固相板酶免法测定人血清游离三碘甲状腺原氨酸

目的 :探讨游离三碘甲状腺原氨酸 (FT3)的酶免疫测定法对于诊断甲状腺功能亢进和监测甲状腺激素补充治疗效果及预后情况的重要意义。方法 :采用聚苯乙烯96孔板作为固相载体 ,利用亲和纯化的兔抗T3 抗体和T3 - β-半乳糖苷酶标记物 ,建立了固相板竞争法。结果 :可测范围为0.48～45.0ng/L ,灵敏度0.13ng/L ,平均批内变异系数为 (n=20)6.4 % ,平均批间变异系数为 (n=8)12.4% ,正常参考范围4.14±0.97ng/L。正常人与甲亢病人能明显分开。结论 :酶免法测定血清FT3,其灵敏度、精密度均达到放免水平 ,且可避免同位素污染     

甲状腺机能亢进症辨证分型与甲皱微循环及TT_3、TT_4、FT_4I和吸~(131)碘率的关系

对甲状腺机能亢进症(甲亢)患者进行了临床辨证分型,同步观察甲皱微循环及检测TT_3 TT_4 FT_4I、吸~(131)碘率,探讨它们之间的关系。结果表明甲亢患者微循环积分明显高于对照组(P<0.01),但不同类型甲亢的血淤情况亦不相同。心肝火旺型的微循环积分低于气滞痰凝型和血瘀型,但TT_3、TT_4、FT_4I明显增高;气滞痰凝型居中;血淤型的微循环积分明显增高,但TT_3、TT_4、FT_4I低于其他两型。吸~(131)碘率三型间无差异(P>0.05)。     

Use of a sensitive enzyme immunoassay for human thyrotropin in the diagnosis of hyperthyroidism

A sensitive, simultaneous sandwich enzyme immunoassay for TSH was evaluated especially for its ability to distinguish hyperthyroid patients from the euthyroid population. A total of 140 patient samples was analzyed by this assay as well as with a two-step sandwich radioimmunoassay. The diagnostic sensitivity of the thyrotropin assay was 92.5% and the specificity was 88%. False negatives by thyrotropin assay included two patients with Graves' disease who were being treated with propranolol at the time of testing and one patient who was considered hyperthyroid while receiving synthroid. Twelve patients with elevated free thyroxine index levels were considered euthyroid and 50% of these had thyrotropin values that were undetectable; most were elderly patients with nonthyroidal illnesses. Although the thyrotropin enzyme immunoassay had good sensitivity and precision for the detection of hyperthyroidism, our data suggest the limitation of a single thyrotropin determination in establishing the euthyroid state, especially in elderly patients with associated nonthyroidal illnesses and hyperthyroxinemia.     

Role of thyroid hormones in regulation of genetic activity of normal and transformed human cells

Thyroid hormones labeled with¹²⁵I are localized on structures of the interphase nucleus and metaphase chromosomes of fibroblasts from 8–10-week human embryos in culture. Meanwhile, although labeled thyroid hormones are present in interphase nuclei of HeLa cells, by contrast with normal cells they are not accepted by their metaphase chromosomes. It is suggested on the basis of the results that the acceptor region of the genome of HeLa cells during transformation have lost their ability to bind their own receptor complexes with thyroid hormones.Laboratory of Cytochemistry and Electron Microscopy, Institute of Biochemistry, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Byullenten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 81–83, July, 1979.     

Triiodothyronine (T3) and Cardiovascular Therapeutics: A Review

Hypothyroidism is associated with an abnormal hemodynamic state characterized by decreased heart rate, stroke volume, output, and contractility, and increased systemic vascular resistance. Since cardiopulmonary bypass (CPB) and surgical stress can induce profound decreases in triiodothyronine (T3) levels, the hemodynamic consequences of "stress-induced" hypothyroidism and T3 repletion are of increasing clinical interest. Available data generally support the likelihood of a beneficial effect associated with T3 replacement in brain-dead organ donors and in cases of low cardiac output following CPB. Although hypotheses have been advanced to account for these salutary effects, the mechanism by which T3 may augment hemodynamic performance has not been precisely defined, particularly in the acute setting. Although additional research is needed to clarify these and other issues, preliminary findings with T3 replacement indicate that such investigation is warranted.     

Increased hepatobiliary clearance of unconjugated thyroxine determines DMP 904-induced alterations in thyroid hormone homeostasis in rats.

4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in Sprague-Dawley rats, DMP 904 produced thyroid follicular cell hypertrophy and hyperplasia, and a low incidence of follicular cell adenoma. The current investigations were designed to determine the mode of action by which DMP 904 disrupts thyroid homeostasis in male rats. Five-day treatment with DMP 904 (300 mg/kg/day) dramatically lowered serum thyroxine (T4) to levels below detectable limits (< 1 microg/dl) by 72 h, with concurrent decreases in triiodothyronine (T3, about a 70% decrease) and increases in thyroid stimulating hormone (TSH; about a three-fold increase). DMP 904 increased [125I]T4 total body clearance (Cl tb) (38.21 +/- 10.45 ml/h) compared to control (5.61 +/- 0.59 ml/h) and phenobarbital-treated rats (7.92 +/- 1.62 ml/h). This increase in Cl(tb) was associated with a significant increase in biliary clearance (Cl bile) of unconjugated [125I]T4 (nearly 80-times control rates) and increased liver:blood ratios of T4, suggestive of enhanced hepatic uptake of T4. A single dose of DMP 904 (200 mg/kg) increased mRNA levels of hepatic cytochrome P450s (CYP 3A1 and CYP 2B1) and UDP-glucuronosyltransferases (UGT 1A1 and UGT 1A2). DMP 904 also induced mRNAs of the canalicular transporter, multi-drug resistance protein-2 (Mrp2) and sinusoidal transporters, organic anion transporting proteins (Oatp1 and Oatp2) within 24 h. Western blot analysis confirmed DMP 904 related increases in Oatp2 protein expression. Collectively, these data suggest that DMP 904 is an agonist of the constitutive androstane receptor (CAR) and pregnane X receptor (PXR) and that the decreased serum levels of T4 and T3 resulted from increased hepatobiliary clearance. However, DMP 904 is distinguished from other compounds associated with similar effects on thyroid hormone homeostasis because its effects were primarily related to increased biliary excretion of unconjugated T4.     

Thyroid Hormones and Cardiovascular Function and Diseases

Thyroid hormone (TH) receptors are present in the myocardium and vascular tissue, and minor alterations in TH concentration can affect cardiovascular (CV) physiology. The potential mechanisms that link CV disease with thyroid dysfunction are endothelial dysfunction, changes in blood pressure, myocardial systolic and diastolic dysfunction, and dyslipidemia. In addition, cardiac disease itself may lead to alterations in TH concentrations (notably, low triiodothyronine syndrome) that are associated with higher morbidity and mortality. Experimental data and small clinical trials have suggested a beneficial role of TH in ameliorating CV disease. The aim of this review is to provide clinicians dealing with CV conditions with an overview of the current knowledge of TH perturbations in CV disease.     

Effect of experimental thyrotoxicosis on oxidative phosphorylation in rat liver, kidney and brain mitochondria

Coupled phosphorylation was examined in liver, kidney and brain mitochondria from rats made thyrotoxic by injecting repeated doses of triiodothyronine. Liver and kidney mitochondria were maximally affected under these conditions, whereas effects on brain mitochondria were marginal. State-3 respiration rates with succinate decreased considerably in all the tissues, whereas glutamate oxidation increased in liver, but decreased in kidney and brain mitochondria. Oxidation rates of beta-hydroxybutyrate decreased in kidney and brain mitochondria but were not significantly affected in liver mitochondria. Oxidation of ascorbate + TMPD was not affected. State-4 respiration rates increased in general with all the substrates resulting in lowering of the RCI. The ADP/O ratios decreased in a site-specific manner in the mitochondria from the three tissues. The content of cytochrome b decreased in all three tissues, whereas the content of cytochrome c + c1 increased in liver and kidney but decreased in brain. The content of cytochrome a, however, was not significantly affected. Basal and Mg2+-stimulated ATPase activities increased in mitochondria of liver and kidney but not in those of brain; total ATPase activities, however, were not altered. The results imply that excessive levels of thyroid hormones over normal in the serum can lead to impairment of mitochondrial energy metabolism in a tissue-specific manner.     

Compressive optic neuropathy (CON) in Graves’ disease caused by hypertrophy of levator and superior rectus muscles: A case report

Rationale:Enlargemento of the medial rectus is the most predominant factor of compressive optic neuropathy (CON) in Graves‘ disease. This case report indicates that CON could develop only from the hypertrophic superior levator and superior rectus (SL/SR) muscle in a patient with poorly controlled Graves‘ disease, and described the possible risk of FT₃-thyrotoxicosis with a prominent goiter to develop the current rare case with a review of the literature.Patient concerns:A 66-year-old woman undergoing endocrine management of hyperthyroidism with prominent goiter visited the Department of Ophthalmology due to right-eye upper-eyelid retraction.Diagnoses:At initial presentation, the right and left margin reflex distance-1 (MRD-1) was 3.2 mm and 2.1 mm, respectively, and no proptosis or visual dysfunction was observed. Despite insufficient hormonal regulation, she refused to undergo goiter removal. The upper eyelid retraction gradually worsened to 7.7 mm of MRD-1, followed by the onset of 20 prism diopters (PD) of the right hypertropia, resulting in right-eye CON after 6 months. Her free thyroxin level was 3.88 ng/dl and free triiodothyronine was 24.90 pg/ml. Computed tomography and magnetic resonance imaging showed only SL/SR enlargement in the right orbit.Interventions:Intravenous steroid and radiation therapy resulted in visual improvement; however, a prominent upper eyelid retraction and 35PD of hypertropia remained in her right eye. Orbital decompression, upper retraction repair, and superior rectus recession were performed to prevent the recurrence of CON and correct any disfigurement.Outcomes:The combination of conventional intravenous steroid pulse therapy, radiotherapy, and orbital decompression was effective, and no recurrence was observed for more than 1.5-years postoperatively.Lessons:Enlargement of the SL/SR muscle complex may independently induce the CON. We believe that strict attention should be paid to patients with triiodothyronine thyrotoxicosis with progressive eyelid retraction and hypertropia.     

Over-the-Counter “Adrenal Support” Supplements Contain Thyroid and Steroid-Based Adrenal Hormones

Objective

To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, “adrenal fatigue,” or “adrenal support,” contain thyroid or steroid hormones.