Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study

BACKGROUND: Infertile women positive for thyroid antibodies suffer from a poor pregnancy/delivery outcome, although conflicting data have been published. Our objective was to investigate if levothyroxine (LT4) exerts any effect on pregnancy and/or delivery rates in thyroid peroxidase antibody (TPOAb)-positive (+) women undergoing assisted reproductive technologies. METHODS: Patients undergoing treatment were screened for TPOAb, thyroid-stimulating hormone (TSH) and free thyroxine (FT4). A total of 72 (15%) out of the 484 euthyroid women selected were TPOAb (+). These 72 patients were randomly divided into two groups: group A (n = 36) underwent LT4 treatment, group B (n = 36) placebo. Group C consisted of 412 women (85%) who were TPOAb negative (-). All patients received controlled ovarian stimulation. The endpoints of treatment were pregnancy rate, miscarriage rate and delivery rate. RESULTS: No differences in pregnancy rate were observed between the three groups. Miscarriage rate was higher in TPOAb (+) in comparison to TPOAb (-) [relative risk: 2.01 (95% CI = 1.13-3.56), P = 0.028]. CONCLUSIONS: The pregnancy rate is not affected either by presence of TPOAb or treatment with LT4. However, TPOAb (+) women show a poorer delivery rate compared to TPOAb (-). LT4 treatment in TPOAb (+) does not affect the delivery rate.     

Role of cytological characteristics of benign thyroid nodules on effectiveness of their treatment with levothyroxine

Introduction

Levothyroxine (LT4) therapy has been used for the treatment of euthyroid nodular goiter, but there are controversial results about its usefulness. We aimed to evaluate the possible role of benign nodules’ cytological characteristics in response to LT4 therapy.

Material and methods

In total, 93 patients with 128 nodules were included in the study; 74 of the nodules were treated with LT4 (group 1), and 54 of them had no medication (group 2). The subgroups consisted of adenomatous nodules, colloid nodules and cystic nodules.

Results

In group 1, mean thyroid volume and mean nodule volume were reduced significantly (p = 0.002 and p = 0.022, respectively) with low-normal level thyrotropin (TSH) suppression (between 0.3 mIU/ml and 1.0 mIU/ml), while there were no significant changes in group 2. When we evaluated changes of the initial and last nodule volumes in cytological subgroups, only colloid nodules in group 1 had significant reduction (p = 0.040) and the others had no significant changes. By omitting the colloid nodules, when the other nodules were revaluated, there were no significant changes in either group.

Conclusions

On the basis of these results, obtained from a large sample of Anatolian patients, it is possible that LT4 therapy leads to significant reductions of both thyroid volume and nodule size in colloid nodules, but not in other kinds of benign nodules.     

妊娠期亚临床甲状腺功能减退症左甲状腺素治疗剂量探讨

目的：探讨影响妊娠期亚临床甲状腺机能减退（SCH）患者左甲状腺素（L-T4）治疗剂量的因素。方法：42例妊娠期SCH患者,每4周监测甲状腺功能,根据促甲状腺激素（TSH）水平调整L-T4剂量,使每次TSH值均达标。记录首诊时患者体质量、TSH值、甲状腺过氧化物酶抗体（TPO-Ab）水平、产前体质量和新生儿体质量等。使用SPSS17.0对产前L-T4剂量进行多元线性回归分析。结果：产前L-T4剂量与患者体质量及体质量增加值、首诊时TSH值、TPO-Ab水平、新生儿体质量等无明显关系（P〉0.05）。结论：患者首诊时TSH值、体质量、孕期体质量增加值、TPO-Ab水平、新生儿体质量等不能预测产前L-T4剂量,TSH全程控制达标有赖于规律的监测和随访。     

RP-HPLC法检测左旋甲状腺素钠片剂含量及溶出度

【目的】建立左旋甲状腺素钠反相高效液相色谱(RP-HPLC)测定法,检测和比较2种进口的左旋甲状腺素钠片剂的含量和溶出度。【方法】用RP-HPLC法测定2种片剂中左旋甲状腺素钠含量,依照美国药典第23版溶出度测定Ⅱ法测定左旋甲状腺素钠片剂溶出度。色谱条件HypersilBDSC18柱;流动相0.85(mL/100mL)磷酸溶液-甲醇(40∶60);检测波长225nm;流速1.5mL/min。【结果】2种片剂含量占标示量百分率分别为107.74%和99.72%。两种片剂溶出50%和63.2%所需的时间及m值均有极显著性差异(P<0.01)。【结论】两种进口左旋甲状腺素钠片剂的含量无差异,但溶出度存在显著性差异。     

Hypothyroidism and pregnancy: still a controversial issue

Abstract

Subclinical hypothyroidism (SCH) in pregnancy is common, according to literature, affecting up to 15% of pregnancies. It still represents a controversy weather levothyroxine has beneficial effects on pregnancy outcomes. In this retrospective and prospective cohort study, we assessed fetal and maternal outcomes in women with known thyroid status pre-pregnancy, and hypothyroidism during pregnancy. We included 393 pregnant women, 90 (22.9%) diagnosed with overt and 303 with SCH (77.1%). A total of 94 (56%) had positive anti-TPO antibodies. Levothyroxine substitution across all observational periods was suboptimal, mostly during first trimester in both groups of patients (85.4%). There was a difference in the number of live births in favor of group with SCH (p?=?.004). Women with overt hypothyroidism were more likely to develop complications during pregnancy (RR = 1.153, 95%CI = 0.775???1.714) and had positive TPO-antibodies more often (p?=?.022). The only significant association was found between fetal outcomes in women with SCH and positive TPO-antibodies (p?=?.018), while positive Tg-antibodies did not affect the pregnancy outcomes of women with SCH. Moreover, no correlation was observed between outcomes and adequacy of levothyroxine substitution. These results indicate that TPO-antibody positivity could be the most important factor of pregnancy outcomes independent of the TSH levels or adequacy of levothyroxine therapy.     

Effects of levothyroxine suppressive therapy on bone mineral density in premenopausal women

BACKGROUND: Levothyroxine (L-T4) is widely prescribed for treating thyroid disorders, but its effect on bone mineral density (BMD), is being debated. OBJECTIVES: We studied the effect of supraphysiologic doses of L-T4 on BMD in a group of premenopausal women. PATIENTS AND METHODS: We included 50 women (mean age=36.8 +/- 7.6 years) receiving L-T4 for at least 1 year for treating their benign cold thyroid nodules. Serum T3, T4, thyroid-stimulating hormone (TSH), parathyroid hormone (PTH), calcium, and phosphate and urine calcium and sodium levels of all patients were measured. Bone density at femoral neck and lumbar (L1-L4) regions was measured, using dual energy X-ray absorptiometry (DXA). RESULTS: No significant decrease was detected in the bone density of the subjects treated with L-T4 compared with the control group. CONCLUSION: L-T4 treatment for 1 year is not associated with increased risk of osteoporosis in premenopausal women but other potential adverse effects still need to be monitored in women receiving L-T4 especially long-term.     

左甲状腺素钠治疗妊娠亚临床甲减与促甲状腺激素水平的关系研究

目的：探讨左甲状腺素钠（L-T 4）治疗妊娠早期亚临床甲状腺功能减退症（亚临床甲减）抗甲状腺过氧化物酶自身抗体（TPOAb）阳性患者的疗效,并探讨在妊娠中期促甲状腺激素（TSH）水平控制至目标值时的 L-T 4用量与干预前T S H水平的关系。方法选择2012年3～11月辽宁中医药大学附属医院124例妊娠早期亚临床甲减伴TPOAb阳性患者为研究对象,根据首次TSH水平划分为A、B、C 3组,每组均给予L-T4治疗,检测干预前及妊娠中期TSH控制至目标值后的体质量及L-T4用量的差异。结果3组患者干预前及妊娠中期TSH水平控制至目标值时的体质量比较,差异无统计学意义（P＞0．05）,而妊娠中期TSH水平控制至目标值时的L-T4用量相比,差异有统计学意义（P＜0．05）。结论妊娠早期亚临床甲减伴TPOAb阳性患者在体质量无明显差异的情况下,妊娠中期将TSH水平控制至目标值时,L-T4的用量与早期TSH水平相关。     

甲状腺功能减退症的诊治

甲状腺功能减退症（甲减）是由多种原因引起的甲状腺激素合成、分泌或生物效应不足所致的一种全身代谢减低综合征。原发性甲减是其中最常见的类型,主要由自身免疫甲状腺炎如桥本病所致,其他原因包括由于中枢促甲状腺激素释放激素（TRH）或促甲状腺激素（TSH）不足、甲状腺手术或放射性碘治疗导致的甲减。甲状腺激素的测定,包括TSH和游离甲状腺素（FT4）等,是甲减诊断的主要手段。甲减的诊断可分为临床（TSH高,FT4低）或亚临床甲减（TSH高,FT4正常）。甲减治疗的目的是纠正甲状腺功能不足,减轻症状,避免进展至粘液性水肿。甲减通常采用合成的左甲状腺素治疗。尽管典型甲减的诊断、治疗在临床上较为简单,但有相当部分患者治疗并未达到最优化,即使甲状腺功能指标正常仍感觉生活质量较差。本文简述了甲减的病因、分类、诊断和治疗。对部分患者治疗效果不佳的可能原因及优化措施亦进行了讨论。     

小金胶囊联合左甲状腺素钠片治疗桥本氏甲状腺炎的临床研究

目的:探讨小金胶囊联合左甲状腺素钠片治疗桥本氏甲状腺炎的临床研究。方法:选取2017年8月—2019年1月收治的桥本氏甲状腺炎患者106例,按照数字表法将其随机分为两组,对照组应用左甲状腺素钠片治疗,研究组应用小金胶囊联合左甲状腺素钠片治疗,对两组患者临床疗效、甲状腺功能及炎症反应等指标进行分析。结果:研究组的临床治愈比例高于对照组(50.9%vs 18.7%);研究组的T3(2.2±0.5) nmol/L、T4(124.2±17.8) nmol/L、FT3(4.3±0.7) pmol/L及FT4(14.4±2.9) pmol/L与对照组无明显差异(P 0.05),研究组的TSH(1.8±0.2)μIU/L低于对照组(P 0.05);研究组甲状腺抗体水平TG-Ab(253.4±12.8) IU/mL、TPO-Ab(241.3±12.8) IU/mL均低于对照组(P 0.05);研究组IL-8(0.4±0.2) ng/mL、IL-17(7.4±2.1) pg/mL及APN(5.9±1.1)μg/mL低于对照组(P 0.05),研究组的IL-10(91.8±12.6) pg/mL高于对照组(P 0.05);研究组不良反应(22.64%)与对照组(24.53%)无明显差异(P 0.05)。结论:采用小金胶囊联合左甲状腺素钠片治疗桥本氏甲状腺炎患者,能有效改善患者甲状腺抗体水平,调节自身炎症因子平衡,具有较高的安全性,可以在临床中进行进一步推广。