Recent recommendations from ATA guidelines to define the upper reference range for serum TSH in the first trimester match reference ranges for pregnant women in Rio de Janeiro

ABSTRACT Objectives: American Thyroid Association (ATA)'s new guidelines recommend use of population-based trimester-specific reference range (RR) for thyrotropin (TSH) in pregnancy. The aim of this study was to determine first trimester TSH RR for a population of pregnant women in Rio de Janeiro State. Subjects and methods: Two hundred and seventy pregnant women without thyroid illness, defined by National Academy of Clinical Biochemistry, and normal iodine status were included in this sectional study. This reference group (RG) had normal median urinary iodine concentration (UIC = 219 μg/L) and negative anti-thyroperoxidase antibodies (TPOAb). Twin pregnancy, trophoblastic disease and use of drugs or supplements that influence thyroid function were excluded. In a second step, we defined a more selective reference group (SRG, n = 170) by excluding patients with thyroiditis pattern on thyroid ultrasound and positive anti-thyroglobulin antibodies. This group also had normal median UIC. At a final step, a more selective reference group (MSRG, n = 130) was defined by excluding any pregnant women with UIC < 150 μg/L. Results: In the RG, median, 2.5th and 97.5th percentiles of TSH were 1.3, 0.1, and 4.4 mIU/L, respectively. The mean age was 270 ± 5.0 and the mean body mass index was 25.6 ± 5.2 kg/m2. In the SRG and MSRG, 2.5th and 975th percentiles were 0.06 and 4.0 (SRG) and 0.1 and 3.6 mIU/L (MSRG), respectively. Conclusions: In the population studied,TSH upper limit in the first trimester of pregnancy was above 2.5 mIU/L. The value of 3.6 mIU/L, found when iodine deficiency and thyroiditis (defined by antibodies and ultrasound characteristics) were excluded, matches recent ATA guidelines.

Neonatal congenital hypothyroidism screening in Addis Ababa, Ethiopia.

OBJECTIVES: To determine the prevalence of congenital hypothyroidism, establish reference levels for thyroid stimulating hormone (TSH), and determine the cut-off points of TSH level for neonatal screening in congenital hypothyroidism. DESIGN: A cross-sectional study. SETTING: Ghandhi Memorial, Zewditu, Tikur Anbessa and St Paulo's referral hospitals in Addis Ababa, Ethiopia, from July 1996 to January 1997. SUBJECTS: Four thousand two hundred and six consecutive newborns. MAIN OUTCOME MEASURES: TSH and T4 values using standard TSH level estimation approach. RESULTS: The overall mean TSH value was 9.6 mIU/l with standard deviation of 7.8 mIU/l. Transient hypothyroidism occurred in 3.6% of the neonates. No true case of congenital hypothyroidism was identified. The mean(SD) sampling time was 12.8(6.7) hours and the recall rate 4.8%. Most neonates (98.6%) were screened at or less than 24 hours of age. Twins had lower mean TSH value of 7.9(SD=6.4) mIU/l than single neonates with 9.6(SD=7.8) mIU/l, while females had significantly lower mean TSH value of 9.4(SD=7.9) mIU/l than males of 9.8(SD=7.6) mIU/l. The mean TSH level decreased significantly as sampling time increases, the mean TSH level for neonates older than 24 hours is significantly lower than the mean TSH level for those with 24 hours old or less. No significant difference was found in the mean TSH levels in relation to maternal age, parity and gestational age. No significant correlation was found between TSH value and birth weight (r=0.02), height (r=0.03), and head circumference (r=0.02) of the neonates. The most appropriate TSH level cut-off point was found to be at 29.4 mIU/l. The reference range (the range between 2.5th and 97.5th percentiles) for serum thyrotrophin value was higher in the age range of 6 to 12 hours and then declined. CONCLUSION: This pilot study has highlighted important findings, however larger studies should be conducted to assess the magnitude and associated factors of congenital hypothyroidism because congenital hypothyroidism represents one of the most common preventable causes of mental retardation.

Comparison of pituitary and recombinant human thyroid-stimulating hormone (rhTSH) in a multicenter collaborative study: establishment of the first World Health Organization reference reagent for rhTSH.

BACKGROUND: The increasing use of recombinant-DNA-derived materials in therapy and diagnosis poses a new challenge for biological standardization, that of developing reference preparations appropriate for both the native and recombinant products. Here we report the results of an international collaborative study that was carried out under the auspices of WHO to assess the suitability of a preparation of recombinant thyroid-stimulating hormone (rTSH; 94/674) to serve as a potential standard for the calibration of diagnostic immunoassays compared with the International Reference Preparation (IRP) for human TSH (80/558). METHODS: Coded samples were provided to the 33 laboratories in the study, and participants were asked to perform TSH assays currently in use in their laboratories. Twenty-eight laboratories contributed 93 immunoassays in 41 different method-laboratory combinations, and an additional 5 laboratories contributed bioassay data. All data were analyzed centrally at the National Institute for Biological Standards and Control. RESULTS: The results obtained in different laboratories and with different assay systems revealed significant variability between estimates of rTSH relative to the IRP. These ranged from 5. 51 mIU (95% limits, 3.95-7.67 mIU) per ampoule by RIA to 7.15 mIU (95% limits, 6.7-7.63 mIU) per ampoule by immunofluorometric assay. However, the results showed that the assignment of a value of 6.70 mIU per ampoule of 94/674 would give reasonable continuity with the IRP in many assay systems. CONCLUSIONS: The preparation was established as the First WHO Reference Reagent for TSH, human, recombinant, to provide a means of validating assay performance and to maintain continuity with the IRP without compromising clinical data.

Hormona estimulante de la tiroides

La hormona estimulante de la tiroides- TSH por throid stimulating hormone-, liberada por la hipófisis anterior, es principal regulador de la función tiroidea. La secreción de la TSH es controlada por el hipotálmo mediante la hormona liberadora de tirotropina - TRH por thyrotropin releasing hormone-. A su vez, este sistemea regula la liberación de las hormonas tiroides: Tiroxina- T4- y tirotropina- T3-. En la producción de la TSH existe un mecanismo de retroalimentación negativo, que es sensible a las concentraciones de las hormonas tiroideas circulantes, T3 y T4, controladas por el hipotálamo. Colectivamente este sistema se denomina eje hipotálamo-hipofisiario-tiroideo. Cualquier alteraciónen la función del eje influye sobre los niveles sanguíneos de la T4 y T3.

Third generation time-resolved immunofluorometric TSH assay for automatic immunoassay system evaluated.

We evaluated a new, third generation assay for serum thyrotropin (TSH) based on time-resolved fluorescence (AutoDelfia hTSH Ultra) for the 1235 AutoDelfia automatic immunoassay system. The functional sensitivity of the TSH assay was 0.007 mIU l-1 (between-assay CV, 20%). The between-assay imprecision was CV 4.1-7.7%, between TSH concentrations of 0.026 and 23.8 mIU l-1. The within-assay imprecision was CV 1.2-1.5% between TSH concentrations of 0.5 and 12 mIU l-1. The degree of agreement between the AutoDelfia hTSH Ultra assay and a second generation TSH-IRMA was studied. The mean difference was -0.04 (SD 0.28) mIU l-1 at concentrations between 0.22 and 52 mIU l-1. Serum TSH concentrations of euthyroid subjects, hypothyroid and hyperthyroid patients as well as those of patients with non-thyroidal illness, and thyroid carcinoma patients with TSH suppressive thyroxine treatment were analysed. The AutoDelfia automatic immunoassay system offers many benefits in sensitivity, precision, speed, output rate, time and convenience. Overnight runs are possible, and the system is easy to operate.

Analytical variation in immunoassays and its importance for medical decision making.

The analytical variation of immunoassays is at present significantly larger than that of other methods in clinical chemistry. The main sources of this large variation are variation between methods, lot to lot variation, and the large imprecision between-runs and within-runs when the methods are not performed on automated instruments. The variation can be substantially reduced by standardization, by ensuring the comparability between lots, and by automation of the analytical procedure. The extent to which the variation should be reduced is determined by the needs of medical decision making. It is demonstrated using the analytes TSH and CA 15-3 as examples that quality requirements have to be individually specified for each analyte. Such guidelines should be established by teams of international experts. They should include suggestions for reference methods, guidelines on the extent of comparability between routine methods, the maximum allowable deviations from lot to lot, and the minimum requirements for between-run precision. Such guidelines could form the basis for improvements which are directed towards the medical requirements.

Application of sandwich immunoassays for the determination of sample-specific background signals and its use for calibration of immunoassays.

Sample-related background signals in immunoassays can be measured by a variation of the double antibody sandwich principle, in which the unlabelled specific antibody is substituted by a similar unrelated non-specific antibody. This permits differentiation between the analyte-specific and the background signal components for each sample. The method permits selection of sera with no or low analyte content for use as analyte diluent and for defining the zero point of the calibration curve. The method also permits control of analyte content during production processes which may change the background signal as well as identification of samples with atypical background signals. The procedure has been used for the calibration of enzyme immunoassays for alpha-fetoprotein (AFP) and human thyroid-stimulating hormone (TSH).