Enzootic and epizootic adrenal medullary proliferative disease of rats: influence of dietary factors which affect calcium absorption.

Adrenal medullary hyperplasia and neoplasia occur both enzootically and epizootically in untreated laboratory rats. The lesions are typically chromaffin-negative and are found incidentally in animals that have died from unrelated causes or have been killed at the end of long-term toxicity/carcinogenicity tests. Urinary excretion of catecholamines is not usually increased. Environmental, particularly dietary, factors are seemingly much more important than genetic ones as determinants of the incidence of proliferative lesions. Recent observations of enhancement of adrenal medullary proliferative disease in rats by the feeding, in high dietary concentration, of certain polyols (sorbitol, mannitol, xylitol, lactitol), or of lactose, suggested that increased absorption of calcium from the gastrointestinal tract may be a risk factor. This evidence is reported and discussed in the light of other evidence linking disturbed calcium homeostasis with adrenal medullary function in the rat. In man, adrenal medullary proliferative disease is relatively rare and there is no evidence of any relation between the hypercalcaemia associated with hyperparathyroidism and increased risk of phaeochromocytoma. Adrenal medullary proliferative disease in rats is usually seen against a background of multiple endocrine neoplasia, with the pituitary gland, the pancreatic islets and the thyroid C-cells being most commonly affected in addition to the adrenal medulla. A parallel between this situation and Sipple's disease in humans has previously been suggested. We now stress the possible importance of three factors as determinants of enzootic and epizootic adrenal medullary proliferative disease in rats: excessive food intake, excessive dietary levels of calcium and phosphate and excessive intake of other food components, such as vitamin D and poorly absorbable carbohydrates, which predispose to increased calcium absorption.