Clinical EndocrinologyVolume 58, Issue 1 p. 20-21 First-line thyroid function tests − TSH alone is not enough G. J. Beckett, G. J. Beckett University Department of Clinical Biochemistry and, Endocrine Clinic, Royal Infirmary, Edinburgh, ScotlandSearch for more papers by this authorA. D. Toft, Corresponding Author A. D. Toft University Department of Clinical Biochemistry and, Endocrine Clinic, Royal Infirmary, Edinburgh, Scotland Dr A. D. Toft, Endocrine Clinic, Royal Infirmary Edinburgh EH3 9YW, Scotland. Tel.: 0131 5362092/3; Fax: 0131 5362091; E-mail: [email protected]Search for more papers by this author G. J. Beckett, G. J. Beckett University Department of Clinical Biochemistry and, Endocrine Clinic, Royal Infirmary, Edinburgh, ScotlandSearch for more papers by this authorA. D. Toft, Corresponding Author A. D. Toft University Department of Clinical Biochemistry and, Endocrine Clinic, Royal Infirmary, Edinburgh, Scotland Dr A. D. Toft, Endocrine Clinic, Royal Infirmary Edinburgh EH3 9YW, Scotland. Tel.: 0131 5362092/3; Fax: 0131 5362091; E-mail: [email protected]Search for more papers by this author First published: 07 January 2003 https://doi.org/10.1046/j.1365-2265.2003.01690.xCitations: 25Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume58, Issue1January 2003Pages 20-21 RelatedInformation

Clinical EndocrinologyVolume 35, Issue 3 p. 207-212 Iodine-131 treatment of hyperthyroidism: current issues J. J. Farrar, J. J. Farrar Royal Infirmary, Edinburgh EH3 9YWSearch for more papers by this authorA. D. Toft, A. D. Toft Royal Infirmary, Edinburgh EH3 9YWSearch for more papers by this author J. J. Farrar, J. J. Farrar Royal Infirmary, Edinburgh EH3 9YWSearch for more papers by this authorA. D. Toft, A. D. Toft Royal Infirmary, Edinburgh EH3 9YWSearch for more papers by this author First published: September 1991 https://doi.org/10.1111/j.1365-2265.1991.tb03523.xCitations: 49 Dr A. D. Toft, University Department of Medicine, Royal Infirmary, Edinburgh EH3 9YW, UK. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume35, Issue3September 1991Pages 207-212 RelatedInformation

The analytical and diagnostic performance of a new non-isotopic, two-step immunoassay (DELFIA) for the measurement of free thyroxine (free T4) in plasma or serum has been compared with an established second generation analogue radioimmunoassay (SimulTRAC). Both methods had a good diagnostic specificity in pregnancy, thyroid clinic patients, and patients taking anticonvulsant drugs. In patients presenting to a general medical ward the diagnostic specificity of both methods was poor. Two samples appeared to contain substances which produced assay interference by DELFIA but not by SimulTRAC assays. When free T4 was measured by equilibrium dialysis a clear association between sample dilution and free T4 concentration was demonstrated in sick euthyroid patients. In contrast, using samples obtained from patients with known thyroid disease, free T4 was little influenced by sample dilution. The effects of sample dilution on free T4 measured by DELFIA were similar to those found using equilibrium dialysis. It would appear that free T4 measurements have a relatively poor diagnostic specificity in non-thyroidal illness irrespective of the method used.

SUMMARYThe serum levels of a range of analytes known to change with thyroid status were measured in two groups of patients with primary hypothyroidism commencing T4 replacement therapy. One group (group 1; n= 9) had spontaneous hypothyroidism whilst in the second (group 2; n= 10), hypothyroidism had resulted from radioiodine therapy. The replacement dose was increased in 50 μg increments each month to 200 μg/day; this produced similar serum concentrations of thyroid hormones and TSH in the two groups at each dose. Dose‐dependent increases in glutathione S‐transferase (GST) were seen in both groups but changes in alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) activities occurred only in group 1 patients. Group 1 patients had significantly higher levels of GST than group 2 at the 150 μg (P > 0.01) and the 200 μg (P > 0.005) doses of T4, and they had higher activities of ALT (P > 0.01) and GGT (P > 0.02) at the 200 μg dose. Seven patients in group 1 had abnormalities in GST and four had high levels of ALT, whereas three patients from group 2 had high GST concentrations and all had ALT activities within reference limits. The concentrations of the other analytes measured in serum showed the same response to T4 in the two groups, particularly the concentrations of certain transport proteins whose serum concentrations depend on hepatic protein synthesis. These data suggest that patients with spontaneous primary hypothyroidism are more susceptible to hepatocellular damage than patients who have radioiodine‐induced primary hypothyroidism when given oral doses of thyroxine < 150 μg/day.

We describe three patients with a rare, and only recently reported, variant of papillary carcinoma of the thyroid. In each case the clinical presentation and biochemical or serological findings were indicative of benign disease.

Although measurement of thyrotropin (thyroid-stimulating hormone; TSH) by radioimmunoassay was a major advance in the laboratory diagnosis of thyroid failure--replacing the time-consuming TSH stimulation test--it was not sufficiently sensitive to discriminate reliably between euthyroid and hyperthyroid patients. Measurement of the TSH response to thyrotropin releasing hormone (TRH) served this purpose, however. The recent development of TSH assays that are severalfold more sensitive and more specific than conventional radioimmunoassays has allowed distinction of euthyroid from hyperthyroid patients and eliminated the need for the TRH test. Although undetectable levels of TSH, compatible with hyperthyroidism, are occasionally noted in euthyroid patients with severe nonthyroidal illness and during the first trimester of pregnancy, false-positive results are less often recorded for TSH than for free or total thyroid hormone measurements. Measurement of TSH by sensitive immunoradiometric assay is currently the most useful first-line test of thyroid function in patients with suspected thyroid disease and, in addition, has a valuable role in monitoring the dose of thyroxine replacement therapy.

There is increasing evidence from studies of heart rate, liver enzyme activity, bone density and urinary sodium excretion that standard replacement therapy doses of thyroxine which suppress TSH secretion are associated with changes in target organ function similar to, but less marked than, those recorded in overt hyperthyroidism. There is also evidence that in subclinical hypothyroidism it is not only the pituitary thyrotroph which recognizes a minor reduction in serum thyroid hormone levels within the normal range. Although there is no proof that slight ‘overtreatment’ with thyroxine or non-treatment of subclinical hypothyroidism is detrimental to the patient in the long term, the appropriate studies have not been performed. It would seem good clinical practice, however, to treat all grades of thyroid failure and to ensure, if possible, that the dose of thyroxine is adjusted to maintain a normal and detectable TSH level when measured by a sensitive assay system. It must be conceded, however, that with the vagaries of human nature there is always likely to be greater morbidity from patients with hypothyroidism failing to take their medication regularly, than from failure by the medical attendant to make minor adjustments to the dose of thyroxine.

Using a highly sensitive and specific immunoradiometric assay for thyrotropin, we studied thyrotroph function in 232 new patients referred to a thyroid clinic and in 13 patients after treatment for hyperthyroidism. Significant thyrotroph responsiveness to thyroliberin (thyrotropin-releasing hormone, TRH) was found in all patients with values for basal thyrotropin greater than 0.1 milli-int unit/L. In no overtly hyperthyroid patient was any increment in thyrotropin recorded at 20 min after thyroliberin administration. In seven patients, four subclinically hyperthyroid and three who had received treatment, increments in thyrotropin from undetectable basal values were recorded, consistent with incomplete thyrotroph suppression. By use of assays with even higher sensitivity, one may be able to distinguish these patients from overtly hyperthyroid patients.

This study was undertaken to compare the sensitivity of the thyrotrophs to that of other tissues to T4 treatment in hypothyroid patients. To do so, we measured serum total and free thyroid hormones and TSH, in addition to several serum markers of peripheral tissue response to thyroid status, in 21 hypothyroid patients treated with 50-micrograms increments of T4 to a maximum of 200 micrograms daily (group I) and in 104 clinically euthyroid patients receiving a long term constant replacement dose (group II). In group I patients, dose-dependent increases (P less than 0.05) in serum glutathione S-transferase, sex hormone-binding globulin, and angiotensin-converting enzyme occurred, whereas serum T4-binding globulin, creatine kinase, and creatinine levels decreased (P less than 0.05). In both patient groups, abnormally high levels of glutathione S-transferase, sex hormone-binding globulin, angiotensin-converting enzyme, alanine aminotransferase, and gamma-glutamyl transferase were found in some patients during treatment. One or more of these biochemical abnormalities suggestive of hyperthyroidism occurred in 15 (71%) group I patients and 27 (26%) group II patients. These were associated with an undetectable serum TSH (less than 0.1 microU/ml) and raised free T4 concentrations in 13, and raised free T3, T4, and T3 concentrations in only 8, 6, and 1 group I patients, respectively. In group II patients, they were more closely associated with an undetectable TSH (67%) or raised free T4 (85%) level than with raised concentrations of free T3 (33%), T4 (26%), or T3 (0%). The use of high sensitivity TSH assays will permit more accurate adjustment of T4 replacement and minimize abnormalities in peripheral tissue biochemistry indicative of overtreatment.

Conference Abstract| January 01 1986 Exercise-Induced Changes in Left Ventricular Performance in Subclinical Hypothyroidism JC Forfar; JC Forfar 1University Department of Medicine, the Royal Infirmary, Edinburgh EH3 9YW Search for other works by this author on: This Site PubMed Google Scholar CF Wathen; CF Wathen 1University Department of Medicine, the Royal Infirmary, Edinburgh EH3 9YW Search for other works by this author on: This Site PubMed Google Scholar GM Bell; GM Bell 1University Department of Medicine, the Royal Infirmary, Edinburgh EH3 9YW Search for other works by this author on: This Site PubMed Google Scholar WJ Hannan; WJ Hannan 1University Department of Medicine, the Royal Infirmary, Edinburgh EH3 9YW Search for other works by this author on: This Site PubMed Google Scholar WTA Todd; WTA Todd 1University Department of Medicine, the Royal Infirmary, Edinburgh EH3 9YW Search for other works by this author on: This Site PubMed Google Scholar AL Muir; AL Muir 1University Department of Medicine, the Royal Infirmary, Edinburgh EH3 9YW Search for other works by this author on: This Site PubMed Google Scholar AD Toft AD Toft 1University Department of Medicine, the Royal Infirmary, Edinburgh EH3 9YW Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1986) 70 (s13): 17P. https://doi.org/10.1042/cs070017P Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation JC Forfar, CF Wathen, GM Bell, WJ Hannan, WTA Todd, AL Muir, AD Toft; Exercise-Induced Changes in Left Ventricular Performance in Subclinical Hypothyroidism. Clin Sci (Lond) 1 January 1986; 70 (s13): 17P. doi: https://doi.org/10.1042/cs070017P Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1986 The Biochemical Society and the Medical Research Society1986 Article PDF first page preview Close Modal You do not currently have access to this content.

We assessed the analytical and diagnostic performance of a dual-isotope RIA for thyrotropin (TSH) and free thyroxin (FT4) in serum. The mean interassay CVs for these analytes were 7.9% and 5.0%, respectively. The mean minimum detection limit for TSH was 0.25 milli-int. unit/L, the mean analytical recovery 110%. There was good agreement with values for TSH and FT4 measured by alternative RIA procedures. Euthyroid patients were well distinguished from those with overt thyroid disease, although there was a small overlap in the case of TSH. Combining the two results better discriminated these categories and identified those patients with subclinical thyroid disease who had abnormal TSH concentrations but FT4 concentrations within reference limits. Euthyroid women taking estrogen-containing oral contraceptives had normal results for TSH and FT4, as did most pregnant women studied. During the third trimester of pregnancy, TSH concentrations of women with low FT4 concentrations were within reference limits. Similarly, euthyroidism was confirmed in patients with low FT4 due to nonthyroidal illness by the simultaneous finding of a normal TSH concentration.

From clinical observation it would appear that hyperthyroid patients are particularly sensitive to the anticoagulant effects of warfarin. A study was made of clotting factors prothrombin (II), VII, procoagulant VIII (VIIIC), IX and X and of prothrombin ratio (PTR) and partial thromboplastin time with kaolin (PTT-K). These parameters and warfarin levels were measured before and following a single dose of warfarin given to five patients when hyperthyroid and again when euthyroid. Hyperthyroidism was associated with lower activity of factor II and a shorter PTT-K. Warfarin produced a greater fall in factors II and VII and a greater increase in PTR and PTT-K in the hyperthyroid state than in the euthyroid state. The enhanced response to warfarin in hyperthyroidism was, however, relatively greater for the PTR than for the PTT-K. In order to produce adequate protection against intravascular thrombosis by a suitable prolongation of the PTT-K, it may be necessary in hyperthyroid patients to extend the PTR beyond the normal therapeutic range.

We have compared the results of serum thyrotrophin (TSH) measurements using a sensitive immunoradiometric assay (IRMA) with those of conventional thyroid function tests in 299 hospital inpatients with a range of non-thyroidal illnesses. Levels of total thyroxine (T4), free T4, total tri-iodothyronine (T3) and free T3 in the hypothyroid range were recorded in 8%, 15%, 19% and 49% of patients, respectively, whereas TSH (IRMA) was abnormally low in 1%. Furthermore, basal TSH (IRMA) accurately predicted the result of the thyrotrophin-releasing hormone test in 72 of the 74 patients in whom this test was performed and, unlike thyroid hormone measurement, identified patients with subclinical thyroid disease. It would appear that a single basal TSH (IRMA) measurement is the most appropriate screening test for thyroid dysfunction in patients with concomitant acute or chronic illness.