Janet M. Canterbury

Calcium and vitamin D metabolism in children with nephrotic syndrome.

Although abnormalities of calcium and vitamin D metabolism are recognized in children with nephrotic syndrome, longitudinal observations are not available in these patients during periods of relapse and remission. We report observations in 58 children (mean age 10.1 years) with nephrotic syndrome and normal glomerular filtration rate. Hypocalcemia, modest hyperparathyroidism, and strikingly low calcidiol levels were identified during episodes of relapse. Most alterations were transient, and normalized on remission. The plasma concentration of calcitriol, the most active metabolite of vitamin D, was found to be normal in both relapse and remission. In the presence of hypocalcemia and hyperparathyroidism, however, normal plasma calcitriol levels in relapse may be inappropriately low and reflect a state of relative deficiency. Concurrent glucocorticoid therapy did not modify the results. A corollary of our observations is that children with relapsing or protracted nephrotic syndrome are at risk of developing metabolic bone disease, even without impairment of glomerular filtration rate.

The calcemic and phosphaturic effects of parathyroid hormone in the normal and uremic dog

The responsiveness of bone and kidney to highly purified bovine PTH was evaluated in normal (N) and uremic dogs. One group of uremic dogs (uremic-constant solute intake; U-CSI), maintained on a diet containing 1500 mg of phosphorus (P) daily developed the adaptive increases in phosphate excretion (FEPO4) and PTH levels characteristic of uremia. A second group of uremic dogs (uremic-proportional reduction of solute; U-PRS), in which dietary P intake was reduced in proportion to the reduction in GFR, exhibited normal FEPO4 and PTH values. During PTH infusion tubular reabsorption of phosphate per nephron mass decreased 2.5 mg100 ml in U-PRS but only 1.4 in U-CSI (p < .001) and 1.1 in N (p < .001). After PTH the calcemic response was significantly and equally decreased in both U-CSI and U-PRS compared to N. In conclusion, the blunted calcemic response to PTH in uremia does not appear to be the only or predominant factor in the pathogenesis of hyperparathyroidism since the uremic dog treated with proportional reduction of phosphorus intake, which maintains a normal PTH level, also demonstrates this abnormality. The PTH-induced rise in phosphate excretion in the uremic nephron depends on the pre-existing degree of inhibition of renal tubular phosphate reabsorption. Finally, the uremic animals in which an adaptive phosphaturia was prevented (U-PRS) exhibited a magnified response in phosphate excretion per nephron to exogenous PTH infusion.

Emerging concepts of the nature of circulating parathyroid hormones: implications for clinical research.

Publisher Summary Endocrinology has been revolutionized by the development of the radioimmunoassay technique for measuring minute quantities of peptide hormones. First applied to insulin, the principles of the assay have been quickly adapted to the measurement of other circulating peptide hormones. This chapter provides an overview on the radioimmunoassay of parathyroid hormone (PTH). It discusses the biological significance and origin of circulating forms of immunoreactive PTH. An antiserum possessing high affinity for the N-terminal, biologically active portion of the molecule is best suited for the study of the parathyroid secretion control. When long-term secretory rates of the hormone are at issue, an antiserum possessing high affinity for long-lived fragments is useful. Despite limitations, the immunoassay of PTH has proved to be an extraordinarily powerful and useful tool in clinical investigation. The chapter also discusses the existence of predictable circadian changes in the levels of many hormones and electrolytes in blood and urine.

Parathyroid Hormone Activation of Adenylate Cyclase in Liver

Summary The effect of parathyroid hormone (PTH) on the membrane bound enzyme adenylate cyclase in rat and cat liver tissue homogenates was studied. Bovine PTH increased the accumulation of cyclic AMP (cAMP) over a range of 6 × 10−8 − 1 × 10−6 M . The synthetic N-terminal peptide (1–34 amino acids) of the hormone increased the accumulation of cAMP over a range of 6 × 10−9 − 6 × 10−7 M. Compared to well studied stimulators of liver adenylate cyclase, glucagon and epinephrine, PTH produced a greater stimulation than epinephrine but less than glucagon. Calcitonin, thyrotropin, and gastrin did not stimulate the liver adenylate cyclase. Maximal concentrations of the 1–34 peptide and epinephrine were additive but maximal concentrations of the 1–34 peptide and glucagon were only partially additive. The concentration of PTH showing maximal stimulation of liver adenylate cyclase is equivalent to that reported for bone and kidney, the two well studied end organs for the hormone. Although the data suggest that the liver is an end organ for PTH, there is no known physiologic role for this hormone in the liver except for a possible requirement for PTH in liver regeneration.

Effects of cimetidine on parathyroid hormone in chronic uremia.

Recent case reports suggest suppression of immunoreactive parathyroid hormone (iPTH) with cimetidine in two patients with primary hyperparathyroidism. In both patients peptic ulcer disease led to medical treatment with cimetidine. In the first patient given oral cimetidine (800 mg then 400 mg daily) for 8 months, iPTH decreased from 20 times to 6 times normal1. No changes in serum calcium and phosphorus occurred, but inhibition of gastric acid secretion and ulcer healing were demonstrated. In the second patient, a woman with a parathyoid adenoma, cimetidine treatment (1200 mg daily) was associated with a decrease in iPTH levels from a value 2.5 times normal to a normal value2,3. Concommittantly, serum calcium decreased from 11.3 mg/dl to 10.3 mg/dl and serum phosphorus increased from 2.1 mg/dl to 2.7 mg/dl. One month after discontinuation of cimetidine therapy iPTH had rebounded to values thrice normal and serum calcium and phosphorus were 10.8 and 2.3 mg/dl, respectively.

Interrelations Between Phosphorus, Calcium, Parathyroid Hormone, and Phosphate Excretion in the Normal and Uremic Dog

Phosphorus homeostasis is maintained in animals and man by excretion through the kidneys of the same amount of phosphorus absorbed from the intestines on an ongoing basis. There is apparently little impairment of gastrointestinal phosphorus absorption in uremia (1); yet phosphorus balance is well maintained in animals and man with advancing chronic renal disease. This balance is accomplished by progressive increases in fractional excretion of phosphate (\((F{{E}_{P{{O}_{4}}}})\)) by the kidneys and associated increases in para-thyroid hormone (PTH) secretion (2–5).