La Vignera S, Vicari E, Tumino S, Ciotta L, Condorelli R, Vicari L O, Calogero A E
Section of Endocrinology, Andrology and Internal Medicine, Department of Biomedical Sciences, University of Catania, Catania, Italy.
Minerva Ginecol. 2008 Dec;60(6):475-84.
Nodular thyroid disease and osteoporosis share some common factors such as: 1) elevated frequency in the general population; 2) major prevalence in the female sex; 2) incidence proportional to the age. There is a wide debate in literature regarding the real impact of chronic treatment with L-thyroxin (LT4) on the bone mineral density (BMD), especially in post-menopausal women. The aim of this study was to undertake to evaluate the effects of LT4 administration for the treatment of normo-functioning nodular thyroid disease on the BMD in post-menopausal women after one year of continuative treatment. Particular attention was paid in examining the role of some anamnestic risk factors for osteoporosis on the clinical response.
Ninety nine postmenopausal women of age comprised between 50 and 56 years were examined before and after 1 year of therapy with a fixed dose of LT4 for the treatment of nodular thyroid disease by monitoring the following laboratory parameters: thyroid stimulating hormone (TSH), FT4, FT3, antithyroglobulin antibodies [AbTG], hyroid peroxidase antibodies [AbTPO], serum calcium and alkaline phosphatase levels and 24-urinary excretion of calcium and hydroxyproline. Bone mineral density (BMD) was measured by dual X-ray absorptiometry of the lumbar vertebrae.
The results of this study showed that the patients on treatment with LT4 have a slight, but significant reduction of the BMD after 1 year of treatment, associated with increased serum levels of alkaline phosphatase and urinary excretion of hydroxyproline. Comparison between patients with unsuppressed (group A) or suppressed (group B) TSH following LT4 treatment showed that group B patients had significantly lower BMD. The following risk factors influenced, in a statistically significant manner, the BMD: 1) Body Mass Index <19 kg/m(2); 2) the onset of menarche after the age of 15 years; 3) history positive for period of amenorrhoea; 4) nulliparity; 5) surgical menopause; 6) lack of hormonal replacement therapy; and 7) presence of auto-antibodies against thyroid antigens.
LT4 treatment in postmenopausal women reduced significantly the BMD. This treatment should be therefore prescribed with caution in this condition and particularly when the following risk factors are present: surgically driven menopause, constitutional thinness, history of nulliparity, absence of hormonal treatment, positive history of secondary amenorrhoea during the reproductive age, autoimmune thyroid disease and delayed menarche.
结节性甲状腺疾病与骨质疏松症有一些共同因素，如：1）在普通人群中发病率升高；2）女性中患病率较高；3）发病率与年龄成正比。关于左甲状腺素（LT4）长期治疗对骨密度（BMD）的实际影响，尤其是对绝经后女性的影响，文献中存在广泛争议。本研究的目的是评估在连续治疗一年后，LT4治疗功能正常的结节性甲状腺疾病对绝经后女性骨密度的影响。特别关注了一些骨质疏松症的既往风险因素对临床反应的作用。
对99名年龄在50至56岁之间的绝经后女性进行了研究，在使用固定剂量的LT4治疗结节性甲状腺疾病1年前后，监测以下实验室参数：促甲状腺激素（TSH）、游离甲状腺素（FT4）、游离三碘甲状腺原氨酸（FT3）、抗甲状腺球蛋白抗体[AbTG]、甲状腺过氧化物酶抗体[AbTPO]、血清钙和碱性磷酸酶水平以及24小时尿钙和羟脯氨酸排泄量。通过腰椎双能X线吸收法测量骨密度（BMD）。
本研究结果表明，接受LT4治疗的患者在治疗1年后骨密度有轻微但显著的降低，同时血清碱性磷酸酶水平升高和尿羟脯氨酸排泄量增加。比较LT4治疗后促甲状腺激素未被抑制（A组）或被抑制（B组）的患者，发现B组患者的骨密度显著较低。以下风险因素对骨密度有统计学意义上的显著影响：1）体重指数<19kg/m²；2）月经初潮年龄在15岁之后；3）有闭经史；4）未生育；5）手术绝经；6）缺乏激素替代疗法；7）存在针对甲状腺抗原的自身抗体。
绝经后女性接受LT4治疗会显著降低骨密度。因此，在这种情况下应谨慎开此药，尤其是当存在以下风险因素时：手术导致的绝经、体质消瘦、未生育史、无激素治疗、生育年龄继发性闭经史阳性、自身免疫性甲状腺疾病和月经初潮延迟。
