Constantine S. Anast

Decreased Calcium Tolerance in Nongoitrous Cretins

Extract: Response to an exogenous calcium load was studied in 7 thyroid-treated sporadic non-goitrous cretins and in 16 normal children. An intravenous infusion of 10 mg/kg of body weight of calcium as calcium gluconate was infused over a 3-hr period. Serum samples obtained before and at 1.5, 3, 3.5, 4, 5, and 7 hr after the start of the infusion were analyzed for calcium, magnesium, and phosphorus. The basc-line calcium, magnesium, and phosphorus values in serum did not differ significantly in the thyroid-treated cretins and in normal children. The infusion of calcium did not alter magnesium levels and no consistent changes were noted in phosphorus levels in either group. Mean increments in calcium levels, however, were significantly greater in the cretins at 1.5, 3, 3.5, and 4 hr after the start of the infusion. The response to calcium infusion in two children with a thyroid-iodine organification defect was similar to that seen in the normal children.Speculation: It is suggested that the impaired ability of the thyroid-treated nongoitrous cretins to counteract experimentally induced hypercalcemia is the result of calcitonin deficiency

ELEVATED CIRCULATING IMMUNOREACTIVE PARATHYROID MONE (iPTH) IN PREMATURE INFANTS

Serum iPTH was measured in 160 AGA full-term and premature normocalcemic and hypocalcemic infants during the first 96 hours of life. In normal full-term infants, iPTH was low in cord blood and remained low during the first 12 hours of life as serum Ca declined. Thereafter the serum iPTH rose to the mid-normal range. Consistent with our previous studies, in only 20% of serum samples from hypocalcemic full-term infants was iPTH elevated; in the remainder, iPTH was inappropriately low, though usually in the normal detectible range. By contrast, serum iPTH was elevated in 75% of samples of hypocalcemic prematures. Moreover, elevated iPTH was found in approximately 15% and 35% serum samples of normocalcemic full-term and premature infants, respectively. At any given Ca level the serum iPTH appeared to vary inversely with gestational age. The results suggest 1) That parathyroid responsiveness is greater in premature than full-term infants, possibly related to lesser period of exposure to hypercalcemia in utero and 2) That a factor(s) other than parathyroid insufficiency acts in the newborn to reduce plasma Ca; in some infants, compensatory increases in parathyroid activity may be sufficient to maintain normocalcemia, while in others there is either no compensatory increase or the increase is insufficient and hypocalcemia results. It is possible that metabolic clearance of iPTH varies with gestation and accounts, in part, for our findings.

HYPERCALCITONEMIA AND NEONATAL HYPOCALCEMIA

Serum immunoreactive caldtonin (iCT) was measured in 160 full-term and premature normocalcemic and hypocalcemic infants during the first 96 hours of life. The mean ± S.E. of serum iCT in cord blood of normal full-term infants was 150 ± 26 (normal in older subjects <150 pg/ml). After birth the mean serum iCT increased sharply and reached a peak of over 600 pg/ml between 13 and 24 hours of age during the period of decline of serum Ca from relatively high cord values. After 36 hours of age there was a progressive decrease in mean serum iCT to 178 pg/ml at 73-96 hours of age. Though somewhat higher in premature infants, the serum iCT was, in general, inversely related to serum Ca in infants of all gestational ages. The mean serum iCT during the first 96 hours of life (excluding cord blood) in hypocalcemic infants of all gestational ages was approximately twice the mean value of normocalcemic infants (1055 pg/ml vs. 510 pg/ml, p<.01). The incidence of serum iCT greater than 800 pg/ml was 19% in serum samples from normocalcemic infants, as compared to 74% in hypocalcemic infants. On the other hand, serum iCT less than 300 pg/ml were found in 43% of samples from normocalcemic infants, as compared to less than 6% in hypocalcemic infants. The elevated iCT found in the newborn is consistent with the report of increased C-cells and calcitonin concentration in the human neonatal thyroid. The accumulated evidence indicates that hypercalcitonemia warrants serious consideration as a factor in the pathogenesis of neanatal hypocalcemia.

80 Stimulation of Active Intestinal Transport by Actinomycin D

It is well known that actinomycin D, an inhibitor of DNA directed RNA synthesis, alters enzyme activity. Because of similarities in the kinetics of enzymatic reactions and of active intestinal transport, the effect of actinomycin D on the latter was investigated. Observations were made of the active transport of amino acids (L-leucine and cycloleucine), sugar (3-0-methyl-D-glucose) and inorganic sulfate in the small intestine of the rat utilizing the everted gut sac technique of WILSON and WISEMAN. Transport by intestinal segments obtained from actinomycin D treated animals (single injection of 66 μg/100 gms subcut.) was compared with transport by intestinal segments obtained from matched controls. Studies were carried out at time intervals ranging from 1 to 48 h following injection. No significant effect of actinomycin D on transport was noted before 24h. However, active transport of each of the substances studied was markedly increased (2 to 4 fold increase in concentration gradients) in the animals who received actinomycin D 36 to 48 hours previously.Although commonly used to inhibit enzyme activity, actinomycin D has been shown to induce several enzymes in rat liver 24 to 48 hours after the administration of a single dose (ROSEN: Science 146–661 [1964]). This delayed effect is similar to that observed in our study of intestinal transport and suggests a possible relationship between the two. The mechanism by which actinomycin D stimulates intestinal transport is unknown although it possibly acts by inhibiting a substance that normally limits the rate of transport. (SPR)