title: Resistance to thyroid hormone in a patient without thyroid hormone receptor mutations.
abstract: Resistance to thyroid hormone (RTH) is a clinical syndrome characterized by elevated serum thyroid hormone (TH) levels, unsuppressed thyrotropin (TSH) levels, and tissue hyposensitivity to TH. In almost all cases, the genetic basis of RTH lies in mutation of one of the two TH receptor beta (TRbeta) alleles. Recently, patients from several families with phenotypic manifestations of RTH in the absence of TR mutations have been described. We report a case of a 31-year-old woman who presented with goiter, tachycardia, elevated TH levels, unsuppressed TSH, and "inappropriately normal" levels of peripheral TH action markers. In two separate clinical evaluations, the patient exhibited typical clinical and biochemical evidence for peripheral and pituitary RTH. Surprisingly, reverse transcriptase-polymerase chain reaction (RT-PCR) of full-length TRalpha and TRbeta mRNAs, and genomic PCR using primers flanking exons encoding the carboxy-terminal region of TRbeta failed to demonstrate mutations in the TRalpha or TRbeta genes. It is likely that defects in the regulation of TR genes or mutations in transcriptional cofactors involved in TR signaling account for this patient's phenotype.
authors.affiliation: Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: S
authors.initials: S
authors.lastname: Parikh
authors.forename: S
authors.initials: S
authors.lastname: Ando
authors.forename: A
authors.initials: A
authors.lastname: Schneider
authors.forename: M C
authors.initials: MC
authors.lastname: Skarulis
authors.forename: N J
authors.initials: NJ
authors.lastname: Sarlis
authors.forename: P M
authors.initials: PM
authors.lastname: Yen
mesh_terms: D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics; D005221:Fatigue; D005260:Female; D006042:Goiter; D006801:Humans; D007361:Intelligence Tests; D009154:Mutation; D009316:National Institutes of Health (U.S.); D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013610:Tachycardia; D037042:Thyroid Hormone Receptors beta; D018382:Thyroid Hormone Resistance Syndrome / Q000175:diagnosis / Q000235:genetics*; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone; D014284:Triiodothyronine; D014481:United States; D015431:Weight Loss
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011988:Receptors, Thyroid Hormone; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin