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Bone
Matteucci et al., Pisa, Italy, studied bone mineral density (BMD) of lumbar spine and femoral neck in 36 premenopausal women between 20 and 53 years, who were on suppressive L-T4 therapy for a period of 5 to 30 years (mean 6.8 yr). Their mean TSH was 0.08 +/- 0.10 vs. 1.7+/- 0.7 mU/mL in 85 matched controls. BMD at both locations was not different between the two groups, neither was there a correlation between BMD and cumulative dose of L-T4. Also serum osteocalcin was similar in both groups. Kung et al., Hong Kong, studied total body and regional density (BMD) in 46 postmenopausal women on T4 suppressive therapy for more than 1 year (TSH < 0.03 mU/L) who had a low average calcium intake of 545 mg per day subdivided into 3 groups. I. Intranasal calcitonin 200 ug daily for 5 days per week + 100 mg Calcium Sandoz Forte daily, II. calcium alone, and III. placebo. The results showed that group I and II did not have boneloss, while group III showed a loss of 5.0% at the lumbar spine, 6.7% hip, 4.7% trochanter, and 8.8% Ward's triangle after 1 year. Also osteocalcin levels were higher in group III and normal in I and II. No differences were present regarding serum alkaline phosphatase and urinary hydroxyproline excretion. (Comment: Although there is still controversy if BMD decreases on suppressive L-T4 treatment in postmenopausal women, clinicians should consider administration calcium under these circumstances, at least until the controversy has been solved.) Many studies on the issue of suppressive T4 treatment and possible effects on BMD were of the cross-sectional type. Marcocci et al., Pisa, Italy, have therefore prospectively studied BMD in 2 groups of premenopausal women who's daily dose of L-T4 was individually adjusted in order to use the minimal amount necessary to suppress TSH. Group I included 10 patients with non-toxic goiter (mean age 34 yr), treated for at least 2 years, and group II included 19 women treated with total thyroidectomy for differentiated thyroid cancer, given L-T4 for more than 5 years (mean 11 yr). BMD was measured at the lumbar spine, Ward's triangle and trochanter of the femur. No significant change was found in either group, and the authors conclude that, if the minimal suppressive dose is individually adjusted, no accelerated boneloss occurs in this group of patients. Evans et al., Cardiff, United Kingdom, measured BMD in 25 women (mean 56 yr) receiving T4 for primary hypothyroidism and in 25 women (mean age 58 yr) receiving T4 for post l3lI hypothyroidism. From their results they conclude that in these two groups, being either pre- or postmenopausal, and irrespective of the etiology of hypothyroidism, there is no evidence of reduced bone density as compared to control values. Norstedt-Wikner et al., Stockholm, Sweden, evaluated bone turnover by measuring osteocalcin as a marker of bone formation and type-I telopeptide as a marker for bone resorption in 6 hypothyroid and 23 hyperthyroid patients. They found a slight increase in bone formation and resorption in the first group and marked increases of both parameters in the hyperthyroid patients. A similar study was done with regard to hyperthyroidism by Kuo et al., Taipei, Taiwan. They studied markers of bone formation i.e. osteocalcin and carboxyterminal propeptide of type I procollagen (PICP) and of bone resorption, i.e. cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and urinary excretion of deoxypyridinoline (D-Pyr) in 25 patients with Graves' disease before and after antithyroid drug therapy and in 15 matched controls. Hyperthyroid patients had increased levels of all 4 markers, but after therapy markers of bone resorption were significantly decreased and those of bone formation unchanged. Heart Important results on cardiac effects of L-T4 suppressive therapy (suppressed TSH but normal T4 and T3 parameters) have been published over the last years by the group of Biondi et al., Naples, Italy (J Clin Endocrinol Metab 77:334-338,1993 and 80: 2222-2226,1995). They have shown that in these patients basal heartrate is elevated, left ventricular mass is increased and systolic and diastolic heart function is impaired. In this meeting they continue to report their studies in this type of patients, where they now evaluate cardiac performance and exercise tolerance and the effect of adrenergic beta-blockade. They found that in 10 patients, treated for at least 3 years with T4 suppressive therapy, exercise tolerance was substantially impaired (peak workload vs. controls: 81 vs. 121 watts) as was exercise duration (6.4 vs. 9.4 min.). Whereas left ventricular ejection fraction rose in controls during exercise, it fell in patients. After beta-blockade treatment, heart performance increased in patients. (Comment: This group of investigators are to be congratulated with the results of their studies. They unevoqually show that in patients with suppressed TSH, but normal T4 and T3 parameters, and apparently clinically euthyroid, in fact effects are present due to increased thyroid hormone action at the heart. These resuls imply that for instance in patients with multinodular goiter with normal thyroid hormone parameters but suppressed TSH treatment should be installed. To our disappointment installation of treatment in this group of patients, preferably by radioactive iodine, is unfortunately often omitted. In this respect it is also important to mention that these patients, when over 60 years, have an increased probability of about 3 times of developing atrial fibrillation, when followed for 10 years (Sawin et al., N Engl J Med 331:12491252,1994). We even suggest that in patients with multinodular goiter and TSH values in the lower normal range, even without local mechanical symptoms due to the goiter, treatment with radioactive iodine should be considered to prevent future cardiac problems.) Lipids Engler et al., St. Gallen, Switzerland, studied aspects of lipid metabolism in 46 hyperthyroid, 36 hypothyroid, and 43 euthyroid control subjects. They found significantly higher levels of apolipoprotein C-II, and C-III in hypothyroidism, while lower levels were found in hyperthyrodism. Mean HDL-C was higher in hypo- and apolipoprotein-E lower in hyperthyroidism as compared to controls. |
