Urinary excretion of pyridinoline and deoxypyridinoline measured by immunoassay in hypothyroidism.

Abstract

We measured pyridinium cross-links, markers of bone resorption, by an enzyme-linked immunosorbent assay (ELISA) in hypothyroid patients to see whether bone resorption was reduced in hypothyroidism and whether it increased with T4 treatment. Eight hypothyroid patients, whose initial TSH levels were 268.1 +/- 87.7 mU/l (mean +/- SE), were treated with T4 (100 micrograms/day). Urinary excretion of pyridinium cross-links was assayed before and after T4 treatment. Pyrilinks and Pyrilinks-D kits were used. The Pyrilinks assay measures free forms of pyridinoline and deoxypyridinoline together (PYD), while the Pyrilinks-D assay measures deoxypyridinoline (DPD) alone. The Pyrilinks reference ranges for normal subjects are 8-24nmol/mmol creatinine in males and 10-28nmol/mmol creatinine in normal premenopausal females. The DPD reference ranges obtained from normal men and women aged 40-50 years were 3.20 +/- 0.75 (mean +/- SD) nmol/mmol creatinine and 4.55 +/- 1.22 nmol/mmol creatinine, respectively. The sensitivity of the assay was enhanced by simply using less diluted urine samples. Concentrations of both compounds of the urinary pyridinium cross-links were low in untreated hypothyroid patients and increased gradually as thyroid hormone status improved from hypothyroidism to euthyroidism. One month after treatment when the TSH levels in the patients were still as high as 74.4 +/- 44.5 mU/l, urinary PYD excretion has increased to 2.6 times the pretreatment level. When the TSH levels of the patients decreased below 10 mU/l, both PYD and DPD increased significantly to 3.8 and 3.3 times pretreatment values, respectively. Although hyperthyroidism or excess treatment with thyroid hormone has been known to induce bone resorption, this is the first report that urinary excretion of pyridinium cross-links is reduced in hypothyroidism and is normalized by physiological thyroid hormone replacement.