[A family with familial dysalbuminaemic hyperthyroxinaemia].

OBJECTIVE: To report a family of familial dysalbuminaemic hyperthyroxinaemia(FDH). METHODS: Four members, including the female proband, mother, daughter and brother, went through the measurement of thyroid hormone and thyroid-stimulating hormone (TSH). Electrophoretic analysis of the patient's serum proteins was carried out after the patient's serum being incubated with fluorescein isothiocyanate (FITC) labeled thyroxine(T4), The point mutation of Alb gene was determined in all members. RESULTS: The measurements of thyroid hormane and TSH showed that in three members (the proband, her mother and her daughter), the total thyroxine(TT4) serum level was high, the total triiodothyronine(TT3), FT4, FT3 and TSH serum levels were normal. And the enhanced albumin binding of fluorescenced T4 by electrophoresis showed a mutation transition 653 G-->A on DNA coding region of albumin. But in the proband's brother, the thyroid function and the results of electrophoresis of thyroxine-binding protein and determination of albumin gene were normal. CONCLUSION: A family with FDH in China is firstly reported here, a mutation at albumin gene DNA coding region 653G-->A causing enhanced albumin binding of T4 results in high T4 level.

[Effects of maternal hyperthyroidism and antithyroid drug therapy on congenital malformation of newborn infants].

OBJECTIVE: To evaluate the relationship between the incidence of congenital malformations of newborns and maternal hyperthyroidism with antithyroid drug (ATD) therapy during pregnancy. METHODS: The clinical data of 100 cases of pregnant women with hyperthyroidism and their 101 offsprings born in Peking Union Medical College Hospital during 1983-2003 were analyzed retrospectively. According to the maternal thyroid function, and antithyroid drugs taken during the first trimester of pregnancy, subjects were divided into different groups. The incidence of congenital malformations of newborns and risk factors, especially the effects of maternal hyperthyroidism with antithyroid drug therapy were analysed. RESULTS: The prevalence of congenital malformation in infants born to mothers who had hyperthyroidism during pregnancy (6.9%, 7/101) was significantly higher than that of all the infants born in the same hospital during the same period (0.9%, 212/22 765, P < 0.01). The difference of the incidence of malformed infants born to mothers with hyperthyroidism (9.6%, 5/52) or euthyroidism (4.1%, 2/49) during the first trimester was not significant (P > 0.05). The incidence of malformed infants whose mothers received methimazole (MMI; 41.7%, 5/12) was significantly higher than that of mothers treated with propylthiouracil (PTU) (3.6%, 1/28) and without ATDs (1.6%, 1/61), respectively (P < 0.01). The Loglinear model analyses showed that mothers receiving MMI during the first trimester of pregnancy was independent risk factor for the increased incidence of malformation of their infants (L.R. square = 15.668, P = 0.0003). CONCLUSIONS: The risk of congenital malformation in infants whose mothers take MMI during the first trimester may be increased. Therefore, we suggest that MMI should not be used as a choice of drug in treatment of pregnant women with hyperthyroidism.

[Effects of maternal hyperthyroidism and antithyroid drug therapy on thyroid function of newborn infants].

OBJECTIVE: To evaluate the relationship between the incidence of abnormal thyroid function of newborns and maternal hyperthyroidism with antithyroid drug therapy. METHOD: The clinical data of 35 neonates born to mothers with hyperthyroidism from 1983 to 2003 in Peking Union Medical College Hospital were retrospectively analyzed. According to the maternal thyroid function and the antithyroid drugs taken during pregnancy, subjects were divided into different groups. RESULTS: The proportion of abnormal thyroid function in newborn was 48.6% (17/35). The prevalences of primary hypothyroidism, subclinical hypothyroidism, hypothyroxinemia, and central hypothyroidism were 29.4%, 29.4%, 35.3%, and 5.9%, respectively. The incidence of abnormal thyroid function of neonates whose mothers did not take the antithyroid drugs (ATDs) until the third trimester of pregnancy was significantly higher than those without and with ATDs during the first or second trimester (P < 0.01). The incidence of abnormal thyroid function significantly increased in premature neonates, neonates whose mothers with modest or heavy pregnant hypertension, or neonates whose core serum thyroid-stimulating hormone or serum anti-thyroid peroxidase antibodies levels were abnormal. CONCLUSION: The risk of abnormal thyroid function of infants whose hyperthyroid mothers did not take ATDs until the third trimester of pregnancy may be increased. Prompt diagnosis and appropriate treatment of hyperthyroidism in pregnant women are essential for the prevention of neonatal thyroid functional abnormality.

[The clinical characteristics of symptomatic propylthiouracil-induced hepatic injury in patients with hyperthyroidism].

OBJECTIVE: To study the clinical characteristics and factors of symptomatic propylthiouracil (PTU)-induced hepatic injury in patients with hyperthyroidism. METHODS: A retrospective study of the patients diagnosed with symptomatic PTU-induced hepatic injury, admitted to Peking Union Medical College (PUMC) Hospital from January 1993 to December 2002, were carried out with regard to clinical characteristics, laboratory findings and management. In addition, a comparative study was carried out in hyperthyroidism with symptomatic, asymptomatic and without PTU-induced hepatic injury at the same time. Symptomatic PTU induced hepatic injury was defined as the development of hepatitis symptoms or jaundice with at least 3-times elevation of liver function test without other causes. RESULTS: Nine hundred fourteen patients were admitted to PUMC Hospital from January 1993 to December 2002. Clinically overt symptomatic hepatic injury developed in twelve patients [1.3%, age (30 +/- 9) yr, male:female ratio, 1:11] between 7 and 77days after PTU administration. Abdominal distention and fatigue developed in all patients. Serum level of ALT and total bilirubin (TBil) increased to (531.7 +/- 352.0) 113 - 1425 U/L and 67.6 (17.1 - 567.7) micro mol/L, respectively. Prothrombin time prolonged in three cases and plasma ammonia elevated in one case. The types of hepatic injury were hepatocellular in eight, cholestatic in one and mixed in two. None resulted from viral hepatitis and autoimmune hepatitis. There was significant difference in history of side effects of antithyroid agents, PTU dose and abnormal ratio of serum ALT among patients with symptomatic, asymptomatic and without hepatic injury (P < 0.05). However, there were no statistic differences in age, sex, serum levels of T(4), T(3), and increased thyroglobulin antibody, thyroid peroxidase antibody and thyrotrophin receptor antibody at initial diagnosis. The liver function test normalized in all patients from 14 to 140 days after the PTU withdrawal. CONCLUSIONS: Symptomatic hepatic injury usually develops with PTU administration in the first few months, though it is unusual. It may be difficult to predict its development and the patient should be monitored for the liver function in the early stage of PTU administration.

[Clinical validity of anti-thyroperoxidase antibody and anti-thyroglobulin antibody].

OBJECTIVE: To evaluate the clinical validity of anti-thyroperoxidase antibody (anti-TPOAb) and anti-thyroglobulin antibody (anti-TgAb). METHOD: Serum levels of anti-TPOAb and anti-TgAb were assayed using chemiluminescence immunoassay in 434 subjects, including 51 patients with Hashimoto's thyroiditis, 58 with Graves' disease, 68 with nodular goiter, 56 with thyroid adenoma and carcinoma, 56 with subacute thyroiditis, 65 with euthyroid non-thyroid endocrine disease, 35 with euthyroid non-thyroid autoimmune diseases, and 45 euthyroid controls. RESULTS: The highest level and most positive results of serum anti-TgAb and anti-TPOAb were observed in patients with Hashimoto's thyroiditis (median 373 and 6 974 U/ml, positive rate 84.3% and 86.3%), followed by patients with Graves' disease (median 84 and 1 369 U/ml, positive rate 44.8% and 72.4%). Serum anti-TgAb and anti-TPOAb were also more common in patients with subacute thyroiditis and other autoimmune diseases than in the controls. CONCLUSION: The assay of serum anti-TPOAb and anti-TgAb by chemiluminescence immunoassy are useful in the differential diagnosis of autoimmune thyroid disease.

[Propylthiouracil-induced overt hepatic injury in patients with hyperthyroidism].

OBJECTIVE: To study the incidence, clinical features and related factors of propylthiouracil (PTU)-induced hepatic injury in patients with hyperthyroidism. METHODS: A prospective study were carried out in 70 patients of hyperthyroidism with normal liver function. Every patient was treated with PTU 300 mg/d until the thyroid functions recovered to normal, following by decease and maintenance PTU dose in period of six months. Liver function, including serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL), thyroid function (serum thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine and thyrotropin) and blood routine items were measured before therapy and once a month for six months after PTU therapy was begun. RESULTS: Sixty-four cases of 70 patients completed the therapy for 6 months. Hepatic injury developed in 33 patients (51.6%). Asymptomatic, transient hepatic injury was shown in 22 patients (34.4%). Slight symptomatic hepatic injury occured in 6 cases (9.4%) and overt hepatic injury in 5 patients (7.8%) after PTU administration. However, all the patients who developed overt hepatic injury did not stop PTU. Hepatic function returned normal one month after stopping PTU. No one finally suffered from viral hepatitis and autoimmune hepatitis in patients of symptomatic and overt hepatic injury. CONCLUSIONS: PTU-induced symptomatic hepatic injury is not rare and usually develops within the first few months of PTU administration. Its clinical course is relatively benign. However, it may be difficult to predict its development, so all patients should be monitored for liver function test during the administration in early stage.