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Relationship Between the Concentration and Rate of Change of Calcium and Serum Intact Parathyroid Hormone Levels in Normal Humans^*

G. A. BRENT, M. S. LEBOFF, E. W. SEELY, P. R. CONLIN and E. M. BROWN

Endocrine-Hypertension Unit and the Department of Medicine, Brigham and Women’s Hospital Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Meryl S. LeBoff, M.D., Endocrine-Hypertension Unit, Brigham and Women’s Hospital, Ambulatory Clinical Center, 221 Longwood Avenue, Boston, Massachusetts 02115.

We employed variable rates of infusion of EDTA or calcium gluconate to examine the relationships between the concentration and rate of change of serum total and plasma ionized calcium and serum immunoreactive intact PTH concentrations in normal subjects. Use of a sensitive immunoradiometric assay specific for PTH-(1-84) made it possible to determine the full range of PTH responses to perturbations in the extracellular calcium concentration. By progressively increasing the rate of administration of calcium gluconate or EDTA during rapid or slow infusions, linear rates of change in the serum calcium concentration were achieved in eight men. The slopes were 2-fold greater during the rapid infusions. Both the calcium infusions decreased serum PTH-(1–84) levels from a mean of 23.2 ± 2.0 (±SE) to 6.4 ± 1.0 and 5.6 ± 1.0 ng/L for the rapid and slow infusions, respectively, with no obvious rate dependence. The rapid or slow EDTA infusions increased serum PTH levels to the same maximal extent (95.0 ± 20.2 and 99.9 ± 14.5 ng/L, respectively), also with no significant rate dependence. Thus, there was no effect of the rate of change of calcium on the PTH response, which was reflected in similar inverse sigmoidal relationships between PTH and serum total and plasma ionized calcium when the data for the slow and rapid infusions were pooled separately. Similar sigmoidal curves were found in normal women. These data suggest the feasibility of using calcium and EDTA infusions combined with an intact PTH assay to define the relationships between circulating levels of PTH-(1–84) and calcium in states of normal and deranged parathyroid physiology.

^* This work was performed at the Clinical Research Center, Brigham and Women’s Hospital (Boston, MA), and data were organized and analyzed using the Clinfo data management and analysis system (NIH Grant M01-RR-02635-05). Additional support was provided by NIH Grants 5-M01-RR-02035, AM-36801, and AM-01600; the Training Program in Endocrinology DK-07529; and the Training Program in Hypertension 5T-32HL-07609-03.

Supported by NIH Physician-Scientist Program Award 5-K12-AM01401.

Received February 16, 1988.

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