The consequences of inappropriate treatment because of failure to recognize the syndrome of pituitary and peripheral tissue resistance to thyroid hormone

Refetoff, Samuel; Salazar, Ángel; Smith, Terry J.; Scherberg, Neal H.

doi:10.1016/0026-0495(83)90114-2

Cited by 53 publications

(15 citation statements)

References 44 publications

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“…Doses of triiodothyronine that achieved highly elevated serum values, ranging from 600-1100 ng/dl (normal range, 85-180 ng/dl) in both the proband and control, completely suppressed the TSH response to thyrotropinreleasing hormone in the normal subject (<0.1 microunits/ml in all serum samples) but only partially suppressed TSH in the proband (Fig. 2), as found in other subjects with GRTH (30). During triiodothyronine treatment basal prolactin concentration paradoxically increased without suppression of its response to thyrotropin-releasing hormone.…”

Section: Examination Of the Responses Of Patients Tomentioning

confidence: 62%

Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta.

Sakurai

Takeda

Ain

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

252

110

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The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. We have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine -* cytosine replacement in the codon for amino acid 340 resulted in a glycine --arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor 13 gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor (3 gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.

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Section: Examination Of the Responses Of Patients Tomentioning

confidence: 62%

Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta.

Sakurai

Takeda

Ain

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

252

110

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“…These subjects belong to four unrelated families in which, in addition to TR␤ gene sequencing, linkage analyses have excluded the involvement of the TR␤ gene in two (Msn and Mch) and the TR␣ gene in all four (15,16). The phenotype of these subjects was not different from that of individuals with RTH due to TR␤ gene mutations (15)(16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the proposita probably has a new mutation, as neither parent and none of five siblings (not shown in Fig. 1) expressed the RTH phenotype (15,17). The study for linkage to SMRT was not informative because the proposita is homozygous for both markers.…”

Section: Family Mmamentioning

confidence: 99%

Search for Abnormalities of Nuclear Corepressors, Coactivators, and a Coregulator in Families with Resistance to Thyroid Hormone without Mutations in Thyroid Hormone Receptor β or α Genes¹

Reutrakul

Sadow²,

Pannain³

et al. 2000

The Journal of Clinical Endocrinology & Metabolism

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The syndrome of resistance to thyroid hormone (RTH) is characterized by decreased tissue responsiveness to thyroid hormones. Inheritance is usually autosomal dominant due to mutations in the ligand-binding domain or adjacent hinge region of the thyroid hormone receptor ␤ (TR␤) gene. Six of 65 families with the RTH phenotype studied in our laboratory had normal TR␤1 and TR␤2 gene sequences. Their clinical characteristics were not different from those of subjects with TR␤ gene mutations. Four of the 6 families were amenable to linkage analysis, and TR␣ involvement was excluded. Candidate genes were then evaluated for their possible involvement in the RTH phenotype in these 4 families: 2 coactivators [NCoA-1 (SRC-1) and NCoA-3 (AIB-1)], 2 corepressors (NCoR and SMRT), and a coregulator (RXR␥). DNA was obtained from 8 affected subjects and 41 of 45 living first degree relatives. In 2 of the 4 families, the mode of inheritance could be determined by pedigree analysis and was found to be autosomal dominant. Linkage analyses were performed using polymorphic markers near or within the 5 candidate genes. When analyses were not informative or linkage could not be excluded, direct sequencing of the genes in question was performed.Involvement of NCoA-1 was excluded in all four families assuming autosomal dominant inheritance. Roles for NCoR, SMRT, and NCoA-3 were excluded in three and a role for RXR␥ was excluded in two of the four families. However, if the two families without proven dominant mode of inheritance were compound heterozygous, only the involvement of NCoA-1 could be excluded in both. Roles for NCoR, SMRT, and RXR␥ were excluded in one of these two families. Thus, NCoA-1 and RXR␥ genes were not found to be the cause of RTH in subjects without TR gene mutations even though the absence of NCoA-1 and RXR␥ is the cause of RTH in mice. Involvement of other candidate genes in the mediation of thyroid hormone action as well as intracellular hormone transport needs to be explored in these families with non-TR␤, TR␣ RTH. (J Clin Endocrinol Metab 85: 3609 -3617, 2000)

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“…Serum free T4 and free T3 levels in these patients are elevated despite the fact that they appear to be clinically euthyroid and often have an elevated serum TSH (Refetoff et al 1967(Refetoff et al , 1983). Confirmation of their euthyroid status with peripheral parameters is important in the delineation of this syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…It is apparent, however, that the ultimate determinants of the thyroidal status of the patient are the biological effects of thyroid hormones (Bantle et al 1980). In patients with thyroid hormone resistance there is a discrepancy between serum free thyroid hormone concentrations and peripheral thyroid hormone effects (Refetoff et al 1967(Refetoff et al , 1983). This study was undertaken to compare serum free thyroid hormone concentrations with several markers of peripheral tissue response to thyroid hormone in patients with hyperthyroidism, hypothyroidism and euthyroidism with goiter before and after the standard forms of treatment.…”

mentioning

confidence: 99%

Relationship between serum free thyroid hormone concentrations and target organ responsiveness in thyroid disease patients before and after treatment.

Yoshida¹,

Sato

Kaise

et al. 1989

Tohoku J. Exp. Med.

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The consequences of inappropriate treatment because of failure to recognize the syndrome of pituitary and peripheral tissue resistance to thyroid hormone

Cited by 53 publications

References 44 publications

Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta.

Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta.

Search for Abnormalities of Nuclear Corepressors, Coactivators, and a Coregulator in Families with Resistance to Thyroid Hormone without Mutations in Thyroid Hormone Receptor β or α Genes¹

Relationship between serum free thyroid hormone concentrations and target organ responsiveness in thyroid disease patients before and after treatment.

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The consequences of inappropriate treatment because of failure to recognize the syndrome of pituitary and peripheral tissue resistance to thyroid hormone

Cited by 53 publications

References 44 publications

Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta.

Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta.

Search for Abnormalities of Nuclear Corepressors, Coactivators, and a Coregulator in Families with Resistance to Thyroid Hormone without Mutations in Thyroid Hormone Receptor β or α Genes1

Relationship between serum free thyroid hormone concentrations and target organ responsiveness in thyroid disease patients before and after treatment.

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Product

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About

Search for Abnormalities of Nuclear Corepressors, Coactivators, and a Coregulator in Families with Resistance to Thyroid Hormone without Mutations in Thyroid Hormone Receptor β or α Genes¹