OBJECTIVETo evaluate the results of treatment of infants with congenital hypothyroidism (CH) with a low initial dosage of levothyroxine.

METHODS138 newborns with primary CH detected by neonatal screening were divided into 3 groups according to levels of serum TSH, TT(3) and TT(4): sub-clinical CH (TSH >50 mU/L), mild CH (TT(4) <54 nmol/L), severe CH (TT(4)<54 nmol/L and TT(3)<1.2 nmol/L). The initial dose of levothyroxine was (3.5 +/-1.0) microg/(kg.d) for sub-clinical CH group, (4.3 +/-0.7)microg/(kg.d) for mild CH group and (4.7 +/- 0.6)microg/(kg.d) for severe CH group. Follow-up evaluation was carried out at 1, 2 and 3 months of age by measuring serum levels of TT(3), TT(4) and TSH. The time, when clinical signs and symptoms were eliminated and serum levels of TT(3), TT(4) and TSH normalized, was recorded. Development Quotient (DQ) testing was performed when CH cases were about 2 years old.

RESULTSThe mean initial dose of levothyroxine in 138 cases was (4.3 +/-0.9)microg/(kg.d). In one month the serum TT(3) and TT(4) levels returned to normal, while for TSH levels 67.4 % cases reached normal range in 2 months and 84.1 % in 3 months. Two months after therapy, the levels of TT(3) and TT(4) reached to the upper half of normal range and there were no signs or symptoms of hypothyroidism. The time for all cases in 3 groups to reach the normal clinical and biochemical indicators was similar (P=0.925). The dosage for cases with low circulating thyroxine before treatment was higher than that of the other groups (P<0.01). The average DQ score of 18 cases after treatment was 116.7 +/- 17.0.

CONCLUSIONhe levothyroxine dosage of (4.3 +/- 0.9)microg/(kg.d) is appropriate for the initial treatment of the majority of infants with CH. However it is better to individualize the dosage for each case.

Congenital Hypothyroidism ; Female ; Humans ; Hypothyroidism ; drug therapy ; Infant, Newborn ; Male ; Thyrotropin ; blood ; Thyroxine ; administration & dosage ; blood ; Triiodothyronine ; blood

BACKGROUNDPreparing hyperthyroid patients for thyroid surgery with a combination of antithyroid drugs and thyroxine has long been controversial because this combination usually results in only partial inhibition of thyroid function. We therefore used large doses of antithyroid drugs to completely inhibit the synthesis of thyroxine and render the thyroid gland defunctionalized. We then administered physiologic doses of thyroxine to inhibit thyroid-stimulating hormone secretion. We have named this treatment "sequential thyroid defunctionalization followed by thyroxine supplementation."

METHODSFour hundred and seventy-one hyperthyroid patients seen at our hospital were divided into experimental and control groups. The control group was treated preoperatively with antithyroid drugs and iodine preparation. The experimental group was further divided into four subgroups and treated with "sequential thyroid defunctionalization followed by thyroxine supplementation". Each of the four subgroups received different doses of antithyroid drugs and thyroxine for differing time periods. Thyroid function was assessed at each stage of treatment, as were operative blood loss volumes and postoperative complications.

RESULTSCompared to the control group, the four experimental groups showed less thyroid congestion and surface varices at surgery. Patients in subgroup A also had thyroid glands that were almost histologically normal. The mean operative blood loss volume of the experimental group was less than that of the control group (326 +/- 163) ml in the control group; (196 +/- 57) ml in subgroup A; (230 +/- 71) ml in subgroup B; (240 +/- 80) ml in subgroup C; and (312 +/- 97) ml in subgroup D). The postoperative complication rate of the experimental group was 8.64% (21/243) whereas that of the control group was 17.54% (40/228).

CONCLUSIONSSequential thyroid defunctionalization followed by thyroxine supplementation is effective in reducing the bleeding volume and postoperative complication rate in selected hyperthyroid patients undergoing thyroidectomy.

Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Hyperthyroidism ; physiopathology ; surgery ; Male ; Middle Aged ; Thyroid Gland ; pathology ; physiopathology ; Thyroidectomy ; Thyroxine ; administration & dosage

OBJECTIVETo investigate the changing of T4 5'-and 5-deiodinase within rat brain under various iodin-nutritional states.

METHODSAnimal model of iodine-deficiency rat was performed and the rats were divided into 4 groups by the intake of iodine-nutrition, and then killed at an age of 20 days. The thyroid hormones level in serum was measured by ELISA and the activity of T(4) 5'-and 5-deiodinase within brain was analyzed.

RESULTSIn less-iodine (LI) group,TT4 and FT4 were accounting for 3.5% of the neutral-iodine (NI) group's, and FT3 was 174.0% of NI group's (P < 0.05). In NI group,TT4 and FT4 were 114.5% and 127.7% of NI group's (P < 0.05). In high-iodine (HI) group, TT4 and FT4 were 61.86% and 62.0% of NI group's, and FT3 was 184.9% of NI group's (P < 0.05). In LI group, the activity of T4 5'-deiodinase tissue of per gram (1.95 +/- 0.32) ngT3.microgT4(-1).h was significantly higher than that of NI group (P < 0.05), and the activity of 5-deiodinase (1.38 +/- 0.21) ngrT3.microg T4(-1).h(-1) is significantly less than that of NI group (1.59 +/- 0.23) (P < 0.05). In HI group the activity of T4 5'-and 5-deiodinase tissue of per gram (1.12 +/- 0.19 and 1.73 +/- 0.36) ngrT3.microgT4(-1).h(-1)was significantly less than that of NI group (P < 0.05).

CONCLUSIONThe activity of T4 5'-deiodinase in iodine deficiency heightens and that in iodine excess is debased, the activity of T4 5-deiodinase in iodine deficiency and in iodine excess is debased.

Animals ; Brain ; enzymology ; Female ; Iodide Peroxidase ; metabolism ; Iodine ; administration & dosage ; deficiency ; Male ; Rats ; Rats, Wistar ; Thyroxine ; blood ; Triiodothyronine ; blood

OBJECTIVETo investigate the subchronic toxicity of soy isoflavones (SIF) in male rats.

METHODFifty Sprague-Dawley rats were randomly divided into 5 groups, 10 rats per group. SIF were given to rats in different groups by gavage at dose of 0, 0.2, 0.5, 1.5, and 4.5 g/kg bw, respectively for 13 weeks. Clinical manifestations, body weight, and food consumption were observed weekly. At the end of the study, urinalysis, hematology, clinical chemistry, total testosterone, and follicle-stimulating hormone were tested, and histopathological examinations were performed.

RESULTSNo mortality, ophthalmic abnormalities or treatment-related clinical signs were identified during the study. As compared with the control group, significantly lower body weights and food consumption were observed in 1.5 and 4.5 g/kg bw groups. In clinical chemistry tests, triglyceride was significantly decreased and high-density lipoprotein cholesterol was significantly increased in all SIF-treated groups. Total testosterone levels were significantly lower in 0.50, 1.50, and 4.5 g/kg bw dose groups than in the control group. Microscopic examination showed that the mammary glands exhibited hyperplasia and excreted latex in rats of the 4.5 g/kg bw group. No changes attributable to treatment of SIF in other parameters were found.

CONCLUSIONSIF at high dosages caused significant endocrine disruption in male rats. The no observed adverse effect level (NOAEL) of SIF to male rats in this study is considered to be 0.20 g/kg bw.

Animals ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Follicle Stimulating Hormone ; blood ; Isoflavones ; administration & dosage ; chemistry ; toxicity ; Male ; Rats ; Rats, Sprague-Dawley ; Soybeans ; chemistry ; Thyroxine ; blood ; Triiodothyronine ; blood

BACKGROUNDType 1 deiodinase (D1) plays an important role in the metabolism of thyroid hormone and has close relationship with thyroid function. In this study we explore the effects of iodine intake on D1 activity and its mRNA expression and its possible mechanism.

METHODSForty-eight Wistar rats were randomly divided into six groups with 8 in each: low iodine (LI), normal iodine (NI), five-fold iodine (HI(5)), ten-fold iodine (HI(10)), fifty-fold iodine (HI(50)), one hundred-fold iodine (HI(100)) group. Three months, six months and twelve months after admistration of potassium iodate, they were sacrificed and thyroids were excised. The expression of D1 mRNA in the thyroid tissue was determined by RT-PCR and D1 activity was analyzed by (125)I-rT3 as substrate. The thyroid hormone was measured with radioimmunoassay method.

RESULTSCompared with NI group, D1 mRNA expression in LI groups slightly decreased, and D1 activity greatly increased. Both T(3) and T(4) in thyroid tissue significantly decreased, but the T(3)/T(4) ratio increased. D1 mRNA expression decreased in all HI groups, and D1 activity was significantly lower in HI groups. There was a tendency of decrease in D1 activity with increased doses of iodine intakes. There was no significant difference in T(4) in thyroid tissue between HI groups and NI group, but a tendency of decrease in T(3) level was found in all HI groups.

CONCLUSIONSIn the case of iodine deficiency, D1 activity increased greatly in order to convert more T(4) to T(3). Excess iodine can inhibit both D1 mRNA expression and its activity to protect organism from being injured by excessive T(3).

Animals ; Iodide Peroxidase ; genetics ; metabolism ; Iodine ; administration & dosage ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Thyroid Gland ; enzymology ; Thyroxine ; blood ; Triiodothyronine ; blood

This paper summarises the current evidence on neuro-developmental deficits in the early (< 1 month of age) treated congenital hypothyroid and the influencing factors. A literature search revealed only few citations that compared outcome with matched controls. In all but one, the median age of treatment onset was >2 weeks. Mean Global IQ scores are about 10 points lower and remain identifiable in adulthood. Verbal and performance scores are usually similar. Deficits persisting into adolescence and adulthood involve the visuomotor, memory, attention and posture domains. Lower academic performance is common in the early years. Prenatal factors associated with a worse prognosis are aetiology (dysgenesis), low birth weight, associated complications and severity of hypothyroidism. Postnatal factors are age at onset of treatment (>1 month), lower thyroxine dose at onset (<8 mcg/kg/day), late normalisation of thyroid function (>2 weeks after treatment), and a lower socio economic family status. The author proposes the evaluation of a multi centre cohort with a median age of treatment onset <1 week, TSH normalisation by <3 weeks with treatment thyroxine levels maintained in the 3rd quartile for age. The outcome of this cohort should indicate if current targets in management need to be revised.
Adolescent ; Adult ; Child ; Child, Preschool ; Congenital Hypothyroidism ; complications ; drug therapy ; Developmental Disabilities ; etiology ; Humans ; Infant, Newborn ; Nervous System Diseases ; etiology ; Thyroxine ; administration & dosage

OBJECTIVETo investigate the therapeutic effect of low-dose thyroxin in elderly patients with refractory heart failure (RHF) and euthyroid sick syndrome (ESS).

METHODSFifty-four elderly patients with RHF and ESS were randomized into conventional treatment group (n=32) and L-thyroxine group with additional oral L-thyroxine at the daily dose of 6.25-25 microg (n=22). The changes in the plasma levels of brain natriuretic peptides (BNP), left ventricular ejection fraction (LVEF), and cardiac function (NYHA level) of the two groups were compared after 1 month of treatment.

RESULTSFive patients receiving conventional treatment died due to severe arrhythmia during the treatment, and in the other 27 patients, the levels of plasma BNP, LVEF, and cardiac function showed no significant improvements after 1 month of treatment (P>0.01). In L-thyroxine group, no death or severe arrhythmia occurred, and the levels of plasma BNP, LVEF, and cardiac function were significantly improved after the treatment (P<0.01). No thyrotoxicosis occurred during the administration of L-thyroxine in the latter group.

CONCLUSIONLow-dose L-thyroxine in addition to the conventional treatments may enhance the therapeutic effect in elderly patients with RHF and ESS.

Aged ; Aged, 80 and over ; Chronic Disease ; Drug Therapy, Combination ; Euthyroid Sick Syndromes ; complications ; drug therapy ; Female ; Heart Failure ; complications ; drug therapy ; Humans ; Male ; Middle Aged ; Thyroxine ; administration & dosage

We present a case of a 41-day-old girl with diffuse hemangiomatosis on her chin, right thigh, occipital area, and liver. She also had hepatomegaly, heart failure, and hypothyroidism. Hemangiomatosis did not respond to 2 weeks of oral administration of prednisolone, but was successfully treated with propranolol. After 2 years of propranolol treatment, the lesions of hemangiomatosis nearly disappeared. Hypothyroidism was controlled by levothyroxine replacement. As hemangiomatosis regressed, thyroid function was normalized. Propranolol may have adverse effects including hypotension, hypoglycemia, bronchoconstriction, and restlessness, but she did not experience such adverse effects. Propranolol could be the first choice for diffuse neonatal hemangiomatosis (DNH). Our case also suggests that thyroid function test is needed in patient with DNH.
Administration, Oral ; Bronchoconstriction ; Chin ; Female ; Heart Failure ; Hepatomegaly ; Humans ; Hypoglycemia ; Hypotension ; Hypothyroidism ; Liver ; Prednisolone ; Propranolol ; Psychomotor Agitation ; Thigh ; Thyroid Function Tests ; Thyroid Gland ; Thyroxine

OBJECTIVETo study the best observation time for drug administration and withdrawal in the treatment of children with transient congenital hypothyroidism,seeking an objective basis for the safe drug withdrawal.

METHODSLevothyroxine was prescribed for 1 144 children diagnosed with congenital hypothyroidism (CH) and according to the results levothyroxine was adjusted to a maintenance dosage. Examinations were performed periodically including physical and mental development, thyroid ultrasonography,and blood levels of T3, T4, TSH. For the patients with a small maintenance dosage of levothyroxine (15.0 - 16.6 g/d) and all the examinations normal, levothyroxine was withdrawn at 2 - 3 years, and the children were followed up and reexamined after 1 month, 2 months, and 10 months, respectively. Permanent drug withdrawal was determined for children with all the examinations normal. Once abnormal TSH occurred, levothyroxine was prescribed again, and followed up continuously.

RESULTLevothyroxine was withdrawn from 157 children. During the follow up, for 15 children (9.55%) levothyroxine were prescribed continuously, and for 142 children permanent drug withdrawal (confirmed with transient CH) was determined. Abnormal TSH of various degrees was detected in 48 cases: 25.48 % (40/157),4.46 % (7/157), and 0.64 % (1/157) were detected at 1, 2 and 10 months after drug withdrawal, respectively. In 15 children levothyroxine was prescribed again for the remarkably high TSH, and the other 33 with mildly abnormal TSH finished the treatment since TSH normalized during follow-up.

CONCLUSIONAfter 2 - 3 years of regular treatment, levothyroxine can be withdrawn from children with normal T3, T4, TSH, physical and mental development, and thyroid function. The best observation time for drug withdrawal should be 2 - 3 months. If T3, T4 and TSH levels are in the normal range, drug can be withdrawn safely. Once abnormal results were detected during follow-up, levothyroxine should be administrated continuously.

Child ; Child, Preschool ; Congenital Hypothyroidism ; blood ; drug therapy ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Thyrotropin ; blood ; Thyroxine ; administration & dosage ; blood ; therapeutic use ; Time Factors ; Triiodothyronine ; blood ; Withholding Treatment

OBJECTIVETo investigate the effects of ammonium perchlorate (AP) on thyroid functions and mRNA expression levels of thyroglobulin (Tg) and thyroperoxidase (TPO) genes of rats.

METHODSThirty SD male rats were randomly divided into six groups: control group, iodine-deficient group, low dose AP group (130 mg/kg), moderate dose AP group (260 mg/kg), high dose AP group (520 mg/kg) and high iodine-combined group. After the rats were exposed orally for 90 days, serum free-thyroxine (FT(4)), free-triiodothyronine (FT(3)) and thyroid stimulating hormone (TSH) were measured using radioimmunoassays. mRNA expression levels of thyroglobulin (Tg) and thyroperoxidase (TPO) genes were detected by real-time quantitative PCR.

RESULTSSerum FT(4) levels in moderate dose AP group and high dose AP group were [(9.540 ± 1.327) fmol/ml] and [(6.509 ± 1.949) fmol/ml] respectively, which were significantly lower than that [(13.505 ± 1.276) fmol /ml] in control group (P < 0.05 or P < 0.01). Serum TSH level in high dose AP group was [(1.227 ± 0.295) mIU/L], which was significantly higher than that [(0.545 ± 0.282) mIU/L] in control group (P < 0.05). The mRNA expression levels of thyroglobulin (Tg) gene in all groups exposed to AP were significantly lower than that in control group (P < 0.01). The mRNA expression level of thyroperoxidase (TPO) gene in high dose AP group was significantly higher than that in control group (P < 0.05).

CONCLUSIONAP can reduce the serum FT(3) and FT(4) levels of rats, increase the serum TSH level of rats and decrease obviously the mRNA expression levels of Tg and TPO genes. In addition, high iodine can reduce the toxic effects of AP on thyroid gland of rats to some extent.

Animals ; Iodide Peroxidase ; genetics ; metabolism ; Iodine ; administration & dosage ; Male ; Perchlorates ; toxicity ; Quaternary Ammonium Compounds ; toxicity ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Thyroglobulin ; genetics ; metabolism ; Thyroid Gland ; drug effects ; metabolism ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood