Circulating forms of parathyroid hormone detected with an immunofluorometric assay in patients with primary hyperparathyroidism and in hyperparathyroidism secondary to chronic renal failure

In patients with uremia, intact parathyroid hormone (PTH) measurement appears to overestimate the biologically active hormone in circulation. The recent description of the accumulation in these patients of a non-intact PTH form measured by the standard immunometric assays, re-opened the question. In this study we submitted serum samples from 7 patients with primary hyperparathyroidism (PHP) and from 10 patients with hyperparathyroidism secondary to chronic renal failure (SHP) to preparative HPLC in order to discriminate the molecular forms measured by our currently used immunofluorometric assay for intact PTH. The elution profile obtained with the HPLC system showed two clearly defined peaks, the first one corresponding to a lower molecular weight form, and the second to the intact PTH (1-84) form. In patients with SHP the area under the curve for the first peak (mean 29.5 percent, range 20.6 to 40.4 percent) was significantly greater than that observed for patients with PHP (mean 15.6 percent, range 5.6 to 21.9 percent). This confirms previous studies showing accumulation of molecular forms of slightly lower molecular weight, presumably PTH (7-84), in patients with SHP and, to a lesser extent, in patients with PHP. The real necessity of assays that discriminate between these two molecular forms is debatable

Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism

Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF) are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD) is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR) and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 + 7.2 years) hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 + 5.2 years) without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 + 6.6 years (mean+SD). Analysis of VDR gene polymorphism by restriction fragment lenght polymorphism (RFLP) was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5 percent BB, 42.5 percent and 37 percent bb did not differ significantly from the values obtained for group II (16 percent BB, 36 percent Bb and 48 percent bb) or for group III (10.2 percent BB, 47.6 percent Bb and 41.8 percent bb). No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurence of osteoporotic fractures with advancing age.

Radioimmunoassay of carboxyl and amino terminal fragments of parathyroid hormone for the evaluation of secondary hyperparathyroidism in chronic renal failure

1. Some parameters of calcium and phosphorus metabolism and the radioimmunoassay of plasma concentrations of both the carboxyl (COOH) (residues 53-84) and amino (NH2) terminal (residues 1-34) fragments of parathyroid hormone (PTH) were measured to evaluate secondary hyperparathyroidism in 68 patients with chronic renal falure (CRF), 34 of whon were on hemodialysis therapy. 2. The upper limits of the normal values for serum PTH-NH2 and PTH-COOH concentrations were 28 and 146 pmol/l, respectively. Patients with mild CRF (plasma creatinine (CRp) 1.2-2 mg/dl) hadh normal mean serum total calcium, low mean phosphorus, undetectable plasma levels of PTH-COOH concentration and normal fractional excretion of phosphorus (FEP). Patients with moderate CRF (CRp2.1-4 mg/dl) had normal mean serum concentrations of both total calcium and phosphorus, and elevated mean levels of both plasma PTH-COOH and PTH-NH2 associated with increased FEP. Patients with end-stage CRF (CRp > 4mg/dl) and those on hemodialysis had elevated mean serum phosphorus levels and decreased mean serum total calcium concentrations compared with those with mild and modetate CRF, and more pronounced, increases in both mean plasma PTH-COOH and PTH-NH2. 3. The logarithm of plasma PTH-NH2, but not PTH-COOH, concentration correlated positively with FEP and serum phosphorus concentration and negatively with total serum calcium concentration, while the logarithms of both PTH-NH2 and PTH-COOH levels correlated positively with CRp. 4. Calcium infusion (2 mg Kg-1 h-1 for 90 min) in eight patients with high plasma levels of PTH-NH2, and PTH-COOH resulted in a significant decrease of plasma PTH-NHL but not of plasma PTH-COOH concentration. 5. These data demonstrate increased plasma PTH levels in moderate renal failure and suggest that the assay of plasma PTH-NH2 rather than PTH-COLL is more appropriate for the evaluation of secondary hyperparathyroidism in chronic renal failure

Circulating molecular forms of parathyroid hormone in primary and secondary hyperparathyroidism

To study the circulating forms of parathyroid hormone (PTH), sera from 5 patients with primary hyperparathyroidism (PHP) and 12 patients with secondary hyperparthyroidism due the chronic renal failure (SHP) were submitted to gel filtration chromatography. The eluent samples were analyzed using two sequence-specific radioimmunoassays (RIA), one amino-terminal (NH2), the other carboxyl-terminal (COOH). The results obtained with the NH2RIA showed a single molecular form in both groups co-eluting with the intact hormone. The COOH assay identified several molecular forms with a broader distribution in the SHP patients. These results confirm the diagnostic superiority of the NH2 assay under both conditions