Skeletal Changes in Disturbances of the Parathyroid Glands

Abstract

Introduction Knowledge as to the function of the parathyroid glands has been built up from observation in several fields. Previous to 1924, the principal physiologic approach was to observe the sequelae of extirpation of the glands in animals. Since 1924 (9), it has been possible to reverse the situation by the injection of Collip's parathyroid extract (18 and 17). In 1926, Mandl (20) demonstrated that a corresponding hyperparathyroidism occurs spontaneously in patients suffering from parathyroid adenomas, and quite recently it seems to have been established that the same condition may follow simple hyperplasia of these glands (3) under the influence perhaps of an over-production of hormone by the anterior lobe of the pituitary (11 and 15). Arguing from clinical and laboratory studies on material of this sort, it is now generally believed that hyperparathyroidism, either spontaneous or induced, causes an excessive amount of calcium and phosphate to pass from the bones into the blood, resulting eventually in the generalized skeletal condition known as osteitis fibrosa cystica or von Recklinghausen's disease (24). Removal of an abnormal gland or cessation of extract injection slows up the outward calcium and phosphate tide, following which normal processes, only dimly understood, slowly return calcium phosphate to the bones until calcium ion concentration in the plasma falls to normal levels. There is excellent recent literature covering most of the phases of parathyroid function and dysfunction (2, 5, 8, and 25) and much of this ground has been surveyed in reviews (13, 16, and 30). Sketched in the merest outline, the situation is about as follows: State of Calcium in the Blood The circulating plasma of a normal subject contains from 3 to 6 mg. per cent of phosphate (higher in children, lower in adults), 10 mg. per cent of calcium, and about 6.5 grams per cent of protein. At these concentrations, about 5 mg. per cent of the calcium is combined with protein and thus rendered physiologically inert, while about 5 mg. per cent is ionized and therefore free in solution in the plasma and physiologically active (21). (See Fig. 1.) The actual calcium ion concentration at any one time is the resultant of an equilibrium between the total calcium and the total protein present in the plasma. It is important to the body that the calcium ion concentration of the plasma remain within the physiologic range of from 4.25 to 5.25 mg. per cent. Below this minimum, excitability of nerve, muscle, and other excitable tissues increases until at very low levels tetany occurs. Above this maximum, nerve excitability falls, metastatic calcification occurs in soft tissues (particularly those that are relatively alkaline, 29), kidney tissue is damaged by the act of eliminating excess calcium and phosphate, and kidney stones may form because of the high concentration of calcium and phosphate in the urine.