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Rate and Concentration Dependence of Parathyroid Hormone Dynamics during Stepwise Changes in Serum Ionized Calcium in Normal Humans^*

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

Address all correspondence and requests for reprints to: Paul R. Conlin, M.D., Endocrine-Hypertension Division, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115.

The relationship between circulating levels of PTH and the concentration and rate of change of ionized calcium (Ca₁ was studied in normal humans by measuring intact PTH during stepwise changes in Ca₁. Six normal subjects received two different citrate infusion protocols that produced stepwise decreases in Ca₁; one infusion produced a rapid decrement in calcium, and a second infusion produced a slower approach to the same (0.05 mmol/L) decline in calcium for each of four steps. The rapid decline in Ca₁ resulted in a more marked increase in levels of PTH, which subsequently fell to levels similar to those with the slower infusion. For similar absolute changes in calcium, the mean maximal increment in PTH levels was significantly greater with the rapid infusion (36.4 ± 3.1 ng/L) than with the slower infusion (19.4 ± 2.1 ng/L; P = 0.001). Six additional subjects received infusions of citrate and calcium in a stepwise manner to induce either decreases or increases in Ca₁, followed by a return to baseline. During induced hypocalcemia, when calcium was changing slowly or not at all(i.e. at the plateau of each calcium change) PTH levels were not affected by the direction of change in calcium and appeared to be dependent upon the calcium concentration per se. At elevated levels of Ca₁, the PTH response to a stepwise decrease in calcium was blunted over that seen when Ca₁ declined to or below baseline. Thus, the relationship between Ca₁ and levels of PTH is dependent not only on the concentration but also on the rate of change in calcium, particularly during induced hypocalcemia; different rates of change in calcium result in different inverse sigmoidal relationships betweeen PTH and Ca₁. When calcium is changing slowly or not at all, however, PTH levels appear to be dependent on the calcium concentration per se and are not affected by the previous direction or rate of change. Therefore, the role of the extracellular calcium concentration in the control of PTH secretion is part of more complex and dynamic regulatory mechanisms.

^* Presented in part at the Annual Meeting of the American Society of Bone and Mineral Research, September 1989. This study was performed at the Ambulatory Clinical Center, Brigham and Women’s Hospital (Boston, MA), and data were organized and analyzed using the Clinfo data management and analysis system (NIH Grant 5-MO1- RR-02635). Additional support was provided by NIH Grants 5-RO1-DK-36796 and 5-RO1-DK-41415, the Training Program in Endocrinology (5-T32-DK-07529), the Training Program in Hypertension (5-T32–07609), and the Specialized Center of Research (SCOR) in Hypertension (2-P50-HL-36568).

Received February 27, 1990.

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