Differences between sporadic and multiple endocrine neoplasia type 2A phaeochromocytoma

Abstract

OBJECTIVES Phaeochromocytoma may be either sporadic or part of a familial cancer syndrome. We have investigated whether there are differences between sporadic and MEN 2A phaeochromocytomas. DESIGN A retrospective study. We analysed age at presentation, sex, mode of presentation, clinical data, laboratory and imaging techniques, treatment, pathology and follow‐up. PATIENTS Forty‐six patients diagnosed with phaeochromocytoma between 1979 and 1995 (23 sporadic and 23 familial) at the Hospital Universitario Virgen de la Arrixaca (Murcia, Spain), a tertiary referral centre. RESULTS Mean age at presentation was 47 ± 16 years for sporadic and 38 ± 11 years for familial phaeochromocytoma (P < 0.05). The most common clinical feature and the presenting feature in cases of isolated phaeochromocytoma was hypertension. Of the MEN 2A patients, 52% were asymptomatic at diagnosis and only 35% presented with hypertension. Levels of adrenaline, noradrenaline, dopamine and metanephrines in a 24‐hour urine connection confirmed the diagnosis in 95% of the isolated and 91% of the familial phaeochromocytomas. Computed tomography located 100% of the sporadic and 76% of the familial phaeochromocytomas (P < 0.02). All the MEN 2A phaeochromocytomas were bilateral compared with none of the sporadic phaeochromocytomas (P < 0.001). All the patients with familial phaeochromocytoma underwent bilateral adrenalectomy. The patients with sporadic phaeochromocytoma had the affected gland or the tumour, if extraadrenal, removed. CONCLUSIONS In comparing sporadic and MEN 2A phaeochromocytoma we found differences in age at presentation, mode of presentation, clinical data, duration of clinical features, imaging findings bilaterality and type of surgical treatment required.

Pheochromocytomas detected by biochemical screening in predisposed subjects are associated with lower prevalence of clinical and biochemical manifestations and smaller tumors than pheochromocytomas detected by signs and symptoms

“…This difference can be explained by the fact that the other studies included children in their studies (2,4,14). The mean ages of the patients with MEN2, VHL, and NF included in our study are comparable with those reported in the literature (4,6,13,15,16). The higher age range of our hereditary paraganglioma patients increases the mean age of the hereditary patient group in total.…”

“…Patients with a SDHx mutation, MEN2 disease, or VHL disease are advised to be screened for pheochromocytoma annually. In case of increased plasma/urinary catecholamines or their metabolites, additional radiological investigation should be performed to identify the culprit lesion (2,6,13,27). The prevalence of pheochromocytoma is quite low in patients with NF, and therefore, screening is not recommended in all patients, but it may be justified in those patients with NF with hypertension, or in those patients who will undergo provocative interventions, such as surgery or pregnancy (7).…”

“…Our data is in line with those of Pomares et al, (13) who compared patients with sporadic pheochromocytomas and patients with pheochromocytomas caused by the MEN 2A syndrome. They reported similar differences in age at presentation, clinical signs and symptoms, radiological findings, and unilateral pheochromocytomas versus bilateral pheochromocytomas (13). We included patients with pheochromocytomas detected by screening for several hereditary syndromes predisposing to pheochromocytomas (MEN 2A syndrome, NF1, VHL disease, and familial paraganglioma syndrome) and patients presenting with sporadic pheochromocytomas.…”

The clinical genetics of phaeochromocytoma and paraganglioma

“…This is consistent with increased levels of metanephrine, which is a catecholamine O-methylated metabolite of epinephrine, detected in plasma and excreted in urine in these patients (13). Interestingly, only half of the patients with MEN2A harbouring a phaeochromocytoma present with it, which might be explained by earlier presentation with medullary carcinoma of the thyroid or family screening (8).…”

“…Clinically, there are three main subtypes of MEN 2; 1) MEN2A is characterised by medullary thyroid cancer in 95% of patients, phaeochromocytoma in 40-50% and primary hyperparathyroidism in 20%-30%; 2) MEN2B accounts for approximately 5% of MEN syndromes and has medullary thyroid cancer in 100%, phaeochromocytoma in 50% of cases, a Marfanoid body habitus, and multiple mucosal ganglioneuromas; however, it is not associated with hyperparathyroidism. 3); the third group is the rarest RET proto-oncogene associated MEN2 which represents familial medullary thyroid cancer alone (8,9). Identification of phaeochromocytoma is vital in these patients with MEN2 to avoid perioperative hypertensive crisis during thyroidectomy for medullary thyroid carcinoma.…”