Parathyroid Hormone In Man Research Articles

Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism

We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk.

Conjugated linoleic acid is related to bone mineral density but does not affect parathyroid hormone in men

The relationships between conjugated linoleic acid (CLA) status, bone, body composition, and the effect of CLA on calciotropic hormones are unclear. A cross-sectional study was designed to examine the association between c9, t11 CLA status in erythrocyte membranes (RBC) and body composition. This preceded a dose-response trial investigating if c9, t11 CLA affected parathyroid hormone (PTH). It was hypothesized that (1) higher c9, t11 CLA status in RBC will be associated with a lower fat and higher bone mass and that (2) PTH will be reduced by 30% after supplementation of c9, t11 CLA. Fifty-four men (age, 19-53 years) were included in the cross-sectional analysis, of which 31 were studied in the dose-response trial and randomized to 1 of 3 groups: placebo (n = 10), 1.5 g/d (n = 11), or 3.0 g/d (n = 10) of c9, t11 CLA for 16 weeks. Men with RBC c9, t11 CLA status above the median had higher whole body bone mineral density (BMD) (1.359 ± 0.024 vs 1.287 ± 0.023 g/cm2; P = .04) and whole body lean mass (WBL) percentage (78.8% ± 0.9% vs 75.3% ± 1.0%; P = .01), whereas body mass index (24.8 ± 0.5 kg/m2 vs 27.3 ± 0.9 kg/m2; P = .01) and whole body fat mass percentage (17.3% ± 0.9% vs 21.3% ± 1.1%; P = .007) were lower. In regression analysis, RBC c9, t11 CLA status accounted for a significant proportion (r2 = 0.10) of the variation in whole body BMD (P = .03). There were no time or treatment differences among any bone or biomarkers of bone metabolism including PTH. These findings indicate that RBC c9, t11 CLA status, a reflection of long-term (~4 months) dietary CLA intake, positively relates to BMD. However, c9, t11 CLA supplementation does not appear to affect PTH in healthy men.

Factors associated with elevated or blunted PTH response in vitamin D insufficient adults

The purpose of this study was to examine factors associated with high or low parathyroid hormone (PTH) levels in relationship to vitamin D insufficiency. This was a cross-sectional study consisting of 516 healthy men and women, aged 30-85, all Caucasians with vitamin D insufficiency [serum 25(OH)D<45 nmol L(-1)]. The group was divided into quartiles by PTH levels and the highest and lowest quartiles were compared with regard to various factors likely to affect calcium metabolism. We used stepwise multivariable logistic regression to determine the independent association between PTH levels and other variables for men and women separately. We found that men in the lowest PTH quartile were significantly younger, had less energy intake, lower body mass index (BMI) and better kidney function compared with the highest PTH quartile. They had also higher ionized calcium, insulin-like growth factor (IGF1) and testosterone and were more likely to smoke. Women within the lowest PTH quartile were younger, had lower BMI and magnesium values and higher IGF1 levels and were more likely to smoke. Stepwise multivariate regression showed that IGF1, testosterone and BMI were significantly associated with PTH in men (R(2)=0.472) but smoking, BMI and kidney function in women (R(2)=0.362). Our results indicate that during vitamin D insufficiency, factors other than calcium and vitamin D may modify PTH response. These factors may be different between sexes and we have identified novel factors, IGF1 and testosterone in men which may be compensatory in nature and confirmed previous factors such as smoking, BMI and kidney function in women.

Effects of Selective Testosterone and Estradiol Withdrawal on Skeletal Sensitivity to Parathyroid Hormone in Men

Gonadal steroid withdrawal increases bone turnover and causes bone loss in men, but the underlying mechanisms have not been defined. We previously reported that gonadal steroid deprivation increases the skeletal sensitivity to the bone resorbing properties of PTH infusion in men, but it is not known whether this effect is mediated by the absence of androgens, estrogens, or both. The objective of the study was to determine the selective effects of testosterone and estradiol withdrawal on the skeletal sensitivity to PTH infusion in healthy adult men. We randomly assigned 58 healthy men between the ages of 20 and 45 yr to receive treatment with combinations of a GnRH analog, an aromatase inhibitor, and hormone add-back therapy to produce the following treatment groups: group 1 (testosterone and estradiol deficient, n = 16); group 2 (testosterone sufficient but estradiol deficient, n = 12); group 3 (testosterone deficient but estradiol sufficient, n = 14); and group 4 (testosterone and estradiol sufficient, n = 16). Twenty-four-hour PTH infusions were performed at baseline and after 6 wk of therapy. Serum N-telopeptide (NTX), C-telopeptide (CTX), osteocalcin (OC), and amino-terminal propeptide of type I procollagen (P1NP) were measured every 6 h during the PTH infusions. Serum testosterone levels fell into the castrate range in groups 1 and 3, whereas estradiol levels were similarly reduced in groups 1 and 2. Gonadal steroid levels in the replaced groups were unchanged from baseline. Serum NTX levels measured before PTH infusion did not change in group 4 (+T, +E) but increased significantly in all other groups. A similar pattern was observed in serum CTX, although the increase in group 2 (+T, -E) was not significant (P = 0.12). Preinfusion concentrations of both OC and P1NP fell in most groups, but these changes were significant in group 2 (+T, -E) for both OC and P1NP and group 4 (+T, +E) for P1NP only. Serum NTX and CTX increased during PTH infusions in all groups at all time points (P < 0.001). In the eugonadal group (group 4 +T+E), the increase in NTX was the same at wk 0 and 6, whereas in all the other groups, the PTH-induced increase in serum NTX was significantly greater at wk, 6 compared with wk 0. The same pattern emerged for CTX, although the difference in group 3 (-T,+E) was not significant (P = 0.12). Serum OC and P1NP levels fell during PTH infusions in all groups and at all time points (P < 0.001), but no significant differences were observed between wk 0 and 6 in any group. These results demonstrate that the selective suppression of testosterone, estradiol, or both hormones increases the skeletal responsiveness to the bone-resorbing effects of PTH in men. These findings underscore the importance of both androgens and estrogens in male skeletal homeostasis and suggest that changes in skeletal sensitivity to PTH may play an important role in the pathogenesis of hypogonadal bone loss in men.

Effects of Gonadal Steroid Suppression on Skeletal Sensitivity to Parathyroid Hormone in Men

Effects of Gonadal Steroid Suppression on Skeletal Sensitivity to Parathyroid Hormone in Men

Glucose intolerance is associated with altered calcium homeostasis: A possible link between increased serum calcium concentration and cardiovascular disease mortality

Serum calcium concentration has recently been shown to predict cardiovascular mortality in a large health-screening program. Since impaired glucose tolerance (IGT) is an independent cardiovascular risk factor, we examined the association between glucose intolerance and serum calcium in a population-based cohort study. To characterize this association, we measured total serum calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D (1,25-(OH) 2D) levels in a cohort of 1,071 randomly selected white individuals aged 40 to 65 years in whom an oral glucose tolerance test had been completed. In multivariate analyses, the 2-hour plasma glucose was positively associated with increasing total serum calcium and PTH in men and women after adjustment for age, obesity, season, and 25OHD. The adjusted odds ratio (OR) between increasing quintiles of total serum calcium and IGT was 1.63 (95% confidence interval [CI], 1.42 to 1.88). The OR comparing the top with the bottom quintile was 8.5 (95% CI, 4.5 to 16.0). The association with quintile of serum PTH was 1.30 (95% CI, 1.14 to 1.49). These data suggest that IGT is associated with an increase in both total serum calcium and PTH that cannot be explained by confounding by aging, obesity, or 25OHD. This relationship may explain the previously observed association between serum calcium and cardiovascular mortality. Whether this association is a manifestation of a shared cellular defect or represents a common relationship with an unknown etiologic factor are important questions for further research.

Calcium Regulating Hormones in Essential Hypertension: Importance of Gender

Alterations of calcium metabolism have been described in human essential hypertension and experimental hypertension. We investigated the interrelationship of parathyroid hormone (PTH) and 1,25(OH)2-vitamin D (1,25(OH)2D) in patients with untreated essential hypertension as compared to normotensive controls. The hypertensive subjects (n = 75; 43 men, 32 women) had a mean blood pressure of 138 +/- 8/95 +/- 5 mm Hg as compared with 120 +/- 11/80 +/- 8 in the normotensive group (n = 40; 22 men, 18 women). Serum PTH was measured with an intact molecule immunochemiluminometric assay and 1,25(OH)2D was measured with radioimmunoassay after HPLC separation. Hypertensive men had PTH levels that were 36% higher than normotensive men (5.3 +/- 2.9 v 3.9 +/- 0.8 pmol/L, P = .005). When blood pressure was analyzed as a continuous variable, there was a direct correlation between it and serum PTH in men (r = .31, P = .004). In women, by contrast, there was no difference in serum PTH between hypertensive and normotensive subjects and no relationship between blood pressure and the serum PTH concentration. Blood pressure was inversely correlated with serum phosphorus levels in both sexes (r = -0.20, P = .04). In men, the elevated serum PTH levels and depressed serum phosphorus levels would have predicted that serum 1,25(OH)2D would be higher in the hypertensive subjects. However, that was not observed, as serum 1,25(OH)2D was slightly lower in hypertensive (38.3 +/- 15.2 pg/mL) than normotensive men (42.7 +/- 11.3, P = .21).(ABSTRACT TRUNCATED AT 250 WORDS)

Age-related rise in parathyroid hormone in man: the use of intact and midmolecule antisera to distinguish hormone secretion from retention.

Circulating levels of parathyroid hormone (PTH) rise with age in normal men and women. To resolve the basis for this observation we measured iPTH in 137 normal men and women, age 23 to 85 years, using two antisera which responded to different portions of the PTH molecule. A midmolecule assay (Mid-PTH) employed antiserum NG-5, which recognizes mid- and carboxy-terminal portions of hPTH, whereas antiserum CK-67, which recognizes determinants in the 1-34 hPTH sequence, was used to measure intact PTH (NH2-PTH). Two-hour fasting urine was collected for measurement of creatinine clearance and excretion indices of phosphorus and cyclic AMP. Serum was analyzed for 25-hydroxyvitamin D (25-OHD) in addition to iPTH. Mid-PTH rose significantly with age in the 72 women (r = 0.38, p less than 0.001) and in the 65 men (r = 0.40, p less than 0.001). NH2-PTH rose with age in women (r = 0.23, p less than 0.05), but a change in men was not significant (r = 0.19, n.s.). Cyclic AMP excretion rose significantly with age in both women (r = 0.42) and men (r = 0.41), whereas phosphorus excretion rose significantly in women only (r = 0.32, p less than 0.01). 25-OHD levels were 27.5 +/- 1.3 ng/ml for women and 26.1 +/- 1.2 ng/ml for men. No change in 25-OHD was observed with age in women, and a significant decrease in men was due entirely to extremely high values in three young subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies of circulating parathyroid hormone in man by a homologous amino-terminal specific radioimmunoassay.

A homologous radioimmunoassay specific for amino-terminal portion of human parathyroid hormone(PTH) was developed in order to study the clearance of biologically active species of the hormone in the circulation in man. Characterization of the assay system with synthetic analogues of human PTH (1-34) indicated that the carboxyl-terminal region of human PTH(1-34) is an important recognition site. Plasma amino-terminal PTH levels were less than 0.3 ng/ml in all of 35 normal subjects. The levels were elevated above 0.3 ng/ml in 15 of 24 patients with primary hyperparathyroidism. In 5 patients in whom the levels were determined before and after parathyroidectomy, the elevated levels were all normalized within 60 minutes after the removal of adenomata. The disappearance of exogenous human PTH(1-34) was studied after intravenous administration in 17 patients with hypoparathyroidism. A graphical analysis of the data disclosed two major components of the disappearance curve with estimated half-disappearance time of 3 and 28 minutes respectively, suggesting that multiple mechanisms are involved in the clearance of the peptide from the circulation. These results demonstrate usefulness of homologous radioimmunoassay for human PTH(1-34) in diagnosis and management of hyperparathyroidism, as well as in studying the clearance of amino-terminal portion of PTH which is known to represent biological activity.

The effect of chronic metabolic acidosis on the end organ responsiveness to parathyroid hormone in man.

To examine the effect of prolonged metabolic acidosis on the responsiveness of end organs to PTH, we measured the changes in serum ionized calcium and the urinary excretion of calcium and phosphorus in response to a 10-h infusion of parathyroid extract (PTE) before and after 9 days of metabolic acidosis. During the first hours of PTE infusion, the increases in ionized calcium were slower during acidosis, but the maximal increments in ionized calcium (0.5 +/- 0.1 and 0.4 +/- 0.1 mg/dl, respectively) were not different. Moreover, the PTE-induced increments in the fractional excretion of phosphate during acidosis and the control study were not different. Fractional excretion of calcium before the infusion of PTE was higher in acidosis than in control (3.7 +/- 0.3% compared to 0.8 +/- 0.3%; P less than 0.01). However, at 10 h of the infusion, when the maximal effect of PTE was observed, the fractional excretions of calcium in control and acidosis were not significantly different. These data suggest that prolonged metabolic acidosis has little or no effect on bone or renal responsiveness to PTH.

Porto-systemic gradient of immunoreactive parathyroid hormone in man

Systemic and portal levels of immunoreactive parathyroid hormone (iPTH) were evaluated as possible tumor markers for intraabdominal neoplasms in 170 patients. There was no significant difference between the systemic levels of iPTH in patients with pancreatic cancer, other intraabdominal tumors, or benign abdominal conditions. The portal iPTH levels were also comparable. In all patient groups the portal iPTH levels were consistently higher than the systemic levels; the mean portal iPTH for all patients was 31.3 ± 1.3 (SEM) μ l-eq/ml, significantly higher than the systemic level of 27.2 ± 1.1 μ l-eq/ml ( P t test). We conclude that iPTH is of no diagnostic value as a tumor marker in either portal or systemic blood. Our observations suggest a site of iPTH synthesis in the gastrointestinal tract drained by the portal venous system. APUD cells of the pancreas or gut are considered possible production sites of iPTH, and liver degradation of the hormone probably occurs in man.

Parathyroid hormone clearance in man

The role of the kidney, liver, and bone and/or muscle, in the metabolic clearance of parathyroid hormone (PTH), has been examined in man. Serum was obtained from the femoral artery and the renal, hepatic, and femoral veins of nine hyperparathyroid patients undergoing selective venous catheterization. The concentration of immunoreactive parathyroid hormone (IPTH) was measured in the samples by radioimmunoassay using an antiserum predominantly specific for the aminoterminal (N-terminal) portion of the PTH molecule. Gel filtration of hyperparathyroid sera demonstrated this antiserum to measure essentially only intact PTH. The mean arteriovenous (AV) difference measured across the liver was 44%; across the kidney, 34%; and across the leg, 16%. These arteriovenous differences were all statistically significant ( p < 0.005). A significant positive correlation was found between the AV difference in IPTH across the kidney and the serum calcium concentration ( r = 0.50, p < 0.05). These studies suggest that both the liver and the kidney play major roles in the clearance of PTH in man and indicate that PTH is cleared by bone and/or muscle as well. The correlation observed between the serum calcium concentrations and the AV differences in IPTH across the kidney suggest that the rate of clearance of PTH in man may be modulated by changes in the concentration of serum calcium.

Control of Renal Tubular Phosphate Reabsorption by Parathyroid Hormone in Man

1. The maximum tubular reabsorption capacity for phosphate relative to glomerular filtration rate (Tm,P/GFR) was found to range from 0·8 to 1·5 mmol/l in 32 normal fasting subjects. In 14 patients with primary hyperparathyroidism and five patients with hyperparathyroidism secondary to vitamin D deficiency or malabsorption values ranged from 0·2 to 0·8 mmol/l. 2. Plasma parathyroid hormone concentrations measured by an immunoradiometric technique ranged from &lt;0·15 to 0·9 ng/ml in the normal subjects and from 0·5 to 10 ng/ml in the patients with hyperparathyroidism. There was no correlation, however, between plasma parathyroid hormone and Tm,P/GFR in either normal or abnormal groups. 3. Plasma parathyroid hormone was lower in 11 out of 13 patients with primary hyperparathyroidism 3 or 4 weeks after tumour removal than immediately before the operation. In all cases there was a rise in Tm,P/GFR, though not all values were normalized. 4. Changes in plasma parathyroid hormone, Tm,P/GFR and plasma and urinary cyclic AMP concentrations were measured during infusion of bovine parathyroid hormone into normal fasting subjects. Phosphate reabsorption fell markedly in response to low doses of parathyroid hormone (0·5 i.u. h−1 kg−1), higher doses (4 i.u. h−1 kg−1) producing little additional change in Tm,P/GFR despite large changes in cyclic AMP excretion. At the highest doses used (8 i.u. h−1 kg−1) apparent saturation of the renal adenylate cyclase occurred. During an infusion of hormone, 0·25 i.u. h−1 kg−1 over 3 h, a fall in Tm,P/GFR was recorded at concentrations of immunoreactive parathyroid hormone within the normal range for endogeneous hormone. At such concentrations it was not possible to detect significant changes in either plasma or urine cyclic AMP. 5. It is concluded that parathyroid hormone is an important regulator of renal phosphate handling under normal physiological conditions. Such a regulatory process has been implicated in the control of vitamin D metabolism.

Reversible Resistance to the Renal Action of Parathyroid Hormone in Man

1. Normal subjects showed a highly reproducible, rapid increase in plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) after an intravenous injection of 200 MRC units of highly purified bovine parathyroid hormone. 2. No significant increase in plasma cyclic AMP was observed after administration of bovine parathyroid hormone to patients with severe chronic renal failure. 3. Even when renal function was not impaired, some patients with primary hyperparathyroidism, who had high concentrations of endogenous parathyroid hormone, showed resistance to bovine parathyroid hormone and when this was injected intravenously it caused only a small increase in plasma cyclic AMP. This resistance was reversible since there was marked improvement in the response after parathyroidectomy, when endogenous parathyroid hormone concentration had fallen. 4. It was possible to reproduce this resistance to the hormone by intravenous infusion of bovine parathyroid hormone into normal subjects. When the hormone (1000 MRC units) was infused over 2 h, after an initial increase there was a progressive decline in plasma cyclic AMP concentration and a fall in urinary cyclic AMP excretion. The response to a standard test stimulus (200 MRC units of bovine parathyroid hormone given as a rapid intravenous injection) was examined at intervals after 1000 units of bovine parathyroid hormone had been infused. Initially, the response was severely impaired; at 4 h, partial recovery had occurred and, 24 h after the infusion, recovery of the response was complete. The resistance was therefore reversible. Infusion of the amino-terminal peptide, fragment 1-34, gave the same effect as infusion of intact hormone. Region-specific assays for the hormone were used to show that the concentration of immuno-assayable hormone remained high during the infusions. 5. The mechanism of this reversible resistance to parathyroid hormone remains to be elucidated; it seems unlikely that circulating hormone fragments could account for the prolonged impairment in the responsiveness to the intact hormone. It is possible that alteration in the formation, intracellular degradation or, perhaps, release of cyclic AMP from the cells, is the cause. Changes in the characteristics of the hormone receptor sites might also explain the phenomenon.

On the lipolytic action of parathyroid hormone in man

An investigation was carried out to determine whether bovine PTH stimulates lipolysis in human fat tissue, whether this action is mediated by cyclic adenosine 3′,5′-monophosphate and whether the N-terminal 1–34 peptide of bovine PTH is responsible for the lipolytic effect. Studies were also performed to determine if parathyroid extract (PTE) produces lipolysis in normal subjects and in patients with pseudohypoparathyroidism in whom there is a defect in the adenylate system in response to PTH in the renal cortex and presumably in the skeletal system as well. It was found that highly purified bovine PTH in the concentration range between 10 −9, M and 10 −5, M stimulated lipolysis in vitro by human fat in a dose-dependent manner. Significant increases in glycerol production were observed at concentrations of PTH as low as 10 −9, M and maximal increases were seen at 10 −6, M. The hormone significantly increased the concentration of cyclic adenosine 3′,5′-monophosphate in fat tissue. The synthetic N-terminal 1–34 peptide of bovine PTH was as effective as the native hormone in stimulating glycerol production at a concentration of 10 −9, M – 10 −6, M. PTE, 100 mU per kg per min for 30 min given intravenously, produced transient increases in the concentration of plasma free fatty acid in each of eight normal subjects, three patients with hypoparathyroidism and eight patients with pseudohypoparathy-roidism. Purified bovine PTH also increased plasma free fatty acid in each of two normal subjects. It is concluded that PTH stimulates lipolysis in human subcutaneous fat, that this action of the hormone is mediated through cyclic adenosine 3′,5′-monophosphate and that the N-terminal 1–34 peptide portion of the hormone is responsible for this lipolytic action. Further, PTE stimulates lipolysis in vivo in man. There appears to be no defect in the adenylate cyclase system in the fat cell in response to PTH in patients with pseudohypoparathyroidism.

Anin vivo experimental model for the study of resistance to the renal action of parathyroid hormone in man

We have previously shown that intravenous administration of highly purified bovine parathyroid hormone (BPTH) to normal subjects results in rapid changes in plasma concentration and urinary excretion of adenosine 3′,5′-cyclic monophosphate (cyclic AMP). These changes appear to be due to the effects of the hormone on the kidney (3), presumably in stimulating adenylate cyclase of the renal cortex (2). We have also shown that resistance to the action of the hormone can occur; patients with severe chronic renal failure (creatinine clearance 25 pmol/ml) and lower excretion rates than normal (< 1.8 nmol/min). No change in plasma cyclic AMP and minimal increase in urinary excretion of the nucleotide occurred when 200 units of BPTH were administered as an intravenous injection to these patients. In some patients with primary hyperparathyroidism and normal renal function, impairment in the response to BPTH was observed. This appeared to be associated with high concentrations of endogenous parathyroid hormone. However, this resistance to BPTH was reversible since marked improvement in the response to exogenous hormone was seen after removal of the parathyroid adenoma, when the concentration of endogonous hormone had fallen (4).

Effect of acute and chronic metabolic acidosis on serum immunoreactive parathyroid hormone in man

The effects of acute and chronic metabolic acidosis on serum immunoreactive parathyroid hormone (iPTH) were studied. Acute metabolic acidosis induced by administration of ammonium chloride (NH4Cl) produced a barely detectable increase in serum iPTH. Chronic NH4Cl administration produced a marked elevation of serum iPTH that was well correlated with the magnitude of acid-induced hypercalciuria but not with the degree of acidosis. Acetazolamide administration produced an equivalent degree of acidosis, but hypercalciuria was minimal and iPTH increased only marginally. Methionine administration caused moderate hypercalciuria and a significant but moderate increase in iPTH. Chronic NH4Cl-induced acidosis produced no hypercalciuria when dietary sodium intake was rigidly restricted, and under these conditions serum iPTH remained normal. When sodium intake was suddenly increased while maintaining the acid load, hypercalciuria appeared and was followed by progressive rise in serum iPTH equivalent to that observed during chronic NH4Cl-induced acidosis in subjects consuming salt ad lib. These results indicate that chronic acidosis elevates iPTH mainly by producing hypercalciuria and that acidosis itself is not a primary stimulus to PTH secretion.

Metabolism of parathyroid hormone: Physiologic and clinical significance

Recent findings concerning the metabolism of parathyroid hormone (PTH) and the heterogeneity, or multiple forms, of circulating PTH have spurred widespread investigation of the nature, origin and physiologic significance of the circulating fragments of PTH. Studies of endogenous PTH in man and cow, and of bovine PTH administered to dogs, have been performed utilizing sensitive, specific immunochemical and radiochemical technics. These studies indicate that fragments of the hormone are responsible for most of the immunoreactive PTH (iPTH) detected in the general circulation and that hormonal cleavage occurs after secretion but not in the intravascular space. Studies of parathyroid effluent plasma have established that the principal secretory product of the parathyroid glands is intact hormone; whether other immunoreactive forms of the hormone are also secreted from the gland is uncertain. In all species studied, the predominant form of circulating hormone is the large fragment consisting of the middle and COOH-terminal portions of the molecule; it lacks more than a third of the NH 2-terminal portion. Because the NH 2-terminal portion of the hormone sequence is required for biologic activity, this large fragment must be biologically inactive. Analysis of cleavage patterns of intact hormone indicates that an NH 2-terminal fragment containing the necessary structural requirements for biologic activity may be produced by this cleavage. This may be of considerable physiologic significance regardless of whether this NH 2-terminal fragment circulates or is present only outside the intravascular space. Although the significance of hormone metabolism is still unclear, the present findings are helpful in the application and interpretation of radioimmunoassays for PTH.

Parathyroid Hormone in Human Plasma

Antigenic recognition of four anti-bovine parathyroid hormone antisera was characterized by their reactivity with bovine hormonal fragments (1-34, 1-13, 14-34, 19-34, 53-84) and human hormone extracted from parathyroid adenomas. All antisera were found to have antibody populations which recognized more than one antigenic determinant and all antisera differed in their specificity and reactivity for the fragments of bovine hormone. By modification of two antisera, GP-1 and GP-133, by preincubation with excess concentrations of 1-34 or 53-84 fragments, antigenic recognition was restricted to defined regions of the hormonal sequence.When assays using these modified antisera were applied to the study of hormones extracted from glands, greater immunochemical similarities were seen between bovine and human parathyroid hormone using assays that were specific for the measurement of amino-terminal portions of the hormones than of the carboxy-terminal portions.When assays using these antisera were applied to the study of endogenous parathyroid hormone in human plasma, the immunoreactive hormone in the general circulation was shown to substantially lack an amino-terminal portion of the sequence of the intact hormone, including an antigenic determinant requiring all or some of the 14-19 region. This deletion accounts, at least in part, for the immunochemical heterogeneity of plasma parathyroid hormone in man. Radioimmunoassay of fractions of peripheral plasma subjected to gel filtration confirms that the dominant form of the immunoreactive hormone in the general circulation of man is a hormonal fragment that is totally devoid of amino-terminal reactivity. Because of this deletion, it can be concluded that most of the immunoreactive parathyroid hormone in the general circulation of man must be biologically inactive.

Evidence for parathyroid failure in magnesium deficiency.

Serum immunoreactive parathyroid hormone (IPTH) was low to nondetectable in spite of hypocalcemia in a patient with chronic magnesium deficiency. The administration of magnesium led to parallel increases in serum IPTH, serum calcium, and renal phosphate clearance. These findings support the view that magnesium depletion may result in impaired synthesis or release of parathyroid hormone in man, or both.