It has been repeatedly shown that human growth hormone (HGH) affects phosphorus metabolism in patients with hypopituitarism and in normal subjects. Injection of HGH leads to a decrease of urinary phosphorus within a day (1-3). Whereas serum phosphorus does not change or rises only slightly in short-term experiments (1), it has been reported that it rises with long-term treatment (4). Whereas the decrease of urinary phosphorus associated with an unchanged or rising serum phosphorus suggests that growth hormone decreases renal clearance of phosphate, the mechanism for these effects has not been defined. In the dog, growth hormone has been shown to raise glomerular filtration rate (GFR), renal plasma flow (RPF), tubular maximal secretion of para-aminohippurate (TmPAH) (5-7), and tubular maximal reabsorption of sulfate (Tmso4) (8). Effects on renal phosphate clearance have not been reported. The present study was undertaken to determine whether HGH affects the ability of the human kidney to reabsorb phosphate. For this purpose, maximum tubular phosphate reabsorption (Tmpo4) was measured before and after administration of growth hormone. Effects of the hormone on GFR and on RPF were also studied.The results indicate that HGH increases the phosphate Tm, the GFR, and the RPF. MATERIAL AND METHODSGrowth hormone was extracted from human pituitary glands removed at autopsy and stored in acetone. Two lots were used in this study: one prepared by Dr. Maurice Raben, and one prepared by ourselves with Raben's method (9). The HGH was dissolved in 1.5 ml of 0.1 N * This work was supported in part by grants from the Paul Govaerts Foundation and the Lekime-Ropsy Foundation.HCl per 100 mg of dry powder, and then diluted with distilled water until 100 mg was contained in 25 ml of solution. The final pH of the solution was about 3.5.Inj ections were given intramuscularly once a day at 7 a.m. Eleven male subjects were studied: one dwarf with hypopituitarism, one hypophysectomized former acromegalic, and nine subjects free of endocrinologic disorders. Brief case descriptions are given in the Appendix.Plan of study. All patients were hospitalized and received constant diets throughout the study. Water intake was ad libitum. After an adjustment period of 5 days, urine was collected in 24-hour pools for determination of nitrogen, phosphorus, sodium, potassium, and calcium. GFR, Tmpo4 and RPF were measured at the end of the control period which lasted 5 days, and on the fourth day of treatment with growth hormone. Treatment with growth hormone was begun on the third day after the control determination of renal function and was continued for 4 days.Renal studies were begun at 8:30 a.m., after food had been withheld for 14 hours. The bladder was catheterized with a rubber catheter, which remained in place throughout the experiment. (For two individuals, VP and DP, who were able to void at will, catheterization was omitted.) Large amounts of water were given by mouth to maintain urine volume. Blood was drawn for blank determination and for c...

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It has been demonstrated recently that human growth hormone (HGH) increases the tubular reabsorption of phosphate in man (1, 2). This effect is probably responsible for the fall in urinary excretion of phosphate and the rise in plasma level of phosphorus produced by growth hormone (GH) and may also explain the elevation of plasma phosphorus found in acromegaly.The action of GH on tubular transport of phosphate is not necessarily a direct one. Since parathormone decreases maximal tubular reabsorption of phosphate (Tmpo4), GH might affect phosphate reabsorption by inhibiting the secretion of parathormone or by preventing its peripheral action.Indeed the first of these two hypotheses receives some support from metabolic studies: the enhancement of gastrointestinal absorption of calcium, which may occur during treatment with HGH (3), might be expected to inhibit parathyroid secretion.The present study has been undertaken to determine whether the action of GH on tubular transport of phosphate could be explained by a decrease in parathyroid secretion or in parathormone activity. For MethodsFemale dogs fed constant diets were used for these experiments. Renal studies were performed 22 hours after the last feeding. The dogs were unanesthetized. The bladder was catheterized with a rubber catheter that remained in place throughout the experiment. Five hundred ml of water was given by stomach tube to increase urine volume. Blood was drawn from an indwelling arterial needle for control blood phosphorus and creatinine.A priming dose of creatinine and phosphate was administered intravenously (20 ml of a 10% creatinine solution, 20 ml of a solution containing Na2HPO4 12 H20, 10%, and KH2PO4, 0.75%o). A sustaining solution containing creatinine and phosphate was then infused at a rate such that a gradual increase of the plasma phosphorus value in the range of 9 to 14 mg per 100 ml was obtained, and serum creatinine value of about 50 to 70 mg per 100 ml was reached.Thirty minutes after the infusion was begun, urine was collected for consecutive periods varying in length from 10 to 15 minutes. Blood was drawn from the artery at the mid-point of each period. Each collection was ended by washing the bladder twice with distilled water and air.After five collection periods, 300 U of PTH 1 was injected intravenously.The infusion of creatinine and phosphorus was maintained, and eight further collections of urine were performed. Three days after such an experiment, intramuscular injections of bovine GH2 were given once a day (1.5 mg per kg per day) for 8 days; on day 8 of treatment, the renal study was repeated. The

Overproduction of the active metabolite of vitamin D 1,25-dihydroxyvitamin D (1,25(OH)2D) has been described in sarcoidosis and other granulomatous diseases. High circulating concentrations of 1,25(OH)2D lead to increased intestinal absorption of calcium, possibly to enhanced bone resorption, and may result in hypercalcaemia and/or hypercalciuria. Data obtained in vivo and in vitro demonstrated that the unregulated production of 1,25(OH)2D lies within the granulomatous tissue and is controlled by glucocorticoids. This abnormal production of 1,25(OH)2D seems to be a general phenomenon of granulomatous processes, which is not exceptional in sarcoidosis, but appears seldom in tuberculosis. These abnormalities, however, are not pathognomonic of granulomatous processes, since they have been described in other diseases such as lymphomas.

The possibility that low-calcium intake in renal stone formers could lead to reduced bone mineral content was investigated in 123 male patients with idiopathic urolithiasis. Radius bone mineral content (BMC) was measured by single photon absorptiometry. Two groups of patients were analyzed: group 1 (n = 63) maintained on a free diet; group 2 (n = 60) maintained on a low-calcium diet (350 mg/day +/- 20 SEM) for 3.9 years +/- 0.6 SEM. The two groups of patients were investigated after a standard reduction of calcium intake for at least 1 week. The urinary excretion of calcium and of hydroxyproline, and the serum alkaline phosphatase activity were higher in both groups than in normal subjects submitted to the same low-calcium diet. Both groups of stone formers showed lowered radius BMC values at 3 cm (distal) and 8 cm (proximal) above the styloid process, but distal BMC was significantly lower in group 2 than in group 1. The results suggest that low-calcium intake could worsen the already decreased BMC of idiopathic renal stone formers.