Limitations of current thyroid function tests / Limitaciones de las pruebas actuales de la función tiroidea

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La estimulación previa con rhTSH mejora la respuesta al tratamiento con radioyodo en pacientes con bocio multinodular tóxico de baja captación / Recombinant human thyrotropin stimulation prior to 131I therapy in toxic multinodular goitre with low radioactive iodine uptake

Introducción. La estimulación con TSH recombinante humana (rhTSH) aumenta la captación tiroidea de yodo, ayudando al tratamiento con radioyodo en el bocio multinodular (BMN) no tóxico. Sin embargo, son escasos los estudios que utilicen rhTSH previo a terapia con radioyodo en el BMN tóxico para controlar la hiperfunción y clínica compresiva. Material y método. Se llevó a cabo un estudio prospectivo en pacientes con BMN e hipertiroidismo. Los pacientes se reclutaron de forma consecutiva y se dividieron en un grupo I, estimulados con 0,3mg de rhTSH antes de recibir radioyodo, y un grupo control o grupo II, sin estimulación previa. Se midió función tiroidea, captación tiroidea de radioyodo, peso tiroideo y síntomas compresivos, y se siguió a los pacientes durante 9 meses. Resultados. Un total de 16 pacientes (14 mujeres) de edad media 69,7años constituyeron el grupo I y 16 pacientes (12 mujeres) de edad media 70,7años, el grupo II. Tras el estímulo con 0,3mg rhTSH en el grupo I, la captación de 131I a las 24h aumentó un 78,4% y la dosis estimada absorbida, un 89,3%. En el grupo II, la dosis estimada absorbida fue inferior a la del grupo I tras la estimulación con rhTSH (29,8Gy vs. 56,4Gy; p=0,001). A los 9 meses, se había controlado el hipertiroidismo en un 87,5% de pacientes en el grupo I, y en un 56,2% en el grupo II (p=0,049). La reducción media de peso tiroideo fue mayor en el grupo I que en el II (39,3% vs. 26,9%; p=0,017), con una tendencia a la mejoría subjetiva de la clínica compresiva en el grupo I, aunque no significativa. Solo 2 pacientes describieron taquicardias tras la administración de rhTSH, que se resolvieron con beta-bloqueantes. Conclusiones. La estimulación con rhTSH a dosis de 0,3mg previa al tratamiento con radioyodo consigue una reducción del tamaño tiroideo y mejoría funcional en pacientes con hipertiroidismo y BMN de baja captación, sin necesidad de ingreso hospitalario (AU)

Aim. Stimulation with recombinant human thyrotropin (rhTSH) increases thyroid radioiodine uptake, and is an aid to 131I therapy in non-toxic multinodular goitre (MNG). However, there are not many studies using rhTSH prior to 131I in toxic multinodular goitre to improve hyperthyroidism and compressive symptoms. Material and method. A prospective study was conducted on patients with MNG and hyperthyroidism. Patients were recruited consecutively and divided into group I, stimulated with 0.3mg of rhTSH before radioiodine therapy, and a control group or group II, without stimulation. Thyroid function, radioiodine thyroid uptake, thyroid weight, and compressive symptoms were measured, and patients were followed-up for 9 months. Results. Group I consisted of 16 patients (14 women), with a mean age 69.7 years, and group II with 16 patients (12 women), with a mean age 70.7 years. After stimulation with 0.3mg rhTSH in group I, 131I uptake (RAIU) at 24h increased by 78.4%, and the estimated absorbed dose by 89.3%. In group II, the estimated absorbed dose was lower than group I after stimulation with rhTSH (29.8Gy vs. 56.4Gy; P=0.001). At 9 months of follow-up, hyperthyroidism was controlled in 87.5% of patients in group I, and 56.2% in group II (P=0.049). The mean reduction in thyroid weight was higher in group I than in group II (39.3% vs. 26.9%; P=0.017), with a tendency towards subjective improvement of compressive symptoms in group I, although non-significant. Only 2 patients described tachycardias after rhTSH administration, which were resolved with beta-blockers. Conclusion. Stimulation with 0.3mg of recombinant human thyrotropin prior to radioiodine therapy achieves a reduction in thyroid weight and functional improvement in patients with hyperthyroidism and multinodular goitre with low uptake, and with no need for hospital admission (AU)

Analytical Evaluation of Portable and Simple FREND Fluorescent Immunoassay for Rapid Quantification of Thyroid-Stimulating Hormone and Free Thyroxine.

BACKGROUND: The FREND™ thyroid stimulating hormone (TSH) and free thyroxine (FT4) assays are newly developed rapid quantitative immunoassays utilizing antibody-conjugated fluorescent nanoparticles in a microfluidic flow system. The FREND system is a simple and portable fluorescence reader with rapid turnaround time (4 - 10 minutes). METHODS: The analytical sensitivity, precision, and linearity were evaluated. For the method comparison, FREND TSH and FT4 levels were compared with those from ADVIA Centaur XP and Abbott ARCHITECT i2000. RESULTS: The limit of detection was 0.047 mIU/L and 5.031 pmol/L in FREND TSH and FT4 assays. FREND system had acceptable linearity and precision of  10% across the assay range (0.05 - 25.0 mIU/L for TSH and 1.4 - 96.8 pmol/L for FT4). The functional sensitivity was 0.057 mIU/L for the TSH assay and 4.644 pmol/L for the FT4 assay. Passing-Bablok regression analysis of TSH data showed good correlation among the three assays. For the FT4 assay, FREND FT4 displayed good correlation with the ARCHITECT FT4 assay, but the intercepts and slopes significantly differed between FREND and Centaur results: [FREND FT4] = 4.799 + 0.600 [Centaur FT4]. CONCLUSIONS: The analytical performance of FREND TSH and FT4 assays was satisfactory for use in the clinical laboratory. The FREND FT4 assay was in concordance with ARCHITECT FT4, but it needs further investigation and harmonization.

Severe acute liver failure and tirotoxicosis: an uncommon association / Insuficiencia hepática aguda grave y tirotoxicosis: una asociación infrecuente

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Prevalence of autoimmune thyroiditis and thyroid dysfunction in healthy adult Mexicans with a slightly excessive iodine intake / Prevalencia de tiroiditis autoinmune y disfunción tiroidea en adultos mexicanos sanos, con una ingestión de yodo levemente excesiva

Objective: the purpose of this study was to evaluate the prevalence of autoimmune thyroiditis and thyroid dysfunction in healthy individuals with no previously known thyroid disease, in an urban area of Mexico City. Subjects and methods: the study was conducted on volunteers with no known thyroid disease. We recruited 427 subjects among the hospital’s medical and administration personnel. All underwent thyroid ultrasound (US) and TSH, free T4 (FT4), total T3 (TT3), thyroid anti-peroxidase (TPOAb) and anti-thyroglobulin (TgAb) antibodies were measured. Hypoechogenicity and thyroid volume were determined by US. Urinary iodine (UI) excretion was also measured. Results: the frequency of autoimmune thyroiditis was 8.4% (36/427) and women were most commonly affected than men (11.6 vs. 4.3% respectively, P=0.008); when including cases of atrophic thyroid, the frequency increased to 15.7% (67/427). Clinical hypothyroidism was detected in 1.2% (5/427) and it was sub-clinical in 5.6% of individuals. A goiter was present in 5.9% (25/427) of volunteers. Median UI was 267 µg/L, (IQR 161.3 - 482.5). Conclusions: in spite of our study’s limitations, the frequency of autoimmune thyroiditis is clearly elevated in the studied population. Further studies are necessary in order to define the prevalence of autoimmune thyroid disease as well as the current iodine nutritional status in our country

Objetivo: el objetivo del presente estudio fue evaluar la prevalencia de tiroiditis autoinmune y disfunción tiroidea en individuos sanos sin enfermedad tiroidea conocida, de un área urbana de la ciudad de México. Material y métodos: el estudio se realizó en voluntarios sin enfermedad tiroidea conocida. Se reclutaron 427 individuos entre personal médico y administrativo del hospital. A todos se les realizó ultrasonido (US) tiroideo, TSH, T4 libre (FT4), T3 total (TT3), anticuerpos anti-peroxidasa tiroidea (TPOAb) y anti tiroglobulina (TgAb). Dentro de la evaluación por US se incluyó la hipoecogenicidad y el volumen tiroideo. También se midió la excreción urinaria de yodo (UI). Resultados: la frecuencia de tiroiditis autoinmune fue de 8,4% (36/427), las mujeres fueron más afectadas que los hombres (11,6 vs. 4,3%, respectivamente, P=0,008), cuando se sumó la tiroides atrófica, esta frecuencia se elevó al 15,7% (67/427) de los estudiados. El hipotiroidismo clínico fue detectado en el 1,2% (5/427) y el subclínico en el 5,6%. El hipertiroidismo clínico solo se observó en el 0,5% (2/427) y el subclínico en el 1,9%. El bocio se identificó en el 5,9% (25/427) de los voluntarios. La mediana de la UI fue de 267 µg/L, RIQ (161,3 - 482,5). Conclusiones: a pesar de las limitaciones de nuestro estudio, es clara la frecuencia incrementada de tiroiditis autoinmune en la población estudiada. Son necesarios más estudios que definan tanto la prevalencia de enfermedad tiroidea autoinmune como el estatus nutricional de yodo actual en nuestro país

Subclinical hypothyroidism: a 'laboratory-induced' condition?

OBJECTIVE: In current literature and guidelines, there is a tendency to define absolute TSH concentrations at which patient follow-up or even pharmaceutical intervention should be initiated. As TSH concentrations depend on the analytical method/platform used for TSH quantification, absolute cut-off values may pose threats for uniform clinical decision-making. In this study we therefore set out to clarify to what extent the method/platform and the reference values applied for TSH influence the clinical interpretation of thyroid parameters. DESIGN AND METHODS: We retrospectively analyzed anonymous TSH results from the Dutch external quality assessment program (EQAS) in relation to reference values advised by different manufacturers. We also examined TSH/free thyroxin (fT4) reference ranges and prevalence of thyroid pathology among different Dutch laboratories, including four cases in which a switch in the measuring platform was made. RESULTS: Our data show that interpretation of thyroid parameters is not only influenced by between-method/platform variation, but is also substantially affected by the variation in TSH/fT4 reference intervals applied in individual laboratories. Additionally, we show that the transition to a novel analytical method/platform can result in a shift in the prevalence of thyroid pathology, especially for subclinical hypothyroidism. CONCLUSIONS: Subclinical hypothyroidism can be a 'laboratory-induced' condition. This is an undesirable situation in regard to the clinical implications such a diagnosis can have for patients.

Thyroid-stimulating hormone and free thyroxine on the ADVIA Centaur immunoassay system: a multicenter assessment of analytical performance.

OBJECTIVES: We assessed the analytical performance of the TSH and FT4 assays on ADVIA Centaur in a multicenter national evaluation. DESIGN AND METHODS: A precision study and a method comparison were performed. Reference values stated by the manufacturer were checked from 379 normal subjects. RESULTS: For TSH and FT4, the intra-assay CVs were below 2.3 and 5.2%, respectively, and the inter-assay CVs below 4.4% and 7.2%, respectively. Therefore, the precision and reproducibility were acceptable. Bland-Altman bias plots revealed good correlation and agreement with Cobas assays. TSH and FT4 data yielded reference ranges of 0.64-3.24 mIU/L and 10.5-18.9 pmol/L, respectively. CONCLUSION: These assays demonstrate reliable characteristics. The reference ranges obtained can be used for interpretation of thyroid function.

[On the method of express-diagnostics of thyroid gland dysfunctions].

The method of express-diagnostics of thyroid diseases on a degree of moisture of the skin integument which is one of clinical attributes of hypothyroidism (a skin is dry, shelled, with sites of keratinization) and hyperthyroidism at which the return picture is observed, i.e. the (increased humidity of a skin is offered. At the same time as a parameter describing a degree of moisture of skin is a relative humidity of the air environment which are taking place above the skin integument in conditions of thermodynamic equilibrium. The instrument is a hermetic glass in which the sensor of humidity is mounted. Studies on the definition of threshold levels of parameter for several groups of patients with clinically confirmed diagnoses of diseases of a thyroid are carried out.

Matrix-dependent bias in total thyroxine measurement on the Beckman Access.

BACKGROUND: Total thyroxine assays continue to be an integral part of thyroid status testing. We experienced a significant number of elevated total thyroxine values in patients with normal thyroid stimulating hormone and thyroxine binding globulin concentrations using the Beckman Access and hypothesized that these were due to a sample matrix effect. METHODS: We compared the total thyroxine assays on the Beckman Synchron, Beckman Access, and Dade Dimension using individual patient specimens and two uniform matrices: a serum pool and an albumin-based matrix that were both supplemented with L-thyroxine to span the linear assay range. RESULTS: Access total thyroxine values in individual patient specimens exhibited sporadic positive bias as high as 77 nmol/l (6 microg/dl) when compared to the Synchron and Dimension. The use of uniform matrices had little effect on the Synchron in comparison to the Dimension but significantly improved the agreement between the Access and the Dimension or Synchron as indicated by a statistically significant improvement in correlation coefficients. CONCLUSIONS: The Access total thyroxine assay is prone to a variable and clinically significant positive bias that is mediated by a component of the sample matrix.

[Clinico-laboratory algorithms for assessing the functional activity of the thyroid gland]. / Kliniko-laboratornye algoritmy otsenki funktsional'noi aktivnosti shchitovidnoi zhelezy.

Three diagnostic algorithms making use of automated chemiluminescent analyzers are proposed for evaluation of the thyroid function, depending on the clinical situation. Laboratory criteria of hypothyrosis and thyrotoxicosis therapy monitoring are discussed. Main variants of disagreement between clinical data and values of thyrotropic hormone and free T4 are presented.

Elecsys TSH, FT4, T4, T-uptake, FT3 and T3. Clinical results of a multicentre study.

6 assays for the assessment of thyroid function (TSH, FT4, T4, T-uptake, FT3 and T3) were targets of the International Multicenter Study on the random access analyzer Elecsys 2010. The aim of the study was to characterize the clinical performance of the assay in method comparison and reference range studies. The assays under evaluation were compared to a broad variety of radio isotopic and non-radio isotopic assays. They are suitable for serum and plasma samples. In case of TSH the study include 2nd and 3rd generation TSH procedures. In general, good to excellent correlations were found between the Elecsys and the respective routine methods. Systematic deviations were extraordinary low in case of TSH, FT4 and T4. Regarding the analysis of T3 and FT3 some systematic deviations in terms of standardization have been observed. Results of Elecsys T4 and Elecsys FT4 were independent of the serum total protein or serum albumin concentrations. In T3 and FT3 Elecsys the results of samples from NTI (non-thyroidal-illness) patients were decreased, reflecting the physiological situation in these patients. Studies using samples from healthy euthyroid as well as untreated hypo- and hyperthyroid individuals enabled us to assess the assays reference ranges.

[Screening of thyroid function proper by calculating the integral index based on data from in vitro radioimmunological testing]. / Skrining funktsii sobstvenno shchitovidnoi zhelezy posredstvom rascheta integral'nogo indeksa po dannym in vitro radioimmunologicheskogo testirovaniia.

A total of 1494 patients were investigated: 803--with the euthyroid state and extrathyroid (nonthyroid) pathology, 493--with primary hyperthyroidism and 101--with primary hypothyroidism; 93 healthy donors (61 women and 32 men) were entered into the control group. The thyroid integral index (II) was used for the assessment of the level of function of the thyroid proper. Normal II values ranged within 0.6-5 rel. units hypothyroidism values were within 0.6 and below this value, hyperthyroidism values--within 5 and above tris value. II calculation made it possible to divide (with 100% accuracy) the patients into 3 groups of the thyroid state: eu-, hypo- and hyperthyroidism. Euthyroidism values by the TSH level were within 1.7-9 mU/l.

[Method for the determination of protein binding of thyroid gland hormones and the detection of antibodies to T4 and T3]. / Methode zur Bestimmung der Proteinbindung der Schilddrüsenhormone und zum Nachweis von Antikörpern gegen T4 und T3.

More than 99% of circulating thyroid hormones are bound with defined capacity and affinity to transport proteins such as thyroxine binding globulin, albumin and prealbumin. Variants of albumin and/or prealbumin, often familial, will bind T4 and sometimes T3 with increased affinity causing higher TT4 and TT3 values respectively. In determining fT4 and fT3 by analogue tracer its binding to protein variants will also lead to falsely raised free parameters. Thus the possibility of a false diagnosis of hyperthyroidism arises. Also the presence of T4 and T3 autoantibodies will cause misleading findings of increased thyroid hormone parameters as against euthyroid metabolism. For determining the pattern of T4 and T3 protein binding as well as autoantibodies radioactive labelled T4 or T3 is incubated with the patients serum. Transport proteins are separated by means of horizontal agarose gel electrophoresis with water cooling. The gel is sectioned and the activity of individual gel particles is measured in a Gammacounter. The activity graph shows with high precision the binding pattern of T4 and T3 to transport proteins. Moreover, this method also serves to determine any possible T4 and T3 autoantibodies, indicated by a peak in the activity graph in the gamma globulin range.

Clinical usefulness and limitations of serum thyrotropin measurement by 'ultrasensitive' methods. Comparisons of five kits.

Five different ultrasensitive thyrotropin (TSH) assay kits (Boots-Celltech, Immunotech, ORIS-CIS, Travenol and Boehringer) have been used for TSH measurements in various conditions. All the kits were based on an immunometric method but differed with regard to components and procedure. The sensitivity appeared essentially the same for the five kits (0.10 microU/ml) as well as the intraassay precision (coefficient of variation less than 12%). In contrast, the interassay coefficients of variation in the low TSH range varied from 12.8 to 21.3%. Discrepancies from kit to kit were observed and accounted for by differences in the components and procedure of the kits. Basal serum TSH was determined in normal subjects (n = 261) and in patients with thyroid dysfunction (n = 392). No overlap was shown between normals and patients with overt hypothyroidism. In contrast, an overlap existed between normals and hyperthyroids for all the kits but one. Measurements in patients with nontoxic goiter showed that TSH may be undetectable in clinically euthyroid patients, whatever the kit used. After TRH stimulation, 95% of the 375 patients tested associated either an absence of response to TRH with undetectable basal TSH values, or a blunted response with low basal TSH levels or normal response with normal basal TSH concentrations. However, 9 patients with suppressed TSH showed a response to TRH and 7 patients with normal basal TSH levels presented an exaggerated response to TRH. Taken together, these results demonstrate that even though ultrasensitive measurements of TSH do not meet the expectation of completely discriminating euthyroid from hyperthyroid patients, ultrasensitive TSH assay kits represent a powerful tool in the diagnosis of thyroid dysfunction, which would eliminate, in most instances, the need for TRH test and diminish thyroid hormone assay requests.

[Measurement of 24-hr whole-body retention of 99mTc-MDP with a thyroid uptake probe (author's transl)].

A new method for measurement of 24-hr whole-body retention (WBR) of 99mTc-MDP, using a thyroid uptake probe was established and its clinical significance was evaluated in various bone diseases. (1) Reproducibility of 24-hr WBR in 9 patients was very good. Correlation coefficient was 0.997 and coefficient of variability was only 1.83%. (2) Radiochemical purity of 99mTc-MDP was 97.8 +/- 0.7% (n = 5), indicating no significant inter-lot variations. (3) 24-hr WBR of normal adult males (n = 5) was 30.0 +/- 4.9%, which was significantly elevated compared to the reported 99mTc-HEDP WBR of 19.2 +/- 1.7%. Whole-body retentions of chronic renal failure, metastatic bone disease and hyperthyroidism groups were significantly elevated compared to that of the normal group. However, WBR of steroid-induced osteoporotic group was significantly decreased. Based on these results, this thyroid uptake probe method was simple, reproducible and accurate to measure 24-hr WBR of 99mTc-MDP. Quantification of WBR of 99mTc-MDP was of great clinical value to diagnose metabolic bone disease and to follow-up metabolic and metastatic bone diseases.

[Comparative studies of commercially available T4-RIA-kits (author's transl)]. / Vergleichende Untersuchungen mit kommerziellen T4-RIA-Kits (I).

The investigation of 4 commercially available T4-RIA-Kits with 350 patient sera have shown that: The separation of hypo-, eu- and hyperthyroid values is easier with kit a) and d) than with b) and c), though all kits give acceptable values under routine conditions. For the determination of the "normal range" not less than 100 patient sera are necessary. The time needed for 100 determinations is 2 to 3 hr. A general recommendation for one of the tested T4-RIA-Kits cannot be made since the choice depends also on local circumstances.

[Comparative studies of commercially available T4-RIA-Kits (author's transl)]. / Vergleichende Untersuchungen mit kommerziellen T4-RIA-Kits (II).

The investigation of the tested commercially available T4-RIA-Kits have shown that: The separation of hypo-, eu- and hyperthyroid values is better with kits a) and f) than with b),c),d) and e), though all kits give acceptable values under routine operating conditions, kit b) takes less time and work than the other tested kits, depending on the kit used, the time needed for 100 determinations varies between 1,5 and 4 hr. A general recommendation for one of the tested T4-RIA-Kits cannot be made since the choice of a kit depends not only on the criteria discussed but also on local circumstances.