Resistance to thyroid hormone (RTH) is an autosomal dominant disorder that's characterized by inappropriate normal or elevated TSH levels despite of the elevated thyroid hormone levels. RTH is distinguished from the TSH secreting pituitary adenoma by performing the TRH stimulation test, TSH alpha subunit measurement and sellar MRI. A 23 year old woman visited our hospital complaining of fatigue, palpitation and heat intolerance and she had an anterior neck mass. She had elevated total T3, free T4 and TSH levels. The serum TSH levels were increased during the TRH stimulation test before and after T3 suppression. The serum TSH alpha subunit showed a normal response and the serum TSH alpha subunit/TSH molar ratio did not increase over 1.0 with TRH stimulation. Thyroid hormone receptor beta gene mutation was identified. Although a left pituitary microadenoma was revealed on sellar MRI, the patient was diagnosed as having pituitary RTH with a nonfunctioning pituitary microadenoma. We report here on a patient with pituitary RTH and a nonfunctioning pituitary microadenoma, and this is the first such case in Korea.
Fatigue ; Female ; Glycoprotein Hormones, alpha Subunit ; Hot Temperature ; Humans ; Molar ; Neck ; Pituitary Neoplasms ; Thyroid Gland ; Thyroid Hormone Receptors beta

Thyroid hormone resistance (RTH) is a rare autosomal dominant disease characterized by reduced tissue sensitivity to thyroid hormone. Approximately 90% of subjects with RTH have mutation in the thyroid hormone receptor beta (TRbeta) gene. Approximately 10% of subjects diagnosed as having RTH do not carry mutation in the TRbeta gene. We report a 12-year-old male. The patient was euthyroid in spite of high total and free T4 and T3 concentrations, while TSH is slightly increased. TSH response to TRH stimulation was normal, and TSH values to TRH stimulation after T3 suppression revealed partial response. Sequence analysis of TRbeta gene showed no mutation. We report a case of RTH without mutations in the TRbeta gene.
Child ; Humans ; Male ; Sequence Analysis ; Thyroid Gland* ; Thyroid Hormone Receptors beta ; Thyroid Hormone Resistance Syndrome*

Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; Thyroid Hormone Receptors beta ; genetics ; Thyroid Hormone Resistance Syndrome ; genetics

In thyroid hormone resistance syndrome (THR) TSH levels are normal or elevated despite thyroid hormone levels being elevated. THR is distinguished from TSH-producing pituitary adenoma by TRH stimulation and alpha-subunit tests, thyroid hormone receptor (TR) beta gene analysis, and sellar MRI. A 24-year old man with diffuse goiter visited our hospital complaining of fatigue, heat intolerance, palpitation, and weight loss. He had elevated total T3 and free T4 levels, but normal TSH levels. Serum TSH levels during TRH stimulation tests performed before and after T3 suppression showed normal and non-suppressible responses, respectively. The serum basal alpha-subunit test result was normal. A TR beta gene R438H mutation was identified, and a pituitary mass with cystic change was identified by sellar MRI. We report a case of THR with a mutation (R438H) in the TR beta gene, the first case of its kind in Korea.
Fatigue ; Genes, erbA ; Goiter ; Hot Temperature ; Korea ; Pituitary Neoplasms ; Receptors, Thyroid Hormone ; Thyroid Gland ; Thyroid Hormone Receptors beta ; Thyroid Hormone Resistance Syndrome ; Weight Loss

Resistance to thyroid hormone (RTH) is a rare inherited syndrome characterized by diminished response of the target tissue to thyroid hormone caused, in the majority of cases, by mutation of the thyroid hormone receptor beta (THRbeta) gene. Despite elevated serum levels of free thyroid hormones and thyroid stimulating hormone (TSH), the paucity of symptoms and signs of thyroid dysfunction suggest RTH. We report the case of a 9-year-old girl with goiter. Her thyroid function tests showed increased serum levels of free thyroxine, triiodothyronine, and TSH. The genetic analysis of THRbeta confirmed a novel mutation in exon 9; this was a heterozygous C-to-T change in the 327th codon, substituting threonine for isoleucine (T327I).
Child ; Codon ; Exons ; Female ; Goiter ; Humans ; Isoleucine ; Threonine ; Thyroid Function Tests ; Thyroid Gland* ; Thyroid Hormone Receptors beta* ; Thyroid Hormone Resistance Syndrome ; Thyroid Hormones ; Thyrotropin ; Thyroxine ; Triiodothyronine

Resistance to thyroid hormone (RTH) is a condition caused by a mutation in the thyroid hormone receptor gene. It is rarely reported in individuals with no family history of RTH or in premature infants, and its clinical presentation varies. In our case, a premature infant with no family history of thyroid diseases had a thyroid stimulating hormone level of 85.0 µIU/mL and free thyroxine level of 1.64 ng/dL on a thyroid function test. The patient also presented with clinical signs of hypothyroidism, including difficulties in feeding and weight gain. The patient was treated with levothyroxine; however, only free thyroxine and triiodothyronine levels increased without a decrease in thyroid-stimulating hormone levels. Taken together with thyroid gland hypertrophy observed on a previous ultrasound examination, RTH was suspected and the diagnosis was eventually made based on a genetic test. A de novo mutation in the thyroid hormone receptor β gene in the infant was found that has not been previously reported. Other symptoms included tachycardia and pulmonary hypertension, but gradual improvement in the symptoms was observed after liothyronine administration. This report describes a case involving a premature infant with RTH and a de novo mutation, with no family history of thyroid disease.
Diagnosis ; Goiter ; Humans ; Hypertension, Pulmonary ; Hypertrophy ; Hypothyroidism ; Infant ; Infant, Newborn ; Infant, Premature ; Receptors, Thyroid Hormone ; Tachycardia ; Thyroid Diseases ; Thyroid Function Tests ; Thyroid Gland ; Thyroid Hormone Receptors beta ; Thyroid Hormone Resistance Syndrome ; Thyrotropin ; Thyroxine ; Triiodothyronine ; Ultrasonography ; Weight Gain

BACKGROUNDResistance to thyroid hormone (RTH) is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor β (TRβ). We report the clinical and laboratory characteristics and the genetic analysis of a patient with this rare disorder and his family members.

METHODSThe clinical presentations and changes of thyroid function tests (TFTs) including magnetic resonance imaging (MRI) of pituitary and other laboratory tests were analysed. TFTs of his family's members were detected as well. Direct DNA sequencing of the TRβ gene was done for those with abnormal TFTs.

RESULTSThe RTH child had goiter, irritability, aggressiveness, and sudoresis. His TFTs showed high levels of circulating free thyroid hormones (FT(4) and FT(3)) and normal thyroid-stimulating hormone (TSH) concentrations. He felt worse when treated as hyperthyroidism (Grave disease) with thiamazole and his clinical presentations got improved obviously when treated as RTH with bromocriptine without obvious advert effect. We identified a novel missense mutation, A317D, located in exon 9 of the gene of this boy and his mother. His mother had not any clinical presentation, but having abnormal TFTs results.

CONCLUSIONSThis patient reported here was concordant with the criteria of RTH. The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel mutation was found in the TRβ, A317D, of this family. This research verified the phenomena that there is a clinical heterogeneity within the same mutation of different RTH patients.

Child ; Diagnosis, Differential ; Humans ; Male ; Mutation, Missense ; Thyroid Hormone Receptors beta ; genetics ; Thyroid Hormone Resistance Syndrome ; diagnosis ; genetics ; therapy

Resistance to thyroid hormone (RTH) is a syndrome characterized by reduced sensitivity to the thyroid hormone. It is generally caused by mutations in the thyroid hormone receptor beta (TRbeta) gene. On the basis of its clinical features, two different forms of this syndrome have been described: generalized resistance and pituitary resistance. A total of 122 TRbeta gene mutations have been identified thus far. A 38-year-old woman presented with intermittent palpitation. Thyroid function tests revealed elevated levels of free T4 and TSH. TSH alpha-subunit levels were 0.41 mIU/mL, and magnetic resonance images of the sellar region evidenced no abnormal findings. The TSH response to TRH stimulation was found to be normal. The sequence analysis of the TRbeta gene verified a missense mutation in exon 11, and the observed amino acid alteration was a substitution of a valine for a methionine at codon 349. We report the first case of a woman with RTH, which was found to be caused by a missense mutation (V349M) in the TRbeta gene.
Adult ; DNA Mutational Analysis ; Female ; Humans ; *Mutation, Missense ; Thyroid Function Tests ; Thyroid Hormone Receptors beta/*genetics ; Thyroid Hormone Resistance Syndrome/*diagnosis/*genetics

Syndrome of resistance to thyroid hormone(RTH) is inherited by an autosomal dominant trait, and characterized by elevated thyroid hormone levels with reduced responsiveness of the pituitary and peripheral tissues to thyroid hormone action. All of the reported RTH patients have various mutations in the ligand-binding domain coding region of the thyroid hormone receptor beta gene. A 21-year-old man visited our hospital complaining of fatigue. He had mild thyroid goiter and intermittent palpitation. Thyroid function test showed elevated total T3, free T4, and TSH levels. Levels of TSH free a-subunit and basal pituitary hormones, except prolactin, were normal. MRI of the sellar region showed no abnormal finding. TSH response to TRH stimulation was normal, and TSH values to TRH stimulation after T3 suppression revealed partial response. Sequeuce analysis of the thyroid hormone receptor beta gene confirmed a heterozygous missense mutation in exon 9; and the amino acid alteration was a substitution of a threonine(ACG) for a methionine(ATG) at codon313. Sequeuce analysis of the parents showed no mutation.We report the first case of a man with RTH caused by a de novo mutation(M313T) in TRbeta gene, confirmed by sequeuce analysis.
Clinical Coding ; Exons ; Fatigue ; Goiter ; Humans ; Magnetic Resonance Imaging ; Mutation, Missense ; Parents ; Pituitary Hormones ; Prolactin ; Receptors, Thyroid Hormone* ; Thyroid Function Tests ; Thyroid Gland* ; Thyroid Hormone Receptors beta* ; Young Adult

OBJECTIVETo detect the gene mutation of thyroid hormone receptor beta (TR beta) in a family with thyroid hormone resistance syndrome.

METHODSThe genomic DNA was extracted from peripheral blood leukocytes of the patient, 14 family members and 7 healthy subjects. The exons 7-10 of TR beta gene were amplified by PCR. The products of PCR were purified and sequenced directly to detect the gene mutation.

RESULTSFive members of this family were confirmed to have the C to G transition mutation at nucleotide 1642 site within exon 10 of TR beta gene, which was a missense mutation causing the substitution of Proline to Alanine (P453A); and also to have the C to T transition mutation at nucleotide 1020 within exon 7 of TR beta gene, which was a synonymous mutation that didn't cause the change of amino acid at this position (F245F). The two mutations were heterozygote. No mutation in the exons 7-10 of TR beta gene were identified in other family members.

CONCLUSIONA family with thyroid hormone resistance syndrome caused by TR beta gene mutation is first founded in Chinese people.

Adult ; Base Sequence ; Child ; DNA Mutational Analysis ; Family Health ; Female ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree ; Polymerase Chain Reaction ; Thyroid Hormone Receptors beta ; genetics ; Thyroid Hormone Resistance Syndrome ; genetics