Immunoreactive Parathyroid Hormone Levels Research Articles

Evidence for Mild Reversible Hyperparathyroidism in Distal Renal Tubular Acidosis

Circulating levels of immunoreactive parathyroid hormone were measured in six patients with distal renal tubular acidosis before and during two years of long-term alkali therapy. Parathyroid hormone level was elevated modestly in five patients before treatment and fell, gradually during treatment to normal or near normal levels. Urine calcium level fell, serum calcium level rose, and renal phosphorus reabsorption rose during treatment. Stopping treatment briefly caused reversion of serum parathyroid hormone and calcium levels and renal phosphorus reabsorption to pretreatment values within eight weeks. Mild hyperparathyroidism is present in renal tubular acidosis and reverses with alkali treatment.

CONGENITAL HYPERPERATHYROIDISM /HPT/AND VITAMIN D DEFICIENCY SECONDARY TO MATERNAL HYPOPARATHYROIDISM /HoPT/

A new case of congenital HPT secondary to maternal HoPT is described. Maternal HoPT appeared 4 days after thyroidectomy performed for a cold nodular goiter during the first month of pregnancy:hypocalcemia /< 80 mg/1/and low serum immunoreactive parathyroid hormone levels /iPTH/were present. Diagnosis of neonatal HPT was based on elevated iPTH levels and evidence of long bones demineralisation and sub-periosteal resorption of the metaphyses. Plasma Ca ranged from 77to 88mg/l and plasma P from 47to 52mg/l.IV Ca load /15mg/kg/3h/ lowered the iPTH levels from 270to 100μlEq/ml /N<c50 μlEq/ml/. Low plasma levels of 25 OHD/ < 4ng/ml/were found at the age of 41days in spite of previous administration of 600u of vit.D for 12days. At the age of 3 months, 15mg of vit.D were given orally: iPTH levels which remained elevated 3weeks before /210μlEq/ml/were found to be normal 8days after this vit.D load/37 μlEq/ml/. It is suggested that in congenital HPT secondary to maternal HoPT, hyperparathyroidism increases the baby needs for vit D. This results in a state of vit D deficiency which in turn maintains a parathyroid hyperactivity. Thus high doses of Vit.D appears to be the treatment of choice in this congenital HPT.

Regulation of circulating parathyroid hormone levels: normal physiology and consequences in disorders of mineral metabolism.

A review of the chemistry, the biosynthesis, the regulation of the secretion and the metabolism of parathyroid hormone (PTH) provides a background to problems related to the determination of immunoreactive PTH levels in the blood of normal subjects and of patients suffering from disorders of mineral metabolism. Immunoreactive PTH measurements have to be interpreted in the light of the immunoheterogeneity encountered and the occurrence of several circulating PTH species with different molecular weights and immunological properties.

Skeletal Resistance to Endogenous Parathyroid Hormone in Patients with Early Renal Failure. A Possible Cause for Secondary Hyperparathyroidism

Studies were carried out to evaluate whether skeletal resistance to acute increments in endogenous parathyroid hormone exists in patients with mild to moderate renal insufficiency. Hypocalcemia was induced with the infusion of ethyl-enediamine-tetra-acetate (EDTA) in 10 normal subjects and 13 patients with mild renal failure. After the induction of hypocalcemia, the concentration of serum calcium increased gradually and reached preinfusion levels by 22 h in the normal subjects; in contrast, the levels of serum calcium in patients with mild renal insufficiency were significantly lower than the preinfusion values even at the end of 26 h following the EDTA infusion. This delayed recovery occurred despite significantly higher levels of serum immunoreactive parathyroid hormone (IPTH) in the patients than in the normal subjects. The increase in the levels of IPTH reflect elevations in the concentrations of biologically active hormone since urinary cyclic AMP increased significantly. Urinary calcium excretion following the EDTA infusion was not different in both groups and, therefore, could not account for the delayed recovery of serum calcium values in the patients with renal insufficiency. These results indicate that secondary hyperparathyroidism exists early in patients with renal failure and such patients have exaggerated parathyroid hormone secretion in response to acute hypocalcemia. The data are consistent with the concept that skeletal resistance to increments in endogenous parathyroid hormone is present in such patients. This abnormality is, at least partly, responsible for the hypocalcemia and secondary hyperparathyroidism of renal insufficiency.

Pseudohypoparathyroidism: Disappearance of the resistance to parathyroid extract during treatment with vitamin D

Serum immunoreactive parathyroid hormone (iPTH) levels were increased in a 15 year old girl with pseudohypoparathyroidism, hypocalcemia, hyperphosphatemia, and minimal phosphaturic and absent hypercalcemic responses to exogenous parathyroid extract (PTE). Following normalization of the serum calcium concentration with vitamin D, serum iPTH and phosphate concentrations returned to the normal range, and phosphaturia could be clearly stimulated and hypercalcemia induced by PTE. On the other hand, the urinary cyclic adenosine 3′,5′-monophosphate (cyclic AMP) excretion could not be stimulated, suggesting that in this case, there appears to be no relationship between the urinary excretion of cyclic AMP and the phosphaturic effect of PTE. The minimal phosphaturic effect and the lack of hypercalcemic effects of PTE in untreated pseudohypoparathyroidism can be explained by the secondary hyperparathyroidism causing elevated iPTH levels rather than by a defect at the level of the receptor sites. A requirement of pharmacologic amounts of vitamin D per se, however, for the responsiveness of patients with pseudohypoparathyroidism to PTE cannot be ruled out.

Hypomagnesemic Hypocalcemia Secondary to Renal Magnesium Wasting

Two patients developed severe hypomagnesemia, hypocalcemia, and hypokalemia as a result of renal wasting of magnesium and potassium shortly after being treated with large doses of gentamicin. When therapy with gentamicin was discontinued renal loss of magnesium and potassium ceased, and serum calcium, magnesium, and potassium returned toward normal. Serum immunoreactive parathyroid hormone levels were inappropriately low during the episodes of hypocalcemia. Both patients represent examples of hypomagnesemic hypocalcemia induced by inappropriate magnesuria, possibly caused by gentamicin. These observations suggest that serum calcium, magnesium, and potassium should be monitored during gentamicin therapy.

The diagnostic value of a radioimmunoassay for parathyroid hormone in human serum.

A radioimmunoassay for the measurement of immunoreactive parathyroid hormone (PTH) in human serum is described. The assay is based on the ability of human parathyroid hormone (h-PTH) to compete with 125I-labelled bovine parathyroid hormone (b-PTH) for binding to a guinea-pig antiserum directed against b-PTH. The linear part of the standard curve was parallel with dose response curves for anti-b-PTH serum reacting with dilutions of sera from patients with primary hyperparathyroidism and from h-PTH purified from human parathyroid adenomas, indicating that levels of immunoreactive PTH could be expressed as b-PTH equivalents. The range in 62 healthy blood donors was 1.1-2.5 ng b-PTH Eg./ml. The reproducibility was satisfactory, and the sensitivity permitted the measurement of PTH concentrations down to 0.8 ng b-PTH Eg./ml. No crossreaction with h-CT, h-STH or h-ACTH was observed. The clinical value of the assay has been considered in a number of patients with various disorders of calcium metabolism, diagnosed and treated conventionally. About 80 per cent of patients with primary hyperparathyroidism had elevated PTH levels on one or more occasions before surgery. In patients with chronic renal failure of other aetiology than primary hyperparathyroidism the levels were usually far higher. Patients with primary hyperparathyroidism and increased S-creatinine had higher PTH levels than those with normal S-creatinine. After parathyroidectomy all previously increased PTH levels became normal or low. High PTH concentrations were found in 3 patients with normocalcaemic hyperparathyroidism who at operation were shown to have parathyroid adenomas. However, in normocalcaemic patients there were also some falsely elevated PTH values which limit the diagnostic value of the assay in this group of patients. Low PTH values were observed in patients with hypercalcaemia due to malignant disorders, indicating that PTH determination may be of some value in the diagnosis of patients with hypercalcaemia of unknown origin.

Ultrastructural and Biochemical Evaluation of Parathyroid Function of Pregnant Cows Administered Disodium Ethane-l-Hydroxy-1, 1-Diphosphonate (EHDP) and Fed a Low Calcium Prepartal Diet

EHDP is a synthetic analogue of pyrophosphate and a potent inhibitor of bone resorption. The objective of this investigation was to evaluate the effects of EHDP on the ultrastructure and function of parathyroid glands stimulated by feeding a low calcium diet to pregnant cows.Two groups of 3 pregnant cows each were fed a low calcium (5 gm/day) diet supplemented with phosphorus (25 gm/day) for approximately 70 days prepartum and up to 2 days postpartum. Cows of one group received a daily subcutaneous injection of EHDP (4 mg/kg/day). Cows of the second group received no EHDP. At parturition cows fed the low calcium diet remained clinically normal and had serum calcium and phosphorus values of 8.05 and 4.3 mg/100 ml, respectively (Fig. 1). EHDP-treated cows developed hypocalcemia (5.44 mg/100 ml), hypophosphatemia (1.49 mg/100 ml), and clinical signs pathogonomic for parturient paresis. Plasma immunoreactive parathyroid hormone (iPTH) levels were as high or higher both prepartum and postpartum than in cows only fed the low calcium diet.

Pseudohypoparathyroidism type II: restoration of normal renal responsiveness to parathyroid hormone by calcium administration.

ABSTRACT A patient with the clinical features of pseudohypoparathyroidism and skeletal resistance to parathyroid hormone is described. The renal defect was similar to that previously reported in Pseudohypoparathyroidism Type II, e.g., increase in the urinary excretion of cyclic AMP in response to parathyroid hormone administration but no rise in the urinary excretion of phosphate. Further studies demonstrated that the renal response could be restoredto normal by the administration of calcium with or without elevated levels of endogenous immunoreactive parathyroid hormone. The renal defect in pseudohypoparathyroidism Type II may be related to abnormal permeability of the tubular cells to calcium in response to parathyroid hormone or cyclic AMP.

Parathyroid function in the alloxan diabetic rat.

Serum immunoreactive parathyroid hormone (IPTH) was measured in control and in alloxan-induced diabetic rats ingesting a normal calcium diet and in control rats ingesting a low calcium diet. Serum IPTH levels in controls ingesting the low calcium diet were three times those of controls on the normal calcium diet. Serum IPTH in diabetic rats was double that in controls. Therefore,the diabetic rat manifests an appropriate parathyroid response to diminished calcium absorption. The deficiency of duodenal calcium binding protein and the duodenal calcium malabsorption previously observed in diabetic rats are not the result of a defect in PTH regulation of vitamin D metabolism. (En-docrinology95: 749, 1974)

Short-term effects of 1,25-dihydroxycholecalciferol on disordered calcium metabolism of renal failure

The short-term effects of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on disordered calcium metabolism were studied in 15 trials in patients with advanced renal failure and, for comparison, in 20 trials in normal persons. The steroid was given orally in doses of 0.027, 0.14, 0.68 and 2.7 μg/day for 7 to 15 days. Calcium absorption and urinary calcium increased after the administration of 0.14 to 2.7 μg/day in normal subjects, but 0.68 to 2.7 μg/day was needed to augment calcium absorption in the patients with uremia. Fecal calcium decreased significantly during metabolic balance studies. Serum calcium increased markedly only in the patients with uremia, and hypercalcemia occurred at a dosage level of 2.7 μg/day. With the increase in serum calcium, the blood levels of immunoreactive parathyroid hormone (iPTH) decreased. Urinary calcium increased substantially only in normal subjects. The steroid corrected the “vitamin D resistance” of uremia, suggesting that the renal production of 1,25-(OH)2D3 in uremia is defective.

Symptomatic skeletal disease in non-terminal renal failure.

Sixteen patients suffering from stable non-terminal renal failure and complaining of skeletal symptoms were studied. Fifteen of the patients were female and all gave a history of analgesic abuse. All patients had radiological, bacteriological or histological evidence of pyelonephritis. All patients had histological osteomalacia and in fifteen this lesion was considered severe. Eight patients showed histological evidence of osteitis fibrosa; this lesion was severe in two patients. These patients had a significantly lower mean serum calcium level, a significantly lower mean serum bicarbonate level, a significantly higher mean serum alkaline phosphatase level and a significantly higher mean serum immunoreactive parathyroid hormone level than a group of uræmic patients not complaining of skeletal symptoms.

Diseases associated with calcium pyrophosphate dihydrate crystal deposition: A controlled study

A comparison of the frequency of hypertension, diabetes mellitus, urate gout, hemochromatosis, azotemia and hyperparathyroidism in 28 pseudogout patients and 22 control subjects with osteoarthritis of the large weight-bearing joints failed to provide statistical evidence of intergroup differences. This may be related to the relatively small number of patients studied and the relatively low incidence of the associated diseases as three patients had findings suggestive of mild, clinically inapparent hemochromatosis, three had histologically proved or chemical hyperparathyroidism and three had urate gout in the pseudogout group. None of the control subjects had hemochromatosis, two had urate gout, and one patient with osteoarthritis had chemical hyperparathyroidism. Immunoreactive parathyroid hormone (PTH) levels were increased in most patients in both groups; serum calcium levels correlated significantly with the PTH values, as did roentgenographic evidence of knee joint degeneration in the women patients. If the associated diseases are causally related to calcium pyrophosphate crystal deposits, these findings suggest that pseudogout, like urate gout, has multiple etiologies. A hypothesis relating the possible effects of sustained low grade hyperparathyroidism to the genesis of the articular lesions has been advanced.

PARATHYROID HORMONE REGULATION IN CHILDREN WITH CHRONIC RENAL DISEASE

The regulation of immunoreactive parathyroid hormone (IPTH) levels has been examined in three groups of children. I. In 5 children with renal insufficiency, 4 had renal osteodystrophy. Calcium infusions of 4 mg/kg/hour for 4 hours reduced IPTH to less than 40% of the elevated baseline levels. Following glucagon administration, which lowered serum calcium in 4 of 5 children, IPTH levels in 3 increased transiently by 20%. These changes indicated that these children had suppressible parathyroid function (non-autonomous). II. In 4 children being hemodialyzed against a bath with Ca++ concentration ranging from 7-8 mg/dl,the (Ca++) of the venous line progressively rose. It also always exceeded that of the arterial line, indicating net calcium absorption by the body. IPTH levels fell as serum(Ca++) increased. These changes indicate that the use of a high(Ca++) in the dialysis bath is useful in suppressing parathyroid hyperactivity. III. Changes in (Ca++), (PO−4) and IPTH were determined following 5 episodes in 4 children of acute transplant rejection being treated by 15 mg/kg of IV prednisolone.(Ca++) fell in all 5. Changes in IPTH levels were not consistent and failed to parallel changes in (Ca++). These changes suggest that high doses of steroids may acutely affect serum (Ca++), independently of their effect on the parathyroid glands. Supported by NIH grants RR-5624, RR-75 and HD-04840.

Hypocalcemia in magnesium-depleted dogs: Evidence for reduced responsiveness to parathyroid hormone and relative failure of parathyroid gland function

The effect of magnesium depletion on serum calcium and magnesium and on the response to the infusion of parathyroid extract (PTE) was evaluated in nine adult mongrel dogs during a control period, magnesium depletion, and following magnesium repletion. Magnesium depletion was associated with a fall in serum magnesium and calcium, and both returned to normal with magnesium repletion. There was a significant direct correlation between the serum concentration of calcium and magnesium in the magnesium-deficient state. During magnesium depletion, there were significant calcemic and phosphaturic responses to PTE, but these effects were reduced; the impaired responsiveness of the skeleton and the kidney to PTE returned to normal after magnesium repletion. Serum levels of immunoreactive parathyroid hormone, measured in two animals during the control and magnesium depletion state, remained stable during magnesium depletion, despite the hypocalcemia present. These results indicate that both impaired responsiveness of the skeleton to parathyroid hormone and reduced secretion of the hormone in response to hypocalcemia exist in dogs with magnesium depletion. Each of these factors probably contributes to a reduced level of serum calcium in magnesium depletion, and they may compound each other and hence aggravate the degree of hypocalcemia.

FUNCTIONAL HYPOPARATHYROIDISM IN NEONATAL HYPOCALCEMIA OF INFANT OF DIABETIC MOTHER

In neonatal hypocalcemia of infants of diabetic mothers (IDM), there is associated hyperphosphatemia and calcemic responsiveness to parathyroid extract, consistent with possible hypoparathyroidism. The serum immuno-reactive parathyroid hormone (PTH) levels of 28 IDM (15 class A; 13 B,C,D) were studied serially in the first 3 days of life to determine the PTH responses to changes in serum Ca. In class A IDM serum Ca fell from 10.35 mg% at birth to 7.84 at 24-48 hours and rose to 8.86 at 72 hours. In class B,C,D IDM the corresponding values were 9.6, 6.5 and 7.1. Serum ionized Ca fell in all IDM (4.2 to 2.5 to 3.2 mg%), serum Mg was unchanged, and serum P rose (6.1 to 7.0 to 8.3 mg%). Changes in serum PTH were not correlated with changes in serum Ca from birth to 24-48 hours(r-0.09). In class A IDM at 24-48 hours serum PTH was 134±14% of cord PTH values (paired t, p-0.06) and at 72 hours was 124±13%. In class B,C,D IDM, in spite of significant falls in serum Ca, PTH was correspondingly 118±16% (not signifleant)and 105±12%. Serum Ca at 72 hours was positively correlated(r-0.67, p-0.05) and serum P negatively correlated (r-−0.75, p<0.05) with PTH responsiveness at 24-48 hours. The present data are consistent with the thesis that functional hypoparathyroidism is a pathogenetic mechanism for neonatal hypocalcemia in infants of diabetic mothers.

PARATHYROID HORMONE SECRETION IN DISORDERS OF CALCIUM METABOLISM STUDIED BY MEANS OF EDTA

ABSTRACT In 22 of 28 cases of primary hyperparathyroidism (PHP) the rise in the serum immunoreactive parathyroid hormone (IRPTH or PTH) level observed in response to lowering of the serum calcium by EDTA, exceeded that obtained in 8 control subjects. In 5 of these 22 patients who were studied again after parathyroidectomy the supranormal response was abolished. Fifteen of these 22 hyper-responsive PHP patients had basal IRPTH levels not exceeding the highest level in the controls and that of other groups of patients investigated (idiopathic hypercalciuria, non-parathyroid hypercalcaemia, operated PHP). Fourteen of the 22 hyper-reactive patients with PHP did not show hypocalcaemia during the infusion of EDTA. The extent of the release of PTH elicited by EDTA in cases of PHP does not as yet allow a prediction of the amount of pathological parathyroid tissue present, although all the PHP patients showing a normal release of PTH had a relatively small mass of parathyroid tissue (up to about 1 g) subsequently removed. In 9 cases of nephrolithiasis (8 of whom had idiopathic hypercalciuria) and in 7 cases of non-parathyroid hypercalcaemia, a normal PTH release was found.

A case of renal tubular acidosis with secondary hyperparathyroidism, lipemia and aminoaciduria with review of Japanese literature.

A 44 year old female with renal tubular acidosis, osteomalacia, lipemia and aminoaciduria is reported. Mild hypocalcemia, marked hypophosphatemia and elevated serum alkaline phosphatase were associated with high serum immunoreactive parathyroid hormone level, which was promptly suppressed by intravenous calcium infusion, indicating secondary hyperparathyroidism. Among 56 cases of renal tubular acidosis so far reported in Japan, patients in the first decade predominated and the male to female ratio was 1 to 3. Osteomalacia was found in 19 and hypergammaglobulinemia in 11 but aminoaciduria was seen only in 2. Marked lipemia was the most unusual aspect in the present case.

Pseudoidiopathic hypoparathyroidism: Hypoparathyroidism with ineffective parathyroid hormone

A patient with hypoparathyroid manifestations—hypocalcemia, hyperphosphatemia, chronic tetany and cataracts—was found to have normal to high levels of serum immunoreactive parathyroid hormone (i-PTH) in a number of assay systems; clinical features of pseudohypoparathyroidism were lacking. Although the bones appeared undermineralized roentgenographically, evidence of rickets and osteomalacia was absent; other causes of hypocalcemia were eliminated by appropriate determinations. Cortical bone dynamics indicated a low bone formation rate and undermineralization, whereas intravenously administered calcium was avidly retained. Calcium balance was negative despite hypocalcemia, primarily because of fecal losses. Gastrointestinal radiocalcium absorption was diminished but correctable by administration of large amounts of vitamin D 2 or magnesium. Magnesium deficiency and gastrointestinal malabsorption as a cause of the findings were excluded (normal fat, xylose and lactose absorption). Renal responsiveness to exogenous PTH was demonstrated by increased cyclic adenosine 3′5′monophosphate (AMP) excretion, decreased mean maximal tubular reabsorption rate for phosphate, and phosphaturia. High levels of i-PTH, which rose markedly in response to phosphate infusion, were found in one radioimmunoassay system; in another system, these same serum specimens showed normal concentrations of i-PTH and no response to phosphate infusion. These data indicate that the patient has ineffective endogenous parathyroid hormone, presumably because of a defect in conversion of secreted proparathyroid hormone into an active form. The varying concentrations in different radioimmunoassay systems support this thesis. The syndrome resembles idiopathic hypoparathyroidism clinically and pseudohypoparathyroidism in that i-PTH is measurable; hence it is suggested it be called pseudoidiopathic hypoparathyroidism.

Evidence for secondary hyperparathyroidism in idiopathic hypercalciuria.

Circulating levels of immunoreactive parathyroid hormone (PTH) were measured in 40 patients with idiopathic hypercalciuria (IH) before and during reversal of hypercalciuria with thiazide, and in four normal subjects before and during induction of hypercalciuria with furosemide. 26 patients with IH had elevated serum PTH levels. The remaining patients had normal levels. Although the correlation was not complete, high PTH levels were generally found in patients who had more severe average urinary calcium losses. When initially elevated. PTH levels fell to normal or nearly normal values during periods of thiazide administration lasting up to 22 months. When initially normal, PTH levels were not altered by thiazide. Reversal of hyperparathyroidism by thiazide could not be ascribed to the induction of hypercalcemia, since serum calcium concentration failed to rise in a majority of patients. Renal hypercalciuria produced by furosemide administration elevated serum PTH to levels equivalent to those observed in patients with IH. The findings in this study help to distinguish between several current alternative views of IH and its relationship to hyperparathyroidism. Alimentary calcium hyperabsorption cannot be the major cause of IH with high PTH levels, because this mechanism could not elevate PTH. Idiopathic hypercalciuria cannot be a variety of primary hyperparathyroidism, as this disease is usually defined, because PTH levels are not elevated in all patients and, when high, are lowered by reversal of hypercalciuria. Primary renal loss of calcium could explain the variable occurrence of reversible hyperparathyroidism in IH, since renal hypercalciuria from furosemide elevates serum PTH in normal subjects. Consequently, a reasonable working hypothesis is that IH is often due to a primary renal defect of calcium handling that leads, by unknown pathways, to secondary hyperparathyroidism.