Adrenal Gland: Structure, Function, and Mechanisms of Toxicity

The adrenal gland is one of the most common endocrine organs affected by chemically induced lesions. In the adrenal cortex, lesions are more frequent in the zona fasciculata and reticularis than in the zona glomerulosa. The adrenal cortex produces steroid hormones with a 17-carbon nucleus following a series of hydroxylation reactions that occur in the mitochondria and endoplasmic reticulum. Toxic agents for the adrenal cortex include short-chain aliphatic compounds, lipidosis inducers, amphiphilic compounds, natural and synthetic steroids, and chemicals that affect hydroxylation. Morphologic evaluation of cortical lesions provides insight into the sites of inhibition of steroidogenesis. The adrenal cortex response to injury is varied. Degeneration (vacuolar and granular), necrosis, and hemorrhage are common findings of acute injury. In contrast, chronic reparative processes are typically atrophy, fibrosis, and nodular hyperplasia. Chemically induced proliferative lesions are uncommon in the adrenal cortex. The adrenal medulla contains chromaffin cells (that produce epinephrine, norepinephrine, chromogranin, and neuropeptides) and ganglion cells. Proliferative lesions of the medulla are common in the rat and include diffuse or nodular hyperplasia and benign and malignant pheochromocytoma. Mechanisms of chromaffin cell proliferation in rats include excess growth hormone or prolactin, stimulation of cholinergic nerves, and diet-induced hypercalcemia. There often are species specificity and age dependence in the development of chemically induced adrenal lesions that should be considered when interpreting toxicity data.