Rickets and Hyperparathyroidism

194

The mode of action of vitamin D in the prevention and cure of rickets is still not understood. In 1921, Howland and Kramer (1) pointed out that the concentration of phosphorus in the serum was usually reduced in human rickets, at times to very low levels, although the concentration of calcium might be within normal limits. This has been confirmed repeatedly and it has been found that the administration of vitamin D results in a prompt rise in the concentration of phosphorus, even to abnormally high levels with excessive dosage. The mechanism through which vitamin D influences the concentration of phosphorus in the body fluids has not been satisfactorily explained. In balance experiments in man (2, 3) and experimental animals (4) it has been shown that during states of vitamin D deficiency absorption of calcium and phosphate from the intestinal tract is reduced and that the administration of vitamin D increases the absorption of these ions. In the rat, the studies of Nicolaysen (5) Careful examination of the data from metabolic studies in the rachitic infant leads to the conclusion that deficient absorption of phosphate from the intestinal tract cannot wholly explain the diminished concentration of phosphate in the plasma. In infants developing rickets on a cow's milk diet, i.e., a diet high in both calcium and phosphorus, the amount of phosphate absorbed from the intestinal tract would be sufficient for the needs of the infant were the phosphate retained rather than excreted in the urine.The excretion of phosphate in the urine must play an important r6le in the regulation of the concentration of phosphate in the body fluids. How is the renal excretion of phosphate controlled and does vitamin D influence the concentration of phosphate in the blood plasma through an effect on the excretion of this ion by the kidneys? The present experiments were conducted to answer these questions. The Renal Excretion of PhosphateWalker (6) and Walker and Hudson (7) have shown that the phosphate of the plasma is filtrable through the glomerular membranes of the amphibian. These workers have also found that under certain conditions active reabsorption of phosphate takes place in the proximal tubules so that the urine in the distal tubules and bladder may be almost phosphate-free. There was no evidence that phosphate was secreted into the lumen of the tubules.In the dog, Pitts (8) has shown that the clearance of phosphate increases as the concentration of phosphate in the plasma increases and approaches the xylose clearance at very high levels of plasma phosphate. At normal levels of phosphate in the blood plasma the urine may be almost phosphate-free and the excretion of phosphate in the urine is only a small fraction of that filtered through the glomeruli. In the mammalian kidney, therefore, reabsorption of phosphate must also take place as the glomerular filtrate passes through the renal tubules.In order to study this tubular reabsorption of phosphate quantitatively, simultaneous determinations of the creatinine and phosphate c...

Section: Methodsmentioning

confidence: 98%

The Renal Excretion of Inorganic Phosphate in Relation to the Action of Vitamin D and Parathyroid Hormone 1

Harrison¹,

Harrison²

1941

194

“…In previous reports from this laboratory evidence of functional hyperactivity of the parathyroid glands in rickets (12) and in pregnancy (13) has been presented. We have used the same approach in our investigation of parathyroid activity in the present series of nephritic patients,' to determine whether the hyperplasia noted by Pappenheimer and Wilens (6) is accompanied by a hyperfunction.…”

mentioning

confidence: 99%

Hyperparathyroidism in Kidney Disease

Highman

Hamilton²

1937

Self Cite

Extensive investigations of the parathyroid glands were instigated by the cure of generalized osteitis fibrosa cystica by surgical removal of a parathyroid adenoma by Mandl (1) in 1925. It was early noted that renal calculi were often found in cases of parathyroid tumor (2). Later work showed that these stones consisted chiefly of calcium phosphate and that the tendency to their formation was definitely decreased when the urine was made more acid (3). Removal of the parathyroid tumor. resulted in the disappearance of this tendency to calculus formation and of the alkalinity of the urine.Albright, Baird, Cope, and Bloomberg (4), in their discussion of 83 cases of parathyroid tumor with hyperparathyroidism, brought out the fact that 43 of these showed clinical evidence of renal damage. These kidney lesions were attributed to damage resulting from the deposition of calcium in the renal parenchyma or to the formation of calculi in the pelves, such calcium depositions being manifestations of primary hyperparathyroidism. However, these authors suggested the possibility that parathyroid enlargement may be secondary to renal impairment: " It seems conceivable therefore that a chronic renal insufficiency with phosphate retention and a high inorganic phosphorus level might likewise cause hyperplasia of all parathyroid tissue which might go on to multiple tumor formation" and later, "In these cases the kidney damage may be the cause and not the result of the parathyroid tumors."p Bergstrand (5) studied the parathyroid glands in an extensive series of autopsies, and in most of the cases where he found them enlarged, there was also some damage to the kidneys. Pappenheimer and Wilens (6) carefully weighed the parathyroid glands from a large series of necropsies. They found the parathyroids taken from unselected nephritics to average more than 50 per cent greater in weight than those taken from non-nephritic controls. Seven severe nephritics showed an increase of 109 per cent over the same control series. The enlargement was diffusely hyperplastic in character, resembling the enlargement which has been reported in rickets (7,8), and which may exist in pregnancy (9, 10). Adenomata were found in only three of 56 nephritics and in two of 74 controls. Jarrett, Peters, and Pappenheimer (11) report that they have induced a similar enlargement of the parathyroids by producing chronic renal insufficiency in rats.In previous reports from this laboratory evidence of functional hyperactivity of the parathyroid glands in rickets (12) and in pregnancy (13) has been presented. We have used the same approach in our investigation of parathyroid activity in the present series of nephritic patients,' to determine whether the hyperplasia noted by Pappenheimer and Wilens (6) is accompanied by a hyperfunction. The patients were selected on the basis of elevation of the blood urea nitrogen, most of them having chronic rather than acute renal insufficiency. The controls were thirtyeight normal persons-thirty women and eight men. Determinations of ca...

“…Hamilton and Schwartz (3) found evidences of increased parathormone in the blood, according to their test, in 9 of 12 rachitic rabbits. In this same communication the authors also reported that the blood calcium of the rachitic rabbits increased immediately and markedly when calcium chloride was administered to the animals by stomach tube, whereas there was a much more moderate rise in the calcium concentration in a series of normal rabbits so tested; the authors have since reported that these results could not be reproduced in other series of rachitic rabbits (4 (8,9) and with the findings of Hoffmann et al (10,11), who demonstrated the presence in blood from pregnant women of a substance which behaves like parathyroid hormone.…”

Section: Review Of Literaturementioning

confidence: 96%

Experience With the Hamilton and Highman Test for Parathyroid Hyperfunction in Chronic Nephritis, Toxic Goiter, and Paget's Disease of Bone

Gilligan¹,

Volk²,

Gargill³

1938

In 1932 Hamilton and Schwartz (1) described a method for the detection of small amounts of parathyroid hormone, three to five units, in preparations of the hormone and in blood. In 1936 Hamilton and Highman (2) presented certain modifications of this test designed to make the method particularly applicable to the detection of abnormally large amounts of parathyroid hormone in the blood of patients suspected of having increased parathyroid function. The test consists, briefly, in measuring the increase in the serum calcium of a rabbit at definite intervals after the rabbit has received an intramuscular injection of the blood or preparation containing parathyroid hormone, the animal being given amounts of calcium chloride solution by stomach tube at definite periods during the experiment.In Highman and Hamilton found abnormally great amounts of parathyroid hormone in the blood of 20 of 23 patients with chronic nephritis and elevated blood urea nitrogen (12). Shelling and Remsen (13) reported a case of renal rickets with elevated concentrations of nitrogen and inorganic phosphorus in the blood, which case showed increased parathyroid hormone in the blood according to the Hamilton and Schwartz test, and at postmortem examination showed four markedly enlarged parathyroid glandules. These authors mention that the results of the Hamilton and Schwartz test were negative in other cases of renal rickets. Bass and Paxter (38) recently performed the "Hamilton test" on two occasions in one patient with renal rickets; on one of these occasions the result was " suggestively positive," on the other trial, negative. 641