新生儿脐带血TT4、TSH与产妇血清TT3、TT4、TSH的比较浅析

目的阐明新生儿期母婴甲状腺功能的变化.方法采用免放法检测72例产妇甲状腺激素水平及其新生儿脐带血TT4、TSH.结果新生儿脐带血TT4、TSH值测定结果正常.产妇血清检测结果TT3、TSH均正常,有23.6%的产妇血清TT4值偏高.结论①产妇TT4水平受甲状腺球蛋白的影响较大,建议检测FT4;②新生儿血TSH标准值为≤5 mU/L,不能完全反映新生儿TSH水平,此标准值值得商榷.     

甲状腺自身抗体阳性妇女孕期干预对婴儿甲状腺功能的影响

目的 探讨甲状腺自身抗体阳性妇女孕期甲状腺功能干预对婴儿甲状腺功能的影响.方法选择产前检查发现的甲状腺过氧化物酶抗体(TPOAb)和(或)甲状腺球蛋白抗体(TgAb)阳性妊娠妇女55例.随机分为干预组(子代为A)36例和非干预组(子代为B)19例,设同期自身抗体阴性对照组(子代为N)30例.选择左旋甲状腺素片作为干预制剂.采用化学发光酶免疫分析法测定3组入选后和分娩前空腹血清TPOAb、TgAb、TSH、TT3、TT4、FT3、FT4水平,同时测定母体尿碘含量.新生儿出生后测定脐血、出生后3～4周及8～10周静脉血TSH、TT3、TT4、FT3、FT4水平.结果干预组、非干预组母体基线血清TSH水平显著高于对照组(P＜0.05).分娩前非干预组与另两组比较,血清TSH增高和TT3、TT4、FT4降低具有统计学差异(P＜0.05或P＜0.01).胎儿出生后脐血TSH水平在B组(7.06±1.31)mIU/L和A组(6.23±1.26)mIU/L均显著高于N组(5.48±1.17)mIU/L(P＜0.01或P＜0.05).出生3～4周新生儿B组血清TSH(3.21±0.70)mIU/L高于N组[(2.72±0.51)mIU/L]和A组[(2.78±0.42)mIU/L,均P＜0.05].出生8～10周婴儿B组血清TSH[(2.99±0.57)mIU/L]高于N组[(2.48±0.68)mIU/L,P＜0.05].多元逐步回归分析,母体TSH、TPOAb及尿碘含量与婴儿TSH独立相关.结论不同甲状腺功能状态的妊娠妇女,其子代出生后的甲状腺功能存在差异.胎儿出生后甲状腺功能与母亲甲状腺自身抗体及孕期甲状腺功能状态有关.     

高龄老年人甲状腺功能检测正常参考值

目的确立80岁以上老年人甲状腺功能正常参考值：方法健康老人81名,分为A组80～89岁高龄老人52名,B组印～69岁老人29名。测定各组血清中三碘甲状腺原氨酸(TT3)、血清总甲状腺素(TT4)、血清游离甲状腺素(FT4)、血清游离三碘甲状腺原氨酸(FT3)及促甲状腺激素(TSH)的含量。结果和结论 80岁以上老年人血TT3为1.22～2．52nmol／L,TT4为59．31～152．49nmol／L,FT4为11．11～22．51pmol／L,FT3为3．28～5．75pmol／L;80岁以上老年男性TSH为0.8～4．2mU/L．女性TSH为0．7-6．1mU/L。     

宿迁地区健康新生儿甲状腺功能正常参考值的研究

目的建立宿迁地区健康新生儿甲状腺功能正常参考值。方法入组健康新生儿500名,抽取72 h 足跟血测定足跟血 TSH。入组200名健康新生儿,出生后14 d 抽取静脉血,检测血清 TT3、TT4、TSH、FT3、FT4。同期选取健康成人120名,检测血清 TT3、TT4、TSH、FT3、FT4。结果本地区健康新生儿72 h 足跟血 TSH 参考范围为0.46~6.59 mIU/ L,14 d 血清 TT3、TT4、TSH、FT3、FT4参考范围分别为1.10~2.62 nmol/ L、81.10~158.28 nmol/ L、0.83~6.39 mIU/ L、3.76~6.66 pmol/ L、10.67~22.27 pmol/ L。与成年人相比较,TSH 差别无统计学意义,TT3、TT4、FT3、FT4差异有统计学意义。结论建立健康新生儿甲状腺功能参考范围值有助于了解新生儿出生后的甲状腺功能水平,根据新生儿72 h 足跟血的 TSH 参考值,建议下调初筛先天性甲状腺功能减退症的切点,以减少其临床漏诊率。     

甲状腺功能与冠心病及其严重程度的相关性研究

目的探讨甲状腺功能与冠心病及其严重程度的关系。方法回顾分析2013年1月至2015年6月在北京大学第一医院因疑诊冠心病进行冠状动脉造影检查并行甲状腺功能检测的患者558例,根据冠状动脉造影结果,分为冠心病组和非冠心病组,分析两组患者甲状腺功能状态,比较甲状腺激素水平和冠心病的关系;采集冠心病组患者的Syntax积分,分析其与甲状腺激素水平的相关性;依据促甲状腺素(TSH)水平进一步分层为升高组、正常组、减低组,分析其与冠心病病变的关系。结果本研究共纳入患者558例,男348例,女210例,平均年龄(62.7±10.9)岁。冠心病组409例(73.3%),平均年龄(63.3±11.0)岁。非冠心病组149例(26.7%),平均年龄(61.2±10.7)岁。两组患者的性别、年龄比较,差异无统计学意义。冠心病组低T3综合征患者比例明显高于非冠心病组(3.4%比1.3%,P=0.018),其他甲状腺功能异常状态两组比较,差异均无统计学意义(均P0.05)。在非低T3综合征患者中分析,冠心病组游离三碘甲状腺原氨酸(FT3)水平低于非冠心病组[(4.52±0.57)pmol/L比(4.65±0.63)pmol/L,P=0.015]。两组患者游离四碘甲状腺原氨酸(FT4)、三碘甲状腺原氨酸(T3)、四碘甲状腺原氨酸(T4)、TSH水平比较,差异均无统计学意义(均P0.05)。非低T3综合征的冠心病,395例患者中根据Syntax积分,低分组264例,中分组59例,高分组72例。FT3水平三组患者比较差异有统计学意义(F=6.260,P=0.002)而TT3、TT4、FT4、TSH水平,三组患者比较差异均无统计学意义。根据冠状动脉病变支数分组,单支病变组160例,双支病变组111例,三支病变组124例,FT3水平三组患者比较差异有统计学意义(F=5.691,P=0.004),TT3、TT4、FT4、TSH水平,三组患者比较差异均无统计学意义。所有患者均进行了TG、TCHO、HDL-C、LDL-C检测,经检验,所有患者的FT3、FT4、TT3、TT4、TSH水平与血脂各组份均未见显著相关性。按正常值范围将FT3、FT4、TT3、TT4、TSH分别分为升高组、正常组、减低组,与冠心病诊断进行卡方检验,FT3、FT4、TT3、TT4差异均无统计学意义,TSH分层与冠心病诊断存在统计学意义(P=0.040)。进一步两两比较,TSH减低组与TSH正常组差异无统计学意义,高TSH组冠心病患者(85.7%)高于TSH正常组(68.6%),差异有统计学意义(P=0.022)。结论甲状腺功能在冠心病组和非冠心病组中差异较小,仅见FT3减低且与冠心病及其严重程度相关。TSH升高可能是影响冠心病发病的因素之一。     

健康高龄老年人甲状腺激素水平变化趋势分析

目的 探讨80岁以上高龄老年人甲状腺激素水平变化趋势.方法 将602例健康志愿者按年龄分为中青年组(20～59岁)226例、老年组(60～79岁)195例和高龄组(80～102岁)181例,采用化学发光法及放射免疫法测定志愿者血清三碘甲状腺原氨酸(TT3)、甲状腺素(TT4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、反T3(rT3)水平,并以SPSS 13.0进行统计分析.结果 老年组与中青年组比较,血清FT3和TT3降低,差异有统计学意义(t值分别为2.793和3.627,均为P＜0.01);高龄组与中青年组比较,TT3、TT4、FT3、TSH、rT3浓度差异有统计学意义(t值分别为10.930、6.065、15.398、-2.933、-5.643,均为P＜0.01);老年组与高龄组比较,TT3、TT4、FT3、TSH、rT3浓度差异有统计学意义(t值分别为8.382、4.298、11.573、-3.383、-5.148,均为P＜0.01).FT3、TT3、TT4浓度与年龄呈负相关(r值分别为-0.51、-0.39、-0.25,P＜0.01),rT3、TSH浓度与年龄呈正相关(r值分别为0.32、0.12,P＜0.01),FT4与年龄无相关.高龄组高于或低于临床正常参考值范围的阳性发生率,在TT3、TT4、FT3、FT4、TSH、rT3中分别为0、0、13.8%、0、6.6%、21%.结论 随着年龄增长,老年人血清甲状腺激素水平及促甲状腺激素均有改变,特别是80岁及以上高龄老年人,血清FT3、rT3、TSH变化更为明显,建议临床设立老年人不同年龄段的血清甲状腺激素正常参考值范围,以减少假阳性的发生率.

Abstract：

Objective To explore the variation tendency of serum thyroid hormone level in the elderly aged over 80 years.Methods The 602 healthy volunteers were divided into 3 groups by age:young group (20-59 years of age,n= 226),elderly group (60-79 years of age,n= 195),and advanced age group (80-102 years of age,n=181).Fasting blood of all persons was harvested,then the levels of serum total triiodothyroxine (TT3),total thyroxine (TT4),free tri-iodothyronine (FT3),free thyroxine (FT4),thyroid-stimulating hormone (TSH) and reverse tri-iodothyronine (rT3) were determined by chemistry luminescence technique and radioimmunoassay.Statistical analysis was made by the software SPSS 13.0.Results The levels of serum FT3 and TT3 were lower in elderly group than in young group (t=2.793,3.627,P=0.005,0.000).There were significant differences in the levels of serum TT3,TT4,FT3,TSH and rT3 between young group and advanced-age group (t =10.930,6.065,15.398,- 2.933,- 5.643,all P = 0.000),also between elderly group and advanced-age group (t= 8.382,4.298,11.573,-3.383,-5.148,all P＜0.001).The levels of serum FT3,TT3 and TT4 were negatively correlated with age (r=- 0.51,-0.39 and -0.25,respectively,all P＜0.01).And the levels of serum rT3 and TSH showed positive relationships with age (r=0.32,0.12,all P＜0.01).There were no relationships between the level of serum FT4 and age.The positive rate of serum TT3,TT4,FT3,FT4,TSH and rT3 concentration beyond the reference value was 0,0,13.8%,0,6.6% and 21% in advanced-age group,respectively.Conclusions The levels of serum thyroid hormone and thyroid-stimulating hormone change with age.The levels of FT3,rT3 and TSH change obviously in the elderly aged over 80 years.It could reduce the false positive rate in clinical practice if normal reference range for serum thyroid hormone levels in different aged elderly is established.     

不同孕期孕妇甲状腺功能相关指标分析

目的 探讨不同孕期孕妇甲状腺激素水平变化及其与抗甲状腺过氧化物酶抗体(TPOAb)之间的关系.方法 377例不同孕期的孕妇,采用固相化学发光酶免疫分析法( ICMA)测定血清促甲状腺激素(TSH)、游离甲状腺激素(FT4)、游离三碘甲状腺原氨酸(FT3)、总甲状腺素(TT4)、总三碘甲状腺原氨酸(TT3)、TPOAb.结果 正常组孕妇早、中、晚期TSH中位数依次上升(均P＜0.05).TPOAb阳性组TSH中位数高于TPOAb阴性组(P＜0.05),TPOAb阳性组中临床和亚临床甲状腺功能减退症(甲减)的患病率高于TPOAb阴性组(P＜0.05).采用FT4及TT4诊断法诊断亚临床甲减患病率分别为18.04％及23.61％;采用TT4及FT4诊断临床甲减的患病率分别为0.27％及5.84％( P＜0.05).结论 应当重视FT4和TT4在妊娠中晚期甲减诊断的差异;应建立孕期正常的甲状腺激素切点值并开展TPOAb的筛查.     

糖尿病血清甲状腺激素水平的变化及其临床意义

对糖尿病患者171例、正常健康成人30例,采用放射免疫分析法测定其甲状腺激素水平.结果糖尿病患者血清总T3(TT3)、总T4(TT4)、游离T3(FT3)、游离T4(FT4)水平均显著低于正常对照组(P值均＜0.01),血清TSH水平无明显变化,rT3水平显著升高,(P＜0.05).结论糖尿病患者血清TH水平下降,rT3升高,TSH无变化对其甲状腺功能的评价具有重要意义.     

糖尿病患者合并低T3综合征35例临床探讨

回顾性分析2014年10月～2017年12月糖尿病患者35例(男20例,女15例,年龄15岁～70岁)。所有患者均无甲状腺机能减退症的病史及临床表现。采用化学发光法,检测总T3(TT3)、总T4(TT4)、游离T3(FT3)、游离T4(FT4)、促甲状腺素(TSH)、r T3水平。对照组为35例血糖控制较好的糖尿病患者,也无甲减病史。结果:糖尿病酮症酸中毒患者总T3(TT3)和游离T3(FT3)降低,反T3(r T3)明显升高(P〈0. 05),血清甲状腺素(T4)、促甲状腺激素(TSH)水平正常。均未使用甲状腺激素。治疗2周后的T4恢复正常。结论:糖尿病合并低T3综合征,多见于有严重的并发症者,是患者疾病危重的信号。     

左旋甲状腺素治疗妊娠期亚临床甲减妇女对后代神经智力发育影响的前瞻性研究

目的 通过前瞻性观察妊娠期亚临床甲状腺功能减退(甲减)妇女左旋甲状腺素(L-T4)治疗后甲状腺功能指标的动态变化和后代神经智力的发育情况,探讨L-T4对妊娠期亚临床甲减妇女后代神经智力发育的影响.方法17例亚临床甲减孕妇未接受治疗(SCH组),23例亚临床甲减孕妇接受L-T4治疗(SCH+LT4组),24例正常孕妇(C组)作为对照组.3组孕妇分别在妊娠12周(G12)、16周(G16)、20周(G20)、24周(G24)、28周(G28)、32周(G32)和(或)36周(G36)接受随访检查,检测血清TSH、TT4、FT4、TT3、FT3、甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb).应用Bayley量表对所有孕妇的后代在14～30月龄检测智力和运动评分.结果SCH组、SCH+LT4组和C组孕妇后代的智力发育指数(MDI)分别为115.12分、118.56分和117.63分;运动发育指数(PDI)分别为115.47分、120.65分和117.50分.与其他两组比较,SCH+LT4组MDI和PDI评分均较高,SCH组MDI和PDI评分均较低,但3组间比较没有统计学差异.SCH组孕妇的血清TSH在妊娠过程中始终保持在2.0 mIU/L以上,各时点都明显高于C组(均P＜0.05);血清TT4和FT4水平除G28和G32外其他时点均略低于同时点C组水平.SCH+LT4组孕妇基础血清TSH水平明显高于其他两组(均P＜0.01),血清TT4和FT4水平则低于其他两组;在接受L-T4治疗后血清TSH水平明显下降,自G12至孕末期始终与C组水平相当,且低于同时点SCH组孕妇的水平;血清TT4和FT4水平则明显升高至与对照组相当的水平.结论L-T4的及时治疗能够维持妊娠早期亚临床甲减患者妊娠全程血清TSH在正常水平,这很可能会避免后代智力和运动能力发育水平的下降.     

Serum free thyroid hormones in subclinical hypothyroidism

Serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations were measured in a group of 52 patients with subclinical hypothyroidism (SH) and in an equal group of age and sex-matched normal controls. SH was defined by normal total T4 (TT4) and total T3 (TT3) concentrations, normal FT4 and FT3 indices, raised TSH levels, in the absence of signs and symptoms of hypothyroidism. Serum FT4 levels averaged 6.1 +/- 1.6 pg/ml (mean +/- SD, p less than 0.001 vs controls), with values below lower normal limits in 33/52 patients; mean FT3 concentrations averaged 3.1 +/- 0.7 pg/ml (p less than 0.001 vs controls), with values below lower normal limits in 8/52 patients. The analysis of results by the Galen and Gambino predictive value model demonstrated a higher sensitivity, but a lower specificity of FT4 as compared to FT3 in the diagnosis of SH. These results indicate that FT4 should be measured in addition to TSH for the diagnosis of impending thyroid failure, thus showing that in many cases patients with so-called subclinical hypothyroidism are actually already mild hypothyroid.     

二甲双胍对促甲状腺素影响的初步研究

目的 观察二甲双胍对血清促甲状腺素(TSH)的影响.方法从2型糖尿病患者中,入选原发性甲状腺功能减退症(甲减)患者48例,组1单用二甲双胍而未予左旋甲状腺素(L-T4)替代治疗(n=17),组2给予L-T4稳定替代量的同时加用二甲双胍(n=19),组3用L-T4稳定替代量和非二甲双胍的其他降糖药(n=12).另外20例甲状腺功能正常的其他甲状腺疾病患者(组4)和30例无甲状腺疾病的患者(组5)作为对照.各组患者均定期检测血清TSH、FT3、FT4、TT3、TT4及血糖等主要指标的变化.结果 治疗12个月与基线时比较,组1为(5.05±1.07)对(2.61±0.91)mU/L(P＜0.01),组2为(2.67±1.03)对(1.35±0.74)mU/L(P＜0.01),两组的FT3及FT4均无明显变化.15例TSH显著降低的患者中有13例(87%)在停用二甲双胍后8～12周内TSH由(1.30±0.71)回升至(2.58±1.02)mU/L(P＜0.01).组3、组4及组5的血清TSH和甲状腺激素的水平均无明显改变.结论 服用二甲双胍可使TSH下降.

Abstract：

Objective To evaluate the effects of metformin on thyrotropin(TSH)levels. Methods From the patients with type 2 diabetes mellitus or metabolic syndrome, 48 patients with primary hypothyroidism were enrolled and grouped. 17 patients were treated only with metformin(group A), 19 patients with metformin and stable L-T4substitution(group B), and the remaining 12 patients with antidiabetic drugs(other than metformin)and L-T4(group C). Meanwhile, 20 euthyroid patients with other thyroid abnormalities(group D)and 30 patients without thyroid diseases(group E)served as control. TSH, FT3, FT4, TT3, TT4, and blood glucose were determined regularly in all these subjects. Results After administration of metformin for 12 months, serum TSH were decreased in group A [(5.05±1.07 vs 2.61±0.91)mU/L, P＜0.01] and group B [(2.67±1.03 vs 1.35±0.74)mU/L, P＜0.01]. No difference was found in FT3and FT4in both groups. TSH levels were raised from(1.30±0.71)to(2.58±1.02)mU/L(P＜0.01)within 8～12 weeks in 13 out of 15 patients after metformin withdrawal. Serum TSH and thyroid hormones in the other 3 groups were not significantly changed. Conclusion Administration of metformin may lead to reduction of serum TSH level.     

Basal oxygen uptake: a new technique for an old test

To assess the metabolic effects of T4 and T3, we measured serum total T4 (TT4), free T4 (FT4), total T3 (TT3), TSH, and basal oxygen uptake (VO2) in eight normal subjects in the basal state and after treatment with L-T3 (T3) and sodium ipodate for 2 weeks. T3 treatment resulted in a rise of serum TT3 from a baseline of 137 +/- 16 (+/- SE) to a peak of 239 +/- 15 ng/dl. Serum TT4 declined from 8.14 +/- 0.56 to 6.08 +/- 0.43 micrograms/dl, FT4 from 1.59 +/- 0.13 to 1.03 +/- 0.05 ng/dl, and TSH from 1.74 +/- 0.24 to 0.56 +/- 0.16 microU/ml. Basal VO2 increased from 2.66 +/- 0.11 to 3.15 +/- 0.09 ml/kg X min. Ipodate, on the other hand, led to a lower serum TT3 concentration (102 +/- 21 ng/dl), higher serum TT4 and FT4 (9.59 +/- 0.5 micrograms/dl and 1.91 +/- 0.13 ng/dl, respectively), and elevated TSH (3.64 +/- 0.14 microU/ml). Basal VO2 was reduced to 2.44 +/- 0.06 ml/kg X min. Linear regression analysis revealed an excellent positive correlation between serum TT3 and basal VO2 (n = 25; r = 0.747; P less than 0.001) and a significant negative correlation between serum TT3 and TSH (n = 26; r = -0.526; P less than 0.01). Serum TT4 and FT4 correlated negatively with VO2 and positively with serum TSH. The higher T4 level during ipodate treatment was associated with lower VO2 and higher TSH, and vice versa when T4 was suppressed while receiving T3. When ipodate was given concomitantly with T3 to five subjects, only the effects of T3, characterized by increased VO2 and decreased TSH, were evident. These data indicate that both basal VO2 and serum TSH are sensitive indices of thyroid hormone activities. The latter gives only the directional change (hyper- or hypothyroidism), while the former more accurately quantitates the magnitude of the derangement. Moreover, it appears that in man, T3, and not T4, is the primary hormone that regulates thermogenesis and TSH secretion.     

Evaluation of L-thyroxine replacement therapy in children with congenital hypothyroidism.

The outcome of L-thyroxine (L-T4) replacement therapy in children with congenital hypothyroidism (CH) remains to be completely evaluated. In this paper the overall pattern of response to L-T4 replacement therapy was studied in a group of 19 children with CH diagnosed by neonatal screening (10 with hypoplastic/aplastic thyroid disease, group H/A; 9 with gland ectopy, group E) who were followed-up for 60 +/- 27 months (mean +/- SD). With 1 exception serum T4 at diagnosis was greater than 2 micrograms/dl in children of group E and less than 2 micrograms/dl in those of group H/A. The initial dose of L-T4 (8-10 micrograms/kg BW/day) was modified in relation to age and weight in order to maintain serum TSH less than or equal to 5 microU/ml and FT3 in the normal range. A general inverse correlation between serum TSH and FT4 or FT3 concentrations was found, and the mean levels of serum FT4 and FT3 were significantly higher according to the following order of TSH results: low TSH (0-0.5 microU/ml) greater than normal (greater than 0.5-5 microU/ml) greater than elevated TSH (greater than 5 microU/ml). TSH levels less than or equal to 5 microU/ml were associated with FT4 values in the upper half of the normal range (54% of observations) or even higher (46%). Elevation of serum FT4 alone with FT3 values in the normal range did not result in clinical thyrotoxicosis, alteration of growth or premature craniosynostosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the effect of L-thyroxin therapy on endothelial functions in patients with subclinical hypothyroidism

Subclinical hypothyroidism (SH) is characterized by normal serum free T4 (FT4), free T3 (FT3) levels and increased serum thyroid-stimulating hormone (TSH) levels. Endothelial dysfunction, which is an early step of atherosclerosis, has been reported in patients with subclinical hypothyroidism. The aim of this study is to evaluate endothelial functions and the effect of L-thyroxin (L-T4) therapy on endothelial functions in SH. Twenty-seven patients with SH and 22 healthy controls were evaluated in terms of endothelial functions, using brachial artery Doppler ultrasonography. After restorating euthyroidism, measurements were repeated. Baseline and nitroglycerin induced diameter (NID) of brachial artery were similar in patients with SH and the control group. Compared to the control group, the patients with SH showed significantly reduced flow-mediated diameter (FMD). Baseline and NID values were significantly higher after LT4 therapy in SH group. FMD also significantly increased after LT4 therapy. Hypothyroidism accelerates atherogenesis through modification of atherosclerotic risk factors and direct effects on the blood vessels. In this study, we observed marked improvement in endothelial functions after L-T4 therapy in SH patients. We suggest that thyroid hormone replacement therapy may help to prevent atherosclerosis in this group of patients.     

Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism

As there are few data on the evaluation of the adequacy of levothyroxine (L-T4) therapy in patients with central hypothyroidism (CH), a prospective study was performed to assess the accuracy of various parameters in the follow-up of 37 CH patients. Total and free thyroid hormones, TSH, and a series of clinical and biochemical indexes of peripheral thyroid hormone action have been evaluated off and on L-T4 therapy. Samples were taken before the daily administration of L-T4. In all patients off therapy, clinical hypothyroidism and low levels of free T4 (FT4) were observed, whereas values of FT3, total T4, and total T3 were below the normal range in 73%, 57%, and 19% of cases, respectively. Most of the indexes of thyroid hormone action were significantly modified after L-T4 withdrawal and exhibited significant correlation with free thyroid hormone levels. During L-T4 replacement therapy, 32 patients had circulating levels of FT4 and FT3 and indexes within the normal range with a mean L-T4 daily dose of 1.5 +/- 0.3 microg/kg BW. Despite normal serum FT4, 3 patients had borderline high values of FT3 and a clear elevation of serum-soluble interleukin-2 receptor concentrations, suggesting overtreatment. Low or borderline low FT4/FT3 levels indicated undertreatment in 2 patients. The clinical parameters lack the required specificity for the diagnosis or follow-up of CH patients. The L-T4 daily dose should be established, taking into account the weight, the age, and the presence of other hormone deficiencies or pharmacological treatment of CH patients. In conclusion, our results indicate that the diagnosis of CH is reached at best by measuring TSH and FT4 concentrations. In the evaluation of the adequacy of L-T4 replacement therapy, both FT4 and FT3 serum levels together with some biochemical indexes of thyroid hormone action are all necessary to a more accurate disclosure of over- or undertreated patients.     

SERUM IODOTHYRONINE CONCENTRATIONS DURING INTRODUCTION OF THYROXINE REPLACEMENT THERAPY IN HYPOTHYROIDISM

Serum concentrations of total and free T4 (TT4 and FT4), total and free T3 (TT3 and FT3), rT3, T4 binding globulin (TBG), T3 uptake (T3U) and TSH were measured in 12 patients with severe hypothyroidism before and during the introduction of replacement therapy with oral T4. The dose of T4 was increased by increments of 50 micrograms at intervals of 4 weeks to a total of 200 micrograms daily. There was a linear correlation between the concentrations of FT3 and FT4 (FT3 = 1.35 + 0.23FT4, r = 0.916, P less than 0.001). The correlation between TT3 and TT4 was more complex: the data were best fitted by the expression TT3 = 0.195 square root TT4, (r = 0.936, P less than 0.001). The relatively greater rise in TT3 initially may reflect a greater binding of T3 by TBG when the concentration of T4 is low. TBG concentration fell after 50 and 100 micrograms of T4 but did not change at the higher doses. There was a simple linear relation between TT4 and rT3 (rT3 = -0.022 + 0.0027TT4, r = 0.921, P less than 0.001). The expected inverse relation between TSH concentration and the thyroid hormones was seen, the three closest correlations being between the logarithm of the TSH concentration and FT3, the ratio T4/TBG and FT4 (r = 0.927, -0.917 and -0.900 respectively). These correlations were significantly better (P less than 0.05) than the correlations with untransformed TSH values. Suppression of TSH occurred while FT3 tended to remain within normal limits, but FT4 was often raised.(ABSTRACT TRUNCATED AT 250 WORDS)     

Free thyroid hormones in evaluating persistently elevated thyrotropin levels in children with congenital hypothyroidism on replacement therapy

Some children with congenital hypothyroidism receiving L-T4 therapy have elevated serum TSH levels despite having normal serum T4 concentrations, suggesting that they have a higher threshold for the feedback regulation of TSH release. To further study this possibility, we determined serum free T4 (FT4) and T3 (FT3) concentrations in two groups of L-T4-treated hypothyroid children. Group A consisted of 10 patients with high serum TSH levels; group B consisted of 10 patients with normal TSH levels. All patients were clinically euthyroid, and serum total T4 and T3 concentrations were similar in the two groups. A third (control) group (C) consisted of randomly selected normal children. The three groups were age matched. Serum FT3 and FT4 were significantly lower in group A compared to group B. Serum FT4 and T4 were higher and TSH was lower in group B compared to group C. The T4/T3 ratio wash higher in both groups of children with hypothyroidism than in group C. We conclude that in most patients a high serum TSH was due to inadequate L-T4 therapy, as shown by free hormone concentrations (low) but not by total hormone levels (normal). This suggests that L-T4 therapy should be monitored by measurement of TSH and free hormone concentrations. The latter also can be used to indicate moderate overdosage, not clinically detectable, as shown by the comparison between groups B and C. Measurement of serum total T4, as indicated by the lack of difference between groups A and B and also by T4/T3 ratio, cannot be considered a reliable index of therapeutic adequacy in such children.