Inhibition of Growth Hormone Secretion in Mild Primary Hyperparathyroidism

Abstract

Introduction: Impairment in growth hormone (GH) secretion has been reported to occur in primary hyperparathyroidism (PHP) with strikingly elevated (>150 pg/ml) plasma PTH and free Ca levels. Patients with these characteristics are relatively few, whereas the great majority of patients with biochemically diagnosed PHP are asymptomatic and show borderline or slightly elevated plasma PTH and Ca levels. We wondered whether also patients in these latter conditions show a defective GH secretory pattern. Methods: In order to answer this question, 8 female subjects (mean age ± SE: 44 ± 1.3 years) were selected at the time of a checkup examination from a larger population of persons in fairly good clinical condition. Inclusion criteria were plasma PTH values slightly above the normal range (up to 50% higher than the maximum limit) with free Ca levels in the upper normal range or slightly higher (experimental group). Normal values in our laboratory are ionized calcium: 1.22–1.42 mmol/ml and plasma PTH: 12–72 pg/ml. A group of 15 age-matched healthy women with plasma PTH and Ca levels in the middle normal range and significantly lower than values found in the experimental group was also selected and used as control. Experimental and control groups were tested with arginine [0.5 mg/kg body weight (BW)] infused intravenously over 30 min and arginine plus GH-releasing hormone (GHRH; 1 µg/kg BW in an intravenous bolus injection). The GH responses to these challenging stimulations were compared between groups. Results: Basal serum GH values were similar in all subjects. Both arginine and arginine plus GHRH induced a significant GH rise in both groups; however, the GH responses were significantly lower in the experimental than in the control group. Mean GH peak was 27.7 and 14.6 times higher than baseline after arginine and 57.5 and 26.6 times higher than baseline after arginine plus GHRH in the control and experimental group, respectively. No significant correlation was observed between PTH or Ca levels and the GH responses to challenging stimuli in any group. Conclusion: These data show that impairment in GH secretion is associated with slightly elevated levels of PTH in the presence of serum Ca values in the upper normal range. GH responses to stimulations were reduced by about 50% in our hyperparathyroid subjects. A long-time duration of this relatively small decline of GH secretory activity may be supposed to contribute to age-related catabolic processes in a large number of patients with mild primary hyperparathyroidism.

Growth Hormone/Insulin-Like Growth Factor-1/PTH Axis in Bone

“…The initially elevated PTH levels gradually fell toward that seen in their controls over the first 6 mo. The ability of GH to suppress PTH secretion has been well documented by this group in previous publications and by other investigators. The reverse is also true in that treatment of acromegaly by lanreotide to reduce GH levels increases PTH concentrations. Interestingly, PTH may inhibit GH secretion as suggested by the association of primary hyperparathyroidism with reduced GH secretion. More to the point, despite the fall in PTH, nephrogenous cAMP and urine phosphate excretion increased, as did 1,25(OH) 2 D 3 levels and markers of both bone formation (N‐terminal propeptide of type 1 collagen [PINP], osteocalcin) and resorption (C‐terminal cross‐linking telopeptide of type 1 collagen [CTX]). Less supportive of the hypothesis is that adjusted serum calcium levels rose initially but fell below baseline by the end of the study, and both serum phosphate and tubular maximum reabsorption rate to glomerular filtration rate (TmP/GFR) steadily increased.…”

“…(4) Interestingly, PTH may inhibit GH secretion as suggested by the association of primary hyperparathyroidism with reduced GH secretion. (5) More to the point, despite the fall in PTH, nephrogenous cAMP and urine phosphate excretion increased, as did 1,25(OH) 2 D 3 levels and markers of both bone formation (N-terminal propeptide of type 1 collagen [PINP], osteocalcin) and resorption (C-terminal crosslinking telopeptide of type 1 collagen [CTX]). Less supportive of the hypothesis is that adjusted serum calcium levels rose initially but fell below baseline by the end of the study, and both serum phosphate and tubular maximum reabsorption rate to glomerular filtration rate (TmP/GFR) steadily increased.…”

Growth hormone and insulin‐like growth factor binding protein‐1 responses to oral glucose in patients with primary hyperparathyroidism

“…Impairment in GH secretion has been reported to occur in primary hyperparathyroidism. 36,37 Baseline GH levels increased 38 after parathyroid surgery, and some patients normalized their GH responses to arginine plus GHRH. 39 After surgery, we found a slight increase in baseline levels that did not reach statistical significance, probably because of the limited number of subjects and the large variability in baseline GH.…”

“…Impairment in GH secretion has been reported to occur in primary hyperparathyroidism 36,37 . Baseline GH levels increased 38 after parathyroid surgery, and some patients normalized their GH responses to arginine plus GHRH 39 .…”