I-Wen Chen

Parathyroid function in infants of diabetic mothers

Serum parathyroid hormone and total and ionized Ca, Mg, and P levels were determined serially from birth to 96 hr of age in 28 infants of diabetic mothers (IDM, 15 Class A, 13 Class B, C, D) and their respective mothers at the time of delivery. In spite of marked decreases in concentrations of serum total and ionized Ca from birth to 24 to 48 hr, there was an insignificant increase in serum PTH values over this period in infants of insulin-dependent mothers. Infants of Class A diabetic mothers had an equivocal PTH response. Nineteen term control infants were similarly examined and had a significant increase in serum PTH postnatally. Relatively higher values of serum ionized Ca at birth in IDM were followed by greater decreases in ionized Ca from birth to 24-48 hr of age, and by decreased neonatal parathyroid function. The data support functional hypoparathyroidism as a basis for the hypocalcemia and hyperphosphatemia of IDM. It is speculated that increased concentrations of serum ionized Ca in utero and suppression of activity in the fetal parathyroid glands may be a cause for the functional hypoparathyroidism.

Neonatal hypermagnesemia: Effect on parathyroid hormone and calcium homeostasis

Twenty pre-eclamptic mothers treated with MgSO4 and their newborn infants were studied prospectively to determine the clinical and biochemical effects of hypermagnesemia. Maternal serum magnesium concentration rose to 4.4 mg/dl at delivery and was accompanied by a fall in maternal serum calcium concentration during labor. Neonatal serum Mg concentration remained elevated for the first 72 hours of life (mean at 72 hours = 3.0 mg/dl). Serum Mg concentration was higher in premature infants and in babies with birth asphyxia and/or hypotonia. Serum Ca concentration was higher and serum PTH was lower in hypermagnesemic study infants when compared to a retrospectively selected, matched froup of control infants. We speculate that elevated serum Mg values in these infants result in a shift of Ca from bone to plasma, and that elevated Mg and Ca concentrations further suppress neonatal parathyroid function.

Pathogenesis of early neonatal hypocalcemia: studies of serum calcitonin, gastrin, and plasma glucagon.

In 64 maternal-infant pairs, we tested the hypotheses that serum calcitonin, serum gastrin, and plasma glucagon concentrations are elevated in infants at risk for early neonatal hypocalcemia, and that elevated serum gastrin and plasma glucagon result in elevated serum calcitonin and low serum calcium values in neonates. Serum Ca declined significantly in neonates at 24 hours of age, and was inversely correlated with serum calcitonin. Cord serum calcitonin, gastrin, and plasma glucagon concentrations rose significantly at 24 hours of age. Cord calcitonin was significantly higher in preterm compared with term infants, and there was no significant difference between asphyxiated and nonasphyxiated preterm neonates; in term neonates cord calcitonin concentration was inversely correlated with Apgar scores at 1 and 5 minutes. Cord calcitonin was not correlated with cord gastrin or glucagon. Cord and 24-hour gastrin and glucagon values were not related to prematurity; cord glucagon, but not gastrin, was related to birth asphyxia. We conclude that (1) serum calcitonin, gastrin, and plasma glucagon values rise postnatally; cord calcitonin is elevated in preterm and in asphyxiated term infants; serum calcitonin concentration does not correlate with the elevated serum gastrin and plasma glucagon values; and at 24 hours of age, decreased serum Ca is correlated with serum calcitonin, and hence calcitonin might play a role in the pathogenesis of early neonatal hypocalcemia.

Hypomagnesemia in infants of diabetic mothers: Perinatal studies

Fifty-six diabetic mothers and their infants were studied prospectively from birth. Twenty-one of 56 IDM had serum Mg less than or equal to 1.5 mg/dl, on at least one occasion during the first 3 days. Serum Mg in these hypomagnesemic infants did not demonstrate the normal increase with postnatal age that was present in normomagnesemic infants. Decreased neonatal serum Mg was related to increased severity of maternal diabetes, young mothers, mothers for lower gravidity, and prematurity. Decreased serum Mg, alone or with decreased ionized or total Ca, did not correlate with neuromuscular irritability in the infants. Decreased serum Mg in IDM was associated with decreased maternal serum Mg, decreased neonatal ionized and total Ca, increased serum P, and decreased parathyroid function. Serum Mg was not related to dietary P intake, or urinary Ca or P excretion. Thus, transitory neonatal hypomagnesemia occurs in IDM; it is speculated that factors causing HM might include maternal HM or neonatal hyperphosphatemia, and that the HM is related to the hypocalcemia and functional hypoparathyroidism of IDM.

The effect of 1,25(OH)2 vitamin D3 supplementation in premature infants

The effects of 1,25(OH) 2 D 3 in the prophylaxis of neonatal hypocalcemia were studied in 32 premature infants. Four groups of eight infants were matched individually for gestation and evidence of birth asphyxia, and given daily 1 μg of 1,25(OH) 2 D 3 , 0.05 μg/kg/day 1,25(OH) 2 D 3 , 400 IU vitamin D 2 , or placebo orally from 12 to 72 hours of age. Prestudy ionized calcium values were 2 D 3 , 1 μg/day, had significantly higher iCa values, 3.6±0.10 mg/dl (mean±SEM) vs 3.2±0.10 mg/dl at 12 hours (paired t, P 2 D 3 had serum PTH values lower than pretreatment, 59±9 vs 137±58 μl-Eq/ml (Wilcoxon Rank, P P 2 D 3 , the average increase being 1.2 vs 2 D 3 may be useful for the prophylaxis of hypocalcemia.

Parathyroid function tests with EDTA infusions in infancy and childhood.

To determine the functional capabilities of the parathyroid glands, 17 EDTA infusions were given to 11 children (ages 1 month to 12 years) and to two mothers of four of the children. Serum ionized Ca fell from 4.1 mg/dl to 3.4 mg/dl. Excessive parathyroid hormone responses were elicited during seven of nine EDTA infusions in five children and in one adult with hypophosphatemic rickets, during the active phase of rickets. In four of five subjects with problems related to hypercalcemia, borderline low or undetectable PTH responses were elicited. Three relatively normal PTH responses were obtained, two in an infant after phosphate-induced hypocalcemic tetany was corrected, and one in a child with a malabsorption syndrome. The renal tubular reabsorption of phosphate was inversely related and the urinary cyclic AMP excretion was positively related to the PTH response. Thus EDTA infusions in infants and children might be useful in the identification of hyper-, normo-, or hypoparathyroid states and would be of value in defining the functional condition of the parathyroid glands in children with deranged Ca or P metabolism.

Oral calcium supplementation in premature and asphyxiated neonates

Biochemical and hormonal effects of oral calcium supplementation in premature and asphyxiated neonates during the first few days of life are described. Eight pairs of infants were matched for gestational age and one-minute Apgar score. One member of each pair served as a control and the other was given supplemental oral calcium (75 mg/kg/24 hr) beginning at 12 and ending at 72 hours of age. The supplemental infants had significantly higher serum calcium values both during the time of supplementation and for 36 hours after supplementation was stopped. The oral calcium supplements had no significant effect on serum concentrations of phosphate, magnesium, 25-hydroxy-vitamin D3, or parathyroid hormone, The incidence of hypocalcemia after 12 hours of age was 0 in eight supplemented infants and three in eight control infants. In patients at risk for hypocalcemia, prospective use of oral calcium supplements during the period when there is inadequate calcium intake from feedings may prevent hypocalcemia, appears to be without deleterious effect on measurable chemical and hormonal factors important in calcium homeostasis, and results in maintenance of higher serum calcium levels after supplementation has been discontinued.

1,25-dihydroxyvitamin D3 in childhood hepatic osteodystrophy

Osteodystrophy frequently accompanies severe childhood hepatobiliary disease. Proposed causes include malabsorption of vitamin D and calcium, and diminished 25-hydroxylation of vitamin D. Two children, ages 23 and 35 months, with radiographic and biochemical evidence of rickets with extrahepatic biliary atresia, were treated with 1,25-dihydroxyvitamin D3. The minimal effective therapeutic dose and efficacy of 1,25-(OH)2D3 in the treatment of rickets associated with severe childhood hepatic disease were determined. Oral 1,25-(OH)2D3 was ineffective at doses of 0.10 microgram/kg/day. Parenteral doses of 0.20 microgram/kg/day effectively produced radiographic, bone mineral (photon absorptiometric), and biochemical evidence of healing. The need for four times the physiologic dose of 1,25-(OH)2D3 by the parenteral route suggested enhanced catabolism of, or end-organ resistance to, 1,25-(OH)2D3 in our patients with severe cholestatic liver disease treated with phenobarbital.

Urinary phosphate and cyclic AMP excretion following citrate-induced hypocalcemic stimulation of the neonatal parathyroid glands

Sixteen neonates, ranging in gestational age from 27 to 41 weeks and in postnatal age from birth to 8 days, were evaluated for their renal response to an endogenous PTH stimulus in 22 separate experiments. The PTH stimulus was generated by the decreased serum ionized Ca that accompanies exchange transfusion with citrated blood. The neonates increased their serum PTH from 95.8 +/- 13.1 to 133.9 +/- 15.4 microliterEq/ml (mean +/- SEM) during the transfusion, while increasing their urinary cAMP from 0.77 +/- 0.11 to 1.45 +/- 0.22 nmol/ml, and their urinary P from 12.9 +/- 2.6 to 30.6 +/- 6.1 mg/dl in the four hours following the exchange transfusion. This response was not related to postnatal or gestational age. We speculate that lack of renal responsiveness to PTH does not play a major role in the pathogenesis of early neonatal hypocalcemia.

182 PLACENTAL IMPERMEABILITY TO PARATHORMONE (PTH) 1|[ndash]|125 IN THE EWE

Studies altering plasma calcium levels have demonstrated that the maternal (M) and fetal (F) parathyroid glands appear to function automonously and suggest a lack of placental permeability to PTH. To determine whether the ovine placenta is permeable to PTH I-125, catheters were placed into the F abdominal aorta and pedal vein and M abdominal aorta and jugular vein in 5 date bred ewes at 121 to 135 days gestation. The studies were conducted 24 to 48 hours after surgery when the M and F arterial blood gases and pH returned to normal. Purified intact bovine PTH (1-84) was iodinated by the chloramine-T method. The placenta transfer of tracer quantities of PTH I-125 was studied in 5 animals in the M→F and 4 in the F→M direction. Simultaneous serial F and M plasma samples were obtained during the 60 minute study period and precipitated with 15% trichloracetic acid and the results expressed as percent dose/liter plasma. During the initial 20 minutes of the study, the t 1/2 was 21 minutes (r= -0.99) in the F and 21 minutes in the M (r=-0.99). In the M→F studies, no more than 0.3% of the injection dose/liter plasma was detected in the F and in the F→M studies, no more than 0.5% of the injected dose/liter plasma was detected in the M at 15 to 30 minutes post injection. Thus, during the 3rd trimester, the ovine placenta is impermeable to PTH I-125. The t 1/2 of PTH I-125 is similar in both the ovine F and M.