OBJECTIVE: It is generally thought that thyroxine-binding globulin (TBG)-deficient individuals are euthyroid and do not require treatment. However, there have been case reports of TBG deficiency combined with hypothyroidism. The purpose of this study was to investigate the relationship between TBG deficiency and thyroid function. METHODS: We reviewed the medical records of 32 patients diagnosed with TBG deficiency between 1997 and 2008 in Soonchunhyang University Seoul Hospital. All were partial TBG deficiency. Eighteen patients had combined hypothyroidism, and 14 patients had normal thyroid function. We compared the TBG, thyroid-stimulating hormone, free thyroxine, and total triiodothyronine levels between these 2 groups. Eighteen patients with TBG deficiency with hypothyroidism started thyroxine medication and continued for 2-3 years. After, they were followed up with thyroid function tests after discontinuing medication for 4 weeks at 2-3 years of age. RESULTS: The TBG level in TBG deficiency with hypothyroidism patients was significantly lower than that in TBG deficiency with normal thyroid function (4.43+/-2.22 mg/L vs. 6.23+/-1.81 mg/L; P=0.02). The percent TBG compared with normal mean TBG level according to age in the hypothyroidism patients was also significantly lower than that of patients with normal thyroid function (13.42%+/-6.92% vs. 19.08%+/-4.87%; P=0.014). Sixteen of 18 patients diagnosed with TBG deficiency with hypothyroidism showed persistent hypothyroidism at 2-3 years of age. CONCLUSION: We conclude that TBG-deficient patients should be observed closely and undergo thyroid function testing in order not to miss hypothyroidism. More investigations of TBG deficiency and thyroid function are needed in the future.
Humans ; Hypothyroidism ; Medical Records ; Seoul ; Thyroid Function Tests ; Thyroid Gland* ; Thyrotropin ; Thyroxine ; Thyroxine-Binding Globulin* ; Triiodothyronine

A child diagnosed with congenital hypothyroidism after newborn screening and follow up thyroid function test at 1 month of life in another general hospital demonstrated euthyroid state with thyroxine(T4) supplementation until the age of 22 months of life, when he was transferred to our hospital, where he was diagnosed as thyroxine binding globulin(TBG) deficiency with low T4 and TBG. Withdrawal of T4 at age of 26 months was associated with hyperthyrotropinemic hypothyroidism. This patient is a case of TBG deficiency associated with hypothyroidism, and in rare instances, TBG deficiency may lead to hypothyroidism requiring hormone supplementation.
Child ; Congenital Hypothyroidism ; Follow-Up Studies ; Hospitals, General ; Humans ; Hypothyroidism* ; Infant, Newborn ; Mass Screening ; Thyroid Function Tests ; Thyroxine* ; Thyroxine-Binding Globulin*

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

Together, neonatal hepatitis and biliary atresia make up approximately 70 to 80% of the causes of neonatal cholestasis. Biliary atresia must be differentiated from neonatal hepatitis as soon as possible in order to institute early surgical intervention. We performed this study to examine whether the measurement of the serum alpha-fetoprotein (AFP) and thyroxine-binding globulin(TBG) was useful for differentiating these two conditions. Serum AFP levels were measured using enzyme immunoassay in 76 infants with cholestasis and serum TBG levels were measured using radio immunoassay in 30 infants with cholestasis and 23 infants without cholestasis. Serum AFP and TBG concentrations in patients were compared with the normal ranges in infants and were expressed as standard deviation (SD) scores. 52.7% of the patients with neonatal hepatitis showed SD scores of AFP higher than 4.0. By contrast, 14.3% of the patients with biliary atresia showed SD scores of AFP highter than 4.0(p<0.005). The patients with either neonatal hepatitis or biliary atresia had TBG concentrations above the normal ranges, but there was no difference between neonatal hepatitis and biliary atresia. The patients with neonatal hepatitis who recovered from jaundice after 6 months of age or progressed to chronic liver disease of died of the liver disease showed hight serum levels of AFP and TBG than the patients who recovered from jaundice before 6 months of age. In conclusion. SD scores of AFP could be used to differentiate between neonatal heptatis and biliary atresia, and SD scores of AFP and TBG might be used as an indicator of prognosis of neonatal hepatitis.
alpha-Fetoproteins* ; Biliary Atresia* ; Cholestasis ; Hepatitis A ; Hepatitis* ; Humans ; Immunoassay ; Immunoenzyme Techniques ; Infant ; Jaundice ; Liver Diseases ; Prognosis ; Reference Values ; Thyroxine-Binding Globulin*

BACKGROUND AND OBJECTIVES: Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL.METHODS: HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio.RESULTS: After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories.CONCLUSIONS: In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.
Amyloid ; Angiotensinogen ; Atherosclerosis ; Cardiovascular Diseases ; Cholesterol ; Complement System Proteins ; Immunoglobulin mu-Chains ; Lipoproteins ; Nitric Oxide ; Plasma ; Proteomics ; Serine Proteases ; Thyroxine-Binding Globulin ; Vascular Cell Adhesion Molecule-1 ; Vitronectin

OBJECTIVE: Hyperstimulation methods are broadly used for in vitro fertilization (IVF) in patients with infertility; however, the side effects associated with these therapies, such as ovarian hyperstimulation syndrome (OHSS), have not been well studied. N-glycoproteomes are subproteomes used for the remote sensing of ovarian stimulation in follicular growth. Glycoproteomic variation in human follicular fluid (hFF) has not been evaluated. In this study, we aimed to identify and quantify the glycoproteomes and N-glycoproteins (N-GPs) in natural and stimulated hFF using label-free nano-liquid chromatography/electrospray ionization-quad time-of-flight mass spectrometry. METHODS: For profiling of the total proteome and glycoproteome, pooled protein samples from natural and stimulated hFF samples were selectively isolated using hydrazide chemistry to obtain the total proteomes and glycoproteomes. N-GPs were validated by the consensus sequence N-X-S/T (92.2% specificity for the N-glycomotif at p<0.05). All data were compared between natural versus hyperstimulated hFF samples. RESULTS: We detected 41 and 44 N-GPs in the natural and stimulated hFF samples, respectively. Importantly, we identified 11 N-GPs with greater than two-fold upregulation in stimulated hFF samples compared to natural hFF samples. We also validated the novel N-GPs thyroxine-binding globulin, vitamin D-binding protein, and complement proteins C3 and C9. CONCLUSION: We identified and classified N-GPs in hFF to improve our understanding of follicular physiology in patients requiring assisted reproduction. Our results provided important insights into the prevention of hyperstimulation side effects, such as OHSS.
Chemistry ; Complement System Proteins ; Consensus Sequence ; Female ; Fertilization in Vitro* ; Follicular Fluid* ; Humans* ; In Vitro Techniques* ; Infertility ; Mass Spectrometry ; Ovarian Hyperstimulation Syndrome ; Ovulation Induction ; Physiology ; Proteome ; Proteomics ; Reproduction ; Sensitivity and Specificity ; Thyroxine-Binding Globulin ; Up-Regulation ; Vitamin D-Binding Protein

OBJECTIVETo investigate the relationship among serum reproductive hormone levels, serum homocysteine (Hcy) levels, metabolic syndrome (MS), and the components of MS in middle-aged and elderly males.

METHODSUsing the cluster and stratified sampling methods and a unified structured questionnaire, we conducted a survey among 948 men aged 40 - 80 years in the rural community, measured their basic physical parameters, and obtained their reproductive hormone levels, serum Hcy concentrations, and metabolism-related indicators. We collected 868 valid questionnaires along with their serum samples, divided the subjects into an MS and a non-MS control group in a 1:1 ratio, and measured their serum Hcy concentrations.

RESULTSAmong the subjects included, 132 were diagnosed with MS. Nonparametric tests showed statistically significant differences between the MS and non-MS groups in the waist circumference (WC), waist-hip ratio (WHR), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) (P < 0.05), but not in age (P > 0.05). Significant differences were also observed between the two groups in the levels of serum tT, SHBG, LH, and FTI (P < 0.05) , but not in the concentrations of serum Hcy (P > 0.05). The concentration of serum Hcy exhibited no correlation with BMI, SBP, DBP, FBG, TG, and HDL-C (P > 0.05) and had no influence on MS.

CONCLUSIONThe concentration of serum Hcy is not significantly correlated with MS, nor with its components. The levels of male serum reproductive hormones are associated both with MS and with its components.

Adult ; Aged ; Blood Pressure ; Body Mass Index ; Homocysteine ; blood ; Humans ; Luteinizing Hormone ; blood ; Male ; Metabolic Syndrome ; blood ; diagnosis ; Middle Aged ; Reproduction ; Rural Population ; Sex Hormone-Binding Globulin ; metabolism ; Surveys and Questionnaires ; Testosterone ; blood ; Thyroxine ; blood ; Waist Circumference ; Waist-Hip Ratio