Effect of rate of calcium reduction and a hypocalcemic clamp on parathyroid hormone secretion: a study in dogs.
BACKGROUND
The parathyroid hormone (PTH) calcium curve is used to evaluate parathyroid function in clinical studies. However, unanswered questions remain about whether PTH secretion is affected by the rate of calcium reduction and how the maximal PTH response to hypocalcemia is best determined. We performed studies in normal dogs to determine whether (a) the rate of calcium reduction affected the PTH response to hypocalcemia and (b) the reduction in PTH values during a hypocalcemic clamp from the peak PTH value observed during the nadir of hypocalcemia was due to a depletion of stored PTH.


METHODS
Fast (30 min) and slow (120 min) ethylenediamine-tetraacetic acid (EDTA) infusions were used to induce similar reductions in ionized calcium. In the fast EDTA infusion group, serum calcium was maintained at the hypocalcemic 30-minute value for an additional 90 minutes (hypocalcemic clamp). To determine whether the reduction in PTH values during the hypocalcemic clamp represented depletion of PTH stores, three subgroups were studied. Serum calcium was rapidly reduced from established hypocalcemic levels in the fast-infusion group at 30 and 60 minutes (after 30 min of a hypocalcemic clamp) and in the slow-infusion group at 120 minutes.


RESULTS
At the end of the fast and slow EDTA infusions, serum ionized calcium values were not different (0.84 +/- 0.02 vs. 0.82 +/- 0.03 mM), but PTH values were greater in the fast-infusion group (246 +/- 19 vs. 194 +/- 13 pg/ml, P < 0.05). During the hypocalcemic clamp, PTH rapidly decreased (P < 0.05) to value of approximately 60% of the peak PTH value obtained at 30 minutes. A rapid reduction in serum calcium from established hypocalcemic levels at 30 minutes did not stimulate PTH further, but also PTH values did not decrease as they did when a hypocalcemic clamp was started at 30 minutes. At 60 minutes, the reduction in serum calcium increased (P < 0.05) PTH to peak values similar to those before the hypocalcemic clamp. The reduction in serum calcium at 120 minutes in the slow EDTA infusion group increased PTH values from 224 +/- 11 to 302 +/- 30 pg/ml (P < 0.05).


CONCLUSIONS
These results suggest that (a) the reduction in PTH values during the hypocalcemic clamp may not represent a depletion of PTH stores. (b) The use of PTH values from the hypocalcemic clamp as the maximal PTH may underestimate the maximal secretory capacity of the parathyroid glands and also would change the analysis of the PTH-calcium curve, and (c) the PTH response to similar reductions in serum calcium may be less for slow than fast reductions in serum calcium.
Estepa
J C
JC
Departamento de Nefrología y Unidad de Investigación del Hospital Universitario Reina Sofía, Spain.
Aguilera-Tejero
E
E
Almaden
Y
Y
Rodriguez
M
M
Felsenfeld
A J
AJ
D000818:Animals; D002118:Calcium / Q000097:blood*; D002614:Chelating Agents / Q000494:pharmacology; D004285:Dogs; D004492:Edetic Acid / Q000494:pharmacology; D006961:Hyperparathyroidism / Q000503:physiopathology; D006996:Hypocalcemia / Q000139:chemically induced / Q000503:physiopathology*; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism*; D013997:Time Factors
D002614:Chelating Agents; D010281:Parathyroid Hormone; D004492:Edetic Acid; D002118:Calcium