The Effect of Acute Hypercalcemia on Growth Hormone Release in Man KAMEL AJLOUNI AND THAD C. HAGEN The Departments of Medicine, Wood Veterans Administration Center and The Medical College of Wisconsin, Milwaukee, Wisconsin ABSTRACT. The growth hormone response to acute hypercalcemia was studied in 9 normal subjects. Growth hormone, calcium, glucose, phosphate and magnesium levels were determined at 30-min intervals during 4-h infusions. Infusions, performed in random order in the subjects, consisted of either normal saline at 3 ml/min for 4 h or 15 mg calcium/kg (calcium gluconate) at 3 ml/min for 3 h followed by normal saline for the fourth hour. Significant hypercalcemia (P < 0.05) was achieved within 60 min
< 0.05) at 60 min and all subsequent determinations during calcium infusion when compared to normal saline infusions. In 6 of the subjects, standard L-dopa provocative testing with an oral dose of 500 mg was performed during normal saline and calcium infusions identical to those described above. Peak growth hormone responses did not differ significantly following L-dopa during saline or calcium infusion. These results suggest that an acute increase in
and maintained throughout the infusion. No change
circulating calcium promotes greater basal growth
in calcium concentrations occurred during normal saline infusions, and phosphate, glucose and magnesium were unchanged in all studies. Growth hormone levels were significantly higher (P
hormone secretion without a synergistic increase in hypothalamic mediated growth hormone release by L-dopa. (J Clin Endocrinol Metab 40: 780, 1975)
T
HE role of calcium in the secretion of neurotransmitter substances, as well as various hormones, has received considerable attention in recent years (1). A positive influence of calcium appears operative in insulin release from the beta cell, the release of steroids from the adrenal, and the release of TSH, LH and vasopressin from their respective cells (2-6). With regard to growth hormone secretion, in vitro studies indicate that cyclic AMP-mediated growth hormone release requires ionized calcium in the medium (7), and that removal of calcium fron incubation media prevents growth hormone release from rat pituitary tissue (8). Little is known regarding the effect of calcium on growth hormone in vivo, therefore, we elected to study the effects of heightened circulating calcium levels on basal and provoked growth hormone release in man. It is the purpose of this communication to report the results of these studies.
Materials and Methods
Received November 20, 1974. Address reprint requests to: Kamel Ajlouni, M.D., Endocrine-Metabolic Section/lllD, Veterans Administration Center, Wood, Wisconsin 53193.
Nine normal male subjects, ages 24-28, were studied on an outpatient basis at the Wood Veterans Administration Center after obtaining signed informed consents. All subjects were within 10% of ideal body weight, and had no family history of diabetes or other endocrine disorder. Following an overnight fast, studies commenced at 7:30 AM with the placement of an indwelling scalp vein needle in an antecubital vein. After needle placement subjects rested for 30 min prior to the initiation of 4-h infusions. Each subject underwent a 4-h normal saline infusion at a rate of 3 ml/min and a 4-h infusion consisting of 15 mg calcium/kg body weight (calcium gluconate) in normal saline delivered over 3 h at 3 ml/min, and a final 1-h infusion of normal saline at 3 ml/min. Infusions were performed on successive days in each subject in random order. Blood samples were obtained at 0, 30, 60, 90, 120, 180 and 240 min for growth hormone, calcium, phosphorus, glucose and magnesium. After a minimum of 48 h, 6 of the 9 subjects underwent L-dopa provocative tests on successive days, again in random order. Each test was performed using an oral dose of 500 mg L-dopa, on one occasion during normal saline infusion and on the other during calcium infusion. The infusions were performed as described above,
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CALCIUM AND GROWTH HORMONE and L-dopa was administered at time 0 of each infusion. Blood samples were again obtained at 30-min intervals between 0 and 240 min for growth hormone, calcium, phosphorus, glucose and magnesium. Sera were obtained quickly from all blood samples and frozen prior to determination of the various parameters. Growth hormone was measured in a modified solid-phase radioimmunoassay (9) with a sensitivity of 0.5 ng/ml, glucose by the glucose oxidase method in a Beckman autoanalyzer and calcium and phosphorus by AutoAnalyzer. Magnesium was determined by a complexometric technique. Data were analyzed statistically by Student's t test for paired data.
Results
The calcium concentrations increased from a baseline of 9.5 ± 0.15 mg/100 ml (X ± SE) to 11.6 ± 0.25 mg/100 ml (X ± SE) at 60 min and reached maximal concentrations of 13.7 ± 0.14 mg/100 ml (X ± SE) at 180 min (Fig. 1). There was no change in calcium concentrations during normal saline infusion. Glucose, phosphorus and magnesium concentrations did not change significantly during calcium or normal saline infusion. The calcium infusions were associated with significantly higher growth hormone levels (P < 0.05) at 60, 90, 120, 150, 180, 210 and 240 min, with maximal levels at 240 min when compared to normal CALCIUM mg/IOOml
l 4
781
saline infusions (Fig. 1). This statistic is somewhat difficult to interpret as the mean basal growth hormone level was higher during the calcium infusions. Accordingly, comparison of growth hormone increments over basal in the same groups indicated that significance (P < 0.01) was achieved at 210 and 240 min. In addition, the growth hormone concentrations at 210 and 240 min during the calcium infusions were significantly higher (P < 0.01) than the basal concentration (the latter two statistical determinations are not depicted in the figure). Following oral L-dopa in 6 subjects, the peak growth hormone concentration was 20.6 ± 5.0 ng/ml (X ± SE) during saline infusion. The corresponding value following L-dopa, administered during calcium infusion, was 22.9 ± 9.2 ng/ml (X ± SE) which was not significantly different; however, growth hormone was significantly higher (P
< 0.05) at 60 min and all subsequent determinations during calcium infusion when compared to normal saline infusions. In 6 of the subjects, standard L-dopa provocative testing with an oral dose of 500 mg was performed during normal saline and calcium infusions identical to those described above. Peak growth hormone responses did not differ significantly following L-dopa during saline or calcium infusion. These results suggest that an acute increase in
and maintained throughout the infusion. No change
circulating calcium promotes greater basal growth
in calcium concentrations occurred during normal saline infusions, and phosphate, glucose and magnesium were unchanged in all studies. Growth hormone levels were significantly higher (P
hormone secretion without a synergistic increase in hypothalamic mediated growth hormone release by L-dopa. (J Clin Endocrinol Metab 40: 780, 1975)
T
HE role of calcium in the secretion of neurotransmitter substances, as well as various hormones, has received considerable attention in recent years (1). A positive influence of calcium appears operative in insulin release from the beta cell, the release of steroids from the adrenal, and the release of TSH, LH and vasopressin from their respective cells (2-6). With regard to growth hormone secretion, in vitro studies indicate that cyclic AMP-mediated growth hormone release requires ionized calcium in the medium (7), and that removal of calcium fron incubation media prevents growth hormone release from rat pituitary tissue (8). Little is known regarding the effect of calcium on growth hormone in vivo, therefore, we elected to study the effects of heightened circulating calcium levels on basal and provoked growth hormone release in man. It is the purpose of this communication to report the results of these studies.
Materials and Methods
Received November 20, 1974. Address reprint requests to: Kamel Ajlouni, M.D., Endocrine-Metabolic Section/lllD, Veterans Administration Center, Wood, Wisconsin 53193.
Nine normal male subjects, ages 24-28, were studied on an outpatient basis at the Wood Veterans Administration Center after obtaining signed informed consents. All subjects were within 10% of ideal body weight, and had no family history of diabetes or other endocrine disorder. Following an overnight fast, studies commenced at 7:30 AM with the placement of an indwelling scalp vein needle in an antecubital vein. After needle placement subjects rested for 30 min prior to the initiation of 4-h infusions. Each subject underwent a 4-h normal saline infusion at a rate of 3 ml/min and a 4-h infusion consisting of 15 mg calcium/kg body weight (calcium gluconate) in normal saline delivered over 3 h at 3 ml/min, and a final 1-h infusion of normal saline at 3 ml/min. Infusions were performed on successive days in each subject in random order. Blood samples were obtained at 0, 30, 60, 90, 120, 180 and 240 min for growth hormone, calcium, phosphorus, glucose and magnesium. After a minimum of 48 h, 6 of the 9 subjects underwent L-dopa provocative tests on successive days, again in random order. Each test was performed using an oral dose of 500 mg L-dopa, on one occasion during normal saline infusion and on the other during calcium infusion. The infusions were performed as described above,
780
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 22 April 2015. at 06:31 For personal use only. No other uses without permission. . All rights reserved.
CALCIUM AND GROWTH HORMONE and L-dopa was administered at time 0 of each infusion. Blood samples were again obtained at 30-min intervals between 0 and 240 min for growth hormone, calcium, phosphorus, glucose and magnesium. Sera were obtained quickly from all blood samples and frozen prior to determination of the various parameters. Growth hormone was measured in a modified solid-phase radioimmunoassay (9) with a sensitivity of 0.5 ng/ml, glucose by the glucose oxidase method in a Beckman autoanalyzer and calcium and phosphorus by AutoAnalyzer. Magnesium was determined by a complexometric technique. Data were analyzed statistically by Student's t test for paired data.
Results
The calcium concentrations increased from a baseline of 9.5 ± 0.15 mg/100 ml (X ± SE) to 11.6 ± 0.25 mg/100 ml (X ± SE) at 60 min and reached maximal concentrations of 13.7 ± 0.14 mg/100 ml (X ± SE) at 180 min (Fig. 1). There was no change in calcium concentrations during normal saline infusion. Glucose, phosphorus and magnesium concentrations did not change significantly during calcium or normal saline infusion. The calcium infusions were associated with significantly higher growth hormone levels (P < 0.05) at 60, 90, 120, 150, 180, 210 and 240 min, with maximal levels at 240 min when compared to normal CALCIUM mg/IOOml
l 4
781
saline infusions (Fig. 1). This statistic is somewhat difficult to interpret as the mean basal growth hormone level was higher during the calcium infusions. Accordingly, comparison of growth hormone increments over basal in the same groups indicated that significance (P < 0.01) was achieved at 210 and 240 min. In addition, the growth hormone concentrations at 210 and 240 min during the calcium infusions were significantly higher (P < 0.01) than the basal concentration (the latter two statistical determinations are not depicted in the figure). Following oral L-dopa in 6 subjects, the peak growth hormone concentration was 20.6 ± 5.0 ng/ml (X ± SE) during saline infusion. The corresponding value following L-dopa, administered during calcium infusion, was 22.9 ± 9.2 ng/ml (X ± SE) which was not significantly different; however, growth hormone was significantly higher (P
