ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00964.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00965.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00966.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The aim of the study was to assess thyroid function, Iodine Intake and exposure to dietary goitrogens of children living in an area with a high prevalence of goitre, in the region of Darfur, Sudan.DESIGN In a village where goitre affected approximately 85% of children, a cross‐sectional survey of thyroid function was performed in children 0–7 years old.PATIENTS Twenty neonates and 190 children, aged 1 month to 7 years, were included.measurements Thyroid hormones, urinary iodide and thiocyanate excretion were measured.RESULTS MeanSD serum T4 was below the normal range at birth (82 ± 50 nmol/l) and in the age group less than 2 years (73·46). Children older than 2 years had even lower serum 14: 37·37 (P>0 001) at 3–4 years and 36·38 (P>0 001) at 5–7 years. Mean serum TSH was 25 8(6 2–107 7) mU/I at birth, 8.3(2. 5–27. 8) In the group less than 2 years, 15. 3(2.9–79.1) at 3–4 years and 16. 4(2.7–98.3) at 5–7 years. The overall prevalence of hypothyroidism (TSH>50 mU/I) was 24%. Mean urinary thiocyanate was high at birth(107·69 pmol/l), normal in the group less than 2 years and higher in children older than 2 years (126·69 pmol/l) (P>0.001). All age groups had a low urinary iodide concentration.CONCLUSION Hypothyroidism was very frequent in each age group. The higher frequency of hypothyroidism observed in weaned children (<2 years) was attributed to the combined effects of Iodine deficiency and goitrogens (thiocyanate and glycosylflav

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00967.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The objective was to evaluate the effect of131I treatment for hyperthyroidism on calcitonin secretion by thyroid C‐cells.DESIGN Determination of basal calcitonin levels and calcitonin secretory reserve before and aiter131I administration.PATIENTS Seventeen hyperthyroid patients (15 female, two male) were studied before, and 2 months after131I treatment, and 12 of these patients were restudied 8 months after131I treatment.MEASUREMENTS Calcitonin response was assessed by measuring basal and post calcium infusion calcitonin levels. Basal TSH, T3, and T4 levels were also determined at each study.RESULTS The rise of plasma calcium resulted in statistically significant increase of plasma calcitonin levels before131I treatment (10.9·2.4 pmol/l), while this response was significantly diminished 2 and 8 months after treatment (2.6·0.7 and 1.6·0.3 pmol/l, respectively). No correlation was found between the calcitonin response and age or plasma TSH.CONCLUSION Our results demonstrate that131I treatment for hyperthyroidism may seriously damage thyroid C‐cells and cause calcitonin defi

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00968.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We wished to determine the abnormality responsible for Generalired Resistance to Thyroid Hormone in a family with this syndrome.DESIGN Molecular biological studies were performed on a mutant human thyroid hormone receptor beta (hTRβ) cloned from fibroblasts of the patient.PATIENTS The patient is from a previously reported family with typical features of Generalized Resistance to Thyroid Hormone, demonstrating goitre, elevated thyroid hormone levels, slightly elevated TSH, and retarded bone age.MEASUREMENTS A cDNA for hTRβ1 was cloned using specific oligonucleotide primers from fibroblast DNA. A mutant hTRβ1 expression vector was constructed, and an in‐vitro expressed mutant receptor was tested for T3 binding. Receptor binding to DNA was studied in a DNA cellulose assay and gel mobility shift assay.RESULTS Two mutations were found in the cloned hTRβ. One was silent but the second changed arginine 438 to histidine. The mutation was present in RNA and genomic DNA, as shown by allele‐specific amplification. The mutated receptor had reduced T3 binding affinity but demonstrated normal binding in a DNA cellulose assay and In a gel mobility shift assay. The receptor did not have altered heat sensitivity.CONCLUSIONS In the T sibship with Generalized Resistance to Thyroid Hormone, resistance to thyroid hormone is apparently produced by a substitution of a histidine for arginine at amino acid 438, which causes reduced binding of receptor to T3, although the receptor remains able to bind to DNA and, for this reason, functions as a dominant negative in affected subjects who are heterorygous with one normal and one mutated

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00969.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE Initial therapy of thyrotoxicosis usually includes beta‐blockade for symptom relief and thionamides to block new thyroid hormone synthesis. In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, we proposed that cholestyramine, an anion exchange resin which binds iodothyronines, when used adjunctively with thionamides and a beta‐blocker, would lower serum iodothyronine levels faster than would standard therapy alone.DESIGN A double blind placebo‐controlled cross‐over design was used with patients randomly assigned to either the treatment or control groups. They received their initial treatment for two weeks (Phase 1) followed by a one‐week washout period, and then crossed to the opposite treatment for two weeks (Phase 2). Standard therapy included atenolol 50 mg daily, individualized dosages of methimazole and either 4 g of cholestyramine or 4 g of placebo powder four times per day.PATlENTS Fifteen patients with thyrotoxicosis (14 Graves' disease, 1 toxic adenoma) participated in this study.MEASUREMENTS Total and free thyroxine and triiodothyronine, as well as thyroid‐stimulating immunoglobulin and thyrotrophin‐binding inhibitory immunoglobulin, were measured weekly.RESULTS Seven patients received cholestyramine and eight patients received placebo during Phase 1. A more rapid decline in all thyroid hormone levels was seen in the cholestyramine‐treated group (F= 4–7,P>0.01) than in the placebo group (F= 2–3.1,P= 0 05).In Phase 2, the eight patients who received cholestyramine showed an additional decline in free thyroxine from weeks one to two, but the overall rate of decline in hormone levels was not different between the groups. Immunoglobulin levels remained unaffected regardless of group, treatment, or time.CONCLUSIONS We conclude that cholestyramine is a safe and effective adjunctive agent in the treatment of thyrotoxicosis and that its greatest efficacy may be during the first few

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00970.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE There is increasing evidence that TSH activates a non‐cyclic‐AMP‐dependent pathway in the thyroid resulting in protein kinase C activation. We have previously demonstrated that TSH activates protein kinase C by causing translocation of protein kinase C from an inactive cytosolic site to its active membrane‐bound form in porcine thyroid cells. In addition, TSH can modify the protein kinase C translocation induced by the phorbol ester, 12‐O‐tetradecanoylphorbol‐13‐acetate. We tested six TSH receptor antibodies for their ability to activate protein kinase C invitro.DESIGN Porcine thyroid cells were incubated with either TSH receptor antibody or immunoglobulin from pooled normal sera. Subsequently, cytosol and membrane compartments were separated and protein kinase C assessed in each compartment.PATIENTS The sera utilized in this study were obtained from patients with confirmed Graves' disease as defined by clinical evidence of thyrotoxicosis, increased free thyroxine index and suppressed TSH and increased radioactive iodine uptakes.MEASUREMENTS Protein kinase C was measured in the cytosol and membrane compartments of the porcine thyroid cells using an enzyme assay.RESULTS Compared to immunoglobulin from pooled normal sera, none of the six TSH receptor antibodies affected either cytosolic or membrane‐bound protein kinase C in porcine thyroid cells. The tumour‐promoting phorbol ester, 12‐O‐tetradecanoylphorbol‐13‐acetate, caused protein kinase C translocation. However, the presence of TSH receptor antibody did not modify the phorbol‐induced protein kinase C transiocation.CONCLUSION These results indicate that unlike TSH, TSH receptor antibodies neither cause translocation of protein kinase C nor modify phorbol‐mediated protein kinase C translo

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00971.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We investigated the early changes following radioiodine therapy for hyperthyroidism, in biochemical indices of bone synthesis and degradation, and their relationship to circulating thyroid hormone concentrations.DESIGN Prospective follow‐up over the first 12 weeks after radioiodine therapy.PATIENTS Six women with clinical and biochemical evidence of hyperthyroidism.MEASUREMENTS Serum Concentrations of T4, free T3 and osteocalcin, and urinary excretion of the pyridinium cross‐links, pyridinaline and deoxypyridinaline, measured before and weekly for 12 weeks after administration of radioiodine therapy.RESULTS Biochemical indices of bone metabolism were elevated prior to treatment. There was a brisk reduction in circulating thyroid hormones levels paralleled by a similar fall In pyridinlum cross‐llnk excretion, which had returned to normal in five patients by the end of the study. There was a positive correlation between pyridinium cross‐link excretion and thyroid hormone concentrations. There was no significant change in serum osteocalcin.CONCLUSIONS Treatment of hyperthyroidism results in prompt correction of the associated increased rate of bone collagen degradation suggesting that effective early correction of hyperthyroidism is desirable to limit its detrimental effect on skelet

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00972.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE AND DESIGN Thyroid dysfunction is known to occur frequently In thalassaemla major, but Its prevalence and severity varies in different cohorts, and the long‐term natural history is poorly described. We evaluated the pituitary/thyroid axis in thalassaemia major patients in a cross‐sectional study and correlated abnormalities with indices of iron overload. Furthermore, the course of thyroid disease in thalassaemia major patients was assessed In a 15‐year longitudinal study.PATENTS AND MEASUREMENTS Cross‐sectional study: pituitary‐thyroid axis function was examined in 37 patients (22 F, 15 M; aged 10–39 years, mean ± SE = 21 ± 1.4) out of a total of 43 who attended the Haematology and Endocrinology Clinics of Hadassah Hospital on a regular basis. The mean pretransfusion Hb level was 85·20 g/l, and all patients except one were treated with desferrioxamine (DF, mean SE dose 20.2·2.6 mg/kg/day). Twenty‐two had hypogonadotrophic hypogonadism (HH). Longitudinal study: 21 thalassaemia major patients were evaluated with TRH tests in 1976 and again in 1985. Fourteen of these and another eight were evaluated in both 1985 and 1991. RESULTS Cross‐sectional study: no patient had any clinical signs or symptoms of hypothyroidism; however, one had abnormally low T4, borderline low FT4 and normal T3 levels associated with an exaggerated TSH response to TRH consistent with mild hypothyroidism. This patient did not have a previous TRH test, but serial basal determinations over 7 years revealed a progressive decrease in thyroid function. Thirty‐six patients had thyrold hormone levels within the normal range. Nine of these (24.3%) had only an exaggerated TSH response to TRH whereas seven others (19%) also had borderline elevated basal TSH levels. TSH response to TRH was not correlated with age, serum ferrltin or liver function tests (ALTorGGT). Longitudinal study: mean TSH response to TRH decreased (P>0.002), and mean T3 levels Increased (P>0.001) between 1975 and 1985. These findings are probably related to the initiation of DF treatment in 1981. During the last 6 years, four patients with previously normal TSH responses to TRH developed elevated peak TSH levels. Mean T3 concentrations decreased and TSH response to TRH increased significantly (P>0.001 for both).CONCLUSIONS (1) In this patient group the thyroid pituitary axis is less sensitive than the gonadal axis to iron‐induced damage; only one out of 37 patients developed mild uncompensated hypothyroidism. (2) As opposed to the gonadal axis, the thyrold gland appears to fail before the centralcomponents ofthe axis. (3) Abnormal thyroid function may be reversible in the early stages. (4) Progression is variable, and it may take years to progress from normal to uncom

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00973.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY