OBJECTIVE: The results of studies examining the influence of T4 therapy upon bone mineral density (BMD) are conflicting. This conflict may, in part, reflect inclusion of patients with varying thyroid disorders. We have therefore examined the influence of preceding thyroid history and T4 therapy on BMD. DESIGN: Case-control studies of patients on long-term T4 therapy who have or have not previously received radioiodine treatment for thyrotoxicosis, as well as previously thyrotoxic patients who have not required T4 replacement. PATIENTS: Twenty-seven premenopausal and 60 postmenopausal females with a past history of thyrotoxicosis and subsequent T4 treated hypothyroidism (group 1), 39 post-menopausal females with a past history of radioiodine treated thyrotoxicosis not receiving T4 (group 2) and 22 post-menopausal females with primary hypothyroidism on T4 (group 3). Female controls individually matched to patients by age and menopausal status. MEASUREMENTS: BMD measured by dual-energy X-ray absorptiometry. Serum biochemistry and tests of thyroid function. RESULTS: No significant differences were found in femoral or lumbar spine BMD measurements between premenopausal patients and controls in group 1 or between group 2 patients and controls. Measurements of BMD at all sites were lower in post-menopausal patients in groups 1 and 2 than in controls; when allowance was made for differences in BMD due to body mass index by analysis of variance, significant reductions in femoral trochanter BMD (3.9%, P < 0.05) and lumbar spine (5.6-8.5%, P < 0.01) BMD results were found in post-menopausal females in group 1 and reductions in femoral trochanter (3.9%, P < 0.01), Ward's triangle (5.6%, P < 0.05) and lumbar spine (8.5%, P < 0.01) BMD results in group 2. Separate analysis of BMD results of those with normal or reduced serum TSH did not affect outcome. BMD measurements were not significantly correlated with duration of T4 therapy, T4 dose, or serum free T4 or TSH in any patient group. CONCLUSIONS: Thyroxine therapy alone does not represent a significant risk factor for loss of bone mineral density but there is a risk of bone loss in post-menopausal (but not premenopausal) females with a previous history of thyrotoxicosis treated with radioiodine.

Absorptiometry, Photon↗

PubMed1992

Radioiodine for hyperthyroidism.

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Humans↗

PubMed1990

Insulin autoantibodies in Graves' disease--before and after carbimazole therapy.

Insulin autoantibodies (IAA) are well documented in patients with insulin-dependent diabetes (IDDM) prior to the administration of insulin and in patients with reactive hypoglycaemia--the insulin autoimmune syndrome (IAS). It has been suggested that IAA can be induced by the administration of drugs containing sulphydryl groups, such as carbimazole, and they have been frequently described in Graves' disease. An alternative explanation is the clustering of autoantibodies in autoimmune disease. We studied 39 patients (37 females, two males, age range 14 to 61 years; mean 33.8 years) with proven Graves' disease and no previous treatment with carbimazole. Fifteen of the 39 patients had a family history of other autoimmune diseases. IAA and thyroid autoantibodies were assayed at diagnosis and monthly thereafter while on treatment with carbimazole, for up to 6 months. IAA were measured using a direct-binding solid-phase ELISA and specificity was confirmed by absorption studies using insulin covalently coupled to Sepharose beads. At diagnosis 33 of the 39 patients (85%) were positive for thyroid microsomal antibodies, 13 (33%) were positive for thyroglobulin antibodies, and 4 (10%) were positive for IAA. All IAA-positive patients had microsomal antibodies at diagnosis, and two had thyroglobulin antibodies in addition. After 4 months on carbimazole, the frequency of thyroid microsomal autoantibodies was unchanged (83%), while that of anti-thyroglobulin antibodies had fallen (8.6%). All four IAA-positive patients remained positive, and studies of binding to human, porcine and bovine insulin demonstrated that one serum, initially human insulin specific, later became cross-reactive with all three. We conclude that low titres of IAA are found in Graves' disease, and are associated with the presence of autoimmunity rather than the carbimazole. Symptomatic hypoglycaemia, however, is rare in Caucasian patients.

Adolescent↗