rainlove 2009-12-7 11:46
子癲前症與甲狀腺功能低下有關
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
November 18, 2009 — 根據發表於11月17日線上第一版BMJ巢式案例控制研究的分析與一篇人口基礎研究，懷孕期間發生子癲前症的婦女，比其他婦女更可能在懷孕後期或之後發生甲狀腺功能低下。
Eunice Kennedy Shriver國立兒童健康與人類發展研究中心(NICHD)執行主任Susan B. Shurin醫師在新聞稿中表示，這些發現認為，有子癲前症病史者有可能發生甲狀腺功能低下。甲狀腺功能低下不難診斷，治療也不昂貴；替代治療可顯著改善病患的生活品質。
【兩篇研究】
這項分析的目標是評估懷孕期間和懷孕後，子癲前症和甲狀腺功能降低之間的關聯，使用懷孕期間巢狀案例研究 (1992-1995年間、未曾生育過之健康美國婦女的子癲前症鈣療預防計畫)的資料。納入分析的第二篇研究，是1995-1997年間以挪威人口為基礎的「Nord-Trondelag Health Study (HUNT-2)」研究，懷孕後進行追蹤，並與挪威的醫療生育登記連結。
子癲前症鈣療預防計畫的研究對象有141名婦女，在妊娠前21週測量血清甲狀腺功能(開始值)，發生子癲前症之後再測(生產前)，141名血壓正常的對照組也在類似的時間點測量血清值，HUNT-2試驗的7,121名婦女在1967年或之後初次生產，隨後測量血清中的甲狀腺刺激素值。
【研究終點】
子癲前症鈣療預防計畫的初步研究終點是甲狀腺功能檢測、人類絨毛膜性腺激素值，以及抗血管新生因子、可溶性fms類酪氨酸激酶1的數值。根據納入前的單胞胎懷孕子癲前症狀態，HUNT-2試驗的初步研究終點是甲狀腺刺激素值超過平均參考界線的勝算比(ORs)。
【甲狀腺刺激素值增加】
發生子癲前症之後，產前樣本的甲狀腺刺激素值，子癲前症鈣療預防計畫組比開始時增加2.42倍，對照組增加1.48倍。至於案例組和對照組的比較，產前與開始時的比率為1.64 (95%信心區間[CI]為1.29 - 2.08)。相較於對照組，子癲前症婦女的游離三碘甲狀腺素值大幅降低(案例組與對照組之比為0.96；95% CI，0.92 - 0.99)。
子癲前症婦女中，產前樣本的甲狀腺刺激素值濃度比對照組更可能超過參考範圍，開始時的樣本則否(校正OR為2.2；95% CI，1.1 - 4.4)。從開始時到產前之甲狀腺刺激素值濃度增加，與產前可溶性fms類酪氨酸激酶值四分位數增加有強烈關聯，不論是發生子癲前症的婦女(趨勢P值 = .002)或無高血壓的對照組(趨勢P值< .001)。
HUNT-2試驗中，初次懷孕時發生子癲前症的婦女比其他婦女更可能發生甲狀腺刺激素值高於參考範圍(> 3.5 mIU/l)。校正OR為1.7 (95% CI，1.1 - 2.5)。此發現更可能反應出缺乏自體免疫過程的低甲狀腺功能，因為子癲前症婦女比較可能有高濃度甲狀腺刺激素而無甲狀腺過氧化酶抗體(校正OR為2.6；95% CI，1.3 - 5.0)。在第1和第2次懷孕都有子癲前症的婦女中，此關聯特別強烈(OR為5.8；95% CI，1.3 - 25.5)。
第一作者、NICHD所屬之流行病學、統計與預防研究小組的Richard J. Levine醫師在新聞稿中表示，這些婦女中有許多人仍然是甲狀腺功能低下[初次懷孕之後超過20年]，這表示，子癲前症病史代表婦女後來會發生甲狀腺功能低下。
這些研究的限制包括，觀察型研究的固有限制，子癲前症鈣療預防計畫在產後缺乏追蹤。
研究作者寫道，子癲前症時，可溶性fms類酪氨酸激酶1之血清濃度增加與後來在懷孕期間發生次臨床性甲狀腺功能低下有關。
隸屬於國家健康研究中心的NICHD與國家心臟、肺臟與血液研究中心(NHLBI)支持本研究。NICHD和NHLBI支持子癲前症鈣療預防計畫。HUNT-2的次研究則是獲得挪威科技大學和中挪威區衛生當局支持。
研究作者之一(Karumanchi博士)宣告與Burroughs Wellcome基金會、Howard Hughes醫學研究中心、美國心臟協會、Abbott, Beckman、Coulter、Roche、Johnson Johnson與貝絲以色列女執事醫院的各種財務關係，研究使用血管新生相關蛋白質進行子癲前症之診斷和治療。
BMJ. 線上發表於2009年11月17日。
Preeclampsia Linked to Hypothyroidism
By Laurie Barclay, MD
Medscape Medical News
November 18, 2009 — Women in whom preeclampsia develops during pregnancy are more likely than other women to have hypothyroidism in late pregnancy or subsequently, according to an analysis of a nested case-control study and a population-based study reported in the November 17 Online First issue of the BMJ.
"The findings suggest that the possible development of hypothyroidism is a consideration in patients with a history of preeclampsia," Susan B. Shurin, MD, acting director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), said in a news release. "Reduced thyroid functioning is easy to diagnose when suspected, and inexpensive to treat. Replacement therapy substantially improves quality of life of affected persons."
Two Studies
The goal of this analysis was to evaluate the association of preeclampsia with reduced thyroid function during and after pregnancy, with use of data from a nested case-control study during pregnancy (the Calcium for Pre-eclampsia Prevention trial of healthy pregnant nulliparous US women during 1992-1995). The second study included in this analysis, the Nord-Trondelag Health Study (HUNT-2), was a Norwegian population-based study during 1995-1997, with follow-up after pregnancy and linkage to the medical birth registry of Norway.
Study subjects were 141 women in the Calcium for Pre-eclampsia Prevention trial who had serum measurements of thyroid function before 21 weeks of gestation (baseline) and after onset of preeclampsia (before delivery), 141 normotensive control subjects with serum measurements at similar gestational ages, and 7121 women in the HUNT-2 who first delivered in 1967 or later and who had subsequent measurement of thyroid-stimulating hormone serum levels.
Study Endpoints
Primary study endpoints in the Calcium for Pre-eclampsia Prevention cohort were thyroid function tests, human chorionic gonadotropin levels, and levels of the antiangiogenic factor soluble fms-like tyrosine kinase 1. Primary study endpoints from HUNT-2 were odds ratios (ORs) for levels of thyroid-stimulating hormone above the reference range, according to preeclampsia status in singleton pregnancies before enrollment.
Thyroid-Stimulating Hormone Levels Increased
After the onset of preeclampsia, thyroid-stimulating hormone levels in predelivery specimens increased 2.42 times above baseline in patients from the Calcium for Pre-eclampsia Prevention cohort vs a 1.48 times increase in control subjects. For case patients vs control subjects, the ratio of the predelivery-to-baseline ratio was 1.64 (95% confidence interval [CI], 1.29 - 2.08). Compared with the control subjects, the women with preeclampsia had a greater decrease in free triiodothyronine levels (case-to-control ratio, 0.96; 95% CI, 0.92 - 0.99).
In women with preeclampsia, predelivery specimens, but not baseline specimens, were significantly more likely than control specimens to have concentrations of thyroid-stimulating hormone above the reference range (adjusted OR, 2.2; 95% CI, 1.1 - 4.4). The increase in thyroid-stimulating hormone concentration from baseline to predelivery was strongly associated with increasing quartiles of predelivery soluble fms-like tyrosine kinase levels, both in women in whom preeclampsia developed (P for trend = .002) and in normotensive control subjects (P for trend < .001).
In HUNT-2, women who had preeclampsia during their first pregnancy were more likely than other women to have thyroid-stimulating hormone levels greater than the reference range (> 3.5 mIU/l). Adjusted OR was 1.7 (95% CI, 1.1 - 2.5). This finding most likely reflected hypothyroid function in the absence of an autoimmune process because women with preeclampsia were more likely to have high concentrations of thyroid-stimulating hormone without thyroid peroxidase antibodies (adjusted OR, 2.6; 95% CI, 1.3 - 5.0). In women with preeclampsia in both their first and second pregnancies, this association was especially strong (OR, 5.8; 95% CI, 1.3 - 25.5).
"Many of these women still had reduced thyroid function [more than 20 years after their first pregnancies]," said lead author Richard J. Levine, MD, MPH, from NICHD's Division of Epidemiology, Statistics, and Prevention Research in Bethesda, Maryland, said in a news release. "This suggests that a history of preeclampsia may predispose women to the later development of reduced thyroid function."
Limitations of these studies include those inherent in observational studies and lack of follow-up beyond delivery in the Calcium for Pre-eclampsia Prevention trial.
"Increased serum concentration of soluble fms-like tyrosine kinase 1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy," the study authors write.
The NICHD and the National Heart, Lung, and Blood Institute (NHLBI), both of the National Institutes of Health, supported this study. The Calcium for Pre-eclampsia Prevention trial was supported by NICHD and NHLBI. This substudy of the HUNT-2 was supported by the Norwegian University of Science and Technology and by the Central Norway Regional Health Authority.
One of the study authors (Dr. Karumanchi) has disclosed various financial relationships with the Burroughs Wellcome Fund, the Howard Hughes Medical Institute, the American Heart Association, Abbott, Beckman, Coulter, Roche, Johnson & Johnson, and Beth Israel Deaconess Medical Center for the use of angiogenesis-related proteins for the diagnosis and treatment of preeclampsia.
BMJ. Published online November 17, 2009.