碘充足地区血清TSH正常值范围及其影响因素的流行病学研究

目的 分析血清TSH测定的影响因素,参考美国国家临床生化协会(NACB)指南,建立中国辽宁碘充足地区血清TSH的正常参考范围.方法 2007年,来自辽宁省3个碘充足地区的5 348人参加了甲状腺疾病的社区调查,进行了TSH、甲状腺自身抗体[甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb)]的测定,并作了甲状腺超声检查和问卷调查.结果 正常人群的TSH分布向右偏斜,接近于对数正态分布.年龄在12～19岁血清TSH水平明显高于其他年龄段(P＜0.01),而其他年龄段之间无统计学差异.血清TSH水平女性[(1.68±1.90)mIU/L]明显高于男性[(1.45±1.92)mIU/L,P＜0.01].因此,年龄大于20岁的健康男性TSH的分布范围是0.43～4.74 mIU/L,健康女性TSH的分布范围是0.48～5.39 mIU/L.甲状腺疾病家族史、甲状腺超声异常、甲状腺抗体阳性均影响TSH的测定水平,非甲状腺疾病对TSH参考范围没有显著影响.结论建立了碘充足地区血清TSH参考范围.

Abstract：

Objective To verify the criteria proposed by National Academy of Clinical Biochemistry(NACB)guidelines in investigating the factors that affect serum TSH determination, and to determine the reference range of serum TSH in iodine-sufficient areas of China. Methods In 2007, 5 348 inhabitants were enrolled from 3 iodine-sufficient areas of Liaoning Province, and were asked to fulfill the questionnaire. Serum TSH, thyroid peroxidase antibody(TPOAb), and thyroglobulin antibody(TgAb)were determined, and thyroid ultrasonography was carried out. Results The distribution of TSH levels was skewed in healthy people and closely fit the curve of Gaussian distribution after logarithmic transformation. The levels of TSH in subjects of 12-19 years of age were significantly higher than those of other age groups(P＜0.01), and no significant difference was found among the latter groups. TSH level in females [(1.68±1.90)mIU/L] was higher than in males[(1.45±1.92)mIU/L, P＜0.01]. The reference range of TSH was 0.43-4.74 mIU/L in males, and 0.48-5.39 mIU/L in females. Family history of thyroid disease, abnormal thyroid ultrasonography, and positive thyroid antibodies were the factors that influenced TSH level. Conclusion The reference range of serum TSH in iodine-sufficient areas of China is established.     

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。     

子痫前期患者甲状腺功能变化观察

目的观察子痫前期(PE)孕妇甲状腺功能的变化。方法 174例子痫前期患者,其中轻度PE 83例,重度PE 91例,另选择301例正常妊娠晚期妇女为正常对照组。采用电化学发光技术(ECL)检测血清TSH、FT4、TPO-Ab水平。结果 PE组TSH为2.69(0.58～12.88)mIU/L、FT4为12.13(8.65～17.06)pmol/L、TPOAb为12.55(5.0～98.36)IU/mL,正常对照组分别为2.14(0.56～6.89)mIU/L、12.52(9.30～17.14)pmol/L、8.03(5～21.96)IU/mL,两组患者TSH、FT4、TPOAb相比P均<0.05。PE组轻度PE患者TSH为2.41(0.66～7.77)mIU/L、FT4为12.80(9.27～17.95)pmol/L、TPOAb为13.30(5.0～102.79)IU/mL,重度PE患者分别为3.17(0.14～15.95)mIU/L、11.47(8.53～16.37)pmol/L、11.20(5.0～150.02)IU/mL,轻重度PE患者TSH、FT4、TPOAb相比P均<0.05。子痫前期孕妇血清TSH、TPOAb明显升高、FT4水平明显降低(P均<0.05);与轻度PE相比,重度PE孕妇血清TSH明显升高、FT4水平明显降低(P均<0.05);PE孕妇TPOAb阳性率达12.1%(21/174),与同期筛查组相比P>0.05;子痫前期患者合并各种甲状腺疾病,低T4血症发生率显著高于同期筛查组(P均<0.05)。结论子痫前期患者血清TSH、TPOAb升高、FT4降低。     

重组人促甲状腺素介导分化型甲状腺癌的131I治疗

目的 研究重组人促甲状腺素(rhTSH)介导分化型甲状腺癌131I治疗对内源性TSH、甲状腺球蛋白、FT3、FT4的影响及其清甲成功率.方法 31例(年龄14～70岁,其中女性23例)接受rhTSH介导的131I治疗(甲状腺功能正常组),31例(年龄23～72岁,其中女性22例)停用甲状腺素后的行131I治疗[甲状腺功能减退组(甲减组)]观察注射rhTSH前后血清TSH、FT3、FT4以及甲状腺球蛋白抗体(TGAb)、甲状腺球蛋白浓度变化,以及131I治疗后6～12个月131I全身诊断显像评价其疗效.结果 使用rhTSH前后,血清TSH、甲状腺球蛋白、FT3、FT4的平均浓度分别是(1.08±4.01)和(140.26±27.20)mIU/L(P＜0.05)、(23.75±132.92)和(169.58±178.49)μg/L(P＜0.05)、(4.52±1.16)和(4.42±1.11)pmol/L(P＞0.05)、(15.09±5.83)和(13.66±5.85)pmol/L(P＞0.05).诊断剂量131I-全身显像显示甲状腺功能正常组24/31(77.4%)及甲减组22/31(71.0%)被考虑成功清甲(P＞0.05).以甲状腺球蛋白评价两组131I治疗疗效统计学无显著差异(P＞0.05),甲状腺功能正常组20/31(64.50%)及甲减组18/31(58.06%)被考虑成功清甲.结论 使用rhTSH能有效刺激内源性TSH增高,提高生活质量,获得较高的清甲成功率.使用rhTSH能有效刺激血清甲状腺球蛋白,有利于监测肿瘤残存、复发与转移.

Abstract：

Objective To observe the influence of recombinant human thyrotropin(rhTSH)on serum concentration of endogenous thyrotropin(TSH), free triiodothyronine(FT3), free thyroxine(FT4), thyroglobulin antibody(TGAb), and thyroglobulin(Tg). To evaluate the efficacy of rhTSH-aided radioiodine treatment in patients with differentiated thyroid carcinoma(DTC). Methods The study recruitment took place between November 2007 and March 2009. 62 patients(including 45 females)with biopsy confirmed DTC had undergone total or nearly total thyroidectomy, and received 131I treatment. 31 patients(including 22 females), median age of 45 years(23-72), received radioiodine treatment 4 weeks after L-thyroxine(T4)withdrawal. The other 31 patients(including 23 females), median age of 44 years(14-70), underwent rhTSH-aided radioiodine treatment. Before and after rhTSH injection, serum TSH, FT3, FT4, TGAb, and thyroglobulin were tested. Post-radiotherapy whole body scan was performed 5 to 7 days after radioiodine treatment and qualitatively and blindly evaluated by two nuclear medicine physicians. Follow-up took place 6 to 12 months after radioiodine treatment. The efficacy of rhTSH-aided radioiodine treatment was evaluated by whole body scan with diagnostic dose radioiodine. SPSS 13.0 statistical software was applied. Results (1)Before and after rhTSH-aided radioiodine treatment, the serum TSH was(1.08±4.01)vs(140.26±27.20)mIU/L(P＜0.05), thyroglobulin(23.75±132.92)vs(169.58±178.49)μg/L(P＜0.05), FT3(4.52±1.16)vs(4.42±1.11)pmol/L(P＞0.05), and FT4(15.09±5.83)vs(13.66±5.85)pmol/L(P＞0.05),respectively.(2)rhTSH-aided radioiodine ablation treatment had the same effect as L-T4withdrawal aided. The complete response ratio was 77.4% vs 71.0%(P＞0.05)by radioiodine whole body scan of diagnostic dose. Conclusion rhTSH-aided radioiodine treatment of DTC was effective and safe, and did at least at equivalent degree as did L-T4withdrawal. Furthermore, Serum thyroglobulin level could be effectively stimulated by rhTSH with tumor relapse or metastasis.     

水源性高碘摄入对学龄儿童甲状腺功能和甲状腺疾病的影响

目的探讨高碘摄入对儿童甲状腺功能和甲状腺抗体及甲状腺疾病的影响。方法在3个高水碘浓度的村庄对学龄儿童进行流行病学调查和样本采集。触诊甲状腺,检测饮用水碘含量和尿碘水平,测定垂体-甲状腺激素(TSH、FT3、FT4)水平和甲状腺自身抗体(TPOAb、TGAb)水平。结果 3个调查点的水碘中位数分别156.95μg/L、241.26μg/L和433.63μg/L;MUI为319.30μg/L、473.17μg/L和764.17μg/L;TSH为3.22 mU/L、4.27 mU/L和3.27 mU/L;FT3为6.00 pmol/L、5.83 pmol/L和5.96 pmol/L;FT4为17.29 pmol/L、17.62 pmol/L和16.36 pmol/L。TSH水平在水碘241.26μg/L、UI为200～299μg/L即超过适宜量情况下较高。3个调查点TSH高于正常值上限的异常率分别为18.2%、36.1%和14.7%;FT3分别为21.2%、5.6%和14.7%;TSH和FT3均无检测出低于正常值下限的。103名被检者的TGR为18.4%,发现亚甲减患者24例,亚甲减检出率为23.3%。100～199μg/L尿碘组无亚甲减患者,200～299μg/L尿碘组亚甲减检出率43.7%,≥300μg/L组的检出率20.7%。TPOAb、TGAb阳性率各为2.1%。结论水源性高碘摄入可导致高碘性甲状腺肿流行,引起部分机体甲状腺功能异常,造成亚甲减发病率升高。建议对此开展深入研究。     

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.     

Graves病患者甲状腺激素水平正常后sTSH长期抑制机制的探讨

目的 探讨临床上部分Graves病(GD)患者经抗甲状腺药物(ATD)治疗后甲状腺激素水平达到正常,但促甲状腺素(TSH)仍长期处于被抑制状态的机制.方法 入选初发122例GD甲亢患者,予以初始等效剂量的ATD治疗,每月随访时根据甲状腺功能测定的结果酌情减量,并适时添加左旋甲状腺素(L-T4).当甲状腺激素(FT3、FT4)水平持续正常3个月即达随访标准,复查FT3、FT4、sTSH、TSH受体抗体(TRAb),并根据TRAb是否阳性分组比较.结果 122例GD甲亢患者经(7.1±1.1)个月的ATD治疗后,甲状腺激素水平均已经达到正常3个月.随访时,58例TRAb转为阴性,64例TRAb持续阳性.两组甲状腺激素水平无差异, TRAb阳性组的sTSH水平明显低于阴性组[0.044 mIU/L(0.001～4.163 mIU/L) vs 1.749 mIU/L(0.079～4.646 mIU/L),P＜0.01];血清sTSH水平与TRAb呈明显负相关(r=-0.539,P＜0.01),与FT3、FT4、年龄、病程、治疗时间、L-T4剂量、L-T4添加时间等均无相关性.结论 药物治疗过程中,甲状腺激素水平正常的GD患者,其TSH水平长期受抑制的原因与高水平TRAb相关,可能由于TRAb直接与垂体内TSH受体结合,通过超短环反馈抑制TSH的分泌所致.     

甲状腺动脉栓塞术后并发脑栓塞及甲亢危象一例

患者女性,36岁,心悸、多汗、乏力4年,加重伴手抖、易激动1月入院,因该病人甲亢病史4年,不能坚持规律服药,内科治疗期间多次复发(未曾应用过放射性碘治疗),而选择行甲状腺栓塞术。甲状腺功能示:FT335.8pmol/L(3.09～9.83pmol L),FT488.0pmol/L(8.07～26.26pmol/L),TSH2.0mIU/L(3     

浅谈临床应用贝克曼全自动化学发光免疫分析仪检测甲状腺素的效果

目的综合评价临床应用贝克曼全自动化学发光免疫分析仪检测甲状腺素的效果。方法采用贝克曼全自动化学发光免疫分析仪测定T3、T4、FT3、FT4、TSH含量,分别计算批内精密度、批间精密度、回收率和线性范围。结果 T3、T4、FT3、FT4、TSH的批内精密度分别为4.40%、4.90%、3.00%、4.50%、3.50%,批间精密度分别为6.90%、5.30%、3.50%、6.20%、4.80%;回收率分别为96.7%、95.5%、97.1%、95.6%、96.4%,线性范围分别为0.15～12.3 nmol/L、3.9～387.0 nmol/L、0.3～30.8 pmol/L、1.3～155.0 pmol/L、0.01～150.0 mIU/L。结论临床应用贝克曼全自动化学发光分析系统测定甲状腺功能具有灵敏度高,可报告范围宽,测定速度快,重复性好等优点,适合于临床应用。     

肝硬化患者血清促甲状腺激素和甲状腺素水平变化及其临床意义*

目的分析血清TSH、FT3、FT4水平与肝硬化肝功能损害程度的相关性。方法对我院于2013年7月至2015年6月收治的肝硬化患者120例和门诊体检为无异常的健康者120例的临床资料进行回顾性分析。对比健康人和肝硬化组患者血清促甲状腺激素（TSH）、血清游离三碘甲状腺原氨酸（FT3）和血清游离甲状腺素（FT4）水平和肝功能指标白蛋白（ALB）、总胆红素（TBIL）水平,将肝硬化组患者按照Child-Pugh改良分级法分为A、B、C三组,对比三组患者血清TSH、FT3和FT4水平以及肝功能指标ALB和TBIL水平。结果肝硬化组患者血清TSH水平为（8.64±1.22） mIU/L,高于健康人（3.96±0.67） mIU/L（t=36.833,P=0.000）,FT3和FT4水平分别（3.16±0.51pmol/L、10.29±1.43pmol/L）,均低于健康人（6.09±0.94 pmol/L、19.20±3.42 pmol/L）（t值分别为30.013、26.330,均P=0.000）。肝硬化组患者血清ALB水平为（29.64±3.61） g/L,低于健康人（45.62±5.40） g/L（t=26.950,P=0.000）,血清TBIL水平为（45.96±4.19）μmol/L,高于健康人（13.52±2.16） μmol/L（t=75.385,P=0.000）。肝功能分级越高,患者血清TSH随之升高,但组间相比,差异无显著性（F=2.262,P=0.159）,FT3和FT4水平随肝功能分级升高而降低,组间相比,差异具有显著性（F值分别为7.737和5.286,P值分别为0.029和0.037）。肝功能分级越高,患者血清ALB越低,组间相比差异具有显著性（F=8.629,P=0.025）,血清TBIL水平随肝功能分级升高而升高,组间相比差异具有显著性（F=8.854,P=0.024）。TSH、FT3和FT4水平与血清ALB和TBIL水平的Pearson相关分析显示TSH水平和肝硬化组肝功能指标ALB和TBIL无相关性（r=-0.096,P=0.296;r=0.115,P=0.159）,FT3和FT4水平与肝功能指标ALB呈正相关（r=-0.468,P=0.031;r=0.391,P=0.045）,和TBIL水平呈负相关（r=-0.491,P=0.029;r=-0.435,P=0.036）。结论肝硬化患者肝功能损害程度越高,血清甲状腺激素FT3和FT4的水平越低,且与FT3和FT4水平呈负相关,肝功能受损会影响患者血清TSH水平,但无线性相关性。     

二甲双胍对糖尿病患者血清促甲状腺激素水平的影响

目的探讨二甲双胍对未服用甲状腺激素的糖尿病患者血清甲状腺激素和促甲状腺激素水平的影响。方法测定未服用甲状腺激素的糖尿病患者的血清游离三碘甲腺原氨酸（FT3）、游离甲状腺素（FT4）、总三碘甲腺原氨酸（TT3）、总甲状腺素（TT4）和促甲状腺激素（TSH）的水平，并分析其与是否服用二甲双胍的关系。结果未服用二甲双胍组与服用二甲双胍组的血清FT3（4.65±0.68vs4.59±0.67pmol/L）、FT4（17.88±3.26vs17.75±2.85pmol/L）、TT3（1.79±0.42vs1.77±0.38nmol/L）、TT4（107.9±22.1vs109.2±22.1nmol/L）和lnTSH（0.49±0.83vs0.47±0.87mU/L）之间的差异无统计学意义（P〉0.05）。结论未服用甲状腺激素的糖尿病患者在服用二甲双胍期间促甲状腺激素的水平不受影响。     

Reference intervals of serum thyroid function tests in a previously iodine-deficient area.

AIM: We undertook the present study to establish reference data for serum thyroid function tests in a previously iodine-deficient area. METHODS: Data from 4298 individuals, 20-79 years of age were available for the present analysis. Thyroid function (thyrotropin [TSH], free triiodothyronine [FT(3)], and free thyroxine [FT(4)]) and serum autoantibodies to thyroperoxidase (anti-TPOAb) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. RESULTS: A reference population was selected comprising 1488 persons (825 men) by excluding subjects with known thyroid diseases, and with yet unknown thyroid disorders such as goitre, inhomogeneous thyroid pattern, nodules, hypoechogenicity and anti-TPOAb seropositivity. Reference intervals for serum TSH, FT(3), and FT(4) were 0.25-2.12 mIU/L, 3.8-7.0 pmol/L, and 8.3-18.9 pmol/L, respectively. Reference serum TSH levels were not comparable to the reference values that were recently established for the U.S. population and most reference values slightly differed from the reference values provided by the manufacturers. CONCLUSIONS: The reference ranges of thyroid function tests in this formerly iodine-deficient region are distinct from the reference ranges that were established in areas with iodine sufficiency. Creating a reference population in the present setting should include thyroid ultrasound in order to exclude yet undiagnosed thyroid disorders.     

The influence of caloric deprivation and food composition on TSH, thyroid hormones and nuclear binding of T3 in mononuclear blood cells in obese women

In vivo changes in thyroid-stimulating hormone (TSH), thyroxin (T4), triiodothyronine (T3) and nuclear binding of T3 (NBT3) in mononuclear blood cells were studied in obese women during seven days of caloric deprivation (maximum 1,100 kcal/d). In seven women given a high protein diet (80% protein, 7% carbohydrates, 7% fat) and in two women who fasted (group 1), total T3 (TT3) decreased from 1.66 +/- 0.43 nmol/L to 1.11 +/- 0.32 nmol/L (P less than .01), free T3 (FT3) decreased from 5.7 +/- 1.1 pmol/L to 4.3 +/- 1.6 pmol/L (P less than .01), and free T4 (FT4) increased from 17.8 +/- 2.3 pmol/L to 21.1 +/- 2.0 pmol/L (P less than .01). In five women given a carbohydrate diet (Dextrin-maltose 100%) (group 2), thyroid hormones were unchanged, TT3 was at start 1.66 +/- 0.24 nmol/L and after seven days 1.43 +/- 0.26 nmol/L (NS), FT3 changed from 6.4 +/- 1.8 pmol/L to 6.0 +/- 2.1 pmol/L (NS) and FT4 changed from 20.4 +/- 5.1 pmol/L to 20.6 +/- 3.1 pmol/L (NS). The caloric intake and the weight reduction was the same in the two groups. Basal TSH and TSH after thyrotropin-releasing hormone (TRH) (TSH+30min) declined in both groups. In group 1, basal TSH declined from 1.88 +/- 1.07 microU/mL (P less than .03), and TSH+30min declined from 12.44 +/- 7.49 microU/mL to 9.38 +/- 5.97 microU/mL (P less than .03). In group 2, basal TSH declined from 2.09 +/- 0.87 microU/mL to 1.66 +/- 0.92 microU/mL (P less than .03), and TSH+30min declined from 15.63 +/- 7.90 microU/mL to 11.93 +/- 7.20 microU/mL (NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transient elevation of triiodothyronine caused by triiodothyronine autoantibody associated with acute Epstein-Barr-virus infection.

A unique 16-year old female patient presented after acute Epstein-Barr virus (EBV) infection with severe primary hypothyroidism. Her thyroid test results were thyrotropin level (TSH) of 198 mU/L (normal, 0.4-4 mU/L), free thyroxine [FT(4)], 2.5 pmol/L (normal, 10-25 pmol/L), total triiodothyronine (TT(3)) > 19.5 nmol/L (normal, 1.3-2.7 nmol/L), and free triiodothyronine (FT(3)), 0.77 pmol/L (normal, 3.3-6.3 pmol/L). She had high titers of thyroglobulin and thyroid peroxidase autoantibodies. In vitro triiodothyronine (T(3))-binding measured by radioimmunoprecipitation was 86% (normal, up to 8.5%) and thyroxine (T(4))-binding 8.2% (normal, 6.4%). Serum immunoglobulin G (IgG) absorption, achieved by protein-G Sepharose beads, decreased TT(3) toward normal. Levothyroxine treatment normalized the low baseline FT(4) and FT(3) values, and suppressed TSH to normal. However, TT(3) remained highly elevated and returned to normal after 20 months, while T(3 )binding gradually decreased. Thus, her severe hypothyroidism was masked by this unusual phenomenon. Thirty-four patients with EBV infection (15 with acute disease and 19 with previous infection) were tested for thyroid hormone levels. EBV antibodies (early antigen immunoglobulin M [IgM] and IgG and anti-Epstein-Barr virus nuclear antigen [EBNA] IgG) were measured by enzyme-linked immunosorbent assay (ELISA). In 15 patients with acute EBV the mean TT(3) level was 2.47 +/- 0.39 nmol/L (5 had TT(3) values above normal) compared to a mean TT(3) of 1.70 +/- 0.53 nmol/L in 19 subjects with previous infection (p < 0.0005; only 1 had a TT(3) result above normal), with no differences in FT(4) and TSH concentrations between the two groups. Acute EBV infection may be associated with transient mild to severe TT(3) elevation as a result of assay interference by anti-T(3) autoantibodies.     

Free thyroxine values in dried blood spots on filter paper in newborns are related to both gestational age and birth body weight

The results of free thyroxine (FT4) measurements in dried blood spots on filter paper in 744 euthyroid newborns (616 at term, 128 preterm), 10 newborns with congenital hypothyroidism and 4 euthyroid newborns with congenital TBG deficiency are reported. FT4 was measured by column adsorption chromatography of free hormone followed by radioimmunoassay in the eluate. FT4 values averaged 24 +/- 0.2 pmol/L (mean +/- SE) in euthyroid newborns, 23.0 +/- 0.9 pmol/L in euthyroid newborns with TBG deficiency (p = NS), and 5.7 +/- 0.4 pmol/L in hypothyroid newborns (p less than 0.001 vs both groups). Total T4 (TT4) values in newborns with TBG deficiency were not different from those in hypothyroid newborns, but were significantly lower than those in euthyroid newborns without TBG abnormalities. FT4 values were higher in full-term newborns than in preterm newborns (25.2 +/- 0.3 vs 21.2 +/- 0.5 pmol/L, p less than 0.001). In both full-term and preterm newborns FT4 values in dried blood spots increased with birth body weight (bbw), virtually plateauing when bbw was greater than 2,500 g. The cut-off values established on the basis of the bbw (8.0 and 13.1 pmol/L for a bbw of less than or equal to 2,500 g and greater than 2,500 g, respectively) showed higher specificity and predictive value of positive results than the cut-off values based on the gestational age. In any case, the sensitivity, specificity and predictive values of FT4 determinations proved to be higher than those of TT4 and TSH measurements.(ABSTRACT TRUNCATED AT 250 WORDS)     

FREE THYROXINE (FT4) AND FREE TRIIODOTHYRONINE (FT3) IN AUTONOMOUS THYROID NODULES

Total and free thyroid hormones (T3, T4, FT3 and FT4), TSH and its response to TRH were determined in sixty-three patients affected by autonomous thyroid nodules: mean concentrations of free T3 (FT3) were significantly higher in hot nodules (suppressing extranodular tissue on the scan) as compared to warm ones, even in those cases where total T3 and T4 were within normal ranges (hot nodules, group as a whole: 8.8 +/- 3.5 pg/ml; warm nodules: 5.3 +/- 1.2; hot nodules with normal total T3 and T4 concentrations: 7.5 +/- 3). Also the clinical condition of thyrotoxicosis appeared to be correlated with FT3 concentrations (toxic patients, group as a whole: 9.6 +/- 4.0 pg/ml; euthyroid patients: 6.8 +/- 3.1; toxic patients with normal values of T3 and T4; 8.3 +/- 2.8). On the contrary the correlation of total and free thyroid hormone concentrations with the response of TSH to TRH was not significant.     

Abnormalities of hypothalamic-pituitary-thyroid axis in patients with primary empty sella

Primary empty sella (PES) is a very frequent neuroradiological finding in the general population, that can induce hypopituitarism. Some studies focused on the association of PES with GH deficiency (GHD) or hypogonadotropic hypogonadism (HH), while data regarding the involvement of hypothalamic-pituitary-thyroid (HPT) axis, despite sporadic reports of central hypothyroidism, or the occurrence of hypoadrenalism (HA) are scanty. In this study, thyroid function and TSH response to exogenous TRH injection (TRH/TSH) were investigated in 43 patients [10 men and 33 women; aged (mean +/- SD), 48+/-12 yr] with PES: 22 patients had total and 21 partial PES. Forty healthy subjects (9 men and 31 women; aged 46+/-12 yr) were enrolled as a control group. Central hypothyroidism was found only in 2/43 cases, whereas one patient showed primary hypothyroidism. In euthyroid patients, mean serum TSH levels were significantly lower than controls (TSH: 1.0+/-0.7 vs 1.4+/-0.6 mU/l, p<0.01) and 79% of them showed abnormal TRH/TSH responses (TRH test was performed in 34 euthyroid patients: 17 cases with total and 17 cases with partial PES), but mean serum free T4 (FT4) and free T3 (FT3) values were not significantly lower than controls (FT4: 15.9+/-0.4 vs 15.0+/-2.1 pmol/l, p=NS; FT3: 5.3+/-1.2 vs 5.8+/-1.5 pmol/l, p=NS). Moreover, no significant differences were evident in mean serum TSH, FT4 and FT3 between patients with total and partial PES (TSH: 1.1+/-0.7 vs 0.9+/-0.8 mU/l, p=NS; FT4: 16.3+/-2.6 vs 15.7+/-2.2 pmol/l, p=NS; FT3: 5.4+/-1.3 vs 5.2+/-0.8 pmol/l, p=NS) and the TRH/TSH peak was impaired or exaggerated/delayed in 9 and 3 patients with total and in 12 and 3 cases with partial PES. No significant differences in the prevalence of abnormal TRH/TSH responsiveness were found between patients with partial or total PES (chi2=1.6, p=NS). Other impairment of pituitary function was detected in 23/43 patients: GHD was present in 15 cases, HH in 11 and central HA in 5 patients. Isolated or combined hypopituitarism was present in 17 and in 6 patients, respectively. In conclusion, pituitary dysfunction is very frequent in patients with PES, but central hypothyroidism occurs rarely. The entity of arachnoid herniation into the sellar fossa does not play a significant role on the degree of HPT axis dysfunction.     

Anti-iodothyronine autoantibodies in a girl with hyperthyroidism due to pituitary resistance to thyroid hormones.

In the present study, we report the uncommon case of a 9.6-yr-old girl with circulating anti-T3 autoantibodies (T3-Ab) and hyperthyroidism due to inappropriate secretion of TSH (IST). The diagnosis of IST was based on the findings of normal TSH levels (2.4 mU/L) in the presence of high free T4 (28.2 pmol/L) and free T3 (FT3) levels, as measured by direct measurement methods based on "one-step" analog tracer (28.0 pmol/L) and "two-step" Lisophase (13.3 pmol/L) techniques. The discrepancy between the two measurements suggested a methodological interference due to T3-Ab in "one-step" technique, being the "two-step" methodology unaffected by the presence of such autoantibodies. T3-Ab were documented by high nonspecific binding of serum to labeled T3 (38.0% vs 4.3 +/- 2.1% in controls). The clinical picture of hyperthyroidism, the qualitatively normal TSH responses to TRH and T3 suppression tests, the normal pituitary imaging and the values of some parameters of peripheral thyroid hormone action compatible with hyperthyroidism indicated that the patient was affected by pituitary resistance to thyroid hormones (PRTH). Chronic treatment with dopaminergic agent bromocriptine (7.5 mg/day) did not cause TSH secretion to be suppressed, while the administration of thyroid hormone analog TRIAC (1.4 mg/day) inhibited TSH release (from 2.4 to 0.2 mU/L). As a consequence, circulating thyroid hormone levels normalized and euthyroidism was restored. During TRIAC administration, FT3 levels, measured by "one-step" analog tracer technique, gave spuriously high values due to the methodological interference of T3-Ab (15.2 vs 4.3 pmol/L as measured by "two-step" Lisophase technique).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fatty acid induced changes in circulating total and free thyroid hormones: in vivo effects and methodological artefacts

Elevated levels of nonesterified fatty acids (NEFA) are frequently found in acute illnesses, and they may contribute to changes in serum thyroid hormone concentrations in nonthyroidal illnesses (NTI) by displacing protein bound hormones. We therefore examined the effects of low and raised plasma NEFA levels on circulating total and free thyroxine (TT4 and FT4) and triiodothyronine (TT3 and FT3) concentrations, the Free T4 Index (FT4I) and TSH, in a randomized crossover study in 10 normal subjects. Subjects ate either a high carbohydrate breakfast (low NEFA protocol) or a high fat breakfast followed by an iv injection of 1000 u heparin (high NEFA protocol). Possible biological effects of changes in FT4 and FT3 were evaluated by a 200 micrograms iv TRH test. Free T4 and T3 were measured by a direct analogue method (AFT4 and AFT3). In a similar high NEFA study, but without TRH, FT4 was also measured by equilibrium dialysis (DFT4) and a 2-step RIA method (2-step FT4). Acute elevations of plasma NEFA from 0.67 +/- 0.08 mmol/L to a peak of 2.6 +/- 0.54 mmol/L resulted in a prompt reciprocal fall of mean TT4 (-8.7%, p less than 0.01), AFT4 (-30%, p less than 0.005) and TT3 (-11.5%, p less than 0.01) and AFT3 (-16%, p less than 0.005); DFT4 rose significantly from 23.7 +/- 1.9 pmol/L to 33.0 +/- 3.7 pmol/L (+39%, p less than 0.025) and 2-step FT4 rose by 16% (p less than 0.05). TSH levels declined consistently from 3.3 +/- 0.5 mIU/L to 2.6 +/- 0.4 mIU/L (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)     

Early adaptation of thyrotropin and thyroglobulin secretion to experimentally decreased iodine supply in man.

Five healthy male volunteers (aged 25 to 28 years) were studied both after 4 weeks of treatment with 200 micrograms iodine/d orally (PO) and following experimental iodine depletion by treatment with 3 x 300 mg perchlorate/d PO over a 4-week period, in an attempt to better define the early adaptive responses to an alteration in iodine supply in thyroid function. Intrathyroidal iodine, serum triiodothyronine (T3), free T3 (FT3), thyroxine (T4), free T4 (FT4), reverse T3 (rT3), thyroxine-binding globulin (TBG), thyroglobulin (Tg), and thyrotropin (TSH) levels (10-minute sampling over 24 hours) were measured at the end of iodine administration and at the end of perchlorate treatment. Thyroid volume was determined by sonography, and iodine content was determined by fluorescence scintigraphy. TSH pulses were analyzed by computer-assisted programs. Comparing both experimental situations, perchlorate treatment significantly reduced intrathyroidal iodine concentration (4.0 +/- 1.3 to 3.0 +/- 1.2 nmol/mL, P less than .05), but thyroid volume and total serum T4, T3, FT3, and TBG levels were not altered. Mean 24-hour serum TSH levels (1.8 +/- 0.3 to 1.0 +/- 0.3 mU/L, P less than .001), amount of TSH secreted/pulse (0.5 +/- 0.1 to 0.3 +/- 0.1 mU/L, P less than .001), and FT4 levels (15.7 +/- 1.7 to 14.3 +/- 1.4 pmol/L, P less than .005) were significantly diminished, whereas Tg levels (18.6 +/- 10.0 to 35.1 +/- 14.0 ng/mL, P less than .01) were significantly increased. Thyroid-specific antibodies were normal and were not altered by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)