Metabolic Response to Growth Hormone Administration, with Particular Reference to the Occurrence of Hypercalcuria

Abstract

ExtractThe effect of human growth hormone (GH) administration (5 mg daily) was studied in 12 children with short stature, in an attempt to elucidate the cause of the hypercalcuria which so commonly occurs at the initiation of GH therapy. Complete metabolic balances were determined for Ca, P, N, Na, K, and Cl; and urine was analyzed for hydroxyproline, stable Sr, Pb, Mg, 137 Cs, F, and creatinine. Some subjects had determinations of basal metabolic rate (BMR) and of ultrafiltrable serum Ca. In keeping with the reports of others, levels of N, P, K, Na, and Cl in urine all declined, as did that of 187 Cs; Mg excretion fell slightly. Ten of the 12 children with short stature (6 of whom had subnormal plasma GH responses to a variety of stimuli) had hypercalcuria; 3 of these had an increase in urine Ca in the face of a low Ca diet (170 mg/24 hr). Fecal Ca declined in some subjects and rose in others. Ultrafiltrable serum Ca did not change.A majority of the subjects showed an increase in the urinary excretion of F, Sr, Pb, and hydroxyproline.The effect of the hormone was also studied in three patients with idiopathic hypoparathyroidism; two of these responded with an increase in urine Ca.The magnitude of the rise in urine Ca could not be correlated with changes in BMR, changes in creatinine clearance, or changes in Na excretion; it was positively correlated with the increases in Sr and Pb in urine. SpeculationWe have evidence that the hypercalcuria accompanying GH administration is not due to increased gastrointestinal absorption, alterations in serum Ca, or changes in metabolic rate or renal function; nor is it mediated via parathyroid activity. These considations, plus the fact that the hypercalcuria is accompanied by hydroxyprolinuria and an increase in the urinary excretion of three "bone seekers" (Sr, Pb, and F), lead us to postulate that the hormone enhances bone resorption, either per se or via "sulfation factor."

Growth Hormone, Body Composition, and Aging

“…In the GH‐deficient rat, deficient albumin synthesis is corrected by GH 77–79 ; in the dwarf mouse, cell‐mediated immunity is restored by G H plus thyroxine 80–82 . In hyposomatotropic patients, hGH stimulates the intestinal absorption of Ca 83 . This effect may reflect the ability of GH to accelerate renal conversion of 25‐hydroxy vitamin D to 1,25‐dihydroxy vitamin D 84,85 …”

“…Administration of hGH to the GH‐deficient child causes the bones to grow both in length and in width, with concomitant maturation of the epiphyses and gain in bone density 97,98 . These effects on linear growth, mineralization, and maturation, reflect not only the actions of somatomedins on the cartilaginous growth plates but also the stimulation of intestinal Ca absorption, 83 and the augmentation of renal 1,25‐dihydroxy vitamin D synthesis 84,85 and renal tubular PO 4 reabsorption 97 …”