新版妊娠期甲状腺功能障碍治疗指南发布

《临床内分泌学与代谢杂志》8月12日发表的内分泌学会2012年新版临床实践指南(CPG)指出，在治疗妊娠期和产后女性的甲状腺功能障碍时，临床医生应谨慎解读血清游离甲状腺素水平，使用丙基硫氧嘧啶作为孕早期甲状腺功能亢进的一线治疗药物，并建议哺乳女性每天摄入250 mcg碘，以确保通过母乳每日为婴儿提供100 mcg碘(J. Clin. Endocrinol. Metab. 2012 Aug. 1;97:2543-65 [doi: 10.1210/jc.2011-2803])。

新版指南是由内分泌学会联合亚洲和大洋洲甲状腺学会、欧洲甲状腺学会及拉丁美洲甲状腺学会在2007年CPG基础上修订更新完成。

新版CPG的关键建议与2007年旧版CPG的不同之处在于：

•谨慎解读妊娠期间的血清游离T4水平。如果进行游离T4检查的话，每个实验室应确立针对妊娠女性的参考值范围。非妊娠期的总T4范围为5~12 mcg/dl或50~150 nmol/L，将此范围乘以1.5，所得结果即为孕中期和孕晚期的参考范围。另外，妊娠期间检测游离甲状腺素指数(‘校正T4’)也是一种可靠的检测方法。

•如果有丙基硫氧嘧啶(PTU)的话，应将其作为孕早期甲状腺功能亢进的一线治疗药物。这是因为甲巯咪唑(MMI)可能会引起先天异常。如果没有PTU，或者患者不能耐受PTU或使用PTU后出现不良反应，那么也可使用MMI。FDA报告的最新分析显示，PTU在极少数情况下可能引起重度肝毒性反应。因此，建议临床医生在孕早期结束后把治疗药物从PTU改为MMI。现有数据显示，MMI和PTU治疗妊娠女性的效果相同。

•哺乳女性应每天摄入250 mcg碘，以确保通过母乳每日为婴儿提供100 mcg碘。这是因为最新研究显示，妊娠期间使用的一些维生素-矿物质制剂可能无法提供充足的碘，并且这些研究也提示在哺乳期间应继续使用碘补充剂。

•对于一些妊娠女性，建议测定22周胎龄前的甲状腺受体抗体(TRAb)。这些女性包括目前患有Graves病、妊娠前有Graves病和131-I(放射性碘)治疗或甲状腺切除术史、前一胎患有Graves病、或既往TRAb水平升高的女性。作此建议是因为TRAb可自由通过胎盘，并能刺激或抑制胎儿甲状腺。TRAb阴性且不需抗甲状腺药物治疗的女性的胎儿或新生儿发生甲状腺功能障碍的风险极低。

指南作者在是否建议所有刚怀孕的女性进行普遍筛查的问题上未达成共识。一些作者建议在第9周或首次就诊时对所有妊娠女性进行血清TSH筛查，而另一些作者既不建议也不反对这么做。

尽管在这一问题上未达成共识，但作者们均一致认为，临床医生应在产前和围产期对高危女性进行筛查。这些女性包括：年龄＞30岁且具有自身免疫性甲状腺疾病或甲状腺功能减退家族史；甲状腺肿大；甲状腺抗体，主要是甲状腺过氧化物酶抗体；提示甲状腺功能减退症的症状或临床体征；1型糖尿病，或其他自身免疫性疾病；不孕；既往早产史；既往头部或颈部放射治疗或既往甲状腺手术；目前正在接受左旋甲状腺素替代治疗。

所有作者均声明无相关经济利益冲突。

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By: DOUG BRUNK, Clinical Endocrinology News Digital Network

When treating women with thyroid dysfunction during and after pregnancy, clinicians should use caution interpreting serum-free thyroxine levels, use propylthiouracil as the first-line drug during for hyperthyroidism in the first trimester, and advise breastfeeding women to maintain a daily intake of 250 mcg of iodine to ensure breast milk provides 100 mcg of iodine/day to the infant.

These mark some of the changes the Endocrine Society made to its 2007 Clinical Practice Guideline (CPG) for the management of thyroid disease during pregnancy and the postpartum.
     
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Pregnant women may be under the care of multiple health care professionals ... making the development of guidelines all the more critical.
 
"Pregnancy may affect the course of thyroid diseases and conversely, thyroid diseases may affect the course of pregnancy," Dr. Leslie De Groot, lead researcher from the University of Rhode Island, Kingston, said in a prepared statement. "Pregnant women may be under the care of multiple health care professionals including obstetricians, nurse midwives, family practitioners and endocrinologists making the development of guidelines all the more critical."

In order to update the Endocrine Society’s 2007 CPG, Dr. De Groot and a task force of 12 other experts reviewed existing medical literature on the topic and followed the approach of the U.S. Preventive Services Task Force and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system to evaluate the strength of each recommendation. The effort, published online in the Aug. 12 issue of the Journal of Clinical Endocrinology & Metabolism, included collaboration with the Asia and Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society (J. Clin. Endocrinol. Metab. 2012 Aug. 1;97:2543-65 [doi: 10.1210/jc.2011-2803]).

"At present, with the exception of studies on iodide nutrition, only a few prospective, randomized intervention trials have been published in this area [of thyroid dysfunction during pregnancy]," the authors wrote. "We are aware of large-scale prospective intervention trials that are ongoing. Nevertheless, in the past decade many high-quality studies have modified older dogmas and profoundly changed the ways in which these patients are managed."

Key recommendations in the 2012 clinical practice guideline that differ from the 2007 version include the following:

• Use caution in the interpretation of serum-free T4 levels during pregnancy. "Each laboratory should establish trimester-specific reference ranges for pregnant women if using a free T4 assay," the authors wrote in a supplemental index in which they summarized changes between the 2007 and 2012 versions of the guideline. "The non-pregnant total T4 range (5-12 mcg/dL or 50-150 nmol/L) can be adapted in the second and third trimesters by multiplying this range by 1.5-fold. Alternatively, the free thyroxine index (‘adjusted T4’) appears to be a reliable assay during pregnancy."

• Use propylthiouracil (PTU), if available, as the first-line drug for treatment of hyperthyroidism during the first trimester. This is because of the possible association of methimazole (MMI) with congenital abnormalities. MMI "may also be prescribed if PTU is not available or if a patient cannot tolerate or has an adverse response to PTU," the authors wrote. "Recent analyses reported by the FDA indicate that PTU may rarely be associated with severe liver toxicity. For this reason, we recommend that clinicians should change treatment of patients from PTU to MMI after the completion of first trimester. Available data indicate that MMI and PTU are equally efficacious in treatment of pregnant women."

• Breastfeeding women should maintain a daily intake of 250 mcg of iodine. This ensures that breast milk provides 100 mcg iodine/day to the infant. "These changes are in response to recent publications indicating that some vitamin-mineral preparations used during pregnancy may not provide adequate iodine intake, and that iodine supplements should be continued during breastfeeding," the authors explained.

• Measure thyroid receptor antibodies (TRAb) before 22 weeks’ gestational age in a subset of mothers. This includes mothers with either current Graves’ disease, a history of Graves’ disease and treatment with 131-I (radioiodine) or thyroidectomy before pregnancy, a previous neonate with Graves’ disease, or previously elevated TRAb. This approach is recommended because thyroid receptor antibodies "freely cross the placenta and can stimulate or inhibit the fetal thyroid," the authors wrote. "Women who have negative TRAb and do not require antithyroid drugs have a very low risk of fetal or neonatal thyroid dysfunction. This change makes more explicit the timing and indications for measurement of TRAb in pregnancy."

The authors could not reach agreement on universal screening recommendations for all newly pregnant women. Some recommend screening of all pregnant women for serum TSH abnormalities by the 9th week or at the time of their first visit while others recommended neither for nor against universal screening of all pregnant women for TSH abnormalities at the time of their first visit.

Despite their differences on universal screening recommendations, the authors unanimously agreed that clinicians should perform targeted screening of high-risk women during the prenatal and perinatal periods. This includes women over age 30 years and those with a family history or autoimmune thyroid disease or hypothyroidism; a goiter; thyroid antibodies, primarily thyroid peroxidase antibodies; symptoms or clinical signs suggestive of thyroid hypofunction; type 1 diabetes mellitus, or other autoimmune disorders; those with infertility; a prior history of preterm delivery; prior therapeutic head or neck irradiation or prior thyroid surgery; and those currently receiving levothyroxine replacement.

No member of the task force disclosed relevant financial conflicts of interest.