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

OBJECTIVETo report a family of familial dysalbuminaemic hyperthyroxinaemia(FDH).

METHODSFour members, including the female proband, mother, daughter and brother, went through the measurement of thyroid hormone and thyroid-stimulating hormone (TSH). Electrophoretic analysis of the patient's serum proteins was carried out after the patient's serum being incubated with fluorescein isothiocyanate (FITC) labeled thyroxine(T4), The point mutation of Alb gene was determined in all members.

RESULTSThe measurements of thyroid hormane and TSH showed that in three members (the proband, her mother and her daughter), the total thyroxine(TT4) serum level was high, the total triiodothyronine(TT3), FT4, FT3 and TSH serum levels were normal. And the enhanced albumin binding of fluorescenced T4 by electrophoresis showed a mutation transition 653 G-->A on DNA coding region of albumin. But in the proband's brother, the thyroid function and the results of electrophoresis of thyroxine-binding protein and determination of albumin gene were normal.

CONCLUSIONA family with FDH in China is firstly reported here, a mutation at albumin gene DNA coding region 653G-->A causing enhanced albumin binding of T4 results in high T4 level.

Adult ; Base Sequence ; DNA Mutational Analysis ; Family Health ; Female ; Humans ; Hyperthyroxinemia, Familial Dysalbuminemic ; blood ; genetics ; Male ; Pedigree ; Point Mutation ; Polymerase Chain Reaction ; Thyrotropin ; blood ; Thyroxine ; blood ; Thyroxine-Binding Proteins ; genetics ; Triiodothyronine ; blood

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

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

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

Monogenic disorder is a single gene disorder resulted of a single mutated gene. Monogenic disorder has benefits in early diagnosis and precious prediction of disease course. Furthermore, monogenic disorder could provide an informative knowledge to the understanding of related pathophysiology. Thyroid monogenic disorder could occur in various steps, such as thyroid development, hormonogenesis, TSH-receptor signaling, thyroid hormone transport and end organ response. Here, we reviewed of congenital hypothyroidism, congenital hyperthyroidism and thyroid hormone resistance syndrome.
Congenital Hypothyroidism ; Early Diagnosis ; Hyperthyroidism ; Thyroid Gland ; Thyroid Hormone Resistance Syndrome