The Effect of Thyroid Disease on Calcium Metabolism in Man 1

Abstract

Abnormal thyroid function profoundly alters calcium metabolism. In 1929, Aub, Bauer, Heath, and Ropes (1) demonstrated in patients on constant low calcium diets that urinary and fecal excretion of calcium and phosphorus is frequently increased in hyperthyroidism and lower than normal in myxedema. These changes could not be ascribed to elevation of metabolism per se (1) acidosis (2) or vitarmin D deficiency (3); they were observed even in the absence of the parathyroid glands (4, 5). In addition, roentgenographic evidence of skeletal demineralization has been described in patients with thyrotoxicosis (6).The conventional balance techniques which have been used in the study of calcium metabolism in thyroid disease measure only net effects: they do not measure the processes of deposition and resorption of calcium. An indication of the skeletal turnover of calcium, however, can be obtained from serial observations of the specific activity of radioactive calcium (Ca45) in blood and urine after intravenous injection (7,8).The present study was designed to define the alterations in calcium metabolism in thyroid disease in man by using Ca45 and the technique of isotope dilution. Observations have been made in euthyroid, hyperthyroid, and myxedematous subjects, and, for purposes of comparison, in additional euthyroid patients with Paget's disease and with hypoparathyroidism. MATERIALS AND METHODSAll patients (Table I) were on the metabolic ward and were ambulatory throughout the study. Diets, which were constant and of neutral ash, contained from 0.08 to 0.23 grams of calcium per day (Table II). In order to avoid tetany, the two hypoparathyroid subjects were given 0.31 and 0.57 grams, respecfively, of calcium in their diets per day. Fluid intake was maintained at 2,000 to 2,500 ml. per day. Complete collections of urine and stool were begun after six days on the fixed diet. A three-day control collection of urine and feces was obtained prior to the administration of Ca.The stock solution of Ca"Cl, 2 was acidified with concentrated HCI, added to 0.9 per cent NaCI solution to give a final concentration of approximately 0.5 j&c per ml.saline at a pH of 6, and autoclaved. Five to seven microcuries were injected from a calibrated syringe into an antecubital vein one hour before breakfast. Blood samples were obtained by venipuncture from the opposite arm at frequent intervals. Fractional urine collections were made for the first three days following injection, and daily thereafter. Stool collections were made TABLE I

Quantitation of Calcium Metabolism. Theory*

“…In another analysis, Krane and associates (7) define the Ca pool of man at time t as: Pt = body retention of radioactivity at time t/serum SA at time t (Equation 46). As defined, this "pool" must necessarily be a function of time.…”

“…They state: "The concept of a calcium 'pool' makes no assumption based on the shape of the curves, but reflects the fact that a lower specific activity at any time means a larger mass of dilution." (7). In other words, the "pool at time t" becomes a rather complex function of P and of v0+ and VT.…”

“…[5] Absorption can also be determined by Va = Vi -VF +Vf, [6] and the fraction absorbed is a = va/vi. [7] In scheme II, some Ca that leaves via Vd returns to it via va, but diluted with vi. In other words, VF contains some unabsorbed Vd and vi.…”

Hypercalcaemia in thyrotoxicosis with and without hyperparathyroidism

“…There is increased bone formation as well as increased bone destruction (Krane et al, 1956) and these changes may occur in the absence of radiographic evidence of bone disease (Adams et al, 1967). The bones involved are spine, ribs and pelvis, and less frequently skull, hands and long bones (Werner, 1962).…”

Calcium Metabolism of the Normal Rhesus Monkey*

“…Data obtained on patients with carcinoma, multiple myeloma, and thyroid disorders indicate that the excretion of Ca45 is disturbed in these situations, for the urine: feces excretion *A portion of this paper was presented at the Fifth International Congress on Nutrition, Washington, D. C., September 1, 1960. This study was ratios ranged between 3:1 and 1: 3 (3)(4)(5)(6). In spite of these anomalies, the "endogenous" excretion of calcium by normal human beings and normal monkeys appears to be similar, and quite unlike that by the dog and the rat.…”