Immunoreactive Parathyroid Hormone Levels Research Articles

Bone aluminum and histomorphometric features of renal osteodystrophy.

To evaluate the relationship between aluminum and the characteristics of bone disease in uremia, bone aluminum content and quantitative histomorphometric analysis of bone were evaluated in bone biopsies from 59 uremic patients undergoing maintenance hemodialysis. Biopsies were classified as showing 1) pure osteomalacia (OM) in 23 cases, 2) osteitis fibrosa (OF) in 13, 3) mixed in 7, and 4) mild lesions in 16. There were no significant differences in levels of serum calcium or alkaline phosphatase between the groups, but serum phosphorus levels were slightly higher in those with OF. Serum immunoreactive parathyroid hormone levels were greater in the patients with OF and mixed lesions than in patients with OM or mild lesions (P less than 0.01). Bone aluminum exceeded normal in all groups (P less than 0.01), with values of 175 +/- 18 mg/kg dry wt in OM patients, 46 +/- 7 of OF patients, 81 +/- 29 in mixed subjects, and 67 +/- 7 in patients with mild lesions. Bone aluminum was significantly higher in the OM patients than in any other group (P less than 0.01); also, bone aluminum correlated with the quantitative measure of unmineralized osteoid in OM (r = 0.67; P less than 0.001); no correlations existed for the other groups. There were inverse correlations between bone aluminum and the serum immunoreactive parathyroid hormone (r = -0.35; P less than 0.01) and resorbing surface on biopsy (r = -0.44; P less than 0.001). Bone aluminum correlated with the duration of hemodialysis in patients with OF with mixed and mild lesions (r = 0.49); no relation was seen in OM patients, and bone aluminum was higher for the duration of dialysis, suggesting that aluminum may accumulate more rapidly in OM subjects. These findings are consistent with but do not prove the hypothesis that aluminum plays a pathogenic role in dialysis osteomalacia; the mechanism by which aluminum accumulates remains unknown.

Intestinal Calcium Transport: Effect of Cimetidine

Recently cimetidine (Tagamet), a widely used drug for peptic ulcer disease, was found to decrease serum levels of calcium and immunoreactive parathyroid hormone in patients with hyperparathyroidism. Since parathyroid hormone action is closely related to calcium homeostasis, we studied the effect of cimetidine on intestinal calcium transport. An in vivo perfusion technique was used for the study of net transport and lumen to mucosa flux of 45calcium. Our results indicate a significant decrease in net calcium transport and lumen to mucosa flux of 45calcium in the rats injected with cimetidine, compared to control rats. Direct addition of cimetidine to the perfusion solution did not alter transport rates significantly. The mechanism by which cimetidine affects calcium transport may be secondary to its effect on the release of parathyroid hormone from the parathyroid gland or an effect on vitamin D metabolism.cimetidine intestine calcium

Bone resorption and humoral hypercalcemia of malignancy: stimulation of bone resorption in vitro by tumor extracts is inhibited by prostaglandin synthesis inhibitors.

Extracts of tumors from patients with humoral hypercalcemia of malignancy (HHM) were tested using an in vitro bone resorption assay in order to investigate the pathogenesis of the hypercalcemia. Bone resorption was assessed by comparing the percent release of previously incorporated 45Ca from paired halves of newborn mouse calvaria. Saline extracts of three out of five tumors from HHM patients caused a significant increase in 45Ca release relative to controls. Extracts of liver and non-HHM tumor did not cause significant resorption. Tumor-stimulated bone resorption was blocked by indomethacin and eicosatetraynoic acid, inhibitors of the synthesis of prostaglandins (PGs) and related metabolites of arachidonic acid, whereas resorption stimulated by parathyroid hormone (PTH), PGE2, or 1,25-(OH)2D3 was not. Furthermore, levels of immunoreactive PTH or PGE2 in tumor extracts were not sufficient to account for the degree of resorption observed. These observations indicate that PTH or PGE2 are not responsible for the bone resorption caused by extracts of tumors from these patients with HHM. Furthermore, they suggest that hypercalcemia in these patients may result from bone resorption stimulated by the local production in bone of PGs or related metabolites of arachidonic acid in response to a humoral factor elaborated by the tumor.

Effect of age on serum immunoreactive parathyroid hormone and its biological effects.

Immunoreactive parathyroid hormone (iPTH) levels, nephrogenous cAMP (ncAMP), and tubular maximum phosphate reabsorption (TmP) were measured in 10 young and 12 healthy volunteers. The fasting urinary calcium to creatinine ratio (Ca:Cr) was also quantitated as an index of bone resorption. Aging was attended by increased iPTH levels (6.9 +/- 0.8 vs. 3.4 +/- 0.4 mu leq/ml; P less than 0.01) as well as increased ncAMP levels (2.48 +/- 0.28 vs. 1.12 +/- 0.21 nmol/100 ml glomerular filtrate; P less than 0.005) and decreased TmP (2.9 +/- 0.2 vs. 4.1 +/- 0.2 mg/100 ml glomerular filtrate; P less than 0.005), indicating that the increased iPTH levels reflected the biological effects of the hormone. A significant positive correlation of iPTH and ncAMP and a significant negative correlation of iPTH and TmP were observed. The Ca:Cr was increased in the older volunteers (0.10 +/- 0.02 vs. 0.05 +/- 0.01; P less than 0.05). The elderly subjects had significantly decreased daily calcium ingestion, serum phosphate and albumin, and creatinine clearance. Our findings suggest that the increased biological effects of PTH in the elderly subjects may contribute to the increases in Ca:Cr and bone loss that occur with age.

Episodic secretion of parathyroid hormone in the dog.

This study was designed to determine whether parathyroid hormone (PTH) is secreted episodically, to characterize any such rhythms, and to see whether the rhythms can be altered by stimulating PTH secretion using constant hypocalcemia. We collected blood samples at 1-min intervals for 1 h from the precava or postcava of conscious dogs during normocalcemia or induced, constant hypocalcemia. In two anesthetized normocalcemic dogs we catheterized a caudal thyroid vein and collected all the effluent blood in 1-min fractions. Immunoreactive PTH (IPTH) concentrations were determined in quadruplicate, and the results were subjected to spectral analysis. In both the precava and postcava of normocalcemic dogs, there were regular oscillations in IPTH levels with a period of 12 min (range, 10-15 min) and a +/- 14% variation about the overall mean. Although significant two- to fourfold changes in IPTH levels still occurred during constant hypocalcemia, there was no significant rhythmicity. Significant cycles in IPTH concentration (mean 8.4-min period) were observed in thyroid venous effluent plasma during normocalcemia, confirming that the phenomenon represented episodic secretion that was not affected by pentobarbital anesthesia.

Effect of Parathyroid Hormone on Vitamin D Metabolism in Osteopetrosis

Indices of vitamin D metabolism were studied before and after infusion of bovine parathyroid hormone extract in three children with osteopetrosis. Basal serum concentrations of calcium, alkaline phosphatase, and 25-hydroxyvitamin D tended to be low. Serum immunoreactive parathyroid hormone levels were in the upper normal range in two patients. A marked increase in urinary cyclic adenosine 3':5'-monophosphate (cAMP) in all patients was solely due to an increase in the nephrogenous cAMP. The basal concentration of 1,25-dihydroxyvitamin D was clearly more than the upper limit of normal range in all three patients and increased after parathyroid extract infusion in one patient. The basal serum levels of 24,25-dihydroxyvitamin D were within normal limits and tended to decrease after parathyroid extract infusion in two of the patients. Parathyroid hormone and 1,25-dihydroxyvitamin D act in concert to increase calcium resorption from bone, and the increased serum levels of both these factors may reflect lack, or unresponsiveness, of target cells in bone.

The “calcium clamp”: effect of constant hypocalcemia on parathyroid hormone secretion

This report describes acute studies of parathyroid hormone (PTH) secretion and metabolism in conscious dogs, performed with a new technique, the "calcium clamp." Bolus injections and graded infusions of either calcium (Ca) or EGTA, respectively, increase or decrease plasma Ca to desired levels in 1-2 min; rapid determination of plasma Ca permits feedback control of the infusion rates to maintain the desired Ca concentration for prolonged periods. Using this technique, we have examined the effect in five dogs of a sustained (1 h) decrease in plasma Ca from 9.6 to 7.6 mg/dl on the secretion of PTH. Plasma immunoreactive PTH (IPTH) concentration in precaval blood increased within 1 min, peaked at 4-10 min (greater than 5 times control), but thereafter declined gradually to 57% of the maximum at 60 min, despite ongoing and constant hypocalcemia. Abrupt restoration of normocalcemia caused IPTH levels to decrease with an apparent half-time of 3.0 +/- 0.3 min (mean +/- SE). Thus, external feedback-regulated control of plasma Ca is possible in experimental animals. IPTH concentrations decline from the maximum during constant hypocalcemia, a new observation that suggests that PTH secretion and/or metabolism are altered progressively by the hypocalcemia.

1,25-dihydroxycholecalciferol stimulates osteoclasts in rat bones in the absence of parathyroid hormone.

Three experiments were carried out to test the time course of effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on the ultrastructural morphometry of osteoclasts. The addition of lactose to a vitamin D-deficient diet with a high calcium and phosphate content, fed to weanling rats for 4 weeks, ensured normacalcemia and normophosphatemia and allowed thyroparathyroidectomy without ill effects. In these vitamin D-deficient thyroparathyroidectomized rats, iv injection of 50 ng 1,25-(OH)2D3 resulted in significant changes in the osteoclasts in the metaphysis of the tibiae compared to those in corresponding controls; the size of these cells, their nuclei, ruffled borders, and clear zones enlarged after 6 h and the number of osteoclasts increased after 48 h. Serum calcium and serum phosphate levels increased after 12 h in one experiment, but not in a second experiment. Serum 25-hydroxyvitamin D and serum immunoreactive parathyroid hormone levels were undetectable. Mineralization of metaphyseal bone matrix was normal, as quantified by histomorphometry. When, dependent on the mineral content in the diet, mineralization was impaired and the volume density of the osteoid seams was increased, activation of osteoclasts by 1,25(OH)2D3 was not seen until 12--24 h after injection. It is concluded that a physiological dose of 1,25-(OH)2D3 stimulates the activity of osteoclasts in the absence of parathyroid hormone.

Reduced serum levels of 1 alpha,25-dihydroxyvitamin D during long-term total parenteral nutrition.

Painful bone disease, characterized by patchy osteomalacia and inactive bone, can develop in patients treated with total parenteral nutrition for more than 3 months. Serum levels of 1 alpha,25-dihydroxyvitamin D (1 alpha, 25(OH)2D), 24,25-dihydroxyvitamin D and 25-hydroxyvitamin D were measured in seven adults and five children treated with parenteral nutrition for 9 to 60 months. Serum levels of 1 alpha, 25(OH)2D were markedly reduced, while levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were normal. Serum calcium and phosphorus levels were normal or slightly increased, and immunoreactive parathyroid hormone levels were normal or low. Renal function was normal or minimally reduced. Skeletal symptoms disappeared and serum 1 alpha, 25(OH)2D levels rose to normal in one patient when nutrient infusions were discontinued for 6 weeks. Removal of calcium from the nutrient solution for 2 to 4 days was associated with no change in serum 1 alpha, 25(OH)2D in two patients. The cause of the reduction in serum levels of 1 alpha, 25(OH)2D and its role in the pathogenesis of bone disease in these patients remain uncertain.

Regulation of calcium homeostasis in the fetal and neonatal rat.

Circulating levels of calcium (Ca) and immunoreactive parathyroid hormone (IPTH), and the renal cyclic AMP responses to PTH, calcitonin (CT), and vasopressin (VP) were measured in fetal and neonatal rats. Serum Ca increased from a mean value of 9.1 mg/dl on the 19th day of gestation to 10.9 on day 20. Circulating IPTH decreased from 875 pg/ml to 213. Serum Ca declined rapidly after birth to a nadir of 7.6 by 3 h and IPTH increased to 2,006 pg/ml, indicating that fetal and newborn parathyroids are capable of responding appropriately to changes in circulating Ca. Renal responsiveness to hormones was assessed in vitro in the presence of methylisobutylxanthine, a phosphodiesterase inhibitor. The tissue cyclic AMP response to PTH and CT (15- to 18-fold over basal) was greatest at gestational days 18 and 19, progressively declined throughout the remainder of gestation, and remained low during the first 24 h after birth (6- to 7-fold). Renal cyclic AMP response to VP remained consistently low throughout this period. The depressed renal cyclic AMP response to PTH at the time of birth may contribute to the hypocalcemia found in newborn rats.

The effect of 1α-hydroxyvitamin D 3 on renal function in normal subjects

The effects of short-term administration of 1 μg daily of 1α-hydroxyvitamin D 3 (1αOHD 3) on plasma biochemistry and renal function have been studied in six normal subjects using the 51Cr-labelled edetic acid ( 51Cr-EDTA) infusion method to measure glomerular filtration rate. 1αOHD 3 was administered for two weeks, subjects being studied before treatment, at the end of the first and second weeks of treatment and one week after stopping treatment. Mean plasma creatinine concentration rose throughout the four weeks of the study, but this change was not statistically significant. Plasma creatinine levels in fact decreased in two subjects after 1αOHD 3 administration. There was no significant change in glomerular filtration rate as measured by the 51Cr-EDTA infusion method or in endogenous creatinine clearance. Plasma phosphate levels increased in all subjects during 1α0HD 3 administration and the maximum tubular reabsorption capacity for phosphate relative to the glomerular filtration rate (Tm po4/GFR) increased in five. There were no significant changes in plasma calcium or immunoreactive parathyroid hormone levels. It is concluded that short-term administration of 1αOHD 3, 1 μg daily, has no direct adverse effect on glomerular filtration rate in subjects with normal renal function.

Renal phosphate wasting after successful kidney transplantation: 1-alpha vitamin D therapy in patients with normal parathyroid gland activity.

1 alpha-hydroxycholecalciferol was tried as a therapy for renal phosphate wasting in kidney allograft recipients with normal parathyroid gland activity. During a 3-week period of treatment we observed a significant rise in renal phosphate threshold concentrations and plasma phosphate levels paralleled by a significant decrease in serum immunoreactive parathyroid hormone levels and a significant increase in intestinal calcium absorption. It is suggested that 1 alpha-hydroxycholecalciferol acts on renal phosphate handling in a dual fashion: one is by suppression of parathyroid hormone and the other by restoration of 1,25-dihydroxycholecalciferol levels to an appropriate level.

Biochemical evaluation of patients with cancer-associated hypercalcemia: evidence for humoral and nonhumoral groups.

In 50 consecutive patients with cancer-associated hypercalcemia, we measured nephrogenous cyclic AMP, tubular phosphorus threshold, fasting calcium excretion, plasma 1,25-dihydroxyvitamin D, and immunoreactive parathyroid hormone as determined by four region-specific antiserums. Nephrogenous cyclic AMP excretion was elevated in 41 patients and suppressed in nine (means, 5.85 vs. 0.51 nmol per 100 ml of glomerular filtrate). There was no overlap between these groups. When compared with 15 patients with primary hyperparathyroidism, the group with increased cyclic AMP excretion had similar reductions in tubular phosphorus threshold; higher fasting calcium excretion (means, 0.66 vs. 0.25 mg per 100 ml of glomerular filtrate, P < 0.01); marked reductions in 1,25-dihydroxyvitamin D (means, 20 vs. 83 pg per milliliter, P < 0.001); and lower levels of immunoreactive parathyroid hormone in all four assays. The data suggest that elevated excretion of nephrogenous cyclic AMP may be a useful marker of humorally mediated cancer-associated hypercalcemia, that this type of hypercalcemia is common, that the humoral factor responsible for this syndrome is not native 1-84 parathyroid hormone, and that the various subtypes of cancer-associated hypercalcemia are biochemically distinguishable from primary hyperparathyroidism.

Plasma Levels of Immunoreactive Parathyroid Hormone in Relation to Starvation Hypocalgaemia in Dairy Cows

The hypocalcaemia caused by parturition and onset of lactation in high-production dairy cows was mimicked by subjecting cows to starvation periods before and after partus. The changes in plasma calcium, phosphate and magnesium were followed and compared with immunoreactive parathyroid hormone (iPTH) in 2 cows. During the starvation periods before partus, the cows developed hypocalcaemia with no or only small changes in the plasma concentration of magnesium. After the onset of hypocalcaemia, the concentration of iPTH increased on the average 3–4-fold and the raised hormone levels lasted about 24 h after start of refeeding. An increase in plasma phosphate occurred somewhat later than the rise in iPTH and lasted longer. After partus hypocalcaemia developed, together with smaller increases in iPTH concentration (about 2-fold). The post-partum starvation period again resulted in hypocalcaemia and raised iPTH concentrations. In conclusion, starvation and parturition induced inverse changes in plasma calcium and iPTH in dairy cows. The increases in plasma iPTH were reversible and considered secondary to the hypocalcaemia. Through the effect of paratyroid hormone, plasma calcium was normalized and phosphate concentration increased. Therefore, fatal hypocalcaemia which may occur following the course of parturition and onset of lactation is not due to impaired PTH secretion.

Evolution of serum calcium (Ca), phosphorus (P), magnesium (Mg), immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) levels in infants of diabetic mother (IDM) from 2 hours to 5 days of life

In order to study the pathogenesis of hypocalcemia in IDM, determinations of serum levels of Ca, P, Mg, iPTH and iCT were performed in 15 IDM (gestational age : 36.7 ± 1.3 weeks ; birth weight : 3755 ± 617 g) at 2, 24, 48 h and 5 days. Infants were infused with glucose and fed with human milk. Serum Ca (mg/dl, mean ± SD) decreased from 2 (8.6 ± 0.6) to 24 h (7.1 ± 1.2, p < 0.001) and remained low at 48 h and 5 days (7.5 ± 0.5). Serum Mg (mg/dl ; mean ± SD) decreased from 2 h (1.8 ± 0.2) to 24 h (1.6 ± 0.2, p <0.02) and returned to normal levels at 5 days. There was no significant change in serum P (6.3 ± 1.7 and 7.0 ± 1.2 mg/dl at 2 h and 5 days). Serum iPTH - undectable (<25 μlEq/ml) in 6 IDM and ranging from 27 to 160 μlEq/ml in 7 at 2 h (normal range in children : < 100) - showed a sustained increase until 5 days (184 ± 119 μlEq/ml, p<0.01). Serum iCT was undectable (<150 mg/ml) in 9 IDM and ranged from 150 to 180 pg/ml in 4 at 2 h ; it showed a marked increase at 24 h (536 ± 208 pg/ml, p<0.001) and by 5 days returned to mostly undectable values. Our findings indicate that hypocalcemia of IDM takes place during the first day of life ; in most IDM there is evidence for parathyroid responsiveness ; hypercalcitoninemia is present during the first 48 h. These data suggest that in IDM 1) Ca metabolism is similar to that of other premature infants and 2) hypocalcemia is mostly the consequence of the abrupt interruption of the large maternal Ca supply.

Regulation of renal adenylate cyclase by parathyroid hormone

This study reports the effects of the removal of endogenous PTH by thyroparathyroidectomy (TPTX) on the recovery of the reduced renal cAMP response to parathyroid hormone (PTH) in rats with chronically elevated PTH secondary to diets deficient in either vitamin D or calcium. After TPTX and infusion with a calcium-glucose solution of the vitamin D-deficient rat, calcium and PTH fell from 5.8 mg/dl and 2,509 pg/ml, respectively, to 4.8 mg/dl and 160 pg/ml at 48 h. There was a partial restoration of response to PTH, assessed by assay of renal cortical adenylate cyclase activity from 64% of control activity prior to TPTX to 84% of control activity at 48 h. When rats fed the diet deficient in calcium were TPTX, serum PTH fell rapidly from 2,811 to 200 pg/ml at 5 h with no further change at 21 h, whereas calcium did not change (5.3 mg/dl). PTH-dependent adenylate cyclase activity increased from 59% of control activity prior to TPTX to 87% at 5 h and 100% of control activity at 21 h after TPTX. Each diet produced similar increases in the serum level of immunoreactive PTH, and the rate of disappearance of the circulating hormone after TPTX was also similar for both groups of rats. The data indicate a slow, partial recovery of the enzyme response to PTH after TPTX of the vitamin D-deficient rat over the time period studied, whereas the recovery was rapid and complete in rats fed the diet deficient in calcium.

Effects of semistarvation on skeletal homeostasis.

Rats were semistarved over a 7-week period, resulting in a loss of 28.2 +/- 1.6% (SEM) of their initial body weights, while ad libitum fed controls gained 15.1 +/- 1.8% (SEM). Bone loss occurred and skeletal turnover was markedly reduced in the semistarved rats, as evidenced by a paucity of osteoid and osteoclasts, failure of the bone to assume a tetracycline label, and reduced urinary hydroxyproline excretion. Despite these changes, there were no alterations of serum or bone alkaline phosphatase activity with semistarvation, and analysis of tibial mineral content revealed reductions only in magnesium and sodium. The malnourished animals, however, were hypercalciuric and hypophosphatemic. Semistarvation had no effect on circulating levels of immunoreactive parathyroid hormone or 25-hydroxyvitamin D, but did result in reduced serum levels of corticosterone, insulin, and 1,25-dihydroxyvitamin D. Therefore, it appears that the effects of semistarvation on the rat skeleton are osteoporotic rather than osteomalacic, and that the defect is the consequence of reduced bone turnover. The contribution which the abnormalities of bone-regulating hormones play in the genesis of this skeletal lesion remains to be determined.

BONE DISEASE ASSOCIATED WITH TOTAL PARENTERAL NUTRITION

An unusual metabolic bone disease which developed in 11 adults receiving total parenteral nutrition (TPN) for more than 3 months was characterised by the insidious onset of bone pain which became very severe and caused considerable disability. Serum levels of calcium, phosphorus, 25-hydroxy-vitamin D, and serum immunoreactive parathyroid hormone were normal. Patchy osteomalacia with impaired mineralisation and decreased bone turnover were seen on histomorphometric analysis of bone biopsy specimens. All patients receiving long-term TPN had hypercalciuria, but no biochemical features that distinguished patients with symptoms from those without. Skeletal symptoms generally resolved 1-2 months after stoppage of the TPN infusions, despite nutritional deterioration. The pathogenesis of this syndrome remains unknown.

Failure of cimetidine to affect calcium homeostasis in familial primary hyperparathyroidism (multiple endocrine neoplasia, type 1).

Recent reports that cimetidine, a blocker of histamine H2 receptors, lowered serum calcium and/or immunoreactive parathyroid hormone (PTH) concentrations in primary or secondary hyperparathyroidism prompted us to administer the drug (300 mg, orally, every 6 h) to two patients with hyperparathyroidism accompanying familial multiple endocrine neoplasia type 1. The patients were hypercalcemic (10.9--11.2 mg/dl), hypophosphatemic (2.0--2.4 mg/dl), and hypercalciuric (greater than or equal to 410 mg/24 h), with elevated urinary cAMP and phosphate clearance and inappropriately high serum immunoreactive PTH levels. Multiple observations of these variables over 5 weeks of cimetidine treatment showed no systematic changes; in particular, serum and urinary calcium did not change, and there was no evidence of a decreased PTH effect on the kidneys. The data offer no support for the treatment of familial hyperparathyroidism with cimetidine.

Parathyroid hormone metabolism and its potential as a uremic toxin.

Secondary hyperparathyroidism is a universal complication of chronic renal failure. It has been proposed that the markedly elevated levels of immunoreactive parathyroid hormone (i-PTH) in uremia may represent a "uremic toxin" responsible for many of the abnormalities of the uremic state. Plasma i-PTH consists of a mixture of intact hormone, a single-chain polypeptide of 84 amino acids, and smaller molecular weight hormonal fragments from both the carboxy- and amino-terminal portion of the PTH molecule. The hormonal fragments arise from metabolism of intact PTH by peripheral organs as well as from secretion of fragments from the parathyroid glands. The structural requirements for the known biological actions of PTH reside in the amino-terminal portion of the PTH molecule. Carboxy-terminal fragments, biologically inactive at least in terms of adenylate cyclase activation, hypercalcemia, or phosphaturia, depend on the kidney for their removal from plasma, and thus accumulate in the circulation in chronic renal failure. It is unknown at the present time if other biological effects of these carboxy-terminal fragments may contribute to some of the biochemical alterations observed in uremia. The most significant consequence of increased PTH levels in uremia is the development of bone disease characterized by osteitis fibrosa. In addition, it would appear that PTH plays an important role in some of the abnormal electroencephalographic patterns observed in uremia. This may be due to a potential role of PTH in increasing calcium content of brain. Parathyroid hormone also has been implicated as a pathogenetic factor in many other alterations present in uremia, i.e., peripheral neuropathy, carbohydrate intolerance, hyperlipidemia, and other alterations. Unfortunately, outstanding clinical research is lacking in this field and conclusive experimental data are practically nonexistent. Further studies are necessary if one is to accept the concept of PTH being a significant "uremic toxin."