Influence of Thyroglobulin (Tg) Autoantibodies on Tg levels Measured by Different Methodologies: (IMA, LC-MS/MS and RIA).

CONTEXT: Serum thyroglobulin (Tg) measured by Immunometric assays (IMA) is prone to underestimation due to Tg autoantibody (TgAb) interference, often prompting reflex Tg measurement by liquid chromatography/tandem mass spectrometry (MS) or radioimmunoassay (RIA). OBJECTIVE: IMA, MS and RIA methodologies were used to measure serum Tg in TgAb-negative (TgAb-) and TgAb-positive (TgAb+) patients with either distant metastatic thyroid cancer (DTC) or hyperthyroidism (HY) - patients in whom a detectable serum Tg would be expected. CONCLUSIONS: 1) Between-method Tg variability necessitates method continuity when monitoring the Tg trends of TgAb- DTC patients. 2) The presence and concentration of TgAb appeared to have a lowering effect on serum Tg measured by all methodologies (IMA, MS and RIA). 3) Since the reliability of Tg measured in the presence of TgAb is often uncertain, the TgAb trend (measured by the same method) may be a useful surrogate DTC tumor marker.

Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status.

Background: Despite being the most performed laboratory endocrine investigation, the optimum use of thyroid tests (thyrotropin [TSH] and thyroid hormone [TH] measurement) is open to question and the interpretation of the results from these tests can be ambiguous. The American Thyroid Association (ATA) with its expertise support the endeavor of the U.S. Centers for Disease Control (CDC) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) to improve and maintain standardization and harmonization of thyroid testing. ATA mandated an international interdisciplinary working group panel to survey the status of thyroid testing by reviewing the recent literature to revise or update the criteria as needed in mutual agreement and to inform clinical care. Summary: This review represents the conclusions on the clinical use of current routine TSH and TH (thyroxine [T4] and triiodothyronine [T3]) assays, taking into account geographic differences in disease prevalence and clinical and laboratory practice among writing members. The interaction between physiological, pathophysiological, and pharmacological factors and thyroid assays can affect their measurements and confound result interpretation. These factors need to be considered in the clinical context of the patient for appropriate test ordering and result interpretation. Despite significant advances in laboratory methods over the past 50 years, routine thyroid assays remain susceptible to idiosyncratic analytical interference that may produce spurious results. Improved standardization needs to be demonstrated through ongoing international efforts before results from different assays can be considered equivalent. Emerging technology (e.g., mass spectrometry) shows promise for improved analytical performance, but more evidence of its clinical utility and improved throughput is required before it can be considered for routine use. Close clinical-laboratory collaboration is encouraged to overcome and avoid the pitfalls in thyroid testing as well as resolve clinically discrepant results. The evidence base supporting the conclusions of this review is summarized in four detailed online technical supplements. Conclusions: Over the past five decades, testing for TSH, T4, and T3 has evolved from manual radioisotopic immunoassays to nonisotopic multiplexed immunometric assays using highly automated equipment. Despite these technical advances, physicians and laboratorians performing these analyses must understand limitations of these methods to properly order tests and interpret results.

Laboratory Thyroid Tests: A Historical Perspective.

Background: This review presents a timeline showing how technical advances made over the last seven decades have impacted the development of laboratory thyroid tests. Summary: Thyroid tests have evolved from time-consuming manual procedures using isotopically labeled iodine as signals (131I and later 125I) performed in nuclear medicine laboratories, to automated nonisotopic tests performed on multianalyte instruments in routine clinical chemistry laboratories. The development of isotopic radioimmunoassay techniques around 1960, followed by the advent of monoclonal antibody technology in the mid-1970s, led to the development of a nonisotopic immunometric assay methodology that forms the backbone of present-day thyroid testing. This review discusses the development of methods for measuring total thyroxine and triiodothyronine, direct and indirect free thyroid hormone measurements and estimates (free thyroxine and free triiodothyronine), thyrotropin (TSH), thyroid autoantibodies (thyroperoxidase, thyroglobulin [Tg] and TSH receptor autoantibodies), and Tg protein. Despite progressive improvements made in sensitivity and specificity, current thyroid tests remain limited by between-method differences in the numeric values they report, as well as nonspecific interferences with test reagents and interferences from analyte autoantibodies. Conclusions: Thyroid disease affects ∼10% of the U.S. population and is mostly managed on an outpatient basis, generating 60% of endocrine laboratory tests. In future, it is hoped that interferences will be eliminated, and the standardization/harmonization of tests will facilitate the establishment of universal test reference ranges.

In-hospital morbidity and brain metrics of preterm neonates born 1998-2009.

AIMS: To describe the survival, in-hospital morbidity, brain metrics and two-year neurodevelopmental outcomes of two extremely preterm cohorts and discuss the contribution of changes in clinical practice to these outcomes. METHODS: Retrospective comparative cohort study, of two cohorts of neonates born <28 weeks gestation: 47 infants born 1998-2000 and 39 infants 2006-2009. RESULTS: Comparing historical to the contemporary cohort respectively, admission temperature (35.9 degrees C, 36.5) and CRIB (Clinical Risk Index in Babies) score (5.4, 3.1) improved. Inotrope support fell significantly (55.3%, 28.2%). High frequency ventilation days fell (8.0, 2.7). CPAP days increased significantly (32.2, 47.9). Chronic lung disease at 36 weeks corrected age fell significantly (61.7%, 38.5%). Red cell transfusions decreased in number (7.1, 4.8) and volume (96.2ml/kg, 70.4ml/kg). Retinopathy of prematurity (ROP) rates dropped significantly (66.0%, 28.2%). Survival was not significantly different. Nutritional improvements included shorter days to first enteral feed (3.4, 2.0), target protein (5.4, 4.3) and lipid levels (7.1, 4.1) with better breastfeeding rates at discharge (19.2%, 38.5%). By 36 weeks z scores for weight (-0.90, -0.39) were improved but not length (-1.94, -1.26) or head circumference (-0.72, -0.69). MRI brain metrics showed a significant improvement in bifrontal (59.2, 65.9), biparietal (73.7, 79.3) and transcerebellar diameter (50.6, 52.6) with improved neurodevelopmental outcome at two years. CONCLUSION: The contemporary cohort had better initial physiological stability, less chronic lung disease and retinopathy, improved body growth at 36 weeks and brain metrics at term equivalent. Improvement in neurodevelopment at two years has been seen and further analysis will be important to understand the impact of the changes in clinical care.

Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP).

Antibodies are widely used biomarkers for the diagnosis of many diseases. Assays based on solid-phase immobilization of antigens comprise the majority of clinical platforms for antibody detection, but can be undermined by antigen denaturation and epitope masking. These technological hurdles are especially troublesome in detecting antibodies that bind nonlinear or conformational epitopes, such as anti-insulin antibodies in type 1 diabetes patients and anti-thyroglobulin antibodies associated with thyroid cancers. Radioimmunoassay remains the gold standard for these challenging antibody biomarkers, but the limited multiplexability and reliance on hazardous radioactive reagents have prevented their use outside specialized testing facilities. Here we present an ultrasensitive solution-phase method for detecting antibodies, termed antibody detection by agglutination-PCR (ADAP). Antibodies bind to and agglutinate synthetic antigen-DNA conjugates, enabling ligation of the DNA strands and subsequent quantification by qPCR. ADAP detects zepto- to attomoles of antibodies in 2 µL of sample with a dynamic range spanning 5-6 orders of magnitude. Using ADAP, we detected anti-thyroglobulin autoantibodies from human patient plasma with a 1000-fold increased sensitivity over an FDA-approved radioimmunoassay. Finally, we demonstrate the multiplexability of ADAP by simultaneously detecting multiple antibodies in one experiment. ADAP's combination of simplicity, sensitivity, broad dynamic range, multiplexability, and use of standard PCR protocols creates new opportunities for the discovery and detection of antibody biomarkers.

Evaluation of risk-factor-based screening for thyroid peroxidase antibody positivity in pregnancy.

OBJECTIVE: To determine whether risk-factor-based screening for thyroid dysfunction in pregnancy performs well for detecting thyroid peroxidase antibodies (TPOAb), a marker for autoimmune thyroid disease. STUDY DESIGN: We prospectively evaluated pregnant women for thyroid dysfunction using The Endocrine Society's eleven screening questions. Serum was analysed for TPOAb. RESULT: We enrolled 546 women. TPOAb positivity was higher in women with a personal (odds ratio (OR) = 8·0; 95% confidence interval (CI) = 1·7-37·4; P = 0·02) or family history of thyroid disease (OR = 2·7; 95% CI = 1·3-5·7; P = 0·02). There was no association between the number of positive responses and TPOAb positivity (P = 0·41). Risk-factor-based screening missed 18 women (33%) with TPOAb. CONCLUSION: One-third of women with TPOAb were missed by the case-finding method. A personal or family history of thyroid disease was most strongly associated with TPOAb positivity.

Marginal Iodine Status and High Rate of Subclinical Hypothyroidism in Washington DC Women Planning Conception.

INTRODUCTION: Subclinical hypothyroidism during pregnancy has been associated with adverse maternal and fetal outcomes. A subset of pregnant women in the United States have been shown to have mild iodine deficiency. No study has evaluated the thyroid and iodine status of women who are planning to become pregnant in the near future. METHODS: Thyroid function tests, thyroid antibodies, and urine iodine levels were evaluated in women presenting for preconception screening and counseling. A thyrotropin (TSH) level above 3.0 mIU/L was considered abnormal. RESULTS: One hundred and forty one women enrolled in the study. The median TSH level was 1.70 mIU/L (range 0.43-5.3 mIU/L). Sixteen women (11%) had a TSH above the upper limit of normal (>3.0 mIU/L). Eleven women (8%) were positive for TPO-Ab and 21 women (15%) for TgAb. Twenty-three women (16%) were positive for at least one thyroid antibody (TPOAb and/or TgAb). Median serum TSH concentrations were higher in women with detectable antithyroid antibodies than in women who were antibody negative (2.2 mIU/L vs. 1.7 mIU/L; p=0.005). The median urinary iodine concentration was 100.5 µg (range 19-843 µg/L). DISCUSSION: The present cohort exhibited the lowest median urinary iodine concentration levels to date reported in the United States for women in their childbearing years. One out of every nine women (11%) had thyroid function tests consistent with subclinical hypothyroidism.

Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes.

CONTEXT: Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). OBJECTIVE: The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. METHODS: A total of 589 samples from 495 patients, 243 TgAb-/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. RESULTS: The frequency of TgAb+ was 58%, 41%, 27%, and 39% for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb- samples, clinical sensitivities and specificities of 100% and 74%-100%, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41% to 86%. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20% of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. CONCLUSIONS: Tg-IAs remain the method of choice for Tg quantitation in TgAb- patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20% additional cases. The Tg-RIA will detect Tg in approximately 35% cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40% of TgAb+ cases in patients with disease need further evaluation.

Serum thyroglobulin (Tg) monitoring of patients with differentiated thyroid cancer using sensitive (second-generation) immunometric assays can be disrupted by false-negative and false-positive serum thyroglobulin autoantibody misclassifications.

CONTEXT: Reliable thyroglobulin (Tg) autoantibody (TgAb) detection before Tg testing for differentiated thyroid cancer (DTC) is critical when TgAb status (positive/negative) is used to authenticate sensitive second-generation immunometric assay ((2G)IMA) measurements as free from TgAb interference and when reflexing "TgAb-positive" sera to TgAb-resistant, but less sensitive, Tg methodologies (radioimmunoassay [RIA] or liquid chromatography-tandem mass spectrometry [LC-MS/MS]). OBJECTIVE: The purpose of this study was to assess how different Kronus (K) vs Roche (R) TgAb method cutoffs for "positivity" influence false-negative vs false-positive serum TgAb misclassifications that may reduce the clinical utility of reflex Tg testing. METHODS: Serum Tg(2G)IMA, TgRIA, and TgLC-MS/MS measurements for 52 TgAb-positive and 37 TgAb-negative patients with persistent/recurrent DTC were compared. A total of 1426 DTC sera with TgRIA of ≥ 1.0 µg/L had false-negative and false-positive TgAb frequencies determined using low Tg(2G)IMA/TgRIA ratios (<75%) to indicate TgAb interference. RESULTS: TgAb-negative patients with disease displayed Tg(2G)IMA, TgRIA, and TgLC-MS/MS serum discordances (% coefficient of variation = 24 ± 20%, range, 0%-100%). Of the TgAb-positive patients with disease, 98% had undetectable/lower Tg(2G)IMA vs either TgRIA or TgLC-MS/MS (P < .01), whereas 8 of 52 (15%) had undetectable Tg(2G)IMA + TgLC-MS/MS associated with TgRIA of ≥ 1.0 µg/L. Receiver operating characteristic curve analysis reported more sensitivity for TgAb method K vs R (81.9% vs 69.1%, P < .001), but receiver operating characteristic curve cutoffs (>0.6 kIU/L [K] vs >40 kIU/L [R]) had unacceptably high false-negative frequencies (22%-32%), whereas false positives approximated 12%. Functional sensitivity cutoffs minimized false negatives (13.5% [K] vs 21.3% [R], P < .01) and severe interferences (Tg(2G)IMA, <0.10 µg/L) (0.7% [K] vs 2.4% [R], P < .05) but false positives approximated 23%. CONCLUSIONS: Reliable detection of interfering TgAbs is method and cutoff dependent. No cutoff eliminated both false-negative and false-positive TgAb misclassifications. Functional sensitivity cutoffs were optimal for minimizing false negatives but have inherent imprecision (20% coefficient of variation) that, exacerbated by TgAb biologic variability during DTC monitoring, could cause TgAb status to fluctuate for patients with low TgAb concentrations, prompting unnecessary Tg method changes and disrupting Tg monitoring. Laboratories using reflexing should limit Tg method changes by considering a patient's Tg + TgAb testing history in addition to current TgAb status before Tg method selection.

How sensitive (second-generation) thyroglobulin measurement is changing paradigms for monitoring patients with differentiated thyroid cancer, in the absence or presence of thyroglobulin autoantibodies.

PURPOSE OF REVIEW: To discuss new insights regarding how sensitive (second-generation) thyroglobulin immunometric assays (TgIMAs), (functional sensitivities ≤0.10 µg/L) necessitate different approaches for postoperative thyroglobulin monitoring of patients with differentiated thyroid cancer (DTC), depending on the presence of thyroglobulin autoantibodies (TgAbs). RECENT FINDINGS: Reliable low-range serum thyroglobulin measurement has both enhanced clinical utility and economic advantages, provided TgAb is absent (∼75% DTC patients). Basal [nonthyroid-stimulating hormone (TSH) stimulated] TgIMA measurement obviates the need for recombinant human TSH stimulation because basal TgIMA below 0.20 µg/L has comparable negative predictive value (>95%) to recombinant human TSH-stimulated thyroglobulin values below the cutoff of 2 µg/L. Now that radioiodine remnant ablation is no longer considered necessary to treat low-risk DTC, the trend and doubling time of low basal thyroglobulin values arising from postsurgical thyroid remnants have recognized prognostic significance. The major limitation of TgIMA testing is interference by TgAb (∼25% DTC patients), causing TgIMA underestimation that can mask disease. When TgAb is present, the trend in TgAb concentrations (measured by the same method) can serve as the primary (surrogate) tumor-marker and be augmented by thyroglobulin measured by a TgAb-resistant class of method (radioimmunoassay or liquid chromatography-tandem mass spectrometry). SUMMARY: The growing use of TgIMA measurement is changing paradigms for postoperative DTC monitoring. When TgAb is absent, it is optimal to monitor the basal TgIMA trend and doubling time (using the same method) in preference to recombinant human TSH-stimulated thyroglobulin testing. When TgAb is present, interference renders TgIMA testing unreliable and the trend in serum TgAb concentrations per se (same method) can serve as a (surrogate) tumor-marker.

In search of an unstimulated thyroglobulin baseline value in low-risk papillary thyroid carcinoma patients not receiving radioactive iodine ablation.

BACKGROUND: The clinical use of serum thyroglobulin (Tg) as a tumor marker in papillary thyroid cancer (PTC) patients following total thyroidectomy continues to evolve, due in part to the introduction of more sensitive (second generation) Tg immunometric assays (Tg(2G)IMA, functional sensitivity ≤ 0.10 ng/mL), and the implementation of new recommendations against radioactive iodine ablation (RAIA) for patients at the lowest risk of recurrence. As a result, there is a need to establish the optimal timing and interpretation of serum Tg values while on levothyroxine-induced suppression of thyrotropin (TSH) in thyroidectomized PTC patients with a thyroid remnant. This study examines the pattern of decline and eventual baseline value of unstimulated Tg (uTg) concentrations following total thyroidectomy in patients with low-risk PTC who did not receive RAIA. METHODS: The medical records of consecutive patients with thyroid cancer seen at the Los Angeles County + USC Medical Center were retrospectively reviewed. Serial uTg and TSH values from Tg-antibody negative low-risk PTC patients treated with total thyroidectomy and no RAIA were analyzed. Patients were stratified by degree of TSH suppression to assess the effect on uTg. Serial postoperative uTg values were evaluated for the temporal pattern of decline and ultimate baseline. Patients with medullary thyroid cancer (MTC) were studied as a surgical reference group. RESULTS: Records from 577 consecutive thyroid cancer patients were reviewed, of which 36 met all criteria for inclusion. By 6 months, uTg fell to <0.5 ng/mL in 61% of patients and all patients demonstrated uTg < 0.5 ng/mL 2 years after surgery. During a median follow up of 5.7 years, uTg values remained below this level. The median uTg values in patients with papillary microcarcinoma, PTC, and MTC were similar at 0.11, 0.12, and 0.09 ng/mL, respectively. Further decline in uTg was not observed once the TSH was <0.5 mIU/L. CONCLUSIONS: The uTg values during TSH suppression in Tg antibody-negative, low-risk PTC patients who did not receive RAIA were below 0.5 ng/mL by 6 months postoperatively in most cases and remained stable over the duration of patient follow-up.

Thyroglobulin antibody (TgAb) methods - Strengths, pitfalls and clinical utility for monitoring TgAb-positive patients with differentiated thyroid cancer.

Thyroglobulin autoantibodies (TgAb) are detected at diagnosis or during treatment in approximately 25% of patients with differentiated thyroid cancer (DTC). When present, TgAb interferes with thyroglobulin (Tg) measurement causing falsely low or undetectable Tg immunometric assay (IMA) values that can mask disease. Guidelines mandate that every Tg test have TgAb measured simultaneously and quantitatively by immunoassay and not a recovery test. The propensity and magnitude of TgAb-Tg interference relates to both Tg and TgAb concentrations and the class of Tg method used. Because the TgAb trend reflects changes in thyroid tissue mass, TgAb concentrations serve as a surrogate post-operative DTC tumor marker. A rising, or de novo appearance of TgAb may indicate recurrence, whereas a progressive decline suggests successful treatment. This review focuses on the technical limitations of current TgAb methods, characteristics of TgAb interference with different classes of Tg method, and the clinical value of monitoring TgAb trends as a surrogate DTC tumor marker.

Psychosocial characteristics and poly-drug use of pregnant women enrolled in methadone maintenance treatment.

Pregnant women with substance dependency are a high-risk psychiatric and obstetric population, with their infants also at elevated neonatal risk. This paper draws on prospective, longitudinal data from a regional cohort of 81 methadone-maintained (MM) and 107 comparison women and their infants to describe the obstetric, socio-familial and mental health needs of women in methadone maintenance treatment during pregnancy. Of particular interest was the extent and pattern of maternal licit and illicit drug use over the course of pregnancy. Results showed that MM women had complex reproductive histories, chronic health problems, and were subject to high rates of socioeconomic adversity and comorbid mental health problems. During pregnancy, more than half continued to use licit and illicit drugs, although there was a general trend for drug use to reduce over time. No differences were observed between women maintained on low (12.5-61.0mg/day) and high (61.1-195.0mg/day) doses of methadone, with the exception of opiate abuse which was higher in the low dose group (p=.07). Findings highlight that pregnant women enrolled in MMT and their infants represent a vulnerable group with complex, social, obstetric and psychiatric needs. They also reinforce the need for services that can provide on-going wrap-around, multidisciplinary and multiagency care for these high risk dyads, both during pregnancy and in the transition to parenthood.

Clinical review: Clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC).

CONTEXT: Thyroglobulin autoantibodies (TgAb) are primarily measured in serum in conjunction with thyroglobulin (Tg)--the primary tumor marker used to monitor patients with differentiated thyroid cancers (DTC). Every specimen needs TgAb testing to authenticate that the Tg measurement is not compromised by TgAb interference. When present, TgAb concentrations per se can be monitored as a surrogate tumor marker. OBJECTIVES: The aims of the study were: 1) to review published reports concerning whether there are associations between DTC, thyroid autoimmunity (Hashimoto's thyroiditis), and the presence of TgAb; and 2) to evaluate the methodological factors that influence TgAb interference with serum Tg testing. DATA SOURCES: PubMed was used to identify studies published over the last 55 yr that focused on DTC relationships with thyroid autoimmunity and the presence of thyroid autoantibodies. RESULTS: Many studies have reported significant associations between papillary thyroid cancer and Hashimoto's thyroiditis that may have a favorable prognostic significance. TgAb is detected in approximately 20% of DTC patients and may be a more specific thyroid tumor marker than thyroid peroxidase antibodies. TgAb interferes with Tg immunometric assay (IMA) measurements, causing falsely low/undetectable Tg values, especially when TgAb concentrations are high and serum Tg concentrations (measured by RIA) are low. TgAb concentrations respond to changes in Tg-secreting thyroid tissue such that the TgAb trend can be used as a more reliable surrogate DTC tumor marker than Tg IMA. Current TgAb assays may not always detect interfering TgAb because of insensitivity and specificity differences. It is critical to retain the same method for long-term TgAb monitoring. CONCLUSIONS: Patients with Hashimoto's thyroiditis frequently have TgAb detected and may have a higher risk for papillary thyroid cancer. Although TgAb interferes with Tg IMA measurements, TgAb trends can be used as a surrogate DTC tumor marker in preference to Tg IMA, provided that the same method is used.

Effect of environmental perchlorate on thyroid function in pregnant women from Córdoba, Argentina, and Los Angeles, California.

OBJECTIVE: To determine whether environmental perchlorate exposure adversely affects thyroid function in women in the first trimester of pregnancy. METHODS: First-trimester pregnant women were recruited from prenatal clinics in the Los Angeles County Hospital, Los Angeles, California, and in the Hospital Universitario de Maternidad dependent Universidad Nacional de Córdoba, Córdoba, Argentina, between 2004 and 2007. Spot urine and blood specimens were obtained during the clinic visit. Urinary perchlorate, iodine, and creatinine were measured, and thyroid function tests were performed. RESULTS: The study included 134 pregnant women from Los Angeles, California (mean gestational age ± SD = 9.1 ± 2.2 weeks), and 107 pregnant women from Córdoba, Argentina (mean gestational age = 10.0 ± 2.0 weeks). Median urinary iodine values were 144 µg/L in California and 130 µg/L in Argentina. Urinary perchlorate levels were detectable in all women (California: median, 7.8 µg/L [range, 0.4-284 µg/L] and Argentina: median, 13.5 µg/L [range, 1.1-676 µg/L]). Serum thyroperoxidase antibodies were detectable in 21 women from California (16%) and in 17 women from Argentina (16%). Using Spearman rank correlation analyses, there was no association between urinary perchlorate concentrations and serum thyrotropin, free thyroxine index, or total triiodothyronine values, including within the subset of women with urinary iodine values less than 100 µg/L. In multivariate analyses using the combined Argentina and California data sets and adjusting for urinary iodine concentrations, urinary creatinine, gestational age, and thyroperoxidase antibody status, urinary perchlorate was not a significant predictor of thyroid function. CONCLUSIONS: Low-level perchlorate exposure is ubiquitous, but is not associated with altered thyroid function among women in the first trimester of pregnancy.

Serum TSH determinations in pregnancy: how, when and why?

Improvements in the sensitivity of the serum TSH assay have revolutionized our strategies for investigating thyroid function and firmly established TSH as the first-line thyroid function test for most clinical situations, including pregnancy. As a single hormone determination, serum TSH provides the most sensitive index to reliably detect thyroid function abnormalities. Normal thyroid function is important to ensure the best possible pregnancy outcome; in addition, disorders of the thyroid gland are relatively frequent in women of childbearing age. The aim of this article is, therefore, to present relevant information on analytical, as well as clinical, aspects regarding serum TSH determination and its usefulness to detect subtle thyroid function abnormalities associated with the pregnant state, namely overt and subclinical hypothyroidism and hyperthyroidism. As these disorders are associated with poor pregnancy outcome, the authors of the present article are in favor of serum TSH measurement for all pregnant women.

Serum Basal thyroglobulin measured by a second-generation assay correlates with the recombinant human thyrotropin-stimulated thyroglobulin response in patients treated for differentiated thyroid cancer.

BACKGROUND: Recombinant human thyrotropin (rhTSH) stimulation is frequently used to assess the disease status of patients treated for differentiated thyroid cancer (DTC) when basal (unstimulated) thyroglobulin (b-Tg) is below the assay sensitivity limit. The objective of this study was to determine relationships between the b-Tg and the 72-hour rhTSH-stimulated Tg (rhTSH-Tg) using a second-generation immunochemiluminometric assay with a functional sensitivity of 0.05 ng/mL (microg/L). METHODS: Serum Tg was measured in paired b-Tg and rhTSH-Tg specimens from 1029 rhTSH tests performed on 849 TgAb-negative patients during long-term monitoring for DTC. RESULTS: Basal Tg correlated with rhTSH-Tg across b-Tg concentrations ranging from 0.05 to 1000 ng/mL (microg/L) (r = 0.85, p < 0.0001). The b-Tg concentration was unrelated to age, sex, basal TSH, 72-hour TSH, or the Tg fold response (rhTSH-Tg/b-Tg). Further, only 2/655 (0.3%) tests with b-Tg below 0.1 ng/mL (microg/L) had rhTSH-Tg above 2.0 ng/mL (microg/L) (2.9 and 3.8 ng/mL [microg/L], respectively). Thirty-three patients with three or more rhTSH tests performed over a 2- to 5-year period displayed high indexes of individuality for both the 72-hour TSH and the Tg fold response (indexes of individuality = 0.30 and 0.38, respectively). Basal Tg measured using a first-generation assay with a functional sensitivity of 0.9 ng/mL (microg/L) failed to reliably detect an rhTSH-Tg response above 2.0 ng/mL (microg/L). CONCLUSIONS: An rhTSH-Tg response above 2.0 ng/mL (microg/L) was highly unlikely when b-Tg was below 0.1 ng/mL (microg/L). Second-generation b-Tg measurements correlated with the degree of rhTSH-Tg stimulation and thus the likelihood of having rhTSH-Tg above the customary cut-off of 2.0 ng/mL (microg/L), whereas b-Tg measured by a first-generation assay did not. Correlations between four different assays showed that the use of a fixed Tg cut-off was influenced by assay selection. Patients receiving repetitive rhTSH tests had highly reproducible rhTSH-Tg/b-Tg fold responses, suggesting that repetitive testing is unnecessary and that second-generation measurement of b-Tg trends without rhTSH stimulation would be satisfactory for the long-term monitoring of most patients with DTC.