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PURPOSE: Controversy exists as to whether patients with subclinical hypothyroidism benefit from treatment. Two randomized trials reported that hypothyroid symptoms improved following thyroid hormone replacement therapy. However, during the initial treatment of overt hypothyroidism with levothyroxine, three studies have demonstrated short-term (6 to 12 months) 5% to 13% reductions in bone density. The current study measures bone density during the initial treatment of subclinical hypothyroidism. PATIENTS: Seventeen postmenopansal women with subclinical hypothyroidism (elevated serum thyrotropin [TSH] and normal serum free thyroxine concentrations) and no prior history of thyroid disease were randomly assigned to levothyroxine treatment or no treatment and followed prospectively. Patients in the treatment group had similar initial serum TSH concentrations (9.8 [plus or minus].3 versus 8.4 [plus or minus]2.7 [micro]U/mL) but were slightly older (68 [plus or minus] 7 years versus 60 [plus or minus] 5 years [p (0.02]). The average dose of levothyroxine needed to normalize serum TSH concentration was 0.072 [plus or minus] 0.027 mg. RESULTS: Bone density determinations were not significantly different between the two groups at baseline. After 14 [plus or minus] 1 months, singlephoton absorpfiometry of the wrist decreased by 1.8% [plus or minus] 3.2% in the untreated patients and 0.5% [plus or minus] 4.1% in the levothyroxine-treated patients (p = NS). Dual-energy X-ray absorpfiometry of the lumbar spine decreased by 0.7% [plus or minus] 2.9% in the untreated patients and rose 0.1% [plus or minus] 4.75% in the levothyroxine-treated patients (p= NS). CONCLUSIONS: Unlike the early treatment of overt hypothyroidism, there is no short-term reduction of bone density with levothyroxine treatment of subclinical hypothyroidism in postmenopausal women. These data suggest that potentially symptomatic women with subclinical hypothyroidism should be given a trial of levothyroxine therapy without concern about adverse effects on skeletal integrity.

Treatment with the thyroid hormone thyroxine is used to replace deficient levels of this hormone in patients with hypothyroidism (reduced thyroid function) or to suppress the growth of abnormal thyroid tissue. However, L-thyroxine therapy can cause bone loss. Thyroid hormone treatment decreases bone density by enhancing bone resorption, a process in which the bone is dissolved and absorbed into tissue. A recent study suggested that bone loss may be reduced by carefully monitoring thyroxine treatment. This is accomplished by measuring the levels of a pituitary hormone, thyroid-stimulating hormone (TSH), which activates the release of thyroxine from the thyroid gland. Increased levels of thyroxine are normally associated with reduced levels of TSH. Hence, in patients with hypothyroidism or reduced levels of thyroxine, replacement therapy with L-thyroxine should increase blood levels of thyroxine and reduce TSH levels to normal values. Patients who are taking L-thyroxine to suppress abnormal thyroid growth require more than the replacement doses. Such patients do not develop symptoms from large L-thyroxine doses, but are considered to have subclinical hyperthyroidism, a condition characterized by elevated blood levels of thyroxine. Hence, in patients requiring suppressive L-thyroxine treatment, TSH levels are usually reduced to subnormal, or below normal values. Several studies have shown that subclinical hyperthyroidism resulting from excessive doses of L-thyroxine is associated with bone loss, particularly in women who have not stopped menstruating. Although careful monitoring of L-thyroxine treatment helps to reduce bone loss, there will always be some degree of bone loss, which in the long-term may contribute to the occurrence of hip fracture. Hence, the need for L-thyroxine treatment must be carefully considered, and the dose of L-thyroxine necessary to reduce the TSH level should be related to the clinical condition. For example, large doses of L-thyroxine are appropriate in patients with malignant thyroid cancer, whereas lower doses of the hormone may be used in patients with benign, or nonmalignant, growths of the thyroid gland. The long-term effects of L-thyroxine treatment require further study. (Consumer Summary produced by Reliance Medical Information, Inc.)