URINARY-EXCRETION OF PYRIDINOLINE AND DEOXYPYRIDINOLINE MEASURED BY IMMUNOASSAY IN HYPOTHYROIDISM

OBJECTIVE We measured pyridinium cross-links, markers of bone resorpti on, by an enzyme-linked immunosorbent assay (ELISA) in hypothyroid pat ients to see whether bone resorption was reduced in hypothyroidism and whether it increased with T4 treatment. DESIGN AND PATIENTS Eight hyp othyroid patients, whose initial TSH levels were 268.1 +/- 87.7 mU/l ( mean +/- SE), were treated with T4 (100 mu g/day). Urinary excretion o f pyridinium cross-links was assayed before and after T4 treatment. ME ASUREMENTS Pyrilinks and Pyrilinks-D kits were used. The Pyrilinks ass ay measures free forms of pyridinoline and deoxypyridinoline together (PYD), while the Pyrilinks-D assay measures deoxypyridinoline (DPD) al one. The Pyrilinks reference ranges for normal subjects are 8-24nmol/m mol creatinine in males and 10-28nmol/mmol creatinine in normal premen opausal females. The DPD reference ranges obtained from normal men and women aged 40-50 years were 3.20 +/- 0.75 (mean +/- SD) nmol/mmol cre atinine and 4.55 +/- 1.22 nmol/mmol creatinine, respectively. RESULTS The sensitivity of the assay was enhanced by simply using less diluted urine samples. Concentrations of both compounds of the urinary pyridi nium cross-links were low in untreated hypothyroid patients and increa sed gradually as thyroid hormone status improved from hypothyroidism t o euthyroidism. One month after treatment when the TSH levels in the p atients were still as high as 74.4 +/- 44.5 mU/l, urinary PYD excretio n has increased to 2.6 times the pretreatment level. When the TSH leve ls of the patients decreased below 10 mU/l, both PYD and DPD increased significantly to 3.8 and 3.3 times pretreatment values, respectively. CONCLUSIONS Although hyperthyroidism or excess treatment with thyroid hormone has been known to induce bone resorption, this is the first r eport that urinary excretion of pyridinium cross-links is reduced in h ypothyroidism and is normalized by physiological thyroid hormone repla cement.