The Parathyroid Hormone and Aminoaciduria in Vitamin—D Deficiency Rickets

Abstract

Secondary hyperparathyroidism hasbeen known t o occur in vitamin-D deficiency rickets and is considered t o be necessary t o maintain normal serum calcium in the presence of deficient gastrointestinal absorption of calcium [l, 51. Using intravenous calcium infusions t o maintain mild hypercalcaemia with the idea of suppressing parathyroid function, a marked drop in phosphate excretion was found in nine cases of vitamin-D deficiency rickets [3]. Using the same technique Scriver, et al. [19] reported the disappearance of hyperaminoaciduria in one case of vitamin-D deficiency rickets. However, it was shown by Lavender t Pullman [ 151 that calcium can directly affect the kidney tubules enhancing phosphorus transport, an effect not mediated by the parathyroids. No direct action of calcium on the hyperaminoaciduria is known. Our aim has been t o study the effect of parathyroid hormone on the aminoaciduria of vitamin-D deficiency rickets and to investigate the possible correlation between the aminoaciduria and the biochemical findings. _ _ _~ Present address: Paediatric Department, Alexandria Medical School, Alexandria, U.A.R. 29 -672888 -4ctn Paediat Scand 56 Material and MethodTen male patients showing vitamin-D deficiency rickets were chosen for the study. Their ages ranged from 10 to 24 months. Clinically all patients showed broad epiphyses, rickety rosary, varying degrees of generalised hypotonia with a history of delay in standing and walking. Radiologically all of them showed a classical rachitic picture. After admission, urine was collected for 6 hours, together with a blood sample. At the end of the sixth hour parathyroid hormone (Lilly) was adminstered subcutaneously in a dose of 5 units per kilogram body weight to all patients. Urine was collected separately for the following 6 hours. Another blood sample was taken two hours after the injection. Serum and urinary calcium and phosphorus were estimated in seven cases. Serum and urinary calcium were determined using the oxalate-permanganate method [13], serum and urine phosphorus by the method described by King & Wootton [13]. The glomerular filtration rate was measured in seven of the rachitic infants using the endogenous creatinine clearance technique [21]. Urinary amino acids were determined in seven cases using a qualitative and semiquantitative two-dimensional paper chromatography procedure as described by Wootton [21]. In the remaining three patients quantitative estimation of the urinary amino acids in the samples collected before and after parathyroid hormone administration was done, by

Vitamin D Deficiency Rickets: Renal Handling of Phosphate and Free Amino Acids

“…It may be tempting to speculate that elevation of GFR might also be the result of endogenous hyperparathyroidism in rickets. Administration of parathyroid extract is often accompanied by an increase in GFR [28,35,36,50], but this finding could not be confirmed by others [33,45,49], and was considered to be the result of crude preparations of parathormone [5]. Furthermore, in two of our three cases, in whom the clearance studies could be repeated after weeks of vitamin D treatment, C In had not returned to normal within this period.…”

“…It may be speculated that vitamin D deficiency itself and/or hypocalcemia are such factors which render the proximal tubule more sensitive to the action of parathormone. This already has been suggested [32,35]. Finally, we know of no reports in the literature where in infants with severe rickets glomerular filtration rates (GFR) had been measured with inulin.…”

“…Hypophosphatemia, hyperphosphatascmia, and phosphate diabetes are considered to be due to secondary hyperparathyroidism, as investigations by several authors suggest [1,3,39,45,50,55,68]. Renal hyperaminoaciduria, on the contrary, is attributed by most investigators to direct effect of vitamin D deficiency [16,35,40]. Recently, however, the group of Scriver, Kooh and Frascr [22,29,65] postulated that hyperaininoaciduria in vitamin D deficiency also may be due to secondary hypcrparathyroidism.…”

The Effect of Calcium Infusions on Renal Handling of Amino Acids in Hypophosphatemic Vitamin D Resistant Rickets

“…Amino acid clearances have been reported to be elevated depending on the age of the patients (4) and the stage of the disease (4, 12). The renal hyperaminoaciduria found in vitamin D deficiency rickets is attributed by some investigators to a direct effect of vitamin D deficiency (5, 16,17) and by others to a secondary hyperparathyroidism (12,14,30). In this context we examined the question whether renal handling of amino acids in hypophosphatemic vitamin D resistant rickets follows a mechanism similar to that in vitamin D deficiency rickets.…”