Histological analysis of surgically removed adrenal masses often fails to d
ifferentiate between benign and malignant tumors. In normal cells, the telo
meric ends of the chromosomes are shortened with each cell division, leadin
g to chromosome destabilization and cellular senescence after a critical nu
mber of cell cycles. Tn tumor cells, telomere shortening is prevented by a
specific DNA polymerase, called telomerase. In an effort to clarify the rol
e of telomerase in the pathogenesis of adrenal tumors, and to test whether
irs activity could serve as marker of malignancy, we measured telomerase ac
tivity in 41 human adrenal tissue samples that were classified both by the
clinical course and by histological examination. Telomerase activity was de
rmined by TRAP ELISA and expressed as high (>50% of positive control telome
rase activity), medium (31-50%), low (11-30%), very low (less than or equal
to 10%), or absent (0%) The 8 normal adrenal tissue samples showed very lo
w levels of telomerase activity. Mean telomerase activity also very low in
3/3 incidentalomas, 6/6 Gushing adenomas, 6/6 Conn adenomas, 7/7 adrenocort
ical carcinomas, sig benign pheochromocytomas, and 2/3 malignant pheochromo
cytomas. In contrast, one malignant pheochromocytoma showed high telomerase
activity. These data indicate that telomerase activity may not be a suitab
le marker for malignancy in the adrenal gland. Our results also challenge t
he current dogma of close correlation between cell dedifferentiation and te
lomerase activity.