For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
Inviting an author to review:
The difference that ‘capitalism’ makes: on the merits and limits of critical political economy in African Studies
Find an author and click ‘Invite to review selected article’ near their name.
Search for authorsSearch for similar articles
39
views
Article has an altmetric score of 8
17
references
 Top references
cited by
4
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      273
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      General Error Analysis in the Relationship between Free Thyroxine and Thyrotropin and Its Clinical Relevance

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background. This treatise investigates error sources in measurements applicable to the hypothalamus-pituitary-thyroid (HPT) system of analysis for homeostatic set point computation. The hypothalamus-pituitary transfer characteristic (HP curve) describes the relationship between plasma free thyroxine [FT4] and thyrotropin [TSH]. Objective. We define the origin, types, causes, and effects of errors that are commonly encountered in TFT measurements and examine how we can interpret these to construct a reliable HP function for set point establishment. Design and Methods. The error sources in the clinical measurement procedures are identified and analyzed in relation to the constructed HP model. Results. The main sources of measurement and interpretation uncertainties are (1) diurnal variations in [TSH], (2) TFT measurement variations influenced by timing of thyroid medications, (3) error sensitivity in ranges of [TSH] and [FT4] (laboratory assay dependent), (4) rounding/truncation of decimals in [FT4] which in turn amplify curve fitting errors in the [TSH] domain in the lower [FT4] range, (5) memory effects (rate-independent hysteresis effect). Conclusions. When the main uncertainties in thyroid function tests (TFT) are identified and analyzed, we can find the most acceptable model space with which we can construct the best HP function and the related set point area.

          Related collections

          Most cited references17

          • Record: found
          • Abstract: found
          • Article: not found

          Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease.

          Stig Andersen, Klaus Michael Pedersen, Niels Henrik Bruun … (2002)
          High individuality causes laboratory reference ranges to be insensitive to changes in test results that are significant for the individual. We undertook a longitudinal study of variation in thyroid function tests in 16 healthy men with monthly sampling for 12 months using standard procedures. We measured serum T(4), T(3), free T(4) index, and TSH. All individuals had different variations of thyroid function tests (P < 0.001 for all variables) around individual mean values (set points) (P < 0.001 for all variables). The width of the individual 95% confidence intervals were approximately half that of the group for all variables. Accordingly, the index of individuality was low: T(4) = 0.58; T(3) = 0.54; free T(4) index = 0.59; TSH = 0.49. One test result described the individual set point with a precision of +/- 25% for T(4), T(3), free T(4) index, and +/- 50% for TSH. The differences required to be 95% confident of significant changes in repeated testing were (average, range): T(4) = 28, 11-62 nmol/liter; T(3) = 0.55, 0.3--0.9 nmol/liter; free T4 index = 33, 15-61 nmol/liter; TSH = 0.75, 0.2-1.6 mU/liter. Our data indicate that each individual had a unique thyroid function. The individual reference ranges for test results were narrow, compared with group reference ranges used to develop laboratory reference ranges. Accordingly, a test result within laboratory reference limits is not necessarily normal for an individual. Because serum TSH responds with logarithmically amplified variation to minor changes in serum T(4) and T(3), abnormal serum TSH may indicate that serum T(4) and T(3) are not normal for an individual. A condition with abnormal serum TSH but with serum T(4) and T(3) within laboratory reference ranges is labeled subclinical thyroid disease. Our data indicate that the distinction between subclinical and overt thyroid disease (abnormal serum TSH and abnormal T(4) and/or T(3)) is somewhat arbitrary. For the same degree of thyroid function abnormality, the diagnosis depends to a considerable extent on the position of the patient's normal set point for T(4) and T(3) within the laboratory reference range.
          Article 0 comments Cited 133 times – based on 0 reviews     Review now
          Article has an altmetric score of 55
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index.

            Andreas Jostel, W David J Ryder, Stephen M Shalet (2009)
            TSH secretion in hypopituitary patients may be decreased due to TSH deficiency but it also remains under feedback inhibition by free thyroxine (fT4). We propose a TSH index (TSHI), as 'fT4-adjusted TSH', that corrects for any physiological TSH suppression, to provide a true estimate of pituitary thyrotroph function and any pathological pituitary suppression. A total of 9519 thyroid function tests (TFTs) (Bayer Immuno-1) in 4064 patients of our institution were examined, including 444 patients investigated for hypopituitarism. Based on the physiological log-linear relationship between fT4 and TSH, we estimated the amount of feedback-induced change in log TSH per change in fT4, which allowed the extrapolation of log TSH to a fixed fT4 of 0, defining the TSHI. TSHIs were compared with other measures of pituitary function. Feedback inhibition was estimated to cause a 0.1345 decrease in log TSH (mU/l) for 1 pmol/l increase in fT4 concentration, therefore TSHI = log TSH + 0.1345 x fT4. Patients with lower peak-stimulated GH and cortisol concentrations had a significantly lower TSHI (P < 0.0001). TSHIs measured before pituitary stimulation tests predicted highly significantly the risk of test failure (P = 0.0002). Of all potential fT4-TSH combinations within the current reference ranges, 21.9% were identified as abnormal on the basis of the TSHI. The TSHI provides an accurate estimate of the severity of pituitary dysfunction in hypopituitary patients based on simple TFTs. It predicts the probability of pituitary stimulation test failure and extends the diagnosis of TSH deficiency into areas of the normal TFT reference ranges.
            Article 0 comments Cited 82 times – based on 0 reviews     Review now
            Article has an altmetric score of 7
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Report of the IFCC Working Group for Standardization of Thyroid Function Tests; part 2: free thyroxine and free triiodothyronine.

              Linda Thienpont, Katleen Van Uytfanghe, Graham Beastall … (2010)
              Free thyroxine (FT4) and free triiodothyronine (FT3) measurements are useful in the diagnosis and treatment of a variety of thyroid disorders. The IFCC Scientific Division established a Working Group to resolve issues of method performance to meet clinical requirements. We compared results for measurement of a panel of single donor sera using clinical laboratory procedures based on equilibrium dialysis-isotope dilution-mass spectrometry (ED-ID-MS) (2 for FT4, 1 for FT3) and immunoassays from 9 manufacturers (15 for FT4, 13 for FT3) to a candidate international conventional reference measurement procedure (cRMP) also based on ED-ID-MS. For FT4 (FT3), the mean bias of 2 (4) assays was within 10% of the cRMP, whereas for 15 (9) assays, negative biases up to -42% (-30%) were seen; 1 FT3 assay was positively biased by +22%. Recalibration to the cRMP eliminated assay-specific biases; however, sample-related effects remained, as judged from difference plots with biologic total error limits. Correlation coefficients to the cRMPs ranged for FT4 (FT3) from 0.92 to 0.78 (0.88 to 0.30). Within-run and total imprecision ranged for FT4 (FT3) from 1.0% to 11.1% (1.8% to 9.4%) and 1.5% to 14.1% (2.4% to 10.0%), respectively. Approximately half of the manufacturers matched the internal QC targets within approximately 5%; however, within-run instability was observed. The study showed that most assays had bias largely correctable by establishing calibration traceability to a cRMP and that the majority performed well. Some assays, however, would benefit from improved precision, within-run stability, and between-run consistency.
              Article 0 comments Cited 32 times – based on 0 reviews     Review now
              Article has an altmetric score of 6
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Comput Math Methods Med
                Journal ID (iso-abbrev): Comput Math Methods Med
                Journal ID (publisher-id): CMMM
                Title: Computational and Mathematical Methods in Medicine
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1748-670X
                ISSN (Electronic): 1748-6718
                Publication date (Print): 2013
                Publication date (Electronic): 8 September 2013
                Volume: 2013
                Electronic Location Identifier: 831275
                Affiliations
                1Electronic Engineering, Oterlekerweg 4, 1841 GP Stompetoren, The Netherlands
                2Department of Endocrinology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433
                3Singapore Institute for Clinical Sciences, Brenner Centre for Molecular Medicine, 30 Medical Drive, Singapore 117609
                4Yong Loo Lin School of Medicine, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, No. 07-02, Singapore 117599
                5Office of Clinical Sciences, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857
                Author notes

                Academic Editor: Facundo Ballester

                Article
                DOI: 10.1155/2013/831275
                PMC ID: 3780511
                PubMed ID: 24082916
                SO-VID: 131948fe-d98f-47fb-83a3-c5dc691b8dfd
                Copyright © Copyright © 2013 S. L. Goede and M. K.-S. Leow.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 22 May 2013
                Date revision received : 29 July 2013
                Date accepted : 4 August 2013
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Applied mathematics
                Data availability:
                ScienceOpen disciplines: Applied mathematics

                Comments

                Comment on this article

                scite_
                0
                0
                0
                0
                Smart Citations
                0
                0
                0
                0
                Citing PublicationsSupportingMentioningContrasting
                View Citations

                See how this article has been cited at scite.ai

                scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

                Similar content273

                See all similar

                Cited by3

                See all cited by

                Most referenced authors86

                See all reference authors