Pharmacological interference with in vitro tests of thyroid function

Wenzel, Klaus

doi:10.1016/0026-0495(81)90089-5

Cited by 112 publications

(47 citation statements)

References 177 publications

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“…Group I animals serve as normal control, group II animals served as vehicle control and were orally administered 6 mL/kg corn oil, while groups III, IV, V, and VI animals were orally administered 1, 2, 4, and 6 g/kg EC respectively once per day for seven (7) days. Oral median lethal dose (LD 50 ) of EC in rat is above 5 g/kg [19], and has been confirmed by us in another study to be actually 9487 mg/kg [20], which prompted the tested doses above.…”

Section: Experimental Animals and Study Designmentioning

confidence: 65%

Effect of edible camphor administrations on levels of steroid and thyroid hormones in male wistar rats

Somade¹,

Ugbaja²,

Adebayo³

2017

Am J Res Med Sci

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Background: Edible camphor (EC) is one of the ingredients in the preparation of local infusion for the management and treatment of pile, back pain, and erectile dysfunction, which are practices commonly in the south-western part of Nigeria. Conversely, 2 and 4 g/kg EC significantly increased the serum level of FT3 but was significantly reduced by 6 g/kg EC, and finally, EC administrations did not have any significant effect on serum PSA. Methods: Thirty rats were used for the study, and were divided into six groups of five rats each. Group I animals served as normal control, group II animals served as vehicle control and were orally administered 6 mL/kg corn oil, while groups III, IV, V, and VI animals were orally administered 1, 2, 4, and 6 g/kg EC for seven days. Results: Following EC administrations, there was significant (p < 0.05) decrease in serum total cholesterol (TCHOL) by 4 and 6 g/kg body weight EC. Furthermore, luteinizing hormone (LH), testosterone (TST), and thyroid stimulating hormone (TSH) levels were significantly reduced by the various doses. Conversely, 2 and 4 g/kg EC significantly increased the serum level of free triiodothyronine (fT3), but was significantly reduced by 6 g/kg EC, and lastly, EC administrations did not have any significant effect on serum prostate specific antigen (PSA). Conclusion:We therefore concluded that the use of EC should be with caution, and may contribute to thyroid and hormonal disruption in rats. ARTICLE HISTORY

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Section: Experimental Animals and Study Designmentioning

confidence: 65%

Effect of edible camphor administrations on levels of steroid and thyroid hormones in male wistar rats

Somade¹,

Ugbaja²,

Adebayo³

2017

Am J Res Med Sci

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“…The patient was receiving high doses of psychotropic drugs including chlorpromazine which has been shown to increase the TSH response to TRH. 13 We suggest, therefore, that the grossly raised Ta levels in this patient may be explained in part by her psychiatric illness and possible effects of drug therapy, superimposed on a background of increased TBG due to the contraceptive pill, and hyperthyroxinaemia due to presence of a variant albumin binding T 4.…”

Section: Discussionmentioning

confidence: 75%

Thyroid Function Tests in Patients with Familial Dysalbuminaemic Hyperthyroxinaemia (FDH)

Stewart¹,

Ratcliffe

Roberts

1986

Ann Clin Biochem

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SUMMARY. Two patients with familial dysalbuminaemic hyperthyroxinaemia (FDH) are described in whom the albumin variant resulted in raised total Ta levels, and artefactually raised free T4 using a 'single-step' technique employing an analogue of T 4 as tracer. The first patient was clinically euthyroid and presented with relapse of schizophrenia and abnormal thyroid function tests (total T 4 336 nrnol/L, total T) 4·2 nrnol/L, TSH 1·8 mUlL, free T 4 73 pmol/L), These results led to diagnostic confusion and the patient was treated with a short course of anti-thyroid drugs. The second patient had signs and symptoms of thyrotoxicosis at her first visit but was clinically euthyroid 5 months later when she was 10 weeks pregnant. Thyroid function tests were total T 4 259 nmol/L, total T) 3·6 nrnol/L, TSH 3·8 mUlL, free T 4 46 prnol/L, Further studies showed both patients to be biochemically euthyroid. A variant albumin was confirmed in both patients by a screening test for FDH and by reverse-flow electrophoresis. Family studies on 10 relatives of the first patient identified eight with FDH. A simple screening procedure for the indentification of FDH is described and the use of laboratory tests in suspected cases is discussed.Familial dysalbuminaemic hyperthyroxinaemia (FDH) is a rare autosomal dominant condition in which up to 50% of albumin molecules have an abnormal binding site which binds thyroxine (T 4 ) with an affinity 2G-50-fold higher than normal.

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“…Since the concentration of TBG (0.3 mM) in the normal human serum is much lower than that of TTR (5.4 mM) (Shenkin, 2006;Wenzel, 1981), we hypothesize that PFASs might favor binding to TTR over TBG when they enter the human blood stream. With 16 PFASs tested, some structural characteristics of the binding mode with TTR can be analyzed.…”

Section: Discussionmentioning

confidence: 97%

Binding interactions of perfluoroalkyl substances with thyroid hormone transport proteins and potential toxicological implications

et al. 2016

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A B S T R A C TPerfluoroalkyl substances (PFASs) have been shown to cause abnormal levels of thyroid hormones (THs) in experimental animals, but the molecular mechanism is poorly understood. Here, a fluorescence displacement assay was used to determine the binding affinities of 16 PFASs with two major TH transport proteins, transthyretin (TTR) and thyroxine-binding globulin (TBG). Most of the tested PFASs bound TTR with relative potency (RP) values of 3 Â 10 À4 to 0.24 when compared with that of the natural ligand thyroxine, whereas fluorotelomer alcohols did not bind. Only perfluorotridecanoic acid and perfluorotetradecanoic acid bound TBG, with RP values of 2 Â 10 À4 when compared with that of thyroxine. Based on these results, it was estimated that displacement of T4 from TTR by perfluorooctane sulfonate and perfluorooctanoic acids would be significant for the occupationally exposed workers but not the general population. Structure-binding analysis revealed that PFASs with a medium chain length and a sulfonate acid group are optimal for TTR binding, and PFASs with lengths longer than 12 carbons are optimal for TBG binding. Three mutant proteins were prepared to examine crucial residues involved in the binding of PFASs to TH transport proteins. TTR with a K15G mutation and TBG with either a R378G or R381G mutation showed decreased binding affinity to PFASs, indicating that these residues play key roles in the interaction with the compounds. Molecular docking showed that the PFASs bind to TTR with their acid group forming a hydrogen bond with K15 and the hydrophobic chain towards the interior. PFASs were modeled to bind TBG with their acid group forming a hydrogen bond with R381 and the hydrophobic chain extending towards R378. The findings aid our understanding of the behavior and toxicity of PFASs on the thyroid hormone system.

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Pharmacological interference with in vitro tests of thyroid function

Cited by 112 publications

References 177 publications

Effect of edible camphor administrations on levels of steroid and thyroid hormones in male wistar rats

Effect of edible camphor administrations on levels of steroid and thyroid hormones in male wistar rats

Thyroid Function Tests in Patients with Familial Dysalbuminaemic Hyperthyroxinaemia (FDH)

Binding interactions of perfluoroalkyl substances with thyroid hormone transport proteins and potential toxicological implications

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