The medulla is located primarily in the head of the adrenal glands and accounts for ˜10% of their normal adult weight. The chromaffin cell is the major cell type, named for the yellow-brown color imparted to its epinephrine-containing granules by chromatic salts. Chromaffin cells are rounded or polygonal, with a finely granular cytoplasm and an eccentric nucleus with prominent nucleoli. The cells are arranged in nests or cords. They are surrounded and directly innervated by preganglionic sympathetic nerve fibers and hence are analogous to norepinephrine-secreting postganglionic fibers in the remainder of the sympathetic nervous system. When specific immunostains are used, chromaffin cells have been found in the human adrenal cortex and cortical cells have been found in the adrenal medulla, which provides a cellular basis for potential intraadrenal interactions.23 The medullary blood supply is derived mainly from the capillary plexus draining the cortex. The resulting high intramedullary cortisol levels are thought to be important in inducing the enzyme that converts norepinephrine to epinephrine in the chromaffin cells.

Adrenal medullary hyperfunctional states include adrenal medullary hyperplasia, neuroblastoma, and pheochromocytoma.
There is a close relationship between neural cells of the sympathetic ganglia and chromaffin cells. Small numbers of ganglion cells can be found in the adrenal medulla, and chromaffin cells occur in the sympathetic ganglia. Hence, neoplastic disorders affecting either cell type can arise throughout this system.

The diagnosis of adrenal medullary hyperplasia depends on an increased volume of adrenal medulla in relation to the cortex. There is a diffuse nodular proliferation of normal medullary elements. This condition is seen mainly in families with multiple endocrine neoplasia type 2A and is considered a pre-neoplastic condition (see Chap. 188).