High cathepsin K levels in men with differentiated thyroid cancer on suppressive L-thyroxine therapy

Thyroid. 2008 Jan;18(1):27-33. doi: 10.1089/thy.2007.0186.

Abstract

Background: Thyroid hormone administration is associated with low bone density in some studies. The aim of the present study was to evaluate the influence L-thyroxine, in doses used to treat patients with a history of thyroid carcinoma, on serum cathepsin K and other markers of bone metabolism. Cathepsin K is thought to have a role in osteoclast mediated bone resorption.

Methods: A group of male patients with differentiated thyroid cancer (DTC) on suppressive L-thyroxine therapy (DTC-group; n = 51; mean age 57 years; TSH < 0.1 mU/L) was selected as a model for hyperthyroidism. The results were compared to a group of healthy euthyroid men (control-group; n = 50; mean age 58 years; TSH 1.5 +/- 0.9 mU/L).

Results: In the DTC-group the median value of cathepsin K was 6.9 pmol/L, in the control group 4.8 pmol/L (p = 0.0052; highly significant [h.s.]). There was a significant negative correlation of cathepsin K with age (r = -0.279, p = 0.028). The analysis of various bone associated parameters revealed an increase of serum crosslaps in the DTC-group versus euthyroid controls (p = 0.03). A significant correlation could be found for cathepsin K and osteoprotegerin (p = 0.002).

Conclusion: Cathepsin K is increased by a suppressive L-thyroxine therapy and decreases with increasing age. The increased cathepsin K levels seen in DTC-patients on suppressive L-thyroxine therapy are likely to contribute to accelerated bone degradation in these patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Bone Resorption / blood
  • Bone and Bones / metabolism
  • Carcinoma, Papillary / blood*
  • Carcinoma, Papillary / surgery
  • Case-Control Studies
  • Cathepsin K
  • Cathepsins / blood*
  • Collagen / blood
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Middle Aged
  • Osteoprotegerin / blood
  • Peptide Fragments / blood
  • Thyroid Neoplasms / blood*
  • Thyroid Neoplasms / surgery
  • Thyroxine / pharmacology*

Substances

  • Biomarkers
  • Osteoprotegerin
  • Peptide Fragments
  • glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine
  • Collagen
  • Cathepsins
  • CTSK protein, human
  • Cathepsin K
  • Thyroxine