Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in rodents exert a direct effect on the thyroid gland to disrupt one of several possible steps in the biosynthesis, secretion, and metabolism of thyroid hormones. This includes (a) inhibition of the iodine trapping mechanism, (b) blockage of organic binding of iodine and coupling of iodothyronines to form thyroxine (T 4 ) and triiodothyronine (T 3 )

The adrenal gland is one of the most comm on 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 hydroxyla tion reactions that occur in the m itochondria and endoplasm ic reticulum. Toxic agents for the adrenal cortex include short-chain aliphatic compound s, lipidosis inducers , amphiphilic compounds , natural and synthetic steroids, and chemicals that affect hydroxyla tion. Morphologic evaluation of cortical lesions provides insight into the sites of inhibition of steroidogenesis. The adrenal cortex response to injury is varied. Degeneratio n (vacuolar and granular), necrosis, and hem orrhage are common ndings of acute injury. In contrast, chronic reparative processes are typically atrophy, brosis, and nodular hyperplasia. Chem ically induced proliferative lesions are uncom m on in the adrena l cortex. The adrenal medulla contains chrom af n cells (that produce epinephrine, norepineph rine, 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 pheochrom ocytoma. Mechanism s of chromaf n cell proliferation in rats include excess growth hormone or prolactin, stimulation of cholinergic nerves, and diet-induced hypercalcem ia. There often are species speci city and age dependenc e in the developme nt of chemically induced adrenal lesions that should be considered when interpreting toxicity data.

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