Thyroid Stimulating Hormone Measurement Using a Third Generation Immunometric Assay

Author(s):  
Christine R Squire ◽  
William D Fraser

After an initial evaluation of the standard procedure for performance of a third generation TSH (thyroid stimulating hormone) assay (Amerlite TSH-30) modifications were made to standardize the timing of measurement of light emission following signal reagent addition. By adopting this optimized procedure, a significant improvement in assay sensitivity was achieved when compared to a second generation TSH assay (DAKO). Using the optimized assay the sensitivity was 0·003 mU/L (20 replicates of zero) or 0·009 mU/L [22% CV (coefficient of variation) from the precision profile]. Recovery of added TSH and parallelism of the assay were good. A significant negative bias was detected for the Amerlite TSH-30 assay when compared to the DAKO assay (log y = 0·92 log x − 0·33, n = 210). Excellent discrimination was achieved between euthyroid, hypothyroid and thyrotoxic subjects. A high percentage of thyrotoxic patients had undetectable TSH and the spread of values between thyrotoxic and euthyroid was greater with the third generation assay. In patients receiving thyroxine therapy a higher percentage had detectable TSH values. The optimized Amerlite TSH 30 assay offers improved assay performance when compared to a second generation assay.

Author(s):  
S Chatterjee ◽  
BP O'Malley ◽  
DE Price ◽  
AM Fielding ◽  
R Aitken

Background: In laboratories employing 'front-line' sensitive thyroid-stimulating hormone (TSH) measurement, it is generally accepted that a fully suppressed serum TSH concentration (third-generation assay) alongside normal serum concentrations of free thyroid hormones indicates subclinical hyperthyroidism. However, other explanations are often provided for low but detectable serum TSH concentrations, such as drug effects or non-thyroidal illness. Methods: We investigated 25 consecutive ambulant individuals, identified over an 18-month period as having low but not fully suppressed TSH concentrations (third-generation assay; sensitivity 0.003 mIU/L) with additional free thyroxine (T4), free tri-iodothyronine (T3) and thyroid microsomal antibody estimations and thyroid isotope scanning (technetium). Results: Concentrations of serum hormones (median, inter-quartile range) were: TSH, 0.23, 0.17-0.26 mIU/L (reference range 0.34-5.6 mIU/L); free T4, 14.6, 10.6- 17.6 pmol/L (reference range 10-25 pmol/L); free T3, 6.1, 5.7-6.6 pmol/L (reference range 4.5-7.5 pmol/L). Thyroid antibodies were negative in all but one individual. On isotope scanning, nine individuals had hot nodules and ten individuals had multinodular goitres (MNG). Of the six with normal scans, ultrasound scanning showed a definite MNG ( n = 1) and early MNG ( n = 2). Conclusions: A low but detectable serum TSH concentration, obtained using a third-generation assay, found in an ambulant individual, is frequently a pointer to underlying thyroid disease.


1997 ◽  
Vol 90 (10) ◽  
pp. 547-550 ◽  
Author(s):  
M P J Vanderpump ◽  
R H Neary ◽  
K Manning ◽  
R N Clayton

Many authorities now advocate that the first-line assessment of thyroid function should be measurement of thyrotropin (TSH). The latest serum TSH assays (third generation) are more sensitive than the second generation but the reagents are more costly. We have examined whether overall assay reagent costs would be higher or lower with a third-generation assay, in a laboratory that serves a population of almost 500 000. In a prospective study over six weeks, 505 samples with a second-generation serum TSH less than 0.5 mU/L (303 for screening and 202 for monitoring thyroxine therapy) had an additional third-generation TSH analysis. With a second-generation assay for screening, 11% more free thyroxine (FT4) measurements were required to exclude thyrotoxicosis but there was a 42% saving on the reagent budget compared with a third-generation assay. In patients taking thyroxine, 33% more FT4 measurements were required to exclude over-replacement but the calculated saving in reagent costs was 53%. The costs of all other aspects of the two methods were similar. In this community-based sample, the improvement in sensitivity yielded by the third-generation assay at the lower end of the normal range reduced the number of confirmatory FT4 levels required to exclude thyrotoxicosis or over-replacement with thyroxine, but reagent costs were nevertheless higher than for second-generation assays. In financial terms, there is little justification for use of assays with sensitivity greater than the second generation (0.1 mU/L).


1998 ◽  
Vol 7 (2) ◽  
pp. 65-67
Author(s):  
Renee A. Bobrowski ◽  
Patricia Streicher ◽  
Jeffery S. Dzieczkowski ◽  
Mitchell P. Dombrowski ◽  
Bernard Gonik

Author(s):  
Renee A. Bobrowski ◽  
Patricia Streicher ◽  
Jeffery S. Dzieczkowski ◽  
Mitchell P. Dombrowski ◽  
Bernard Gonik

Author(s):  
Alexandra Stephenson ◽  
Zoya Punjwani ◽  
Markus Eszlinger ◽  
Beata Sawicka ◽  
Artur Bossowski ◽  
...  

Summary Familial nonautoimmune hyperthyroidism (FNAH) is rare and occurs due to a constitutively activating thyroid-stimulating hormone receptor (TSHR) germline mutation. Forty-one families with FNAH have been reported so far. In the study, 17 of 41 families were not diagnosed with FNAH until three generations or more were described with hyperthyroidism. We report a case of FNAH diagnosed in the third generation. The index patient was diagnosed with hyperthyroidism at age 3. Large fluctuations in thyroid hormone levels occurred during anti-thyroid drug treatment, and he developed a goiter. The patient’s mother had similar history, requiring two surgical interventions and radioiodine treatment. The younger brother of the index patient did not experience large thyroid hormone level fluctuations, nor increased thyroid growth. A heterozygous TSHR c.1357A>G mutation, resulting in a M453V amino acid exchange, was detected in all three patients leading to FNAH diagnosis, with complete genotype–phenotype segregation. Based on Sorting intolerant from tolerant (SIFT) and PolyPhen2 scores of 0.01 and 0.99, respectively, an effect on protein function can be assumed. As illustrated by this family with FNAH, total thyr oidectomy is necessary for patients with nonautoimmune hyperthyroidism. Development of goiter is common, anti-thyroid drug treatment is often difficult, and remission of hyperthyroidism does not occur after discontinuation of anti-thyroid drug treatment. Thus, early diagnosis and appropriate treatment of FNAH is necessary to avoid predictable, unnecessary complications and further surgical interventions. Learning points In the study, 19/42 cases of familial nonautoimmune hyperthyroidism (FNAH), including the reported case, were not diagnosed as FNAH until the third generation; this lead to suboptimal treatment and frequent relapses of nonautoimmune hyperthyroidism (NAH). Detection of thyroid-stimulating hormone receptor (TSHR) mutations in patients with suspected FNAH to confirm diagnosis is essential to ensure proper treatment for the patient and further affected family members. NAH will persist without proper treatment by total thyroidectomy. Symptoms and age of onset may vary between family members All family members with a TSHR germline mutation should be monitored with thyroid-stimulating hormone and for symptoms throughout their lives.


1965 ◽  
Vol 97 (12) ◽  
pp. 1303-1318 ◽  
Author(s):  
H. J. Herbert

AbstractIn Nova Scotia one leaf cluster with an adjoining 1 inch of twig taken from the inside of each of 10 apple trees replicated four times is an adequate sample unit to measure the density of the brown mite.The brown mite has one generation with a partial second in some orchards and one with a partial second and partial third in others. The first generation adults in the bivoltine and trivoltine populations lay summer eggs on the leaves and twigs, and diapause eggs on tin twigs. The second generation adults in the bivoltine populations lay only diapause eggs; in the trivoltine populations they lay both summer and diapause eggs. The adults of the third generation lay only diapause eggs.The brown mite is found on both the leaves and woody parts of the tree. In orchards with bivoltine populations the proportion of mites on leaves reached a peak of 80% by mid-July, but thereafter gradually decreased to 10% by the end of August. However, in orchards with trivoltine populations the proportion of mites on leaves reached a peak of 80 to 90% by mid-July, remained constant until mid-August, and thereafter decreased to approximately 40% by the end of August.The number of diapause eggs laid by adults of each generation in both the bivoltine and trivoltine populations varies widely. The eggs are deposited on the trunk as well as on the branches, with the heaviest deposition in the central area of the tree. The diapause eggs laid by adults of the first generation are the last to hatch and those laid by the third generation are the first to hatch the following spring.The factors responsible for the differences in the number of generations and in the number of diapause eggs laid are unknown.


1988 ◽  
Vol 33 (1) ◽  
pp. 51-56 ◽  
Author(s):  
John J. Sigal ◽  
Jana Meislova ◽  
Joseph Beltempo ◽  
Daniel Silver

Parents who had been placed in an orphanage as children rated the behaviour of all their children who were between the ages of 6–18 years on a children's behaviour survey instrument. All families were intact and the parents had not requested professional help for marital problems. A significant number of relationships were found between parental background variables and higher reported levels of conflict with siblings and with parents, dependent-unassertive behaviour, and undemandingness in the children. Although sampling difficulties preclude generalization, the results suggest that repercussion of events in the lives of the first and second generation that are usually pathogenic may be seen in the third generation, even when the second generation may not be grossly adversely affected. These events most frequently related to individual differences in the third generation in the area of undercontrol of aggression directed toward parents and siblings.


1968 ◽  
Vol 46 (3) ◽  
pp. 449-452 ◽  
Author(s):  
A. E. Zimmerman ◽  
C. C. Yip

The effects of increasing or decreasing the endogenous secretion of thyroid-stimulating hormone on the iodinating activity of the rat thyroid gland were investigated. The thyroid iodinating activity of rats on 0.01% propylthiouracil in the drinking water increased linearly for 3 days and reached a maximum of 230 to 240% of the control on or about the fourth day of treatment. The daily injection of thyroxine (10 μg/100 g intraperitoneally) or hypophysectomy resulted in a rapid decrease in the iodinating activity between the first and second day, approaching a basal level by the third day. When the iodinating activity was suppressed for 4 days by daily injections of thyroxine, the activity began to rise on the fifth day after termination of thyroxine treatment.


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