Pheochromocytoma

Abstract

We examined a young man who had a benign giant cell granuloma of the maxilla, which we subsequently diagnosed as a brown tumor associated with hyperparathyroidism. During surgery for the granuloma, the patient developed severe hypertension and was discovered to have an extra-adrenal pheochromocytoma. Oncogene and calcitonin testing for medullary carcinoma of the thyroid was negative. Therefore, despite the presence of both pheochromocytoma and hyperparathyroidism, we concluded that this patient did not have multiple endocrine neoplasia type 2a.

Introduction

We report an unusual case of a patient who had a maxillary brown tumor associated with hyperparathyroidism and an extra-adrenal pheochromocytoma. The fact that there was no medullary thyroid cancer provided evidence that the man did not have multiple endocrine neoplasia (MEN) type 2a.

Case report

A 23-year-old man reported a painful swelling in the right maxilla of 5 months' duration. The patient denied any symptoms of episodic headache, sweating, or palpitations. He had no history of hypertension, thirst, polyuria, or fatigue. He was taking no medication and did not use recreational drugs. His family history was negative for any known abnormalities. The physical examination, including an evaluation of the skin and the thyroid gland, was unremarkable. In particular, he had no manifestation of neurofibromatosis or von Hippel-Lindau disease.

Computed tomography (CT) of the right maxilla suggested the presence of a tumor and showed associated bony destruction and displacement of the dentition (figure 1). The patient underwent an uneventful partial right maxillectomy under general anesthesia, and a 5.2 X 2.4 x 3.5-cm mass was removed. The tumor's pathology was consistent with that of a benign central giant cell tumor (figure 2).

Following surgery, the patient continued to experience progressively worsening facial discomfort. Followup maxillary CT at 6 months detected no decrease in the size of the original tumor area, and he was readmitted for further surgical treatment. Upon the introduction of general anesthesia, the patient experienced an immediate rise in blood pressure--from 120/80 to 200/140mm Hg--and a regular tachycardia of 150 beats per minute. General anesthesia was promptly halted, and further investigations were undertaken.

Laboratory tests. The patient's serum calcium level was 14.0 mg/dl (normal: 8.5-10.5), his phosphate level was 2.38 mg/dl (normal: 2.48-4.49), and his albumin was normal. His intact parathyroid hormone level was 1,116 pg/ml (normal: 10-60). Serum catecholamines drawn at rest through an indwelling line showed norepinephrine at 3,158 pg/ml (normal: [less than]473), epinephrine at 48.3 pg/ml (normal: [less than]59), and dopamine at 35.2 pg/ml (normal: [less than]32). Twenty-four-hour urine collection showed metanephrine at 128 [micro]g/mg Cr (normal: [less than] 216), normetanephrine at 2,899 [micro]g/mg Cr (normal: [less than]477), and vanillylmandelic acid at 13.2 mg/day (normal: [less than]6.7). His basal calcitonin concentration was 28.7 pg/ml (normal: [less than]100) and did not rise on pentagastrin stimulation. RET oncogene testing showed only normal sequences in exons 10, 11, and 13. A mutation (MET 918Thy) in RET exon 16 was ruled out by restriction enzyme analysis.

Imaging. Ultrasound of the abdomen suggested the presence of a vascular mass anterior and superior to the urinary bladder, and magnetic resonance imaging detected a 5.0 x 3.0 x 3.5-cm growth there (figure 3). Ultrasound of the neck also suggested the presence of a mass in the left thyroid. Meta-iodobenzyl guanidine [123]I and somatostatin scans were both negative. No adrenal gland abnormality was seen.

We concluded that the patient had both pheochromocytoma and hyperparathyroidism, and that removal of the pheochromocytoma would take precedence. After 3 weeks of phenoxybenzamine preparation, the patient was admitted to the hospital for 12 hours of intravenous fluid repletion. Surgical exploration detected a mass on the anterior wall of the urinary bladder. Upon manipulation of the mass, the patient's blood pressure rose to 180/110mm Hg; it immediately returned to normal when the blood supply to the tumor was clamped. The postoperative course was uneventful. Pathology of the tumor was consistent with that of an extra-adrenal pheochromocytoma. Followup urine collections for catecholamine products were negative.

Two months later, the patient was readmitted for exploration of the thyroid gland. A 3.0 x 1.0 x 1.5-cm mass was removed from the left inferior lobe. Other parathyroid glands were biopsied, and pathology indicated the presence of a single parathyroid adenoma without parathyroid hyperplasia in the other glands. Other than transient postoperative hypocalcemia, the patient has remained well and has maintained normal calcium levels without the need for supplements.

Discussion

This patient with a giant cell granuloma of the maxilla went on to exhibit hyperparathyroidism and extra-adrenal pheochromocytoma. The unusual features of this case include the fact that the maxillary tumor was initially diagnosed as a benign central giant cell granuloma. This tumor is pathologically indistinguishable from a giant cell tumor of the bone or a brown tumor of hyperparathyroidism. Hyperparathyroidism has been previously noted to be a cause of these granulomas, [1] although more often they manifest in the distal femur or proximal tibia. Surgery was complicated in this case by the presence of an unexpected pheochromocytoma. There has been no previous report of a giant cell granuloma of hyperparathyroidism occurring in association with pheochromocytoma.

It was further expected that this patient would manifest the criteria for MEN type 2a, but there was significant evidence against this conclusion. The constant feature of MEN 2a is a medullary carcinoma of the thyroid, which was very unlikely in this case because of the normal pentagastrin stimulation test and, more important, the negative results on RET oncogene testing. The sensitivity of RET oncogene testing for MEN 2a has been reported to be as high as 97%, while pentagastrin stimulation of calcitonin might be only half as sensitive. [2,3] Moreover, although there have been some reports of solitary parathyroid adenomas in the setting of MEN 2a, it is more common for the associated abnormality to be a parathyroid hyperplasia. [4] Therefore, although this patient could possibly still develop a medullary carcinoma of the thyroid and hence fulfill the criteria for MEN 2a, this appears unlikely.

From the Division of Endocrinology and Metabolism, Department of Medicine, The University of Western Ontario, London, Canada.

References

(1.) Robinson PJ, Woodhead P. Primary hyperparathyroidism presenting with a maxillary tumour and hydrocephalus. J Laryngol Otol 1988;102:l164-7.

(2.) Barbot N, Calmettes C, Schuffenecker I, et al. Pentagastrin stimulation test and early diagnosis of medullary thyroid carcinoma using an immunoradiometric assay of calcitonin: Comparison with genetic screening in hereditary medullary thyroid carcinoma. J Clin Endocrinol Metab 1994;78:114-20.

(3.) Heshmati HM, Gharib H, Khosla S, et al. Genetic testing in medullary thyroid carcinoma syndromes: Mutation types and clinical significance. Mayo Clinic Proc 1997;72:430-6.

(4.) Kraimps JL, Denizot A, Carnaille B, et al. Primary hyperparathyroidism in multiple endocrine neoplasia type IIa: Retrospective French multicentric study. Groupe d'Etude des Tumeurs a Calcitonine (GETC, French Calcitonin Tumors Study Group), French Association of Endocrine Surgeons. World J Surg 1996;20:808-12.

COPYRIGHT 2000 Medquest Communications, Inc.
COPYRIGHT 2000 Gale Group