Journal of Human Hypertension (2003) 17, 73–75 & 2003 Nature Publishing Group All rights reserved 0950-9240/03 $25.00 www.nature.com/jhh
CASE REPORT
Seizures as a presenting symptom of phaeochromocytoma in a young soldier A Leiba1,2, Y Bar-Dayan2, RR Leker3, S Apter4 and E Grossman1 1
Department of Internal Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Israel; 2Health Services Center, IDF MC, Israel; 3Central Neurology Clinic, IDF MC, Israel; 4Department of Imaging, The Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel
New onset of seizures in young adults is frequently related to alcohol withdrawal, toxic exposure, central nervous system trauma and neoplasm. We describe a young soldier presenting to the emergency department with seizures and transient coma. On admission, he had hypertension, marked leukocytosis, hyperglycaemia, acidosis, elevated creatinine and elevated creatine phosphokinase of muscle origin. A thorough
work-up revealed elevated urinary catecholamines, and a left adrenal mass was found on MRI and MIBG scan. The patient underwent laparoscopic adrenalectomy and completely recovered. This is the first description of seizures as a presenting symptom of phaeochromocytoma. Journal of Human Hypertension (2003) 17, 73–75. doi:10.1038/sj.jhh.1001499
Keywords: phaeochromocytoma; convulsion; catecholamines
Introduction A convulsive episode in an adult should initiate a search for an underlying pathology, especially if there is an associated focal aura with secondary generalization, physical and neurological signs or abnormal laboratory results.1 New onset of seizures in young adults can result from drug intoxication, drug withdrawal (eg, ethanol), infections (eg, meningoencephalitis, abscess), ischaemic injury (eg, focal or diffuse), spaceoccupying lesions (eg, tumour or haemorrhage) or metabolic derangements (eg, hepatic or uremic encephalopathy, hypoglycaemia, hyponatraemia, hypocalcaemia or hyperosmolar state). We describe a patient in whom a subtle phaeochromocytoma is believed to cause convulsions.
Case report A 20-year-old soldier presented to the emergency department with generalized seizures followed by loss of consciousness. He was perfectly healthy and had a negative past medical history except for a single left kidney. He had no history of loss of consciousness, syncope or seizures. He had not had elevated blood pressure and denied drinking Correspondence: Prof. E Grossman, Internal Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel. E-mail:
[email protected] Received 17 September 2002; accepted 6 October 2002
alcohol, smoking or drug abuse. He was on no regular medications and his family medical history was unremarkable. A month prior to his admission he noted brief attacks of palpitations. On admission, his physical examination was normal except for an elevated blood pressure of 170/100 mmHg. Neurological evaluation revealed a fully alert young man with no signs of meningeal irritation, the cranial nerves were intact; motor strength was 5/5 in all muscles and the deep tendon reflexes were +2 with flexor plantar response. There were no sensory or cerebellar abnormalities and gait was normal. Laboratory evaluation revealed a white blood cell count of 38 000/mm3; haemoglobin, 12.6 gm/dl; serum creatinine, 2.3 mg/dl; glucose, 330 mg/dl; creatine phosphokinase (CPK) 1200 U/l, and a blood pH of 7.1. Serum levels of electrolytes including calcium and magnesium, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, bilirubin, thyrotropin, B12, folic acid, lactate, aldolase, antinuclear antibodies, antiphospholipid antibodies and ethanol were all within normal limits. Cerebrospinal fluid was normal. Blood cultures were negative. Urinary toxicology screen and urinary porphobilinogen were normal. Electrocardiogram showed borderline short P-R interval without delta waves. Radiograph of the chest was normal; brain computerized tomography (CT) and magnetic resonance imaging (MRI), electro-encephalography, echocardiography, Holter
Seizures as a presenting symptom of phaeochromocytoma A Leiba et al 74
electrocardiography and stress test were all unremarkable. Abdominal ultrasonography showed a single left kidney, about 14 cm in size, without hydronephrosis and with normal-looking parenchyma. Carbamazepine was initiated for a presumptive diagnosis of focal seizures with secondary generalization. After a few days he felt well, his blood pressure returned to normal, and all the laboratory abnormalities were normalized. Urinary catecholamine excretion obtained after discharge were elevated: norepinephrine, 150 mg/ 24 h (no100 mg/24 h); epinephrine, 70.4 mg/24 h (no30 mg/24 h); metanephrines, 1469 mg/24 h (no1000 mg/24 h). Abdominal MRI revealed a 3 3 3 cm3 left adrenal mass (Figure 1). I-123-MIBG scan was consistent with the diagnosis of left adrenal phaeochromocytoma. The patient underwent laparoscopic left adrenalectomy that confirmed the diagnosis of phaeochromocytoma. After a 1-year follow-up, the patient is asymptomatic, has no similar events, and has normal blood pressure levels.
Discussion The clinical features of phaeochromocytoma are because of catecholamine secretion. Hypertension is the most common manifestation.2 It may either be sustained and poorly responsive to therapy or paroxysmal (‘hypertensive crises’). The classical clinical findings of headaches, profuse sweating, tachycardia, nervousness, pallor and fever accompanied by hypertension are well known.3 However, recognition of unusual presentation is less known but not less important because phaeochromocytoma is one of the curable forms of hypertension. Uncommon presentations of phaeochromocytoma seem to be more prevalent than one thought. Central nervous system (CNS) manifestations are relatively rare in phaeochromocytoma. Cerebral ischaemia and symptoms of stroke were rarely described in patients with phaeochromocytoma.4,5 Intracerebral haemorrhage and infarcts were described in a 35-year-old male with phaeochromocytoma.6 We have previously described a child with sudden blindness caused by phaeochromocytoma.7 To our knowledge, this is the first case described in the English literature of convulsions associated with mild hypertension as the presenting symptoms of phaeochromocytoma. The occurrence of seizures may be related to the high catecholamines or to hypertensive encephalopathy.8 Hypertensive encephalopathy is unlikely in our patient, since only mild elevation of blood pressure was recorded during the seizures. Moreover, brain CT and MRI were normal and the seizures stopped with anticonvulsive and not with antihypertensive treatment. Seizures may also be related to an associated brain tumour in Journal of Human Hypertension
Figure 1 MRI of left adrenal phaeochromocytoma: Axial spinecho (a) T2-weighted (2100/90) and (b) coronal postgadolinium T1-weighted (470/12) images. A 3-cm phaeochromocytoma is present in the left adrenal, which is high in signal intensity (arrowheads) on T2-SE (a) and moderately high in signal intensity (arrows) after gadolinium injection (b).
patients with neurofibromatosis. Such a case has been described9 in the past. However, our patient did not have neurofibromatosis and his brain MRI excluded an associated brain tumour. Vaso-spasm of the cerebral circulation because of markedly elevated catecholamines may cause cerebral ischaemia and provoke epileptic focus. This seems to be the mechanism of seizures in our patient. Unfortunately, we did not measure plasma or urinary catecholamines during the seizure
Seizures as a presenting symptom of phaeochromocytoma A Leiba et al
attack, since we did not suspect phaeochromocytoma when he first presented with seizures. Only after his recovery, we evaluated his hypertension and we found elevated urinary catecholamine excretion. Phaeochromocytoma is an important correctable cause of hypertension, but if undiagnosed, as some autopsy series suggest, it may be associated with significant morbidity and mortality.10 Diagnosis is sometimes deferred because of atypical presentations, such as in our patient. Therefore, one should have a high index of suspicion for any unexplained paroxysmal episode that is related to high blood pressure. Our patient’s final diagnosis can explain the laboratory abnormalities seen at his presentation: hyperglycaemia, elevated CPK levels and acute renal failure. Hyperglycaemia and impaired carbohydrate tolerance is related to the suppression of insulin and stimulation of hepatic glucose release by catecholamines. Elevation of CPK of muscle origin occurs as a result of vasoconstriction with ischaemia of skeletal muscle (in our patient it might also be related to the seizure itself). Acute renal failure is related to catecholamine-mediated vasoconstriction and diminished plasma volume. It is also sometimes related to rhabdomyolysis and myoglobinuria. Although the combination of paroxysmal spells or seizures, hypertension, tachycardia and increased catecholamine levelsFas in our patientFis very suggestive of phaeochromocytoma, it might also be related to a rare entity called ‘diencephalic’ or ‘autonomic epilepsy’.11,12 The present case suggests that physicians should be aware of phaeochromocytoma to discover unusual cases.
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