A three-year-old female with a history of recurrent tonsillitis was investigated for failure to thrive and global developmental delay. Clinically, she had a triangular face with low-set ears and intermittent tachycardia. She had growth failure with her weight under the third centile while her height was within normal limits. Other systemic examinations were unremarkable. The presence of an elevated free T4 (FT4) with an inappropriately high thyroid stimulating hormone (TSH) in this patient raised the clinical suspicion of Thyroid Hormone Resistance Syndrome. DNA sequencing confirmed the diagnosis, which showed R243W gene mutation in Thyroid Hormone Receptor-Beta1 (THRB1).
Receptors, Thyroid Hormone ; Thyroid Hormone Resistance Syndrome ; Goiter

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

Thyroid hormone resistance is a rare syndrome of reduced tissue responsiveness to thyroid hormone. We report the case of a 13-month girl with short height and low weight. She was born at 37+6 weeks gestation and weighed 2,470 g. In the neonatal screening test, patients' thyroid stimulation hormone (TSH) level was increased to 13.1 µIU/mL. In follow-up test after getting levothyroxine medication, patients' free T4 level continued to increase and TSH level was normalized. After stop medication, the patient visited Soonchunhyang University Seoul Hospital every 2 to 3 months and done laboratory test, and the result was not changed. Despite good feeding, she consistently shows 5–10 percentile weight and 5–10 percentile height. Her bone age was delayed by 5 months compared to the expected age. In suspicious thyroid hormone resistance, THRβ gene study and brain magnetic resonance imaging (MRI), and T3 suppression test was done. Brain MRI and T3 suppression test shows the exception of pituitary thyroid adenoma. Gene study result was THRβ gene mutation, c.1012C>T (p.Arg338Trp), and heterozygous. This gene mutation was reported at thyroid hormone resistance family. After diagnosis of thyroid hormone resistance, because of the patient is asymptomatic, she does not have medication. We are checking developmental delay, growth delay, and other clinical hypothyroid symptoms.
Brain ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Infant, Newborn ; Magnetic Resonance Imaging ; Neonatal Screening ; Pregnancy ; Seoul ; Thyroid Function Tests ; Thyroid Gland* ; Thyroid Hormone Receptors beta ; Thyroid Hormone Resistance Syndrome* ; Thyroid Neoplasms ; Thyroxine

Familial dysalbuminemic hyperthyroxinemia (FDH) is an inherited disease characterized by increased circulating total thyroxine (T4) levels and normal physiological thyroid function. Heterozygous albumin gene (ALB) variants have been reported to be the underlying cause of FDH. To our knowledge, there have been no confirmed FDH cases in Korea. We recently observed a female patient with mild T4 elevation (1.2 to 1.4-fold) and variable levels of free T4 according to different assay methods. Upon Sanger sequencing of her ALB, a heterozygous c.725G>A (p.Arg242His) variant was identified. The patient's father and eldest son had similar thyroid function test results and were confirmed to have the same variant. Although the prevalence of FDH might be very low in the Korean population, clinical suspicion is important to avoid unnecessary evaluation and treatment.
Adult ; Albumins/*genetics ; Base Sequence ; Female ; Heterozygote ; Humans ; Hyperthyroxinemia, Familial Dysalbuminemic/*genetics ; Pedigree ; Radioimmunoassay ; Sequence Analysis, DNA ; Thyroxine/analysis

BACKGROUND: Owing to its large molecular size, polyethylene glycol (PEG)-precipitable thyrotropin (TSH) can accumulate in the circulation, elevating TSH levels. PEG-precipitable TSH can be used to detect macro-TSH (mTSH) in serum. Our aim was to evaluate the prevalence of mTSH in patients who had undergone thyroidectomy for thyroid cancer. METHODS: Seventy-three thyroid cancer patients and 24 control subjects on levothyroxine (LT4) TSH-suppressive or replacement therapy were evaluated. Screening for mTSH was performed by adding PEG to serum in order to precipitate γ-globulin. A percentage of PEG-precipitable TSH ≥80% was considered suggestive of mTSH. RESULTS: No correlation between free-T4 (fT4) and TSH levels was found. PEG-precipitable TSH was 39.3%±1.9% in thyroid cancer patients and 44.1%±3.9% in controls. Macro-TSH was deemed to be present in one thyroid cancer patient and in two control subjects. Only in the thyroid cancer group was PEG-precipitable TSH found to be negatively correlated with fT4 concentration. No correlation was found between PEG-precipitable TSH and other clinical conditions in any patients. CONCLUSION: The presence of mTSH seems to be a rare phenomenon in thyroid cancer. In some patients with low PEG-precipitable TSH, a reduction in LT4 dosage could be suggested. LT4 dosage adjusted to body weight is the main factor in maintaining TSH in a semi-suppressed or normal range. Evaluation of mTSH could be necessary in patients in whom a balance is required between adequate TSH suppression and the avoidance of unnecessary exogenous hyperthyroxinemia.
Body Weight ; Humans ; Hyperthyroxinemia ; Mass Screening ; Polyethylene Glycols* ; Polyethylene* ; Prevalence ; Reference Values ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Thyrotropin* ; Thyroxine

Inherited thyroxine binding globulin (TBG) disorder can be identified incidentally or through neonatal screening test. TBG excess is characterized by high levels of thyroxine (T4) but normal level of free T4 (fT4), while TBG deficiency presents with low T4 levels and normal fT4 levels. A 27-day-old newborn was brought to the hospital because of hyperthyroxinemia detected by neonatal screening. His T4 level was 18.83 µg/dL (normal range, 5.9-16.0 µg/dL). His mother had no history of any thyroid disease. His fT4 and thyroid stimulating hormone (TSH) levels were 1.99 ng/dL (normal range, 0.8-2.1 ng/dL) and 4.54 mIU/L (normal range, 0.5-6.5 mIU/L), respectively. His serum total triiodothyronine (T3) level was 322.5 ng/dL (normal range, 105.0-245.0 ng/dL). His TBG level was 68.27 mg/L (normal range, 16.0-36.0 mg/L) at the age of 3 months. At 6 months and 12 months of age, his TBG levels were 48.77 mg/L (normal range, 16.0-36.0 mg/L) and 50.20 mg/L (normal range, 14.0-28.0 mg/L), respectively, which were 2 to 3 times higher than normal values. Hormonal studies showed consistently elevated T3 and T4 levels and upper normal levels of fT4 and free T3 with normal TSH levels. His growth and development were normal. TBG excess should be considered as a potential differential diagnosis for hyperthyroxinemia and especially high T3 levels with normal TSH concentration.
Diagnosis, Differential ; Growth and Development ; Humans ; Hyperthyroxinemia ; Infant, Newborn ; Mothers ; Neonatal Screening* ; Reference Values ; Thyroid Diseases ; Thyrotropin ; Thyroxine* ; Thyroxine-Binding Globulin* ; Triiodothyronine

Inherited thyroxine binding globulin (TBG) disorder can be identified incidentally or through neonatal screening test. TBG excess is characterized by high levels of thyroxine (T4) but normal level of free T4 (fT4), while TBG deficiency presents with low T4 levels and normal fT4 levels. A 27-day-old newborn was brought to the hospital because of hyperthyroxinemia detected by neonatal screening. His T4 level was 18.83 µg/dL (normal range, 5.9-16.0 µg/dL). His mother had no history of any thyroid disease. His fT4 and thyroid stimulating hormone (TSH) levels were 1.99 ng/dL (normal range, 0.8-2.1 ng/dL) and 4.54 mIU/L (normal range, 0.5-6.5 mIU/L), respectively. His serum total triiodothyronine (T3) level was 322.5 ng/dL (normal range, 105.0-245.0 ng/dL). His TBG level was 68.27 mg/L (normal range, 16.0-36.0 mg/L) at the age of 3 months. At 6 months and 12 months of age, his TBG levels were 48.77 mg/L (normal range, 16.0-36.0 mg/L) and 50.20 mg/L (normal range, 14.0-28.0 mg/L), respectively, which were 2 to 3 times higher than normal values. Hormonal studies showed consistently elevated T3 and T4 levels and upper normal levels of fT4 and free T3 with normal TSH levels. His growth and development were normal. TBG excess should be considered as a potential differential diagnosis for hyperthyroxinemia and especially high T3 levels with normal TSH concentration.
Diagnosis, Differential ; Growth and Development ; Humans ; Hyperthyroxinemia ; Infant, Newborn ; Mothers ; Neonatal Screening* ; Reference Values ; Thyroid Diseases ; Thyrotropin ; Thyroxine* ; Thyroxine-Binding Globulin* ; Triiodothyronine

We report an anesthetic experience in a clinically euthyroid patient with hyperthyroxinemia (elevated free thyroxine, fT4 and normal 3, 5, 3'-L-triiodothyronine, T3) and suspected impairment of conversion from T4 to T3. Despite marked hyperthyroxinemia, this patient's perioperative hemodynamic profile was suspected to be the result of hypothyroidism, in reference to the presence of T4 to T3 conversion disorder. We suspected that pretreatment with antithyroid medication before surgery, surgical stress and anesthesia may have contributed to the decreased T3 level after surgery. She was treated with liothyronine sodium (T3) after surgery which restored her hemodynamic profile to normal. Anesthesiologists may be aware of potential risk and caveats of inducing hypothyroidism in patients with euthyroid hyperthyroxinemia and T4 to T3 conversion impairment.
Anesthesia ; Conversion Disorder ; Hemodynamics ; Humans ; Hyperthyroxinemia* ; Hypothyroidism ; Sodium ; Thyroxine ; Triiodothyronine

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

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