AGING BULL

An old bull, it is said by those who know, can have his troubles. Incl uded among these are vertebral osteosclerosis and ankylosing spondylos is; this stiffening up limits, rather than accentuates, the value and reproductive potential of a stud bull past his prime. Associated with these abnormalities, however - and not seen in age-matched cows of com parable breeds - are fascinating endocrine neoplasms suggestive of a p attern that could be productive as a model of human hereditary endocri ne abnormalities. Adjacent to the thyroid gland in other vertebrates a re ultimobranchial bodies that are incorporated into the lateral thyro id lobes in primates as the parafollicular 'C cells' of the thyroid. T hese are the cells in man that give rise to medullary thyroid cancer a nd are associated with calcitonin secretion, useful as a tumor marker. In aging bulls of whatever breed, nearly half exhibit abnormality of these ultimobranchial bodies: 20% show hyperplasia, and 30% have frank neoplasia. These ultimobranchial tumors appear in bulls passing 6 1/2 years in age, and are absent in young bulls and all cows of any age. Calcitonin can be demonstrated in the ultimobranchial tumors from bull s, and secretion is stimulated by calcium infusion, though serum calci um remains normal. The ultimobranchial tumors themselves can range fro m hyperplasia through adenoma to metastasizing carcinoma - in fact, re presenting one of the commoner cattle cancers. Parathyroid glands take n from bulls with these ultimobranchial tumors initially show evidence of inhibited secretory activity and morphologic atrophy, but later go on to develop hyperplasia and, eventually, autonomy. Cattle forage on calcium-rich diets. Bulls appear to respond to this calcium excess fr om the positive balance, but breeding cows have the unique calcium def icits of the high net loss of calcium through lactation and the large requirements of calcifying a fetal skeleton. Chronic stimulation of th e APUD-derived ultimobranchial bodies by high calcium intake, not coun terbalanced by calcium losses in the bulls, may account for the develo pment over time of the ultimobranchial neoplasms. Further, a number of the bulls who have the ultimobranchial tumors are found to have multi ple endocrine tumors in other glands - bilateral pheochromocytomas and pituitary acidophil adenomas. These observations focus attention on t he role of calcium as a stimulus to the evolving component parts of mu ltiple endocrine adenopathy in humans, and furnish a model For such in vestigation in the naturally occurring endocrine neoplasia of the agin g bull.