Age-related rise in parathyroid hormone in man: The use of intact and midmoleeule antisera to distinguish hormone secretion from retention

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Abstract
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 midmoleeule 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 < 0.001) and in the 65 men (r = 0.40, p < 0.001). NH2-PTH rose with age in women (r = 0.23, p < 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 < 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. Endogenous creatinine clearance decreased with age in women (r = -0.65, p < 0.001) and men (r = -0.46, p < 0.001). In women, creatinine clearance correlated significantly with Mid-PTH (r = 0.21, p < 0.05), but the relationship of Mid-PTH to age remained significant when the effect of renal function was eliminated in the multiple regression. Creatinine clearance did not correlate significantly with NH2-PTH. Fourteen women with the highest values of NH2-PTH were compared with 12 women with the lowest NH2-PTH levels for multiple indices of PTH action and bone turnover, including urinary excretion indices for calcium, phosphorus, cyclic AMP, and hydroxyproline, and serum alkaline phosphatase activity and 25-OHD. In no case were significant differences observed between the two groups of elderly women. We conclude that increased iPTH with age in women reflects an increase in steady-state levels of intact hormone. Although a similar phenomenon probably occurs in men, results from men in this study did not reach significance. Although it is considered likely that elevated PTH levels may contribute to age-related bone loss, we found no correspondence of iPTH to several measures of PTH action and bone turnover. These results point out the need for a prospective evaluation of the relationship of iPTH to bone loss in elderly men and women.
Funding Information
  • NIH (AG04458-02A2 (TNH))
  • Research Service of the Veterans Administration