TBG Levels Research Articles

A-059 Evaluation of Free Thyroxin Levels in Patients with Low Thyroxin Binding Globulin Concentrations: Is There Interference in the FT4 Indirect Method?

Abstract Background Thyroxine-binding globulin (TBG) is the major carrier of thyroid hormones in serum. Variations in the serum concentration of TBG determine proportional variations in the total serum concentrations of T4 and T3, without implying changes in function, as long as the free fraction remains normal. Several common clinical conditions lead to significant alterations in TBG levels, the most important factor behind low levels being genetic defects. As TBG is encoded by a gene located on the X chromosome, the defects are more easily manifested in males. Differences in FT4 concentrations were observed in sera from subjects with TBG abnormalities, when FT4 are measured by different immunoassays, specially at extremes of TBG concentrations. The objective of this study was to evaluate FT4 levels by indirect method in patients with low TBG concentrations. Methods We analyzed blood samples requesting serum TBG, TSH and FT4 levels from patients admitted to a private reference clinical laboratory in Brazil, from January 01, 2017 to December 31, 2022. Anonymized data on laboratory tests was available from a database of the local Laboratory Information System. All the patients included had TSH within the reference range, 0.4–4.3 mUI/mL (ECLIA, Modular, Roche). FT4 was measured by ECLIA (0.7–1.8 ng/dL) and TBG by ICMA, Immulite, Siemens, 13–39 mcg/mL. Results 357 patients with low TBG levels were evaluated, 220 (62%) men, 137 (38%) women; mean age 35 yrs (19 d to 88 yrs). They were divided in six groups according TBG levels (mcg/mL): <3.5–17 (M 15, F2); 3.5 to 6.0 - 26 (M 20, F 6); 6.1 to 8.0 - 30 (M 25, F 5); 8.1 to 9.9 - 59 ( M 32, F 27); 10.0 to 11.9 - 139 (M 78, F 61); 12.0 to 12.9 - 86 (M 50, F 36). Three patients had FT4 levels above 1.8 (1.85; 1.87 and 1.96) ng/mL, all them male, with TBG levels <3.5; 5.79 and 9.53 ng/mL, respectively. Conclusion FT4 Indirect methods are developed taking into account the presence, in the serum, of a thyroxine binding capacity within the normal range, a fact that does not occur in individuals with extreme TBG deficiency. In this study, we found only one slightly elevated FT4 value among 17 patients with TBG values below 3.5 mcg/mL, suggesting little interference of very low TBG levels in this indirect free T4 method.

TT3, a More Practical Indicator for Evaluating the Relationship Between Sarcopenia and Thyroid Hormone in the Euthyroid Elderly Compared with FT3.

Sarcopenia is a common disease in the elderly, and the thyroid hormone (TH) might participate in the pathogenesis of sarcopenia. However, the results of previous studies were not completely consistent. We performed this study to investigate the association between THs and sarcopenia in a Chinese elderly euthyroid population. A total of 309 Chinese elderly euthyroid subjects with an average age of 85.19 ± 7.8 years were enrolled. Participants were divided into four groups (non-sarcopenia, possible sarcopenia, sarcopenia and serve sarcopenia) according to the consensus update of AWGS in 2019. Serum levels of TT3, FT3, TT4, FT4, TSH, rT3 and TBG were measured. Muscle mass was measured by multifrequency bioelectrical impedance analysis, hand grip (HG) was represented by spring-type dynamometer, and gait speed (GS) was determined by 6-metre walk test. The FRAIL scale was used to assess frailty. Compared to the non-sarcopenia group, the sarcopenia group showed a significant increase in age and FRIAL score, while FT3 and TT3 levels decreased significantly. Partial correlation analysis (adjusted by age, gender and the scores of FRIAL scale) indicated that FT3, TT3 and TSH had significant positive correlations with HG, and there also was a significant positive correlation between TT3 and GS. In addition, after adjusting for age, gender, BMI, ALT, sCr, and score on the FRAIL scale, the multivariate linear regression analysis showed that TT3 was positively associated with muscle strength and negatively associated with sarcopenia risk. There is an association between the low TT3 level and sarcopenia. Therefore, maintaining higher T3 concentrations within the normal range appears to be beneficial for sarcopenia in the elderly. In addition, due to the fluctuation of FT3, TT3 is a more stable and practical indicator to evaluate the relationship between sarcopenia and thyroid hormone in the elderly euthyroid population.

Comparison of thyroid hormone profile (T3, T4, TSH, ANTI TPOAB, & TBG) among fertile and infertile females.

Objective: To compare thyroid hormone profile (T3, T4, TSH, Anti TPOAb, & TBG) among fertile and infertile females. Study Design: Case-control study. Setting: Department of Physiology and Department of Gynecology and Obstetrics, JPMC Karachi, BMSI. Period: Jan 2018 to Jan 2019. Material & Methods: There were 88 participants in the sample, who were split into two groups. Infertile group (group A) and control group (group B). Non-probability purposive sampling was employed because each group's subjects were chosen based on specified standards. In the current investigation, all subjects who met the eligibility requirements were registered. Each subject who took part gave their written consent. Information obtained was held in strict confidence. Data was analyzed using IBM SPSS version 23. Results: Serum T3, T4, TSH, anti TPOAb, and TBG levels differed significantly between the two study groups. There was significant mean difference obtained for TSH and anti TPO antibodies between fertile and infertile samples with p-value less than 0.05. Conclusion: In this study, all the subjects had T3, T4, TSH & TBG levels within the normal pre-pregnancy reference range. A trend towards subclinical hypothyroidism and the incidence of anti-thyroid antibodies was observed within females who had UE infertility, when their thyroid hormone profile was compared with fertile females.

The decrease of T3 / T4 is not hypothyroidism - a new mutation of Serpina7 gene results in partial thyroglobulin deficiency.

To explore an unusual cause of the decrease of T3/T4 through a new mutation of TBG gene in a family, so as to avoid habitual thinking and reduce subsequent over treatment. TSH, free total T4, T3 and free T4, T3 were determined by automatic chemiluminescence immunoassay. The TBG mutation was identified by direct DNA sequencing. A frameshift mutation of p. l372ffs * 32 was found in the TBG gene (c.1114delc) of the patient by direct DNA sequencing, and the proband of the family was heterozygous. In vitro expression showed that the affinity of TBG for T4 decreased. Further examination of the family members showed that T3 and T4 were decreased, while FT3, FT4 and TSH were normal. If the patients with low TT4 and TT3 but normal TSH are found, the serum TBG level and related genes should be detected to determine whether it is TBG deficiency and avoid wrong treatment.

Profound Hypothyroidism 21 Days After Methimazole Initiation in a Patient With Graves’s Disease and Liver Cirrhosis

Introduction: Methimazole is the first line treatment of nonpregnant Grave’s disease (GD) patients with Grave’s ophthalmopathy. It usually results in euthyroidism within 4 to 12 weeks, and it is recommended to check FT4 every 4 to 6 weeks after initiation of therapy. We report a patient with GD who developed profound hypothyroidism 21 days after starting methimazole. Clinical Case: 51-year-old male with decompensated EtOH/NASH liver cirrhosis, Gilbert’s syndrome, and GD presented with severe hypothyroidism 21 days after initiating methimazole treatment. He initially presented to the emergency department (ED) with atrial fibrillation with a HR of 140 and found to have bilateral exophthalmos and lid lag. Labs: TSH <0.01 uIU/L (normal range (nl) 0.27-4.20), FT4 2.6 ng/dl (nl 0.7-1.7), TT4 6.2 ug/dl (nl 4.5-12), TT3 125 ng/dl (nl 71-180), TBG 14 ug/ml (nl 13-39), TSI 344 IU/l (nl 0-0.5), AST 55 IU/L (nl 14-44), ALT 27 IU/L (nl 9-57), Alk Phosphatase 497 IU/L (nl 45-129), Tbili 7.1 mg/dl (nl 0.2-.1), and albumin 2.1 g/dl (nl 3.4-5). He was started on methimazole 40 mg daily and propranolol 20 mg BID. Three days later, FT4 decreased to 1.3 ng/dl, so methimazole was decreased to 20 mg day. Ten days later, FT4 was 0.2 ng/dl and methimazole was reduced further to 10 mg daily. Eight days later, he presented to the ED with severe lethargy and found to have HR of 38 and oral temperature (T) of 94. TSH was 3.49 uIU/L and FT4 <0.1 ng/dl. Sixteen hours after 200 mcg IV levothyroxine, he had normal mental status, HR of 49, and T of 97.9. FT4 increased to 0.5 ng/dl within 48 hours of thyroxine initiation. Urine drug screen was only positive for tetrahydrocannabinol and other work up for severe lethargy and hypothermia was unremarkable. He was discharged on 100 mcg of PO levothyroxine. Conclusion: Only 21 days after starting methimazole, the patient developed severe lethargy associated with hypothermia, bradycardia, and undetectable FT4, with no alternative etiology and prompt response to IV levothyroxine, consistent with profound hypothyroidism. Although the half-life of T4 is shortened in hyperthyroidism, the particularly fast and profound effect of methimazole in this patient was unusual and likely due to a limited extra-thyroidal pool of thyroxine caused by low TBG level. As cirrhosis is usually associated with increased TBG level, he may have a contributing congenital etiology. Reduced levels of other T4 binding proteins, albumin and pre-albumin may also have contributed. Although methimazole clearance can be decreased in liver impairment, no dose adjustment is generally recommended, and even this would not have explained the observed rapid decrease in FT4 level. Methimazole should be used with caution and FT4 should be checked early and more frequently when treating hyperthyroid patients with liver disease and possible alteration in thyroid binding proteins.

An Oral Contraceptive Containing Estetrol 15 MG and Drospirenone 3 MG Has Limited Effects on Endocrine and Metabolic Parameters

Background: Most combined oral contraceptives (COCs) contain ethinylestradiol (EE), an estrogen component known to increase the risk of venous thromboembolic events. Previous phase 2 trials have shown that Estetrol (E4), a naturally-occurring estrogen produced by the human fetal liver, in combination with Drospirenone (DRSP), inhibits ovulation and is associated with favorable vaginal bleeding, safety and tolerability profiles and high user satisfaction. When administered in doses up to 10 mg for less than 3 months, E4 either alone or in combination with DRSP showed limited effects on liver function as well as on metabolic and endocrine parameters. However, the impact of E4 15 mg/DRSP 3 mg, the selected dose for pregnancy prevention (hereafter referred to as E4/DRSP), on metabolic and endocrine parameters was never investigated. Methods: A randomized, open-label, controlled, three-arm parallel study was conducted in 101 healthy volunteers aged 18-50 years with a body mass index between 18.0 and 30.0 kg/m2. Of the randomized individuals, 98 subjects received either E4/DRSP (n=38), EE 30 µg/levonorgestrel (LNG) 150 µg (n=29) or EE 20 µg/DRSP 3 mg (n=31) COCs for six consecutive treatment cycles of 28 days. Endocrine and metabolic parameters were measured at baseline, cycle 3 and cycle 6. Results: FSH and LH decreased with both EE/LNG (-84% and -92%, respectively) and EE/DRSP (-64% and -90%, respectively), whereas E4/DRSP slightly increased FSH (31%) and had minor effect on LH (-8%). Total cortisol increased by more than 100% during treatment with EE/LNG (109%) and EE/DRSP (107%), while E4/DRSP only slightly increased total cortisol (26%). The effects of E4/DRSP, EE/LNG and EE/DRSP on other endocrine parameters including androstenedione (-31%, -49% and -40%) and free testosterone (-50%, -50% and -71%) were similar. Liver proteins, except CRP, increased from baseline in all treatment groups. The increase in angiotensinogen, CBG, and TBG levels was significantly lower for E4/DRSP (75%, 40% and 17%) in comparison with EE/LNG (170%, 152% and 37%) and EE/DRSP (207%, 140% and 70%). SHBG substantially increased for EE/DRSP (251%), while EE/LNG and E4/DRSP had limited effects on SHBG (74% and 55%, respectively). Triglycerides changed to a lesser extent for E4/DRSP (24%) compared to EE/DRSP (66%); EE/LNG increased triglycerides levels by 28%. Moreover, E4/DRSP had minimal impact on lipid parameters including HDL (4%), Apolipoprotein A1 (5%) and Apolipoprotein B (4%) compared to baseline, and no effects on carbohydrate metabolism. Conclusion: These data confirm that E4/DRSP has limited effects on liver proteins, lipid and carbohydrate metabolism, cortisol, and gonadotropins. The effect on other endocrine parameters, including suppression of ovarian steroids, was typical for a COC. In conclusion, combining E4 15 mg with DRSP 3 mg resulted in a different and potentially favorable metabolic profile.

The effect of specific binding proteins on immunoassay measurements of total and free thyroid hormones and cortisol.

Background:Immunoassay (IA) measurements of thyroid hormones have previously given inaccurate results of triiodothyronine (T3), free triiodothyronine (FT3), and free thyroxine (FT4) when concentrations of TBG are low. We evaluate the hypothesis that abnormal concentrations of specific binding proteins (BPs) affect IA measurements and provide results which might misguide the diagnosis and treatment of patients. This study assesses IAs for the measurement of T3, FT3, and cortisol when levels of TBG and CBG are high or low. Comparisons are made between IA and LC-MS/MS.Methods:Serum or plasma samples with high (>95th percentile, n = 25) or low (<5th percentile, n = 27) concentrations of BP were collected. The concentrations of T3, FT3, and cortisol were measured by validated IA and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Spearman correlation and Wilcoxon matched-pairs signed rank analyses were used to compare the two methods.Results:When TBG levels are <5th percentile, the differences between the IA and LC-MS/MS results for T3 and FT3 are statistically significant (T3, p = 0.0011; FT3, p = 0.0003). When CBG levels are >95th percentile, the difference between the IA and LC-MS/MS measurements of cortisol is statistically significant (p = <0.0001).Conclusion:Abnormal BP concentrations appear to affect the accuracy of IA measurements of T3, FT3, and cortisol. The population of patients with either high or low levels of BPs is significant. Our samples reflect that 65% of women aged between 15 and 49 years are taking oral contraceptives in the US, and thus have elevated levels of BPs. In this group, IA results for cortisol are falsely low. Our samples reflect that patients with protein losing diseases have low BP concentrations. Among a group with renal complications, IA measurements of T3 are overestimated, while those of FT3 are underestimated. Are the Food and Drug Administration and diagnostic companies adequately assessing the accuracy of IA tests?

Thyroxine-binding globulin deficiency due to a novel SERPINA7 mutation: Clinical characterization, analysis of X-chromosome inactivation pattern and protein structural modeling

ObjectiveThyroxine-binding globulin (TBG) is the major human thyroid hormone transport protein, encoded by the SERPINA7 gene (Xq22.2). We aim to investigate the molecular basis of partial TBG deficiency (TBG-PD) in a female, by evaluating the X-chromosome inactivation pattern as well as the mutant protein structural modeling. Design and methodsSequencing of the coding region of the SERPINA7 gene was performed in a female with a TBG-PD phenotype and her first-degree relatives. The proband presented with low serum levels of total T3 (TT3) and total T4 (TT4), serum TSH level of 5.4 μUI/mL (normal range, 0.35–5.5), and serum TBG level of 5.5 mg/L (normal range, 13.6–27.2). X-chromosome inactivation pattern was evaluated by methylation analysis of the androgen receptor gene (Xq11.2). Structural analysis of the SERPIN family was performed using Pymol and Areaimol, and PFSTATS for conservation analysis and family-wide investigation of equivalent positions in human homologs. Modeller was used for point mutation structural modeling. ResultsA novel missense SERPINA7 mutation (p.R35W; c.163C > T) was found in heterozygosity in the proband, and in hemizygosity in her affected siblings. The proband X-chromosome inactivation ratio was 20:80. The substitution of an arginine by a tryptophan is predicted to disrupt the protein surface and main electrostatic interactions. Tryptophans are extremely rare (0.1%) in this position. ConclusionsWe report a new SERPINA7 variant associated with TBG-PD in three siblings. We named this variant TBG-Brasilia. The X-chromosome inactivation pattern may have accounted for the rare phenotypic expression in a female. The hydrophobic nature of the mutant is predicted to create an apolar patch at the surface, which results in protein aggregation and/or misfolding, potentially responsible for thyroid hormone transport defect.

Should the TBG Level Be Included Routinely When Assessing Newborns for Congenital Hypothyroidism?

Should the TBG Level Be Included Routinely When Assessing Newborns for Congenital Hypothyroidism?

Effect of Grand Multiparity on Certain Thyroid Function Tests

Background: The physiology of the thyroid gland changes during pregnancy as a result of the effects of increased TBG and hCG levels and enhanced iodine metabolism. These normal hormonal changes can sometimes make thyroid function tests during pregnancy difficult to interpret. Objective: To compare the levels of thyroxine [T4], triiodothyronine [T3], thyrotropin [TSH] and Thyroxine Binding Globulin [TBG] in grand multiparas, nulliparas [control] and primiparas. Materials: A cross-sectional study was performed in 50 non-pregnant ladies as control group, 50 primiparity pregnant women, and 50 grand multiparity pregnant women. All pregnant women were between 10th -14th weeks gestation. Methods: Serum for T4, T3, TSH and TBG were measured by Enzyme-Linked Immunosorbent Assay [ELISA] . Results: When compared to control group, serum levels of T4, T3 and TBG were increased significantly in primiparity and grand multiparity groups, while serum level of TSH was decreased significantly in both groups of pregnant women. Serum level of T4 increased significantly in grand multiparity group comparing to primiparity group. Conclusion: The results suggest that grand multiparity increased the risk of pregnancy-related complication secondary to thyroiddysfunction.

State of the protein-synthesizing function of the placenta with premature rupture of membranes

Zelynskyy O O, Domakova N V. State of the protein-synthesizing function of the placenta with premature rupture of membranes. Journal of Health Sciences. 2014;4(14):57-62. ISSN 1429-9623 / 2300-665X. http://journal.rsw.edu.pl/index.php/JHS/article/view/2014%3B4%2814%29%3A57-62 http://ojs.ukw.edu.pl/index.php/johs/article/view/2014%3B4%2814%29%3A57-62 https://pbn.nauka.gov.pl/works/510389 DOI: 10.5281/zenodo.13272 http://dx.doi.org/ 10.5281/zenodo.13272 The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1107. (17.12.2013). © The Author (s) 2014; This article is published with open access at Licensee Open Journal Systems of Radom University in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. Conflict of interest: None declared. Received: 15.11.2014. Revised 05.12.2014. Accepted: 08.12.2014. State of the protein-synthesizing function of the placenta with premature rupture of membranes Zelynskyy O O, Domakova N V Odessa State Medical University, Odessa A bstract State of the protein-synthesizing function of the placenta with premature rupture of membranes. Zelynskyy OO, Domakova NV Odessa State Medical University, Odessa The aim of the study was to evaluate protein-synthesizing function of the placenta in this category of patients. The research was performed during the 2005-2011 biennium. On the basis of specialized clinical maternity hospital number 5 (Odesa, Ukraine). A comprehensive prospective randomized clinical and laboratory examination of 217 pregnant women and their newborns. There were analyzed during pregnancy, childbirth and newborn status in pregnant women at term PROM 22-34 weeks of pregnancy. There was demonstrated that content TBG in serum of women and II group increased significantly compared with the control group at 32-38 weeks of pregnancy. High levels of TBG remained in the period 39-41 weeks, while at physiological indicators of current assessment AMGF, which is a marker of maternal part of the placenta in women II, III clinical and control groups showed that the most unfavorable for the prediction of perinatal pathology is increasing AMGF content like 32-38 weeks and 39-41 in week compared with the control group. The diagnostic and predictive values of the placenta proteins during PROM are discussed. Key words: premature rupture of membranes, placenta proteins, diagnosis, prognosis.

Using changes in binding globulins to assess oral contraceptive compliance

BackgroundValidity of oral contraceptive pill (OCP) clinical trial results depends on participant compliance. Ethinyl estradiol (EE2) induces increases in hepatic binding globulin (BG) levels. Measuring these BG increases may provide an effective and convenient approach to distinguish noncompliant from compliant OCP users in research settings. This analysis evaluated the usefulness of measuring increases in corticosteroid-, sex-hormone- and thyroxine-binding globulins (CBG, SHBG and TBG, respectively) as measures of OCP compliance. MethodsWe used frozen serum from a trial that compared ovarian suppression between normal-weight and obese women randomized to one of two OCPs containing EE2 and levonorgestrel (LNG). Based on serial LNG measurements during the trial, 17% of participants were noncompliant. We matched noncompliant participants with compliant participants by age, body mass index, ethnicity and OCP formulation. We measured CBG, SHBG and TBG levels and compared change from baseline to 3-month follow-up between the noncompliant and compliant participants. Construction of receiver operator characteristic (ROC) curves allowed comparison of various BG measures. ResultsChanges in CBG and TBG distinguished OCP noncompliant users from compliant users [area under the ROC curve (AUROC), 0.86 and 0.89, p<.01]. Changes in SHBG were less discriminating (AUROC 0.69) ConclusionsEE2-induced increases in CBG and TBG provide a sensitive integrated marker of compliance with an LNG-containing OCP.

Impact of Serum Thyroid Hormones and Estrogen Status on the Risk of Breast Cancer in Kashmiri Women

Estrogen involvement in breast cancer has been established; however, the association between breast cancer and thyroid diseases is controversial. Estrogen-like effects of thyroid hormone on breast cancer cell growth in culture have been reported. The aim of our study was to investigate a possible correlation between the genesis of breast cancer and the levels of serum thyroid hormones. we measured the percentage of free estradiol (E2) and the amounts of sex hormone-binding globulin (SHBG) and thyroid hormones in serum samples from Kashmiri patients with breast cancer (n=50) and normal controls (n=25). The patients were found to have significantly higher free E2 and significantly lower SHBG than controls. Moreover, the serum levels of free triiodothyronine (FT3) and free thyroxine (FT4) were lower in the patients than in controls, while the serum levels of TSH and TBG in the patients were not significantly different from those in controls. These results suggest that the reduction in the serum FT3, and FT4 levels, which is independent of changes in the serum level of free E2, may be one of the risk factors for breast cancer in Kashmir.

SERUM AND TISSUE MUCOPROTEINS AND SIALIC ACID IN THYROID DISEASES

. Objective: To find the correlation coefficient of serum mucoproteins and sialic acid to thyroid tissuein thyroid diseases. Study Design: The study was carried out at J.P.M.C, Karachi. Materials and Methods: A total oftwenty four thyroid patients and twenty normal subjects were studied. The cases were divided into non toxic goiterfourteen, and toxic goiter ten on the basis of clinical and physical examination, thyroid scanning and hormone analysis.Thyroid hormones were estimated in serum. Mucoproteins and sialic acid were estimated in serum as well as in thyroidtissue. Results: Estimations of thyroid hormones and thyroxine binding globulin (T.B.G.) are useful clinically to evaluatethe functions status and diagnosis of different thyroid disorders. Thyroid tissue is mainly composed of glycoprotein,thyroglobulin, and different studies showed that serum glycoprotein fractions varied in different thyroid diseases.Si 4gnificantly increased levels of T were observed in toxic goiter group. The levels of TBG was significantly increased4in non toxic goiter, toxic goiter patients while T /TBG ratio was significantly decreased in non toxic goiter. Coefficientcorrelation ( r) of serum to tissue mucoproteins shows an inverse relationship in non toxic goiter and toxic goiter patients.In non toxic goiter and toxic goiter patients the serum sialic acid levels to tissue sialic acid levels also shows an inverserelationship. Conclusion: Correlation coefficient analysis showed an inverse relationship of serum mucoproteins andsialic acid to thyroid tissue. It signifies that carbohydrate moieties are increased in the blood when the tissue arehyperactive and in the pathological state. It further concludes that thyrotoxic state might be converted into nodular formeven into cancerous form later on.

NODULAR GOITERS

Objective: The purpose of the study was to estimate the levels of amino sugars and glycosylatedproteins in the blood and thyroid tissues of the patients suffering from thyroid disorders. Study design: The study wascarried out at Basic Medical sciences Institute, J.P.M.C. Karachi. Period: From 1990 to 1992. Materials &amp; Methods:Twenty control subjects and 35 thyroid patients (Non toxic goiter = 14, Non toxic nodular goiter = 12 and Toxic nodulargoiter=9) were studied. T4, TBG and T4/TBG ratio, serum and tissue glucose, protein, glycosylated proteins andhexosamine with their correlation coefficient (r) were estimated Results: Significantly raised levels of TBG in non toxicgoiter and toxic nodular goiter while T4/TBG ratio was significantly decreased in non toxic goiter and toxic nodulargoiter. In non toxic goiter patients correlation coefficient analysis showed a direct relationship (serum to tissue levels)of glucose(r=0.47), glycosylated proteins(r=0.40) and hexosamine (r=0.23) while an inverse relationship was found incase of protein(r= -0.38). In non toxic nodular group inverse relationship was only found in proteins (r= -0.48) estimationwhile direct correlation coefficient was observed in glucose (r= 0.29), glycosylated proteins (r=0.13) and in hexosamine(r=0.14). In toxic nodular group hexosamine shows a direct correlation coefficient(r=0.73)while glucose (= -0.53),proteins (r= -0.87)and glycosylated proteins(r= -0.12) have an inverse relationship. Conclusion: It was concluded fromcorrelation coefficient analysis (blood to tissue levels) that in non toxic goiter and non toxic nodular patients glucose,glycosylated protein and hexosamine showed a direct relationship while protein showed an inverse relationship.

352 Serum Thyroid Hormones in Preterm Infants and Relationships to Indices of Severity of Intercurrent Illness

Introduction: In adults a decrease in serum T3 and an increase in rT3 are the most common changes in thyroid hormone levels in response to a variety of acute and chronic illnesses. With more severe illnesses serum T4 levels also decrease and this is associated with a worse prognosis. Thyroid hormone levels in infants are crucially determined by the inter-relationship between gestational and postnatal age but it remains unclear whether changes in thyroid hormone status in response to illness are similar across the wide gestational age range of prematurity. Aim: The purpose of this study was to relate severity of illness at 1, 7, 14 and 28 postnatal days in preterm infant groups 23–27 (n=73), 28–30 (n=160) and 31–34 (n=208) weeks gestation, to the corresponding sera levels of T4, FT4, TBG, TSH, T3, rT3 and T4S. Methods: The British Association of Perinatal Medicine and Neonatal Nurses Association 1992 scoring categories (Arch Dis Child; 67: 868–9) were used as an index of illness severity: Level 1 (maximal intensive care) was compared with Level 2 (high dependency intensive care) combined with Level 3 (special care); infants were scored on 1, 7, 14 and 28 postnatal days. Results: In Level 1 infants there were significant reductions in: T3 at 7 days (28–30 weeks), 14 and 28 days (23–27 and 28–30 weeks); T4 at 7, 14 and 28 days (23–27 weeks), at 14 and 28 days (28–30 weeks), and at day 7 (31–34 weeks); FT4 at 14 days (23–27 weeks). TSH was unchanged in all groups at all ages. Conclusion: The clear message from our data is that T4 and T3 are substantially reduced in infants with severe illness, irrespective of gestational age, yet TSH remains unchanged.

Estudo da Função Tiroideana em Uma População com Mais de 50 Anos

Com objetivo de analisar a freqüência de disfunção tiroideana e de identificar possíveis alterações hormonais decorrentes do envelhecimento, estudamos 198 indivíduos com idade variando de 50 a 85 anos e 106 filhos com idade entre 11 e 49 anos. A prevalência de disfunção tiroideana foi semelhante em ambos grupos (12,6% no grupo de estudo e 14,1% entre os filhos). A presença de um ou dois anticorpos antitiroideanos positivos foi também semelhante entre os grupos (9,1% e 12,3% para os idosos e filhos respectivamente), embora sem correlação disfunção tiroideana. nos idosos. Os níveis séricos de T3 e FT4 foram significantemente menores entre os indivíduos mais velhos quando comparados com os filhos (1,27±0,27 x 1,39±0,31 ng/ml e 0,97±0,29 x 1,18±0,76 ng/dl, respectivamente). Não houve diferença entre os grupos quanto aos níveis de TSH, T4 total e TBG. Concluímos que a prevalência de disfunção tiroideana não foi diferente entre os grupos e que a presença de anticorpos antitiroideanos esteve associada com disfunção da tiróide apenas nos indivíduos mais jovens. A correlação inversa dos níveis de T3 e FT4 com a idade pode refletir uma adaptação à menor necessidade dos hormônios com o envelhecimento.

Thyroid function tests and characterization of thyroxine-binding globulin in the carbohydrate-deficient glycoprotein syndrome type I.

Carbohydrate-deficient glycoprotein (CDG) syndrome is a newly recognized hereditary disorder that presents with psychomotor retardation, cerebellar ataxia, peripheral sensorimotor neuropathy, and, variably, skeletal abnormalities, lipodystrophy, and retinitis pigmentosa. These abnormalities appear to be produced by a defect that causes reduced carbohydrate content in glycoproteins. We studied seven patients with CDG type I belonging to five unrelated families. The concentration of serum TBG, a glycoprotein of hepatic origin, was measured by RIA and T4 saturation and was found to be below the normal range in three of the seven patients and normal in four of them. More than half of the total serum TBG had reduced sialic acid content and localized on isoelectric focusing (IEF) as two prominent bands cathodal to the three major bands of normal TBG. The latter two bands are responsible for the characteristic IEF pattern or CDG syndrome. TBG in patients with CDG had immunoreactivity indistinguishable from that of normal TBG and had normal affinity for T4, T3, and rT3. Serum total T4, T3, and rT3 were below the normal range in seven, five, and seven patients, respectively. The free T4 index was also below normal in four patients, but the free T4 concentration, measured by equilibrium dialysis at low dilution, and serum TSH were in the midnormal range. The serum total T4 and rT3 levels were disproportionately reduced relative to the serum TBG concentration and compared to the concentrations of these iodothyronines in matched subjects with inherited partial TBG deficiency. Chronic illness cannot explain these changes, because, contrary to patients with nonthyroidal illness, those with CDG had significantly higher serum total T3/T4 and lower rT3/T4 ratios. It is concluded that IEF of TBG is a rapid and simple method for the diagnosis of CDG type I and that the abnormal pattern can be detected as early as 5 days postpartum. Patients with CDG are chemically euthyroid, and it is postulated that the reduction in serum iodothyronine concentrations beyond that explained on the basis of low TBG levels may be due to the interference with binding to TBG by an unidentified substance.

Transient hypothyroxinemia in neonates with birth asphyxia delivered by emergency cesarean section.

The aim of this study was to evaluate the effects of prenatal asphyxia on perinatal thyroid function by measuring the levels of serum T4, FT4, T3, rT3, TSH and TBG in twenty-seven asphyxiated full-term infants delivered by emergency cesarean section, at birth and on the 5th day of age. All the babies had a one-minute Apgar score of less than 6 and body weight from 3 to 4.6 kg. The control group consisted of 30 healthy neonates which were delivered by elective cesarean section. The mean values of T4 and FT4 observed in the cord blood of the asphyxiated neonates were significantly lower compared to the matched controls, while there were no differences in concentrations of T3, rT3, TSH and TBG. At five days of life, serum concentrations of T4 and FT4 became normal. These results demonstrate the existence of transient hypothyroxinemia at birth in hypoxic babies delivered by emergency cesarean section.

Evaluation of serum total thyroxine and triiodothyronine and their serum fractions in nonthyroidal illness secondary to congenital heart disease. Studies before and after surgery.

Serum thyroid hormones, serum thyroxine-binding proteins and serum thyroid hormone fractions have been measured in children with congenital heart disease before and after open cardiac surgery. Twenty prepubertal patients, mean (+/- SD) age 3.6 +/- 3.7 yr, were studied before, immediately after, and 24 and 48 h after surgery. A control group of 6 normal prepubertal children was also studied in basal conditions. Serum TSH was normal in all samples collected. Significantly low mean levels of serum TBG (261 +/- 57 vs 456 +/- 71 nmol/L in normals), serum TBPA (2692 +/- 1119 vs 5999 +/- 2226 nmol/L), serum TBG-bound T4, serum TBPA-bound T4, serum TT3, serum TBG-bound T3 and free T3 were found before cardiac surgery in the patients. While serum binding proteins did not change after surgery, significant decrements in serum TT4, serum TBG-bound T4, serum TT3, serum TBG-bound T3, serum albumin-bound T3 and free T3 were observed after surgery. Free T4 and albumin-bound T4 remained normal. Our study shows that many features of nonthyroidal illness were present in our patients before surgery. In this context, the stress of surgery induced further alterations in several parameters of thyroid metabolism. It is concluded that the changes occurring in this model of chronic, as well as acute, nonthyroidal illness reflect adaptative changes, rather than altered thyroid function, as shown by normal serum free T4, serum albumin-bound T4 and serum TSH.