0 1991 Elsevier Science Publishers B.V. All rights reserved 0028-2243/91/$03.50 ... active has been used for measurements in 10 normal pregnant women ...
European Journal of Obstetrics & Gynecology and Reproductioe Biology, 42 (1991) 85-87 0 1991 Elsevier Science Publishers B.V. All rights reserved 0028-2243/91/$03.50
EUROBS
85
01219
Serum concentrations of intact parathyroid hormone during late human pregnancy: a longitudinal study Anne Frglich
‘, Martin
Rudnicki
2, Wiggo Fischer-Rasmussen
2 and Kern Olofsson
2
’ Department of Clinical Chemistry, Herlel, Hospital, Universi& of Copenhagen, and ’ Department of Gynecology and Obstetrics, HLidocre Hospital, University of Copenhagen, Denmark Accepted
for publication
29 April 1991
Summary
In the present study an assay reactive with the intact PTH molecule supposed to be the biological active has been used for measurements in 10 normal pregnant women during the late pregnancy and post-partum. Simultaneously serum concentrations of ionized calcium, phosphate, magnesium and albumin were determined. Serum concentrations of intact PTH were low compared to non-pregnant levels, while concentrations of ionized calcium, phosphate, magnesium (corrected) were unaffected. Pregnancy;
Intact
Parathyroid
hormone:
Ionized
Calcium;
Phosphate;
Introduction
In pregnancy serum concentrations of ionized calcium are unchanged [1,2] from the non-pregnant state despite considerable changes in many factors of importance for the calcium homeostasis. Presumably parathyroidea hormone (PTH) and 1,25dihydroxyvitamin D (1,25(OH),vit D> are important in the regulation of the serum calcium levels as in the non-pregnant. The 1,25(OH),vit D is known to be elevated [3] but attempts to measure PTH concentrations in pregnancy have led to conflicting results [1,4-81. The aim of the present study was to measure the intact PTH, assumed to be the biologically
Correspondence: Anne Frolich, M.D., Department of Clinical Chemistry, Herlev Hospital, University of Copenhagen, Herlev Ringvej. DK-2730, Herlev, Denmark.
Magnesium
active PTH molecule [9], longitudinally in late pregnancy and the simultaneous serum concentrations of calcium, phosphate, magnesium and albumin. Material
and Methods
The study comprised 10 healthy pregnant women consecutively registrated of whom 9 were nulliparous. The mean age was 29 years (range: 21-38 years). All women had normal singleton pregnancies and delivered healthy babies at term (gestational week, mean 39.3, range 38-40). Fiftyone non-pregnant female blood donors acted as controls. The mean age was 28 years (range: 22-36 years). The pregnant women had blood samples taken weekly from the 33rd week of gestation and after delivery (days after delivery, mean 1.4, range l-2). The gestational ages were assessed by ultrasound
86
measurement in the 16th week of’pregnancy by measurement of the biparietal diameter of the fetus. The daily supplementation of D-vitamin was 400 IE of cholecalciferol (multivitamin preparation). No calcium supplementation was given, except for the ordinary advise to have diary products in pregnancy. Serum concentrations of PTH were measured in duplicates by a two-site immunoradiometric assay (IRMA) detecting the intact PTH molecule [IO]. Ionized serum-calcium was determined at pH 7.40 with an ICA Calcium Ion Electrode (Radiometer, Copenhagen, Denmark). The serum total-magnesium was determined by means of atomic absorption spectrophotometry. Serum magnesium was corrected (car) to an albumin concentration of 650 pmol/l, using the following equation [ 111: Serum-magnesium (car) (mmoI/l) = serum-magnesium (mmol/l)/ ((0.3/ 650) X serum-albumin (~mol/l) + 0.7). Serum magnesium is the measured concentration of total serum magnesium. The serum concentrations of phos-
phate and albumin were measured on a serum multianalyzer (Technicon SMAC, U.S.A.). Statistical methods Significance levels were calculated with Student’s t-test for paired and non-paired data and one-way analysis of variance. P < 0.05 was chosen as an indication of a statistically significant difference. Results Serum concentrations of intact PTH were significantly lower in the pregnant women compared to the non-pregnant women, with exception of the value in 38th week of gestation. Post-partum the mean concentration of intact PTH was significantly low compared to the level in non-pregnant women (Fig. 1, Table I). The mean serum concentrations of ionized calcium, phosphate and magnesium (car) did not differ significantly from the concentrations in non-pregnant women [1,2]. The mean concentra-
TABLE I Serum concentrations of parathyroidea hormone (PTH), ionized calcium, magnesium, magnesium (corrected) and phosphate, in 10 pregnant women during late pregnancy and the post partum period, and in 51 non-pregnant women. Gestation (gest.). Standard deviation (SD). * P < 0.05, test for difference between pregnant and non-pregnant women Week of gest.
n
Serum concentrations
of
PTH (pmol/l)
Ionized calcium (mmol/l)
Magnesium (mmol/l) SD
mean
SD
mean
SD
* * * * * * * *
0.04 0.04 0.04 0.03 0.04 0.03 0.05 0.03
0.67 0.78 0.77 0.77 0.76 0.75 0.77 0.78
0.04 0.04 0.04 0.03 0.04 0.03 0.07 0.02
1.12 1.16 1.18 1.20 1.12 1.18
0.10 0.10 0.16 0.04 0.12 0.17
1.04
0.12
0.03
0.68 *
0.10
0.74
0.07
1.30 *
0.17
0.04
0.80
0.07
0.78
0.05
1.09
0.10
SD
mean
SD
mean
* *
0.78 0.78 0.75 0.74 0.65 0.75 0.51 0.75
1.23 1.27 1.22 1.28 1.22 1.26 1.28 1.19
0.08 0.08 0.09 0.05 0.06 0.04 0.03 0.07
0.65 0.75 0.73 0.73 0.72 0.72 0.73 0.74
Post-partum period (n = IO)
1.26 *
0.27
1.26
Non-pregnant women (n = 51)
3.12
0.70
1.28
mean 33 34 35 36 37 38 39 40
10 10 10 10 10 10 8 5
1.65 1.58 1.95 1.99 2.20 2.70 1.26 1.90
* * * * *
Phosphate (mmol/l)
Magnesium corrected (mmol/l)
87
known that 1,25(OH),vit D concentrations possess a regulatory effect on the PTH secretion 1141. References 1 Davis OK, Hawkins
DS, Rubin LP et al. Serum parathyroid hormone (PTH) in pregnant women determined by an immunoradiometric assay for intact PTH. J Clin Endocrinol Metab 1988;67:850-852.
Fig. 1. The mean concentrations and one standard deviation of the intact parathyroid hormone in serum from 10 pregnant women during late pregnancy and post-partum. The normalmean and normal-mean minus 1 standard deviation (SD) in non-pregnant
womenare shown.
tions of total-magnesium were significantly lower compared to the level in non-pregnant women [12]. The serum concentrations of ionized calcium, magnesium and phosphate did not change during the study period. Post-partum serum phosphate was significantly higher compared to the level in non-pregnant women (Table I). Discussion
The mean concentrations of intact PTH in late pregnancy were below the concentration in nonpregnant women. Low concentration of intact PTH in pregnancy compared to non-pregnant levels, has been shown earlier in a cross-sectional designed study using an identical method for measurements of PTH [ll. Normally, PTH is regarded as the most important hormone for maintaining stable concentration of serum calcium, but the present study indicates that other calciotrope hormones in pregnancy may be more important. Davis had suggested that 1,25(OH),vit D may be the primary hormone for providing maternal calcium homeostasis in pregnancy [ 11. The 1,25(OH),vit D greatly increases during pregnancy 13,131. It is
2 Gertner JM, Coustan D, Kliger AS et al. Pregnancy as state of physiologic absorptive hypercalciuria. Am J Med 1986;81:451-456. 3 Kumar R, Cohen WR, Silva P et al. Elevated 1,25didroxyvitamin D plasma levels in normal human pregnancy and lactation. J Clin Invest 1979;63:342-344. 4 Pedersen EB, Johannesen P, Kristensen S et al. Calcium. parathyroid hormone and calcitonin in normal pregnancy and preeclampsia. Gynecol Obstet Invest 1984;18: 156-164. 5 Whitehead M. Lane G, Young 0 et al. Interrelations of calcium-regulating hormones during normal pregnancy. Br Med J 1981:283:10-12. 6 Gillette ME, lnsogna KL, Lewis AM et al. Influence of pregnancy on immunoreactive parathyroid hormone levels. Calcif Tissue lnt 1982;34:9-12. RM et al. Cytochemical 7 Allgrove J, Adami S, Manning bioassay of parathyroid hormone in maternal and cord blood. Arch Dis Child 1985;60:110-1 15. A, Biale Y, Levi M et al. Changes in serum 8 Conforti calcitonin, parathyroid hormone and 25.hydroxycholecalciferol levels in pregnancy and labor. Mineral Electrolyte Metab 1980;3:323-328. SR, Zahradnik RJ, Lavigne JR et al. Highly 9 Nussbaum sensitive two-site immunoradiometric assay of parathyrin. and its clinical utility in evaluating patients with hypercalcemia. Clin Chem 1987;33:1364-1367. Intact PTH, Nichols Institute Diagnostics, San 10 Allegro Juan Capistrano, CA. U.S.A. C et al. Gross errors 11 McNair P, Nielsen SL, Christiansen made by routine blood sampling from two sites using a tourniquet applied at different positions. Clin Chim Acta 1979;98:113-118. FW. Serum magnesium in women 12 Stanton MF, Lowenstein during pregnancy, while taking contraceptives, and after menopause. J Am Coll Nutr 1987;6:313-319. 13 Turner M, Barre’PE, Benjamin A et al. Does the maternal kidney contribute to the increased circulating 1,25-dihydroxyvitamin D concentrations during pregnancy. Mineral Electrolyte Metab 1988;14:246-252. CA, Grooms P et al. Parathyroid 14 Delmez JA. Tindira hormone suppression by Intravenous 1,25dihydroxqvitamin D. A role for increased sensitivity to calcium. J Clin Invest. 1989;83:1349-55.
