Characteristics of pheochromocytoma in a 4-20 year-old population.

BARONTINI M; LEVIN G; SANSÓ G

Bethesda, Maryland, USA

Simposio; First International Symposium on Pheochromocytoma; 2005

Pheochromocytoma Research Support Organization

Hypertension in children and adolescents has become a major health problem recently recognized, and in a significant number of patients it is due to an endocrine tumor. Improvements in genetic and imaging studies and in pharmacological agents have produced important changes in its management. The aim of this study was to establish the characteristics of pheochromocytoma (pheo) in a population of 58 patients between 4-20 years of age studied at our Center. They represented a 23% of the total population of 255 pheo patients studied over a period of 40 years. Pheo was diagnosed by determination of urinary and plasma catecholamines (epinephrine, norepinephrine and dopamine). Urinary vanillyl mandelic acid was also measured as well as urinary normetanephrine and metanephrine, when available. Diagnosis was confirmed at surgery. In familial cases genetic studies were performed. RET proto-oncogene mutations in exons 10, 11 and 16 were determined in DNA obtained from peripheral blood samples, by PCR followed by direct sequencing and/or restriction enzyme digestion. The entire coding region of VHL gene was screened by direct sequencing or by SSCP followed by sequencing. Differences in clinical signs between the under 20-year-old group and the over 20-year-old group were remarkable. In the younger group, there was a marked predominance of severe sustained hypertension (93%), only 7% presented paroxysmal hypertension and none of them was normotensive. Other signs frequently found were headaches (95%), sweating (90%), blurred vision (80%) and encephalopathy (65%) while palpitations (35%) and weight loss (15%) were less frequent. Interestingly, in this group, only one patient had normal values of norepinephrine while 55% of them presented normal levels of epinephrine. Urinary VMA was normal in 4/58 patients. The youngsters studied showed a higher incidence of bilateral  adrenal pheo (34%) and the extra-adrenal pheo (22%). Malignancy was found in 12% of these patients. In addition, the incidence of familial pheo was elevated in these patients (36%). Surprisingly, in contrast with the adult population where the most frequent familial pheos were MEN 2A (15%), the younger population showed a higher predominance of VHL (28%) and a veri low incidence of MEN 2A (2%), MEN 2B (2%), neurofibromatosis (3%) and SDHB (2%). In the VHL group, only 2 patients belonging to one family, showed the R167W mutation, while the others showed novel mutations in conserved amino acids. It may be speculated that the high incidence of VHL in youngsters may account for the biochemical and clinical features they usually present.