Subclinical hyperthyroidism and reduced bone density as a possible result of prolonged suppression of the pituitary-thyroid axis with L-thyroxine.

Spontaneous hyperthyroidism and that due to excessive administration of thyroid hormone result in osteopenia. Bone density was measured in 28 white premenopausal female patients who were taking commonly prescribed suppressive doses of L-thyroxine (mean dose 0.171 +/- 0.035 g) for five or more years. The thyroxine level was 13.5 +/- 2.6 micrograms/dl (normal 8.0 +/- 2.4 micrograms/dl), the free thyroxine index was 4.4 +/- 1.0 (normal 2.4 +/- 0.8), and the triiodothyronine value was 154 +/- 26 ng/dl (normal 132 +/- 32 ng/dl). Basal thyrotropin was undetectable (less than 0.08 microIU/ml) in 23 patients, and thyrotropin measured 20 minutes after thyrotropin-releasing hormone administration was not demonstrable in 13 patients and subnormal in 10 patients. Women who had taken L-thyroxine for 10 or more years (n = 12, age 37 +/- 4 years) had a 9 percent reduction in bone density (0.667 +/- 0.044 g/cm2, p less than 0.01) compared with normal premenopausal age-matched control subjects (n = 56, age 35 +/- 6 years, bone density 0.733 +/- 0.055 g/cm2). It is concluded that prolonged suppressive L-thyroxine treatment may result in mild subclinical hyperthyroidism with adverse effects on bone. Patients requiring suppression of the pituitary-thyroid axis should be given the smallest dose of L-thyroxine necessary to achieve a satisfactory clinical response.