Antibody binding serum T3 in a patient with hepatocarcinoma

Thyroid hormone levels were studied in a euthyroid patient with hepatocellular carcinoma. The thyroid gland was normal at autopsy and both antithyroglobulin and antimicrosomal antibodies were undetectable in serum. Serum triiodothyronine (T3) values as measured by different RIA procedures, showed striking discrepancies suggesting the presence of an endogenous T3 binding antibody. The preincubation of the patient's serum with 125I-T3, followed by a precipitation with polyethyleneglycol showed a 74.8% of binding, confirming the presence of an endogenous factor interfering with T3 assays. Agarose electrophoresis of the patient's serum showed that 125I-T3 migrated mainly with the gammaglobulin fraction (60%). When immunoprecipitation tests with different antihuman antiimmunoglobulins were carried out, a positive binding for immunoglobulin G (11.9%), Fab (8.5%) and lambda chain (9.3%) was noted. Scatchard plot analysis showed a binding affinity of 0.77 X 10(9) liter/mol and a binding capacity of 1.02 nmol/liter. These data suggest that the abnormal serum T3 binding was caused by the presence of a T3 antibody which was shown to be an immunoglobulin G specific only for the lambda chain.     

Menstrual disturbances in various thyroid diseases

The prevalence of menstrual disturbances, including secondary amenorrhea, hypomenorrhea, oligomenorrhea, hypermenorrhea, polymenorrhea and irregular menstrual cycle were prospectively examined in 586 patients with hyperthyroidism due to Graves' disease, 111 with hypothyroidism, 558 with euthyroid chronic thyroiditis, 202 with painless thyroiditis and 595 with thyroid tumor. In the overall patient group, the prevalence did not different from that in 105 healthy controls. However, patients with severe hyperthyroidism showed a higher prevalence of secondary amenorrhea (2.5%) and hypomenorrhea (3.7%) than those (0.2% and 0.9%, respectively) with mild or moderate hyperthyroidism. Moreover, patients with severe hypothyroidism had a higher prevalence (34.8%) of menstrual disturbances than mild-moderate cases (10.2%). Menstrual disturbances in thyroid dysfunction were less frequent than previously thought.     

血清视黄醇结合蛋白在肝损伤中的意义

目的探讨视黄醇结合蛋白(RBP)在不同临床类型肝损伤患者血清中的水平及临床意义。方法对370例肝病患者及50例健康对照者采用日立7600全自动生化分析仪分别测定TBil、ALT、Alb和RBP,并进行统计分析。结果除脂肪肝组外,急性肝炎组、慢性肝炎组、药物性肝炎组、肝硬化组、自身免疫性肝炎组、肝癌组中TBil、ALT水平较对照组显著升高(P0.05),Alb、RBP水平较对照组显著降低(P0.05)。RBP、Alb降低具有一致性,在急性肝炎组、慢性肝炎组、药物性肝炎组、肝硬化组、肝癌组中的RBP异常率更高于Alb异常率(P0.05)。结论 RBP检测可早期灵敏反映肝功能损伤情况,值得临床广泛使用。     

Comparison of serum thyroid microsomal and thyroid peroxidase autoantibodies in thyroid diseases

Recent evidence indicates that human thyroid peroxidase (TPO) has most of the characteristics of the thyroid microsomal antigen. The question of whether TPO accounts for part or all of the antigenic activity recognized by circulating anti-microsomal antigen autoantibody (anti-M Ab) remains to be determined. The availability of an anti-TPO monoclonal antibody and of a highly purified TPO preparation allowed the development of specific and sensitive radioassays for anti-TPO autoantibody (anti-TPO Ab). In this study we compared anti-M Ab and anti-TPO Ab levels in serum from 128 subjects, including patients with Hashimoto's thyroiditis (n = 31), idiopathic myxedema (n = 11), hyperthyroid Graves' disease (n = 45), miscellaneous nonautoimmune thyroid disorders (n = 9), and normal subjects (n = 32). Anti-M Ab and anti-TPO Ab were measured by radioimmunological methods employing two different assay designs: 1) competitive radioassay (CR), based on the inhibition of radioiodinated antibody binding to human thyroid microsomes coated on microtiter wells, using a) [125I]immunoglobulin G (IgG) containing a high anti-M Ab titer (for anti-M Ab determinations), or b) [125I]anti-TPO monoclonal antibody (for anti-TPO Ab); and 2) sandwich immunoradiometric assay (IRMA) using microtiter wells coated with thyroid microsomes (for anti-M Ab determinations) or immunoaffinity-purified TPO (for anti-TPO Ab determinations) and [125I]anti-human IgG antibody. Anti-M Ab also was measured by passive hemagglutination. Anti-M Ab titers by PH closely correlated with anti-TPO Ab levels whether assayed by IRMA (r = 0.905; P less than 0.00001) or CR (r = 0.922; P less than 0.00001). Even closer correlations were found when anti-M Ab and anti-TPO Ab both were measured by the same type of radioassay procedure (IRMA, r = 0.945 and P less than 0.00001; CR, r = 0.957 and P less than 0.00001). No differences in the correlation between anti-M Ab and anti-TPO Ab results were found when the data in patients with different autoimmune thyroid disorders were analyzed separately. Further and more direct evidence for the identity of anti-M Ab and anti-TPO Ab was provided by the ability of purified TPO to completely inhibit the binding to thyroid microsomes of radioiodinated IgG preparations containing high anti-M Ab titers. In conclusion, our results provide strong support for the concept that TPO accounts for virtually all of the antigenic determinants reacting with the autoantibodies commonly termed anti-M antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)     

T3-release from autonomously functioning thyroid nodules in vitro.

Toxic thyroid nodules have been shown to be of clonal origin. In a portion of them, point mutations affecting either the gene of the TSH receptor (TSHr) or the alpha-subunit of stimulating G-protein, consecutively leading to enhanced cAMP levels, which may enhance growth or functional activity of the thyrocyte or both, were recently found. To complement these studies, we evaluated hormone response (i.e. T3 release) in vitro from tissues derived from toxic thyroid nodules as compared directly to the surrounding paranodular tissues as well as tissues derived from euthyroid goiter and from patients with Graves' disease. Experiments were conducted in the presence and absence of bTSH or Graves' immunoglobulines. Tissues obtained during surgery were incubated over 5 h, followed by equilibrium dialysis for 24 h, and determination of free T3 in an aliquot by RIA. Basal T3 release in nodular tissues (n = 10) was significantly higher (median: 7.3 ng/l) compared to paranodular tissues (3.2 ng/l; P < 0.01), tissues derived from euthyroid goiter (1.3 ng/l; n = 12; P < 0.001) and thyroid tissues derived from patients with Graves' disease (2.5 ng/l; n = 6; P < 0.001). Upon stimulation with bTSH (1 IU/l), median T3 concentrations markedly increased to 11.5 ng/l (P < 0.05), 7.3 ng/l (P < 0.05), 4.2 ng/l (P < 0.01) and 3.2 ng/l (P = N.S.), respectively. Stimulation over basal values was 1.6-fold in nodular tissues, 2.3-fold in paranodular tissues, 3.2-fold in euthyroid goiter and 1.3-fold in Graves' disease. In toxic thyroid nodules basal hormone-releasing activities were stimulated by fifteen out of twenty (75%) Graves' sera tested. For comparison, stimulation in other tissues occurred in 45% (paranodular), 80% (euthyroid goiter) and 35% (Graves' disease), respectively. In conclusion, tissue derived from toxic thyroid nodules exhibits enhanced basal hormone release as compared to both, the surrounding paranodular tissues and tissues from euthyroid goiter in vitro, which may reflect constitutional activation of TSHr, alpha-subunit of stimulating G-protein or other so far unknown intermediate by point mutations affecting the respective genes. Hyperactivities in toxic thyroid nodules may be even further enhanced by external stimulators such as TSH or TSH receptor antibodies. The first stimulator may have clinical relevance in patients with toxic thyroid nodules and not yet suppressed TSH; the latter could play a role in the rare Marine Lenhart syndrome.     

Circulating free T3 in pregnancy, liver diseases, diabetes mellitus and thyroid diseases

Measurement of serum concentrations of free triiodothyronine (FT3) is considered to be an accurate index of thyroid function in the patient. In this study, we measured serum concentrations of FT3, free thyroxine (FT4) and reverse triiodothyronine (rT3) by radioimmunoassay in blood samples taken from the navel cord of 20 newborns as well as 20 nonpregnant women, 20 pregnant women, 10 patients with liver diseases, 25 patients with diabetes mellitus, 65 patients with hyperthyroidism, 30 patients with primary hypothyroidism and 29 normal subjects. In pregnant women, serum FT3 and FT4 levels gradually decreased as the pregnancy progressed. In cord blood, FT3 levels were less than a quarter of the values found during the first trimester of pregnancy or that of non-pregnant women, whereas serum rT3 levels were drastically increased. In chronic hepatitis, liver cirrhosis and diabetes mellitus, serum FT3 and FT4 levels were significantly lower than that in the controls. In thyroid diseases, serum FT3 levels varied parallel to other thyroid hormone levels. In primary hypothyroidism, however, serum FT3 levels were still lower than these in the controls after treatment with 1-thyroxine, whereas other thyroid hormone levels and TSH levels returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

自身免疫性甲状腺疾病患者血清纤维化指标观察

目的 观察自身免疫性甲状腺疾病(AITD)患者血清Ⅲ型前胶原(PCⅢ)和透明质酸(HA)水平.探讨其临床意义.方法 按甲状腺功能将114例AITD患者分为3组:①Graves病甲状腺功能亢进(简称甲亢)组(38例),②桥本甲状腺炎甲状腺功能低下(简称甲低)组(35例),③桥本甲状腺炎亚临床甲状腺功能低下(简称哑甲低)组(41例),另设40例健康人作为对照组.用免疫化学发光法检测以上各组人群血清游离三碘甲腺原氨酸(FT3),游离甲状腺素(FT4),超敏促甲状腺激素(sTSH)水平.用酶联免疫吸附试验(ELISA)检测血清PCⅢ水平,用放射免疫分析法(RIA)检测血清HA水平.结果 甲亢组血清FT3,FT4水平[(18.35±6.19),(76.28±23.49)pmol/L]明显高于对照组[(4.75±0.31),(16.12±3.27)pmol/L],sTSH水平[(0.15±0.07)mU/L]明显低于对照组[(3.78±0.15)mU/L],差异均有统计学意义(P＜0.01),甲低组FT3,FT4水平[(3.36±0.26),(6.37±2.19)pmol/L]均低于对照组(P＜0.05),sTSH[(44.58±13.29)mU/L]明显高于对照组(P＜0.01),亚甲低组FT3,FT4水平[(4.86±0.45),(15.26±2.78)pmol/L]与对照组比较,差异无统计学意义(P＞0.05),sTSH[(14.26±4.73)mU/L]明显高丁对照组(P＜0.01).甲亢组血清PCⅢ水平[(4.63±1.22)μg/L]明显高于甲低组[(3.64±1.12)μg/L],亚甲低组[(3.54±1.17)μg/L],对照组[(3.56±1.07)μg/L],组问两两比较差异有统计学意义(P＜0.05),而甲低组,哑甲低组,对照组PCⅢ水平任意两组间比较,差异均无统计学意义(P＞0.05),甲低组血清HA水平[(31.13±10.28)μg/L]高于甲亢组[(22.24±7.22)μg/L],亚甲低组[(22.43 4-7.99)μg/L]和对照组[(23.09±9.19)μg/L],组间两两比较差异均有统计学意义(P＜0.05),而甲低组,亚甲低组,对照组HA水平任意两组比较,差异均无统计学意义(P＞0.05).结论 在排除肝纤维化等病变的情况下,检测甲亢患者血清PCⅢ,对了解早期的心肌纤维化有重要意义,对病程较长的甲亢患者,血清HA,PCⅢ的榆测可作为早期发现肝损伤和纤维化的参考依据.     

The significance of serum fructosamine measurement in patients with thyroid diseases

Serum fructosamine was measured in patients with Graves' disease and primary hypothyroidism. Fructosamine levels and fructosamine per albumin ratio were significantly lower in patients with Graves' disease than in normal subjects, while they were significantly higher in patients with primary hypothyroidism. Fructosamine levels were normalized by treatment in the euthyroid state in patients with Graves' disease. Along with the normalization of thyroid stimulating hormone levels, fructosamine levels returned to the normal range in patients with primary hypothyroidism with treatment. There were significant correlations between fructosamine levels and free triiodothyronine levels, free thyroxine levels, thyroid stimulating hormone levels, hemoglobin A1C levels, albumin levels, and creatine phosphokinase levels. We concluded that it was useful to measure serum fructosamine as an indicator of peripheral metabolic function in patients with thyroid diseases.     

T3 releasing activity by Graves' sera from Graves' thyroid in vitro

The insensitivity of Graves' thyroid to stimulation of cAMP formation by TSH as well as Graves' immunoglobulins in vitro is well known. The present study was performed to find out Graves' sera which may induce a final activation i.e. stimulation of T3 release in Graves' thyroid slices despite this insensitivity of tissue and to characterize determinants responsible for the efficiency of those sera. Out of 20 sera from patients with active untreated Graves' disease 6 were found to stimulate T3 release from Graves' thyroid in vitro. These 6 sera were effective in stimulating different Graves' glands, irrespective of pretreatment with propranolol, thiamazole (methimazole) or thiamazole plus iodine. In contrast, a significant response to bTSH was not observed in any Graves' gland. For comparison, 17/20 of the same sera were able to stimulate T3 release when tested on human goitrous thyroid. Sera which stimulated Graves' slices revealed no higher stimulating activities in goitrous tissue than serum samples which did not. All sera were additionally assessed for TSH binding inhibiting immunoglobulins in a radioreceptor assay. Remarkably, Graves' thyroid stimulating sera had a low or absent TSH binding inhibiting activity. Thus, hormone release from Graves' thyroid in vitro - in contrast to that from goitrous tissue - could only be activated by a minority of Graves' sera. These Graves' thyroid stimulating sera could be characterized to contain a selected spectrum of biologically active antibodies with a high TSH agonistic potency stimulating in the presence of a negligible TSH binding inhibiting activity.