"Aging bull'.

An old bull, it is said by those who know, can have his troubles. Included among these are vertebral osteosclerosis and ankylosing spondylosis; 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 comparable breeds-are fascinating endocrine neoplasms suggestive of a pattern that could be productive as a model of human hereditary endocrine abnormalities. Adjacent to the thyroid gland in other vertebrates are ultimobranchial bodies that are incorporated into the lateral thyroid lobes in primates as the parafollicular "C cells' of the thyroid. These are the cells in man that give rise to medullary thyroid cancer and 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 bulls, and secretion is stimulated by calcium infusion, though serum calcium remains normal. The ultimobranchial tumors themselves can range from hyperplasia through adenoma to metastasizing carcinoma-in fact, representing one of the commoner cattle cancers. Parathyroid glands taken 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 from the positive balance, but breeding cows have the unique calcium deficits of the high net loss of calcium through lactation and the large requirements of calcifying a fetal skeleton. Chronic stimulation of the APUD-derived ultimobranchial bodies by high calcium intake, not counterbalanced by calcium losses in the bulls, may account for the development over time of the ultimobranchial neoplasms. Further, a number of the bulls who have the ultimobranchial tumors are found to have multiple endocrine tumors in other glands-bilateral pheochromocytomas and pituitary acidophil adenomas.