Thyroxine and Thyroxine-Binding Globulin: Discriminant Formulae for the Separation of the Diagnostic Classes of Thyroid Function

Author(s):  
Dennis A Noe

The biochemical classification of thyroid functional status is often accomplished by the use of the thyroxine to thyroxine-binding globulin (T4:TBG) ratio. It has recently been shown, however, that the reference range of the T4:TBG ratio varies with the concentration of TBG. This makes the T4:TBG ratio an unwieldy diagnostic index. A more accurate and economical way to define thyroid function using T4 and TBG measurements is by linear discriminant formulae. This is so because T4 varies linearly with TBG at the T4 reference limits over a wide range of TBG concentrations. Using the T4 reference ranges established by Attwood and Atkin ( Ann Clin Biochem 1982; 19: 101–3), the following formulae are obtained: T4 (nmol/l)—4·05 TBG (mg/l)>94·5 indicates hyperthyroidism; T4 (nmol/l)—2·72 TBG (mg/l)<23·8 identifies hypothyroidism.

Author(s):  
E C Attwood ◽  
G E Atkin

The thyroxine: thyroxine-binding globulin (T4: TBG) ratio is now an established part of the biochemical investigation of thyroid function. Reference ranges have been reported for euthyroid subjects with TBG levels within the range 6–16 mg/l. Routine assay of TBG on all thyroid function tests in this laboratory has suggested that, in patients with low or high TBG levels, the established reference ranges for T4:TBG may not be strictly applicable. A retrospective study has been made of a large number of thyroid function requests, including serum total T4, free T4, TBG, and TSH assays. Evidence is presented to show that in subjects with a TBG level of less than 8 mg/l the reference range for T4: TBG is elevated. Similarly, in subjects with a TBG greater than 16 mg/l, the reference range for T4: TBG is lowered. The data suggest that it is necessary to quote a T4: TBG reference range based on small increments of TBG levels or to relate total T4 reference ranges to those increments.


1981 ◽  
Vol 27 (7) ◽  
pp. 1272-1276 ◽  
Author(s):  
L R Witherspoon ◽  
S E Shuler ◽  
M M Garcia

Abstract How well the free thyroxine index reflects thyroid functional status depends on the degree to which the triiodothyronine uptake test normalizes the effects of thyroxine binding protein concentrations on the total thyroxine concentration. We examined eight triiodothyronine uptake tests in which were used different secondary binders representative of those available in commercial kits. The relation between triiodothyronine uptake and thyroxine-binding globulin concentrations was established by use of sera from euthyroid individuals. We examined the effects of both high (greater than 20 mg/L) and low (less than 10 mg/L) thyroxine-binding globulin concentrations on triiodothyronine uptake. The precision of each assay, expressed as within- and between-run coefficient of variation, was calculated from multiple measurements on high, low, and midrange triiodothyronine uptake serum pools. The effects of variation in temperature and in exposure times were examined. The clinical most useful assays exhibited the ability to reflect a wide range of thyroxine-binding globulin concentrations and demonstrated little or no time or temperature effects.


2020 ◽  
Vol 125 (1) ◽  
pp. 71-78
Author(s):  
Victor Pop ◽  
Johannes Krabbe ◽  
Wolfgang Maret ◽  
Margaret Rayman

AbstractThe present study reports on first-trimester reference ranges of plasma mineral Se/Zn/Cu concentration in relation to free thyroxine (FT4), thyrotropin (TSH) and thyroid peroxidase antibodies (TPO-Ab), assessed at 12 weeks’ gestation in 2041 pregnant women, including 544 women not taking supplements containing Se/Zn/Cu. The reference range (2·5th–97·5th percentiles) in these 544 women was 0·72–1·25 µmol/l for Se, 17·15–35·98 µmol/l for Cu and 9·57–16·41 µmol/l for Zn. These women had significantly lower mean plasma Se concentration (0·94 (sd 0·12) µmol/l) than those (n 1479) taking Se/Zn/Cu supplements (1·03 (sd 0·14) µmol/l; P < 0·001), while the mean Cu (26·25 µmol/l) and Zn (12·55 µmol/l) concentrations were almost identical in these sub-groups. Women with hypothyroxinaemia (FT4 below reference range with normal TSH) had significantly lower plasma Zn concentrations than euthyroid women. After adjusting for covariates including supplement intake, plasma Se (negatively), Zn and Cu (positively) concentrations were significantly related to logFT4; Se and Cu (but not Zn) were positively and significantly related to logTSH. Women taking additional Se/Zn/Cu supplements were 1·46 (95 % CI 1·09, 2·04) times less likely to have elevated titres of TPO-Ab at 12 weeks of gestation. We conclude that first-trimester Se reference ranges are influenced by Se-supplement intake, while Cu and Zn ranges are not. Plasma mineral Se/Zn/Cu concentrations are associated with thyroid FT4 and TSH concentrations. Se/Zn/Cu supplement intake affects TPO-Ab status. Future research should focus on the impact of trace mineral status during gestation on thyroid function.


2004 ◽  
Vol 43 (05) ◽  
pp. 158-160 ◽  
Author(s):  
F. Hartmann ◽  
R. Rödel ◽  
M. Reinhardt ◽  
H.-J. Biersack

Summary:Aim: The diagnosis of abnormalities of thyroid function is generally based on the measurement of thyroid hormones and TSH in blood. The recommended reference ranges for serum T4 and T3 as well as TSH are quite wide as the result of large differences in thyroid function tests in healthy persons. It has been proven that the individual variation within an individual is small, compared with the variation between individuals. We investigated long term variations of these parameters in patients with and without benign thyroid diseases. Methods: We performed long term follow-up serum determinations of T3, T4, and TSH in a total of 150 patients for a time period of 3 to 13 years. The majority of patients had been put on L-thyroxine. Values of total T3, total T4, free T4 were measured with an almost unmodified test (RIA) over the years. Results: The lowest relative coefficient of variation (<10%) was observed in the group of patients who had been treated with L-thyroxine only. Even for TSH, relatively low cofficients of variation were observed in this group. In the group of patients who had not received any medication, T3 and T4 showed also a variation of 10%. FT4 and TSH revealed a wider range of variation. Even after radioiodine therapy, T3 and T4 showed only a quite small variation, while TSH demonstrated a wide range with a variation of >30%. Conclusion: Our data demonstrate that there are only narrow variations of serum T4 and T3 within individuals with and without thyroid disorders.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Salman Razvi ◽  
Sindeep Bhana ◽  
Sanaa Mrabeti

The pituitary hormone, thyrotropin (TSH), is regarded as the primary biomarker for evaluating thyroid function and is useful in guiding treatment with levothyroxine for patients with hypothyroidism. The amplified response of TSH to slight changes in thyroid hormone levels provides a large and easily measured signal in the routine care setting. Laboratories provide reference ranges with upper and lower cutoffs for TSH to define normal thyroid function. The upper limit of the range, used to diagnose subclinical (mild) hypothyroidism, is itself a matter for debate, with authoritative guidelines recommending treatment to within the lower half of the range. Concomitant diseases, medications, supplements, age, gender, ethnicity, iodine status, time of day, time of year, autoantibodies, heterophilic antibodies, smoking, and other factors influence the level of TSH, or the performance of current TSH assays. The long-term prognostic implications of small deviations of TSH from the reference range are unclear. Correction of TSH to within the reference range does not always bring thyroid and other biomarkers into range and will not always resolve the patient’s symptoms. Overt hypothyroidism requires intervention with levothyroxine. It remains important that physicians managing a patient with symptoms suggestive of thyroid disease consider all of the patient’s relevant disease, lifestyle, and other factors before intervening on the basis of a marginally raised TSH level alone. Finally, these limitations of TSH testing mitigate against screening the population for the undoubtedly substantial prevalence of undiagnosed thyroid disease, until appropriately designed randomised trials have quantified the benefits and harms from this approach.


2021 ◽  
Author(s):  
Louise Knøsgaard ◽  
Stig Andersen ◽  
Annebirthe Bo Hansen ◽  
Peter Vestergaard ◽  
Stine Linding Andersen

Objective: The assessment of maternal thyroid function in early pregnancy is debated. It is well-established that pregnancy-specific reference ranges preferably should be used. We speculated if the use of repeated blood samples drawn in early pregnancy would influence the classification of maternal thyroid function. Design: Cohort study Methods: Pregnant women with repeated early pregnancy blood samples were identified in the North Denmark Region Pregnancy Cohort. Each sample was used for the measurement of TSH, free T4 (fT4), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers). Method- and pregnancy week-specific reference ranges were used for classification of maternal thyroid function. Results: Among 1,466 pregnancies included, 89 women had TSH above the upper reference limit in the first sample (median pregnancy week 8), and 44 (49.4%) of these similarly had high TSH in the second sample (median week 10). A total of 47 women had TSH below the lower reference limit in the first sample, and 19 (40.4 %) of these similarly had low TSH in the second sample. Regarding women classified with isolated changes in fT4 in the first sample, less than 20% were similarly classified as such in the second sample. The percentage agreement between the samples was dependent on the level of TSH in the first sample and the presence of TPO- and Tg-Ab. Conclusion: In a large cohort of pregnant women, the classification of maternal thyroid function varied considerably with the use of repeated blood samples. Results emphasize a focus on the severity of thyroid function abnormalities in pregnant women.


Author(s):  
C. F. Cusick

Results are presented on two patients with complete and two with partial thyroxinebinding globulin (TBG) deficiency. All four subjects had lowered serum thyroxine but were clinically euthyroid. While thyroid hormone uptake tests or TBG assay were effective in the recognition of such individuals, indices based on these tests were misleading in assessing their thyroid status. Results within the reference range were obtained with the Immophase Free Thyroxine assay.


1992 ◽  
Vol 38 (7) ◽  
pp. 1365-1370 ◽  
Author(s):  
A R Henderson ◽  
M J McQueen ◽  
R L Patten ◽  
S Krishnan ◽  
D E Wood ◽  
...  

Abstract In 1991, 246 and 136 Ontario laboratories performed total creatine kinase (CK; EC 2.7.3.2) and creatine kinase-2 (CK-2) assays, respectively. A questionnaire mailed to these laboratories requested information about the types of assay used, the origin of their reference ranges, and the source of their instruments and reagents. All laboratories used current test formulations for CK, although seven laboratories did not assay at 37 degrees C. For CK, 69% of all laboratories reported different upper reference limits for men and women (5th-95th percentiles: 160-250 and 115-215 U/L, respectively); 31% reported similar ranges for both sexes. Fifty-six percent derived their own ranges; the remainder used either kit inserts or literature references, and nearly 60% of this latter group claimed to have validated these suggested ranges before use. For 6% of all laboratories, their pediatric ranges were similar to their adult ranges. For CK-2, only 32% used their own reference range; the remainder used kit inserts or literature references, but only 49% of this group validated these ranges before use. Reference limits (5th-95th percentiles) for CK-2 were as follows: activity 6-24 U/L; fraction of CK, 0.022-0.06; and, for mass assays, 5-10 micrograms/L and relative index 0.015-0.04.


Author(s):  
David R. McDowell

Serum thyroxine binding globulin (TBG) values were correlated with other thyroid function test results and with the clinical condition in 680 patients. The estimation of serum TBG was helpful in the evaluation of thyroid status only in those patients who were either acutely ill, were taking the contraceptive pill, or were pregnant. Further, the derived index, thyroxine: TBG ratio, proved to be a better diagnostic index than the thyroxine: tri-iodothyronine uptake ratio and in many cases would have avoided the use of more expensive and time-consuming tests.


2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Stine Linding Andersen ◽  
Peter Astrup Christensen ◽  
Louise Knøsgaard ◽  
Stig Andersen ◽  
Aase Handberg ◽  
...  

Abstract Context Physiological alterations challenge the assessment of maternal thyroid function in pregnancy. It remains uncertain how the reference ranges vary by week of pregnancy, and how the classification of disease varies by analytical method and type of thyroid function test. Design Serum samples from Danish pregnant women (n = 6282) were used for the measurement of thyrotropin (TSH), total and free thyroxine (T4), total and free 3,5,3′-triiodothyronine (T3), and T-uptake using “Method A” (Cobas 8000, Roche Diagnostics). TSH and free T4 were also measured using “Method B” (ADVIA Centaur XP, Siemens Healthineers). Main Outcome Measures Pregnancy week- and method-specific reference ranges were established among thyroid antibody–negative women (n = 4612). The reference ranges were used to classify maternal thyroid function, and results were compared by analytical method and type of thyroid function test. Results The reference ranges for TSH showed a gradual decrease during pregnancy weeks 4 to 14, a gradual increase was observed for total T4, total T3, and T-uptake, whereas free T4 and free T3 showed less variation. When TSH and free T4 were used, Method A classified 935 (14.9%) with abnormal thyroid function, Method B a total of 903 (14.4%), and the methods agreed on 554 individuals. When TSH and total T4 were used, 947 (15.1%) were classified with abnormal thyroid function, and classifications by either total T4 or free T4 agreed on 584 individuals. Conclusions Even when pregnancy week- and method-specific reference ranges were established, the classification of maternal thyroid dysfunction varied considerably by analytical method and type of thyroid function test.


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