ADRENAL-MEDULLARY NODULES IN BECKWITH-WIEDEMANN SYNDROME RESEMBLE EXTRAADRENAL PARAGANGLIA

Clues to mechanisms regulating development and tumorigenesis may be pr ovided by studies of unusual diseases. Beckwith-Wiedemann syndrome (BW S) is a rare congenital disorder apparently related to abnormal regula tion of insulin-like growth factor-2 (IGF-2) production. IGF-2 mRNA ha s been previously localized to the chief cells of extra-adrenal paraga nglia and to adult, but not fetal, adrenal medulla. Expression of IGF- 2 by neuroblastomas has been hypothesized to reflect extra-adrenal par aganglionic differentiation. In the adrenals of a fetus with BWS, we h ave observed both increased numbers of chromaffin cells and organoid n odules resembling extra-adrenal paraganglia. Immunoreactive IGF-2 was observed in both cell types, but was also observed in chromaffin cells in the normal fetal adrenal. The findings suggest autocrine or paracr ine influences of IGF-2 in regulating the number and phenotype of cell s derived from sympathoadrenal precursors in the developing adrenal me dulla as well as in extra-adrenal paraganglia. These results have impl ications for the interpretation of data from neuroblastoma studies.