary to heat stroke and prolonged sunbathing, the subsequent complaints were neither fully compatible with migraine nor with any other primary headache syndrome. MRI of the head including MR angiography and a lumbar puncture were normal and thus, cerebral venous thrombosis, vascular malformations, vasculitis, hemorrhagic and ischemic cerebrovascular accidents, infectious or neoplastic processes, and sinusitis were ruled out. However, on day three after admission the patient was observed during a severe headache with marked tachycardia, sweating, pallor, tremor and anxiety. Blood pressure was 220/110 mmHg, pulse rate 115 beats/min. A working diagnosis of pheochromocytoma was made. Repeated 24 hour urinary catecholamine testing revealed increased levels of norepinephrine (3,200–20,000 nmol; reference interval 62–560 nmol), epinephrine (240–620 nmol; 9–101 nmol), metanephrines (32–115 μmol; 5–7 μmol), aldosterone (260–280 nmol; 11–56 nmol) and vanillylmandelic acid (85–280 μmol; < 34 μmol). MRI of the abdomen showed a 6x6 cm solid right adrenal mass (Fig. 1). The patient’s family history was unremarkable for neuroendocrine tumors. Genetic testing of the patient for mutations of RET, VHL, SDHB and SDHD genes was negative. Using a multidisciplinary approach involving endocrinologists, anesthetists, surgeons and neonatologists, it was decided to treat the patient with phenoxybenzamine (α-adrenoceptor antagonist) and await fetal maturity. Headaches vanished completely. In the 31st week of pregnancy the patient underwent an uncomplicated caesarean section combined with removal of the adrenal mass. Microscopic evaluation confirmed the diagnosis of pheochromocytoma. Pheochromocytoma is a catecholamine-producing tumor arising from the adrenal medulla in 85 % of cases and in the remaining patients from chromaffin cells in or about sympathetic ganglia in the abdomen, pelvis, and rarely in the chest or neck [1]. Tumors with a comparable biochemical and clinical profile include some chemodectomas derived from the carotid body and neuroblastomas; the LETTER TO THE EDITORS