Thyroid disorders are common, affecting more than 10% of people in the US, and laboratory tests are integral in the management of these conditions. The repertoire of thyroid tests includes blood tests for thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine, thyroglobulin (Tg), thyroglobulin antibodies (Tg-Ab), thyroid peroxidase antibodies (TPO-Ab), TSH receptor antibodies (TRAb), and calcitonin. TSH and free thyroid hormone tests are frequently used to assess the functional status of the thyroid. TPO-Ab and TRAb tests are used to diagnose Hashimoto's thyroiditis and Graves' disease, respectively. Tg and calcitonin are important tumor markers used in the management of differentiated thyroid carcinoma and medullary thyroid carcinoma (MTC), respectively. Procalcitonin may replace calcitonin as a biomarker for MTC. Apart from understanding normal thyroid physiology, it is important to be familiar with the possible pitfalls and caveats in the use of these tests so that they can be interpreted properly and accurately. When results are discordant, clinicians and laboratorians should be mindful of possible assay interferences and/or the effects of concurrent medications. In addition, thyroid function may appear abnormal in the absence of actual thyroid dysfunction during pregnancy and in critical illness. Hence, it is important to consider the clinical context when interpreting results. This review aims to describe the above-mentioned blood tests used in the diagnosis and management of thyroid disorders, as well as the pitfalls in their interpretation. With due knowledge and care, clinicians and laboratorians will be able to fully appreciate the clinical utility of these important laboratory tests.
Antibodies ; Biomarkers, Tumor ; Calcitonin ; Critical Illness ; Diagnosis ; Graves Disease ; Hematologic Tests ; Iodide Peroxidase ; Physiology ; Pregnancy ; Receptors, Thyrotropin ; Thyroglobulin ; Thyroid Function Tests ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroiditis ; Thyrotropin ; Thyroxine ; Triiodothyronine

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

BACKGROUNDMaternal thyroid dysfunction is common during pregnancy, and physiological changes during pregnancy can lead to the overdiagnosis of hyperthyroidism and misdiagnosis of hypothyroidism with nongestation-specific reference intervals. Our aim was to compare sequential with nonsequential methods for the evaluation of thyroid function in pregnant women.

METHODSWe tested pregnant women who underwent their trimester prenatal screening at our hospital from February 2011 to September 2012 for serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) using the Abbott and Roche kits. There were 447 and 200 patients enrolled in the nonsequential and sequential groups, respectively. The central 95% range between the 2.5th and the 97.5th percentiles was used as the reference interval for the thyroid function parameter.

RESULTSThe nonsequential group exhibited a significantly larger degree of dispersion in the TSH reference interval during the 2nd and 3rd trimesters as measured using both the Abbott and Roche kits (all P < 0.05). The TSH reference intervals were significantly larger in the nonsequential group than in the sequential group during the 3rd trimester as measured with both the Abbott (4.95 vs. 3.77 mU/L, P < 0.001) and Roche kits (6.62 vs. 5.01 mU/L, P = 0.004). The nonsequential group had a significantly larger FT4 reference interval as measured with the Abbott kit during all trimesters (12.64 vs. 5.82 pmol/L; 7.96 vs. 4.77 pmol/L; 8.10 vs. 4.77 pmol/L, respectively, all P < 0.05), whereas a significantly larger FT4 reference interval was only observed during the 2nd trimester with the Roche kit (7.76 vs. 5.52 pmol/L, P = 0.002).

CONCLUSIONSIt was more reasonable to establish reference intervals for the evaluation of maternal thyroid function using the sequential method during each trimester of pregnancy. Moreover, the exclusion of pregnancy-related complications should be considered in the inclusion criteria for thyroid function tests.

Female ; Humans ; Pregnancy ; physiology ; Reference Values ; Thyroid Gland ; physiology ; Thyrotropin ; blood ; Thyroxine ; blood

BACKGROUNDThe importance of diagnosis of thyroid dysfunction during pregnancy has been widely recognized. Our study was designed to compare two different detection reagents between Abbott and Roche and to establish the gestational related reference intervals for thyroid function tests (TFT) in Chinese women and to assay the reference ranges with the American Thyroid Association recommended standard.

METHODSSerum samples were collected from 693 normal pregnant Chinese women and divided into five groups according to their gestational age: 9-13, 16-20, 24-28, 32-34 and 37-40 weeks. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were determined by two different detection reagents: Abbott Architect I 2000 and Roche Cobas Elecsys 600. The reference ranges of the TFT indexes were calculated according to the National Academy of Clinical Biochemistry (NACB). The 2.5th and 97.5th percentiles of each stage were calculated, and the results were analyzed by one-way analysis of variances, t-test, and Spearman correlation analysis.

RESULTSThyroid hormone levels varied greatly among different gestational stages. TSH levels, as assessed via two different TSH ELISA kits showed consistent changing pattern during pregnancy and displayed linear correlation (P < 0.001). In 9-13 gestational weeks, TSH levels were significantly lower than that of other groups; and in 37-40 gestational weeks, it was higher than that of other groups (all P < 0.001). TSH reference ranges determined by Roche detection reagent in each group were higher than those by Abbott detection reagent (P < 0.01 respectively). FT4 levels were higher in 9-13 gestational weeks than that of other groups (P < 0.001). FT4 levels determined by Roche reagent were higher than Abbott reagent in 9-13 weeks, (P < 0.001), and lower in 24-28 and 37-40 weeks (P < 0.001 and P = 0.016, respectively). The TSH level was correlated with FT4 levels in 9-13 gestational weeks by detection reagents (for Abbott reagent, r=-0.319 for FT4 P < 0.001; for Roche reagent, r=-0.352 for FT4, P <0.001).

CONCLUSIONAccurate evaluation of TFT in pregnant women should be based on the gestational-related reference intervals in Chinese population, and different detection reagents should also establish their own reference intervals.

Adult ; Female ; Gestational Age ; Humans ; Luminescent Measurements ; Pregnancy ; physiology ; Reference Values ; Thyroid Function Tests ; Thyroid Gland ; physiology ; Thyrotropin ; blood ; Thyroxine ; blood

BACKGROUNDGrowing evidence links alternation of the thyroid function to the pathogenesis and progression of Alzheimer disease (AD). However, only a few studies evaluate the association between thyroid hormone levels and neuropsychiatric manifestations in patients with AD. This study aimed to investigate the relationship of thyroid hormone levels and neuropsychiatric symptoms in euthyroid patients with AD.

METHODSForty patients with AD (26 women and 14 men), with no prior AD treatment within 4 weeks before study entry, were evaluated on their thyroid status (total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH)), cognition (Mini-Mental State Examination (MMSE) and Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-cog)), neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI)) and depression (Hamilton Rating Scale for Depression (HAMD(17))). The unique relationship between thyroid hormones and cognitive function and mood was examined with multivariate linear regression analyses. The thyroid status between the neuropsychiatric symptoms group and the non-neuropsychiatric symptoms group was examined with independent-samples t-test.

RESULTSIn euthyroid AD patients with agitation and irritability has lower TSH serum level than those without these symptoms (t = -2.130, P < 0.05; t = -2.657, P < 0.05); and core score of HAMD is significantly associated with the serum level of TSH (β = 0.395, P < 0.01). There is no significant association between thyroid hormone levels and cognition (MMSE, ADAS-cog and its subscale score).

CONCLUSIONThere might be a relationship between thyroid hormone levels and the neuropsychiatric symptoms in euthyroid patients with AD.

Aged ; Aged, 80 and over ; Alzheimer Disease ; blood ; metabolism ; Cognition ; physiology ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Thyroid Gland ; metabolism ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

The aim of the present study is to investigate the alterations of cardiac hemodynamics, sodium current (I(Na)) and L-type calcium current (I(Ca-L)) in the cardiomyopathic model of rats. The model of cardiomyopathy was established by intraperitoneal injection of L-thyroxine (0.5 mg/kg) for 10 d. The hemodynamics was measured with biological experimental system, and then I(Na) and I(Ca-L) were recorded by using whole cell patch clamp technique. The results showed that left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP), +/-dp/dt(max) in cardiomyopathic group were significantly lower than those in the control group, while left ventricular end-diastolic pressure (LVEDP) in cardiomyopathic group was higher than that in the control group. Intraperitoneal injection of L-thyroxine significantly increased the current density of I(Na) [(-26.2+/-3.2) pA/pF vs (-21.1+/-6.3) pA/pF, P<0.01], shifted steady-state activation and inactivation curves negatively, and markedly prolonged the time constant of recovery from inactivation. On the other hand, the injection of L-thyroxine significantly increased the current density of I(Ca-L) [(-7.9+/-0.8) pA/pF vs (-5.4+/-0.6) pA/pF, P<0.01)], shifted steady-state activation and inactivation curves negatively, and obviously shortened the time constant of recovery from inactivation. In conclusion, the cardiac performance of cardiomyopathic rats is similar to that of rats with heart failure, in which the current density of I(Na) and especially the I(Ca-L) are enhanced, suggesting that calcium channel blockade and a decrease in Na(+) permeability of membrane may play an important role in the treatment of cardiomyopathy.
Animals ; Calcium Channels, L-Type ; metabolism ; Cardiomyopathies ; chemically induced ; metabolism ; physiopathology ; Hemodynamics ; physiology ; Male ; Myocardium ; metabolism ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Sodium Channels ; metabolism ; Thyroxine

OBJECTIVETo study the effect of chronic rapid eye movement sleep deprivation on energy metabolism, FT3, FT4 in serum.

METHODSRapid eye movement sleep deprivation of rats were deprived by flower pot, and then the energy metabolism were detected. The FT3, FT4 level in serum was determined by radioimmunoassay kit.

RESULTSRats after sleep deprivation displayed food intake increased from (75.06 +/- 25.37)g/(d x kg) to (122.30 +/- 20.43)g/(d x kg), body weight substantially decreased from (360.89 +/- 43.01) g to (295.97 +/- 37.95) g, body temperature from (37.62 +/- 1.12) degrees C up to the first (39.00 +/- 0.87) degrees C and then reduced to (37.72 +/- 0.84) degrees C, the basal metabolism rate increased significantly from (1.69 +/- 0.36) mlO2/(g x h) to (2.40 +/- 0.09) mlO2/(g x h), compared with the control group( P < 0.05). Sleep deprivation also resulted significantly lower serum thyroxine levels in comparison with the control, serum free triiodothyronine (FT3) level reduced from (3.38 +/- 0.88) pmol/L to (2.38 +/- 0.83) pmol/L, then free thyroxine(FT4) decreased from (14.62 +/- 3.62) pmol/L to (8.26 +/- 2.80) pmol/L (P < 0.05).

CONCLUSIONRapid eye movement sleep deprivation can change energy metabolism remarkable, as well as the alteration of FT3, FT4 levels in serum.

Animals ; Energy Metabolism ; physiology ; Male ; Rats ; Rats, Wistar ; Sleep Deprivation ; blood ; metabolism ; Sleep, REM ; physiology ; Thyroxine ; blood ; Time Factors ; Triiodothyronine ; analogs & derivatives ; blood

OBJECTIVEAlthough several reports documented the association of congenital hypothyroidism (CH) and left ventricular (LV) function in infants or neonates, right ventricular (RV) function in neonates with CH has not been previously studied. The aim of the present study was to assess RV function in neonates with CH before and after thyroxine substitution therapy by quantitative tissue velocity imaging (QTVI) and tissue tracking imaging (TTI).

METHODSFifty-two neonates aged 18-28 days (25 males and 27 females) with CH and 35 healthy neonates aged 18-28 days (16 males and 19 females) were studied by QTVI, TTI as well as conventional pulsed-wave Doppler echocardiography (PWD). The standard apical four-chamber view for long-axis motion of the right ventricle was used for echocardiographic evaluation. Peak systolic displacement (D), peak systolic velocity (Vs), peak early (Ve) and late (Va) diastolic velocity of tricuspid annule were measured, Ve/Va ratio was calculated as well. Transtricuspid flow velocity during early diastole (E) and late diastole (A) were also measured by pulsed-wave Doppler echocardiography. PWD and E/A ratio were calculated too. For each neonate, serum hormone levels of TSH, TT(3), TT(4), FT(3) and FT(4) were measured with a standard chemiluminescent immunoassay. After 1 month of levothyroxine (L-T(4)) substitution therapy in CH neonates, all the echocardiographic evaluations and biochemical tests were re-evaluated. Correlation analysis was also made between serum thyroid hormones levels and right ventricular function.

RESULTSThe indices of right ventricular diastolic function by PWD (E and E/A ratio) in CH group were (45 +/- 10) cm/s and (0.8 +/- 0.3), respectively. Compared with controls, E and E/A ratio in CH neonates were significantly lower (P < 0.001, respectively), while A did not differ between the two groups (P > 0.05). QTVI and TTI showed that right diastolic function (Ve and Ve/Va ratio) as well as right systolic function (Vs and D) in CH group were (3.69 +/- 1.38) cm/s, (0.74 +/- 0.19) cm/s, (4.38 +/- 0.63) cm/s and (0.52 +/- 0.12) cm, respectively. CH neonates had significantly lower Ve, Ve/Va ratio, Vs and D of tricuspid annular velocity (P < 0.001, respectively), whereas there was no significant difference in Va between the two groups (P > 0.05). After 1 month of substitutive therapy, CH neonates showed a significant increase of Ve, Ve/Va ratio, Vs, D, E, and E/A ratio, (6.92 +/- 1.86) cm/s, (1.13 +/- 0.22), (5.92 +/- 1.03) cm/s, (0.78 +/- 0.17) cm, (61 +/- 10) cm/s and (1.1 +/- 0.4), respectively (P < 0.001). Those parameters were positively correlated with serum TT(3), TT(4), FT(3) and FT(4) levels (P < 0.01, respectively), and were negatively correlated with serum TSH levels (P < 0.01, respectively).

CONCLUSIONSOur findings suggest that neonates with CH are associated with right ventricular subclinical systolic and diastolic dysfunction, which can be reversed by early L-T(4) substitution therapy. QTVI and TTI are valuable methods to evaluate right ventricular function in neonates. Systolic and diastolic velocities of the tricuspid annulus measured by QTVI and TTI are useful and accurate to assess RV function in neonates.

Adult ; Blood Flow Velocity ; Child, Preschool ; Congenital Hypothyroidism ; physiopathology ; Diastole ; drug effects ; physiology ; Echocardiography ; Echocardiography, Doppler, Pulsed ; Female ; Heart Ventricles ; drug effects ; physiopathology ; Humans ; Male ; Systole ; drug effects ; physiology ; Thyrotropin ; pharmacology ; Thyroxine ; blood ; pharmacology ; Tricuspid Valve ; physiopathology ; Ventricular Function, Left ; drug effects ; physiology ; radiation effects ; Ventricular Function, Right ; drug effects ; physiology

This study was to determine the daily fluctuation of serum thyroxine (tT4), free thyroxine (fT4), 3,5,3'-triiodothyronine (T3) concentrations in healthy dogs. Thyroid function of these dogs was evaluated on the basis of results of TSH response test. Samples for the measurement of serum tT4, fT4, and T3 concentrations were obtained at 3- hour intervals from 8 : 00 to 20 : 00. Serum tT4, fT4, and T3 concentrations were measured by the enzyme chemiluminescent immunoassay (ECLIA). Mean T3 concentrations had no significant differences according to the sample collection time during the day. Mean tT4 and fT4 concentrations at 11 : 00 were 3.28 +/- 0.86 microgram/dl and 1.30 +/- 0.37 ng/dl, respectively and mean tT4 and fT4 at 14:00 were 3.54 +/- 1.15 microgram/dl and 1.35 +/- 0.12 ng/dl, respectively. These concentrations were significantly high compared with tT4 and fT4 concentrations at 8:00, which were 1.75 +/- 0.75 microgram/dl and 0.97 +/- 0.25 ng/dl, respectively (p < 0.05). According to the sample collection time, mean tT4 and fT4 concentrations changed with similar fluctuation during the day. Based on these results, it was considered that measurement of serum tT4 and fT4 concentrations from 11 : 00 to 14 : 00 might more easily diagnose the canine hypothyroidism in practice.
Animals ; Circadian Rhythm/physiology ; Dogs/*blood ; Female ; Immunoenzyme Techniques/veterinary ; Male ; Thyroid Function Tests/veterinary ; Thyroxine/*blood ; Triiodothyronine/*blood

OBJECTIVETo study the relationship between the TCM Syndrome Differentiation-types of congestive heart failure (CHF) and thyroid hormones, including triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH), and atrial natriuretic peptide (ANP), as well as cardiac function parameters, including left ventricular ejection fraction (LVEF), mean velocity of circumferentid fiber shortening (mVcf) and A peak/E peak (A/E).

METHODSOne hundred patients with CHF were divided into 4 Syndrome Differentiation-type groups, their cardiac function parameters, ANP and thyroid hormones were determined and compared with those in the 23 subjects in the control group.

RESULTSIn CHF patients with edema and blood stasis Syndrome type, the level of plasma ANP was significantly higher than that in the control group (P < 0.05); level of T3 was significantly lower than that in the control group and in CHF patients of other three (Xin-qi deficiency, Yin-deficiency and blood stasis) Syndrome groups (P < 0.01, P < 0.01, P < 0.05 and P < 0.01); levels of LVEF and mVcf were significantly lower than those in the other three Syndrome groups (all P < 0.01). Level of T4 in other three Syndrome groups significantly increased than that in the edema and blood stasis Syndrome type. A/E value showed a higher level in patients of all TCM type than that in the control (P < 0.01). Correlation analysis showed that T3 was positively correlated with LVEF and T4 (r = 0.200, P < 0.05, and r = 0.293, P < 0.01), and negatively correlated with ANP (r = -0.263, P < 0.01); T4 was negatively correlated with A/E (r = -0.226, P < 0.05).

CONCLUSIONThe lowering of T3 and T4 and increasing of ANP may be one of the important reasons for lowering of LVEF in CHF patients with edema and blood stasis Syndrome-type. The decrease of T4 may be one of the important reasons for elevation of A/E and aggravation of left ventricular diastolic dysfunction in CHF patients of all the 4 TCM Syndrome-types.

Adult ; Aged ; Atrial Natriuretic Factor ; metabolism ; Diagnosis, Differential ; Female ; Heart Failure ; blood ; physiopathology ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Myocardial Contraction ; Stroke Volume ; physiology ; Thyroid Hormones ; blood ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood ; Ventricular Dysfunction, Left ; physiopathology ; Ventricular Function, Left