{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T04:57:56Z","timestamp":1770958676291,"version":"3.50.1"},"reference-count":15,"publisher":"BMJ","issue":"6459","license":[{"start":{"date-parts":[[1984,12,15]],"date-time":"1984-12-15T00:00:00Z","timestamp":471916800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.bmj.com\/company\/legal-information\/terms-conditions\/legal-information\/tdm-licencepolicy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br Med J (Clin Res Ed)"],"published-print":{"date-parts":[[1984,12,15]]},"abstract":"<jats:p>Fifteen patients receiving standard thyroxine replacement therapy (100-200 micrograms daily) for primary hypothyroidism and who had persistently raised free thyroxine concentrations in their serum were investigated to see whether the dose being given was too high. In addition to the usual thyroid hormone assays systolic time intervals (which indicate left ventricular contractility) were calculated as accurate reflectors of tissue thyroid activity. All patients showed the expected increased free and total thyroxine concentrations; but mean total and free concentrations of triiodothyronine were normal, while reverse triiodothyronine values were raised. Mean systolic time intervals were significantly reduced as compared with normal and fell within the thyrotoxic range. Seven patients subsequently had their doses of thyroxine reduced by 50 micrograms daily and were reinvestigated one month later. All showed significant falls in circulating thyroxine and triiodothyronine concentrations and an increase in mean systolic time intervals to the normal range. In patients receiving thyroxine replacement therapy for primary hypothyroidism a raised serum thyroxine concentration may indicate tissue thyrotoxicosis and should prompt a reduction of the thyroxine dose.<\/jats:p>","DOI":"10.1136\/bmj.289.6459.1645","type":"journal-article","created":{"date-parts":[[2009,4,2]],"date-time":"2009-04-02T11:00:59Z","timestamp":1238670059000},"page":"1645-1647","source":"Crossref","is-referenced-by-count":70,"title":["Relevance of increased serum thyroxine concentrations associated with normal serum triiodothyronine values in hypothyroid patients receiving thyroxine: a case for \"tissue thyrotoxicosis\"."],"prefix":"10.1136","volume":"289","author":[{"given":"P E","family":"Jennings","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B P","family":"O'Malley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K E","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Northover","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F D","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1984,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF03350495","article-title":"Elevated serum thyroxine concentration in patients receiving \"replacement\" doses of levothyroxine","volume":"5","author":"Ingbar, J.C.; Borges, M.; Iflah, S.","year":"1982","unstructured":"Ingbar JC, Borges M, Iflah S, et al. Elevated serum thyroxine concentration in patients receiving \"replacement\" doses of levothyroxine. J Endocrinol Invest 1982;5:77-85.","journal-title":"J Endocrinol Invest"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1001\/archinte.1982.00340160091020","volume":"142","author":"Salmon, D.; Rendell, M.; Williams, J.","year":"1982","unstructured":"Salmon D, Rendell M, Williams J, et al. Chemical hyperthyroidism. Arch Intern Med 1982;142:511-3.","journal-title":"Chemical hyperthyroidism. Arch Intern Med"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1530\/acta.0.0880691","article-title":"The relationship between levels of thyroid stimulating hormone and of thyroxine and triiodothyronine in blood of hypothyroid patients","volume":"88","author":"Johansen, K.; Hansen, J.M.; Skovster, L.","year":"1978","unstructured":"Johansen K, Hansen JM, Skovster L. The relationship between levels of thyroid stimulating hormone and of thyroxine and triiodothyronine in blood of hypothyroid patients. Acta Endocrinol (Copenh) 1978;88:691-9.","journal-title":"Acta Endocrinol (Copenh)"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1136\/bmj.288.6418.693","article-title":"Total and free thyroid hormone concentrations in patients receiving maintenance replacement treatment with thyroxine","volume":"288","author":"Pearce, C.J.; Himsworth, R.L.","year":"1984","unstructured":"Pearce CJ, Himsworth RL. Total and free thyroid hormone concentrations in patients receiving maintenance replacement treatment with thyroxine. Br Med J 1984;288:693-5.","journal-title":"Br Med J"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/000456328201900106","article-title":"Assessment of optimal L-thyroxine replacement dose by the TRH test","volume":"19","author":"Squire, C.R.; Gimlette, T.M.D.","year":"1982","unstructured":"Squire CR, Gimlette TMD. Assessment of optimal L-thyroxine replacement dose by the TRH test. Ann Clin Biochem 1982;19:26-8.","journal-title":"Ann Clin Biochem"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1056\/NEJM197404182901606","article-title":"Clinical application of thyrotrophin releasing hormone","volume":"290","author":"Hersham, J.M.","year":"1974","unstructured":"Hersham JM. Clinical application of thyrotrophin releasing hormone. N Etlgl Med 1974;290:886-90.","journal-title":"N Etlgl Med"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1210\/jcem-43-1-10","article-title":"Changes in serum triiodothyronine, thyroxine and thyrotropin during treatment with thyroxine in severe primary hypothyroidism","volume":"43","author":"Maeda, M.; Kuzuya, N.; Masuyama, Y.","year":"1976","unstructured":"Maeda M, Kuzuya N, Masuyama Y, et al. Changes in serum triiodothyronine, thyroxine and thyrotropin during treatment with thyroxine in severe primary hypothyroidism. J Clin Endocrinol Metab 1976;43:10-7.","journal-title":"J Clin Endocrinol Metab"},{"key":"ref_8","first-page":"263","article-title":"Carliner 4H, Fisher HL. Systolic time intervals in hypothyroidism; end organ function as a reflection of clinical status","volume":"277","author":"Plotnick, G.D.; Vassar, D.L.; Parisi, A.F.; Hamilton, B.P.","year":"1978","unstructured":"Plotnick GD, Vassar DL, Parisi AF, Hamilton BP, Carliner 4H, Fisher HL. Systolic time intervals in hypothyroidism; end organ function as a reflection of clinical status. Am.7 Med Sci 1978;277:263-8.","journal-title":"Am.7 Med Sci"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0306-4530(84)90017-9","article-title":"The role of 5-HT in the control of TSH and prolactin release in euthyroid subjects as assessed by the respective administration of ketanserin (5-AT, antagonist) and zimelidine (5-HT re-uptake inhibitor)","volume":"9","author":"O'Malley, B.P.; Jennings, P.E.; Cook, N.; Barnett, D.B.; tFD, Rosenthal","year":"1984","unstructured":"O'Malley BP, Jennings PE, Cook N, Barnett DB, Rosenthal tFD. The role of 5-HT in the control of TSH and prolactin release in euthyroid subjects as assessed by the respective administration of ketanserin (5-AT, antagonist) and zimelidine (5-HT re-uptake inhibitor). Psychoneuroendocrinology 1984; 9:13-9.","journal-title":"Psychoneuroendocrinology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1210\/jcem-56-1-185","article-title":"Alterations in systolic time intervals in primary hypothyroidism as a consequence of warming","volume":"56","author":"Northover, B.; O'Malley, B.P.; Rosenthal, F.D.","year":"1983","unstructured":"Northover B, O'Malley BP, Rosenthal FD. Alterations in systolic time intervals in primary hypothyroidism as a consequence of warming. 7 ClGn Endocrinol Metab 1983;56:185-8.","journal-title":"7 ClGn Endocrinol Metab"},{"issue":"1","key":"ref_11","first-page":"187","volume":"50","author":"Invest, Clin","year":"1971","unstructured":"Clin Invest 1971;50:1 187-96."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3109\/00365518409083819","article-title":"Acute effect of exogenous thyroxine dose on serum thyroxine and thyrotrophin levels in treated hypothyroid patients","volume":"44","author":"Soppi, E.; Irjala, K.; Kaihola, H.-L.; Viikari, J.","year":"1984","unstructured":"Soppi E, Irjala K, Kaihola H-L, Viikari J. Acute effect of exogenous thyroxine dose on serum thyroxine and thyrotrophin levels in treated hypothyroid patients. Scand _J Clin Lab Invest 1984;44:353-6.","journal-title":"Scand _J Clin Lab Invest"},{"key":"ref_13","article-title":"Accepted 2","year":"1984","unstructured":"(Accepted 2 October 1984)"},{"key":"ref_14","article-title":"A 24 year old black Senegalese man was first admitted in September 1983 with multiple hypoaesthetic bilateral, symmetrical hypopigmented macules on the neck, face, back, arms, and thighs and nodules on the earlobes. He was found to have symmetrical lesions of the upper branches of the facial, external popliteal, and ulnar nerves and enlargement of the left great auricular nerve. A scraping of the nasal mucosa showed numerous acid fast bacilli. Histopathological examination of an arm lesion showed, below a subepidermal Hopital du Bocage, Centre Hospitalier et LUniversitaire","unstructured":"A 24 year old black Senegalese man was first admitted in September 1983 with multiple hypoaesthetic bilateral, symmetrical hypopigmented macules on the neck, face, back, arms, and thighs and nodules on the earlobes. He was found to have symmetrical lesions of the upper branches of the facial, external popliteal, and ulnar nerves and enlargement of the left great auricular nerve. A scraping of the nasal mucosa showed numerous acid fast bacilli. Histopathological examination of an arm lesion showed, below a subepidermal Hopital du Bocage, Centre Hospitalier et LUniversitaire, Dijon, France"},{"key":"ref_15","article-title":"On 7 January 1984 the dosage of clofazimine was increased to 400 mg daily and prednisolone 1 mg\/kg was introduced; dosages of rifampicin and dapsone remained as before. His condition did not improve, and the lesions remained painful. From 25 January, on five successive days, he was given five plasma exchanges. At each procedure 150% of theoretical plasma volume was exchanged for diluted albumin. On the third day his temperature was normal, and by the sixth day the oedema had resolved and the pain disappeared. Nerve paralysis was only slightly improved. Despite antibiotics, clofazimine, and steroids, which were continued in unaltered dosage until","volume-title":"he developed a second, identical type 1 leprosy reversal reaction. Plasma exchange as before had a similar effect, after which his condition continued to improve","year":"10 March, on 17 February","unstructured":"On 7 January 1984 the dosage of clofazimine was increased to 400 mg daily and prednisolone 1 mg\/kg was introduced; dosages of rifampicin and dapsone remained as before. His condition did not improve, and the lesions remained painful. From 25 January, on five successive days, he was given five plasma exchanges. At each procedure 150% of theoretical plasma volume was exchanged for diluted albumin. On the third day his temperature was normal, and by the sixth day the oedema had resolved and the pain disappeared. Nerve paralysis was only slightly improved. Despite antibiotics, clofazimine, and steroids, which were continued in unaltered dosage until 10 March, on 17 February he developed a second, identical type 1 leprosy reversal reaction. Plasma exchange as before had a similar effect, after which his condition continued to improve."}],"container-title":["BMJ"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/data.bmj.org\/tdm\/10.1136\/bmj.289.6459.1645","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmj.289.6459.1645","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T23:27:44Z","timestamp":1765409264000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.bmj.com\/lookup\/doi\/10.1136\/bmj.289.6459.1645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1984,12,15]]},"references-count":15,"journal-issue":{"issue":"6459","published-online":{"date-parts":[[1984,12,15]]},"published-print":{"date-parts":[[1984,12,15]]}},"alternative-id":["10.1136\/bmj.289.6459.1645"],"URL":"https:\/\/doi.org\/10.1136\/bmj.289.6459.1645","relation":{},"ISSN":["0007-1447","1468-5833"],"issn-type":[{"value":"0007-1447","type":"print"},{"value":"1468-5833","type":"electronic"}],"subject":[],"published":{"date-parts":[[1984,12,15]]}}}