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 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

PURPOSE: Zinc is an essential nutrient, which is required to maintain the normal structure and/or function of multiple enzymes. Therefore, zinc nutriture has been known to influence the physical growth of young children. This study was desinged to evaluate the relationship between blood zinc levels and growth parameters in children. METHODS: Two hundred eighty three children (150 boys and 133 girls) who visited the Youngdong Severance Hospital as short stature were enrolled in this study. Height standard deviation score (Ht. SDS), weight standard deviation score (Wt. SDS), and pubertal stage were obtained for each children. Blood samples were collected for zinc, alkaline phosphatase (ALP), insulin-like growth factor binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1), and free thyroxine (fT4). The relationship between blood zinc levels and growth status, and growth factors were analyzed. RESULTS: The Ht. SDS and Wt. SDS were -0.16+/-0.99, 0.16+/-0.88 respectively for the low blood zinc level group; the Ht. SDS and Wt. SDS were -0.16+/-0.97, 0.08+/-0.93 respectively for the normal blood zinc level group. Between two groups, Ht. SDS, Wt. SDS, bone age, pubertal stage, ALP, and IGF-1 showed no significant differences, while IGFBP-3 and fT4 showed significant differences (P<0.05). The mean zinc concentrations showed no significant difference between the normal stature group and short stature group (101.60+/-41.11 microgram/dL, 93.72+/-35.38 microgram/dL respectively). The Ht. SDS, Wt. SDS, pubertal stage, ALP, and IGF-1 showed no significant correlation with the zinc levels, while the IGFBP-3 and fT4 showed significant correlation (P<0.05). CONCLUSION: We could not find any significant relationship between blood zinc level and growth status. However, interpretation of our results should be cautious in aspect that the result might come from the subjects with mild zinc deficiency. Further study is required to investigate the severe zinc deficiency patients and zinc replacement study.
Alkaline Phosphatase ; Child* ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins ; Thyroxine ; Zinc*

The elderly are a peculiar group in terms of health management, as they often present with non-specific complaints which are challenging to interpret and may not present with the usual clinical picture of a disease. Objective. The study aims to determine the prevalence of thyroid dysfunction among asymptomatic, elderly Filipinos seen at the Philippine General Hospital (PGH). Methodology. Subjects aged 60 years and older seeking out-patient medical consult for non-thyroidal illness at the PGH were recruited. Patients with known thyroid or pituitary disease, previous thyroid or pituitary surgery, intake of medications known to affect thyroid hormone levels and critical illness were excluded. Fasting blood sugar (FBS), lipid profile, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and anti-thyroperoxidase (anti-TPO) levels were taken. Based on FT4 and TSH levels, subjects were classified as overt hypothyroid, subclinical hypothyroid, euthyroid, subclinical hyperthyroid, or overt hyperthyroid. Results. One hundred eighty subjects were recruited, of whom 152 (84%) were female. Hypertension was the most common comorbidity (58.33%), followed by diabetes (36.67%). One hundred sixty-two (90%) were euthyroid, 12 (6.7%) subclinical hypothyroid, 4 (2.22%) subclinical hyperthyroid, and two (1.11%) overtly hyperthyroid. No one was overtly hypothyroid. There was a trend toward increasing prevalence of diabetes, hypertension, low HDL, obesity and overall cardiovascular risk among those with subclinical hypothyroidism. Conclusion. Subclinical hypothyroidism was the most prevalent thyroid dysfunction among asymptomatic elderly included in the study.

Human ; Male ; Female ; Aged 80 And Over ; Aged ; Cardiovascular Diseases ; Diabetes Mellitus ; Hospitals, General ; Hypertension ; Hyperthyroidism ; Hypothyroidism ; Iodide Peroxidase ; Iron-binding Proteins ; Obesity ; Outpatients ; Pituitary Diseases ; Thyrotropin ; Thyroxine

OBJECTIVETo assess the association of thyroperoxidase (TPO) gene polymorphisms with dyshormonogenesis in congenital hypothyroidism (CH).

METHODSThe 17 exons and flanking introns of the TPO gene from 30 randomly selected samples were sequenced for the selection of single nucleotide polymorphisms (SNPs). In 136 patients with dyshormonogenetic CH and 141 healthy controls from the same region, the selected SNPs were genotyped by polymerase chain reaction (PCR) and direct sequencing or PCR-restriction fragment length polymorphism (RFLP).

RESULTSSix SNPs (rs9678281, rs376413622, rs1126797, rs4927611, rs732609 and rs1126799) were selected to determine the genotype for each sample. Among these, rs4927611 and rs732609 showed a significant difference between the two groups in both allelic and genotypic frequencies. With a recessive model of inheritance, rs732609 CC (OR=0.484, 95%CI: 0.253-0.927, P=0.04) and rs4927611 TT (OR=0.32, 95%CI: 0.112-0.915, P=0.047) were greater in the patients.

CONCLUSIONrs4927611 and rs732609 may be associated with dyshormonogenetic CH. rs4927611 TT and rs732609 CC are genotypes associated with potential risk for the disease.

Alleles ; Autoantigens ; genetics ; Base Sequence ; Child, Preschool ; Congenital Hypothyroidism ; blood ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Infant ; Infant, Newborn ; Iodide Peroxidase ; genetics ; Iron-Binding Proteins ; genetics ; Linkage Disequilibrium ; Male ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Risk Factors ; Thyrotropin ; blood ; Thyroxine ; blood

OBJECTIVETo understand the rates of diagnosis on thyroid disease and the differences in the distribution of age groups among those permanent residents, to analyze the relationships among thyroid function, thyroid antibodies and urinary iodine.

METHODSA cross-sectional survey was performed in 1 995 permanent residents in Urumqi, Xinjiang in May, 2013, Among them, 1 906 were healthy adults aged 18-84 age, with mean age as (46.3 ± 14.2) years and 30.4% of them were men. One time 10 ml random urine and blood samples were drown to examine urinary iodine (UI) thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), anti-thyroglobulin (TgAb) and anti-thyroid peroxidase (TPOAb).

RESULTS1) 213 residents were newly diagnosed as having thyroid dysfunction (11.2%, including 78.4% women), hyperthyroidism (clinical and subclinical hyperthyroidism) that accounted for 2.7%, hypothyroidism (clinical and subclinical hypothyroidism) was accounted for 8.5%. Positive rates of TgAb (23.2%), TPOAb (16.6%) were noticed. The median urinary iodine was 134.5 µg/L, with 32% of the subjects were having iodine deficiency, 58% having adequate iodine and another 10% as under excessive iodine. No differences were observed on urine iodine between thyroid dysfunction and euthyroidism or between subjects with positive and negative antibodies. 2) TSH appeared different among age-groups of 18-, 45- and over 60. TSH showed higher in women than in men, with P value as < 0.001. For people with euthyroidism, TSH level in the antibody positive group was significantly higher than the antibody negative group (P < 0.000 1). 3) For people over 60 of age, morbidity of hypothyroidism was significantly higher than those under 60 but with no differences related to hyperthyroidism or the antibody positive rate.

CONCLUSIONUI levels were not significantly related with thyroid function and thyroid antibodies among residents of Urumqi, women showed higher on thyroid dysfunction or the rate of positive antibody. In the antibody positive group, TSH levels were significantly higher than in the antibody negative group. Hypothyroidism was seen higher in the over 60-years-of-age population. Monitoring programs on thyroid function, thyroid antibodies and urinary iodine among people over 60-years-of-age, should be strengthened.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autoantibodies ; blood ; Autoantigens ; blood ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Hypothyroidism ; epidemiology ; Immunologic Tests ; Iodide Peroxidase ; blood ; Iodine ; urine ; Iron-Binding Proteins ; blood ; Male ; Middle Aged ; Thyroid Diseases ; epidemiology ; Thyroid Function Tests ; Thyroid Gland ; physiology ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood ; Young Adult

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