Spontaneous hypothyroidism in the follow up of Graves hyperthyroid patients treated with antithyroid drugs.Aim: Spontaneous hypothyroidism hypothyroidism: see thyroid gland. may follow the natural course of Graves disease (GD) after treatment with antithyroid drugs (ATD ATD Anthropomorphic Test Dummy ATD Attention to Detail ATD Advanced Technology Demonstration AtD Achieving the Dream ATD Atmospheric Technology Division (US National Center for Atmospheric Research) ATD Assistant Technical Director ). Methods: We studied retrospectively 139 remitted Graves hyperthyroid Hyperthyroid Having too much thyroxin stimulation. Mentioned in: Goiter patients treated with ATD, with a follow-up period of 17.5 years (range 6 to 25 years). Elevated serum concentration serum concentration Therapeutics The amount of a drug or other compound in the circulation, both bound to proteins and unbound, the latter of which generally corresponds to the theraepeutically active fraction of thyroid-stimulating hormone thyroid-stimulating hormone (TSH): see thyrotropin. and low serum thyroxine concentrations confirmed the diagnosis. Results: Thirteen patients (median age, 41 years; 26 to 48 years) developed spontaneous hypothyroidism, 4 to 144 months (median, 48 months) following withdrawal of ATD. The prevalence of hypothyroidism was 9.3% and the incidence was 2.3% per year (13/563.6 patients/year of observation). There was no association with types of drugs used or the regimens. Spontaneous hypothyroid Hypothyroid Having too little thyroxin stimulation. Mentioned in: Goiter hypothyroid adjective Referring to hypothyroidism, see there patients showed elevated titers (P = 0.02) of serum antithyroid peroxidase antibody antithyroid peroxidase antibody Endocrinology An antibody in thryoid autoimmune disease–TAD, eg, Hashimoto's thyroiditis, Graves' disease, post-partum TAD, and other autoimmune disorders. See Thyroiditis. (TPOAb) at the end of treatment with ATD, compared with the titers found at the beginning. These patients also had higher titers of TPOAb (P = 0.01) in relation to euthyroid Euthyroid Having the right amount of thyroxin stimulation. Mentioned in: Goiter euthyroid having a normally functioning thyroid gland. patients. In contrast, the changes in serum antithyroglobulin antibody titers were not significant. Conclusions: Because of the shift from euthyroidism to spontaneous hypothyroidism, GD patients demanded a strict follow up after ATD therapy. It seems that there is an effect of TPOAb on thyroid destruction. Key Words: Graves disease, hypothyroidism, antithyroid drugs, thyroid antibodies thyroid antibodies See Antimyeloperoxidase antibody, Antithyroglobulin antibody, Antithyroid peroxidase antibody. , thyroiditis Thyroiditis Definition Thyroiditis is inflammation of the thyroid gland, a butterfly-shaped organ next to the windpipe. Description The thyroid is the largest gland in the neck. . ********** Both Graves disease (GD) and Hashimoto thyroiditis (HT) can present with similar findings including lymphocytic infiltration of the thyroid gland and antithyroglobulin (TgAb) and antihuman thyroid peroxidase (TPOAb) autoantibodies in the serum. The clinical course may also fluctuate between the two disorders. This observation can lead to the assumption that GD and HT may have a partially shared pathogenesis. (1) It has been considered to result from an imbalance between the Th1 and Th2 lymphocyte cytokines Cytokines Chemicals made by the cells that act on other cells to stimulate or inhibit their function. Cytokines that stimulate growth are called "growth factors. secretion. Two opposite pathogenic processes are involved; the predominance of Th2 lymphocytes in GD brings about thyroid cell hyperplasia. Th1 lymphocytes mediate thyroid cell destruction in HT. (1) Besides, there is some evidence that remission in GD patients could be induced by changes in the Th2 to Th1 cytokines. (2) Therefore, spontaneous hypothyroidism may follow the natural course of GD after treatment with antithyroid drugs (ATD). (3,4) The clinical evolution to hypothyroidism becomes evident after radioiodine radioiodine /ra·dio·io·dine/ (-i´o-din) any radioactive isotope of iodine, particularly 123I, 125I, and 131I; used in diagnosis and treatment of thyroid disease and in scintiscanning. and surgical procedures (5,6) and in fact, for some protocols, hypothyroidism is the aim of radioiodine therapy. The ATD have some immunosuppressor effects, (7-9) but it is less probable that these drugs could be active many years after discontinuation of the therapy. There has been no agreement about the development of spontaneous hypothyroidism and its prevalence after ATD treatment in GD. It has been reported in 2.9 to 20% of patients during 0.5 to 27 years of follow up. (3,4,10,11) HT was pointed out as the cause of late spontaneous hypothyroidism (12) but the influence of TgAb and TPOAb is unknown. The purpose of this study was to describe the incidence and the prevalence calculated as density of late hypothyroidism after treatment with ATD in our patients with GD. Some markers that might have contributed to the development of spontaneous hypothyroidism were also analyzed. Patients and Methods We evaluated in a retrospective study retrospective study, a study in which a search is made for a relationship between one phenomenon or condition and another that occurred in the past (e.g. 385 consecutive patients (57 males, 328 females) with Graves hyperthyroidism hyperthyroidism: see thyroid gland. treated with ATD, from February 1976 to February 1995. The diagnosis of hyperthyroidism was made on the basis of signs and symptoms evaluated by the Wayne Clinical Index. (13) All patients had a score higher than 19, indicative of overt hyperthyroidism. (14) They had elevated serum T4, T3 and suppressed TSH TSH thyroid-stimulating hormone; see thyrotropin. TSH abbr. thyroid-stimulating hormone Thyroid-stimulating hormone (TSH) levels (15-18) and when present, ophthalmopathy signs were evaluated using NOSPECS classification. (15) All patients had diffuse goiter goiter: see thyroid gland. as shown by homogeneous I-131 thyroid scan thyroid scan A image obtained from the thyroid gland after oral administration of radioiodine. See Radioactive iodine uptake. distribution, increased 24 hour thyroid I-131 uptake (the mean I-131 uptake was 65.5 [+ or -] 10% and the normal range in our laboratory was 15-31% of the administrated dose), as well as symptoms and signs of hyperthyroidism, including eye signs, presence of serum TgAb and TPOAb and in some patients, and TSH-receptor antibody (TRAb). All the patients received ATD for 12 to 54 months and were divided into four groups as shown in Table 1. Patients were followed with clinical and laboratory control every three months in the first year and every four months during the remaining years. A long-term remission was considered when the patient showed clinical and biochemical signs of euthyroidism for at least 24 months after withdrawal of therapy. Among the 385 GD patients, we observed that 246 patients (63.8%) relapsed and received a dose of radioiodine as definitive treatment. We report here the findings of 139 patients that fulfilled the criteria of lasting remission (Table 1.). Median duration of follow up was 17.5 years (range 6 to 25 years). They were followed every three months in the first year and every four months during the remaining years after withdrawal of ATD therapy, to detect the appearance of spontaneous hypothyroidism. The Ethical Committee of our institution approved the protocol. Serum T4 concentration was determined by radioimmunoassay (RIA (Rich Internet Application) A Web-based application that approaches the speed and elegance of a local application. An RIA may refer to a browser-based application that uses AJAX or another enhanced coding technique. ) with normal range from 5.91 to 154.44 nmol/L. Serum TSH concentration was measured by RIA, (from 1976 to 1986) then by an immunoradiometric assay (TSH IRMA An earlier trade name for a variety of host connectivity hardware and software products originally developed by Digital Communications Associates (DCA) and later acquired by Attachmate Corporation. Irma was not an acronym, rather it was the lady's name. , 2nd generation, from 1986 to 1994). The normal values normal values pl.n. A set of laboratory test values used to characterize apparently healthy individuals, now replaced by reference values. were 0.35 to 5.0 mIU/L. After 1994, an immunoenzymatic method (3rd generation,) was used and the normal values were 0.3 to 4.1 mIU/L. The serum TgAb and TPOAb titers were measured by the tanned red cell hemagglutination hemagglutination /he·mag·glu·ti·na·tion/ (he?mah-gloo-ti-na´shun) agglutination of erythrocytes. he·mag·glu·ti·na·tion n. technique, (17) using available commercial kits. TRAb were determined by a radio receptor assay or using thyroid cell membranes and cyclic AMP cyclic AMP: see adenosine monophosphate. determination as described. (17,18) Patients were considered hypothyroid when serum T4 was below normal (less than 5.91 nmol/L) and serum TSH was elevated (higher than 10 mIU/L for RIA, and higher than 6 mIU/L for the 2nd and 3rd generation assays). An increase in the TgAb or in TPOAb titers greater than or equal to two dilutions was considered positive. Statistical Methods The data were statistically analyzed by the [chi square chi square (kī), n a nonparametric statistic used with discrete data in the form of frequency count (nominal data) or percentages or proportions that can be reduced to frequencies. ] test, Fisher exact test and Mann-Whitney test. The prevalence of hypothyroidism was obtained, and the incidence-density of hypothyroidism was calculated as follows: the number of hypothyroid patients was divided by the sum of patients per year of follow-up until hypothyroidism developed, then added to the number of patients per year who had remained euthyroid. Results The remission patients were all women and were treated for 12 to 45 months (median of 15 months). Spontaneous hypothyroidism after ATD therapy was found in 13 (median age was 41 years; range of 26 to 48 years) out of 139 remission patients (median age was 41 years; range of 13 to 73 years). Ophthalmopathy was observed in 32% of these patients (class III to IV at NOSPECS classification), but in none of those who developed hypothyroidism. No pretibial myxedema pretibial myxedema n. See circumscribed myxedema. was noted in this group of patients and there was no difference in the familial history of autoimmune disease autoimmune disease, any of a number of abnormal conditions caused when the body produces antibodies to its own substances. In rheumatoid arthritis, a group of antibody molecules called collectively RF, or rheumatoid factor, is complexed to the individual's own gamma between these groups. The prevalence of spontaneous hypothyroidism was 9.3% and the incidence-density found was 2.3% or 13/563.6 patients per year of observation. The occurrence of spontaneous hypothyroidism was observed between 4 to 144 months after discontinuation of ATD (median of 4 years). These patients were treated for a median of 15.5 months (range, 11 to 45 months) and there were no differences observed in this outcome considering the different therapeutic regimens used (Table). Furthermore, the measurement of serum TgAb titers at the end of ATD therapy showed no statistically significant difference between the patients with spontaneous hypothyroidism (median, 1/100; range, 0 to 1/25,600) and those of the euthyroid group (median 0; range 0 to 1/1,600). Also, no difference in the serum TgAb titers was noted in the spontaneous hypothyroidism group at the beginning (median 1/100; range 1/100 to 1/400) and at the end of treatment (median 1/100; range 1/100 to 1/1,600). In contrast, the patients who developed spontaneous hypothyroidism showed elevated titers (P = 0.02) of serum TPOAb at the end of treatment with ATD (median 1/26,000; range 1/1,600 to 1/102,400) compared with the titers found at the beginning (median 1/6,400; range 0 to 1/25,600). At the end of treatment with ATD, patients who had developed spontaneous hypothyroidism also had higher titers of TPOAb (median 1/26,000; range 1/1,600 to 1/102,400) compared with those observed in patients who had remained euthyroid (median 1/400; range 0 to 1/102,400; P = 0.01). Among the spontaneous hypothyroid patients, 9 of 13 (69%) had their TPOAb titers increased, while in the euthyroid group, only 43 of 126 (34%) patients had an increase in TPOAb titers. (Fig.) Discussion Spontaneous conversion from hyperthyroidism to hypothyroidism has generally been uncommon. (2) However, after ATD treatment for GD, the prevalence has been reported to be wide, from 2 to 20%. (3,4,10,11) In a series of 110 hyperthyroid patients, Irvine et al (3) observed 6% of overt hypothyroidism and 6% of subclinical hypothyroidism subclinical hypothyroidism An ↑ TSH before or after administration of TRH in the face of normal T3 and T4; SH affects 6-7% of ♀ and 2-3 of ♂, with 5-10% annual rate of progression to overt hypothyroidism in children and in 0.5 to 25 years of follow up. Furthermore, they found that the serum TPOAb was the main marker of the outcome. Wood and Ingbar (4) studied 15 Graves hyperthyroid patients and found 20% overt hypothyroidism 20 to 27 years after they had stopped the ATD treatment. The prevalence of spontaneous hypothyroidism after treatment with ATD in Graves hyperthyroid patients observed in our study was 9.3%, and it is nearly similar to another two surveys. Lamberg et al (10) found 14% of patients to be hypothyroid; however, 11% had subclinical hypothyroidism and 2.9% had overt hypothyroidism. (9) About 18 years later, Leary et al (11) found spontaneous hypothyroidism in 10% after ATD therapy in a follow up of 2 to 18 months after withdrawal of ATD. Spontaneous development of hypothyroidism in patients with GD may be related either to destructive mechanisms (1,2,9) of chronic thyroiditis inherent in the thyroid gland (12,19,20) or to the development of molecules of thyroid-stimulating blocking antibody blocking antibody n. 1. An antibody that combines with an antigen without a reaction but that blocks another antibody from later combining with that antigen. 2. (TSBAb). (21) Although GD and HT are considered separate and distinct clinical pathologic disturbances, they have been found to be interrelated in·ter·re·late tr. & intr.v. in·ter·re·lat·ed, in·ter·re·lat·ing, in·ter·re·lates To place in or come into mutual relationship. in . (1,2,9,19) Indeed, several authors have described histologic findings of chronic thyroiditis in patients with GD. (12,22-24) [FIGURE OMITTED] The relation between the serum titers of TPOAb and the extent of thyroidal infiltration by lymphocytes is also well known. (23-25) In addition, these patients with GD had a tendency to show reduction of all antithyroid antibody antithyroid antibody Thyroid antibody Any antibody directed against 'self' antigens, which may be either cellular components–eg antimicrosomal antibodies or proteins–eg thyroglobulin, of thyroid origin, that are often present in autoimmune diseases; titers during treatment with ATD. (17,18,26) Although in this study we used a hemagglutination assay, less sensitive than radio assay or immunoradiometric methods, we found an elevation in the serum TPOAb titers in patients who developed spontaneous hypothyroidism at the end of treatment with ATD. These values were significantly higher than the serum TPOAb titers in patients who remained euthyroid. Unfortunately, we were not able to detect a specific cut-off level for TPOAb but an elevation of their titers suggested that some thyroid damage should be the cause of this late outcome of ATD therapy. (19,23,24) It is well known that the prevalence of thyroid antibodies increases in women after 60 years of age (27); however, our patients who developed spontaneous hypothyroidism were women between 26 to 48 years old. In the present study, the prevalence of hypothyroidism (9.3%) was higher than that found (3%) by Palmer (28) and others in an elderly population. (29) Furthermore, serum TPOAb levels increase with age in association with the progression of subclinical hypothyroidism to overt hypothyroidism. (30) The Whickham Survey observed a mean incidence of hypothyroidism in the female population of 3.5/1000 survivors/year, but neither a positive family history nor any form of thyroid disease thyroid disease Thyroid disorder Endocrinology Any benign or malignant condition that affects the structure or function of the thyroid gland. See Anaplastic carcinoma of thyroid, Chronic thyroiditis–Hashimoto's disease, Hyperthyroidism, Hypoparathyroidism, was associated with an increasing risk of developing hypothyroidism. (30) Recently, in the NHANES III NHANES III Third National Health & Nutrition Examination Survey Public health A population-based survey conducted by the National Center for Health Statistics, designed to assess the health and nutritional status of the noninstitutionalized Americans survey, (31) serum TSH was associated with positive TPOAb concentrations and the prevalence of clinical hypothyroidism was strongly associated with positive TPOAb, but not with TgAb. These data support our present findings of the importance of measurement of serum TPOAb whereas TgAb seems to be not relevant. Other mechanisms involved in the development of spontaneous hypothyroidism in GD patients treated with ATD may be the presence of TSBAb in the circulation. Tamai et al (21) described that TSBAb was the cause of hypothyroidism in one third of the studied patients. The presence of stimulating and blocking antibodies against TSH receptor has been described in patients with GD, simultaneously or in different phases of the disease. (2,32,33) Because of the methodological difficulty of routine determination of TSBAb, and because of its very low occurrence and its quick disappearance from the serum with the administration of thyroid hormone Thyroid hormone Any of the chemical messengers produced by the thyroid gland, including thyrocalcitonin, a polypeptide, and thyroxine and triiodothyronine, which are iodinated thyronines. See Hormone, Thyrocalcitonin, Thyroid gland, Thyroxine , (34) we can only speculate the possible influence of this mechanism on the development of spontaneous hypothyroidism. Finally, our data showed that the significant prevalence of spontaneous hypothyroidism pointed out that the GD treatment with ATD demanded a strict follow up for a long period after discontinuation of the drugs. According to these data, we believe that serum TPOAb levels are an important marker of evolution to hypothyroidism and the enhancement of its levels after withdrawal of ATD may be useful as an indicator of the outcome. References 1. Fisfalen ME, Palmer EM, Van Seventer GA, et al. Thyrotropin-receptor and thyroid peroxidase-specific T cell clones and their cytokine Cytokine Any of a group of soluble proteins that are released by a cell to send messages which are delivered to the same cell (autocrine), an adjacent cell (paracrine), or a distant cell (endocrine). profile in autoimmune thyroid disease. J Clin Endocrinol Metab 1997;82:3655-3663. 2. Lesho E, Jones RE. Hypothyroid Graves' disease Graves' disease: see thyroid gland. . South Med J 1997;90:1201-1203. 3. Irvine WJ, Gray RS, Toft AD, et al. Spectrum of thyroid function in patients remaining in remission after antithyroid drug therapy for thyrotoxicosis thyrotoxicosis /thy·ro·tox·i·co·sis/ (thi?ro-tok?si-ko´sis) a morbid condition due to overactivity of the thyroid gland; see Graves' disease. thy·ro·tox·i·co·sis n. . Lancet 1977;2:179-181. 4. Wood LC, Ingbar SH. Hypothyroidism as a late sequela sequela /se·que·la/ (se-kwel´ah) pl. seque´lae [L.] a morbid condition following or occurring as a consequence of another condition or event. se·quel·a n. pl. in patients with Graves' disease treated with antithyroid agents. J Clin Invest 1979;64:1429-1436. 5. Van Welsum M, Feltkam TE, De Vries de Vries. For some persons thus named use Vries. MJ, et al. Hypothyroidism after thyroidectomy Thyroidectomy Definition Thyroidectomy is a surgical procedure in which all or part of the thyroid gland is removed. The thyroid gland is located in the forward part of the neck (anterior) just under the skin and in front of the Adam's apple. for Graves disease: a search for an explanation. Br Med J 1974;4:755-756. 6. Reid DJ. Hyperthyroidism and hypothyroidism complicating the treatment of tyrotoxicosis. Br J Surg 1987;74:1060-1062. 7. Hallengren B, Forsgren A, Melander A. Effects of antithyroid drugs on lymphocyte function in vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment. in vi·tro adj. In an artificial environment outside a living organism. . J Clin Endocrinol Metab 1980;2:298-301. 8. McGregor AM, Petersen MM, McLachan SM, et al. Carbimazole and the autoimmune response in Graves' disease. N Engl J Med 1980;303:302-307. 9. Weetman AP. Graves' disease. N Engl J Med 2000;343:1236-1248. 10. Lamberg BA, Salmi sal·mi n. pl. sal·mis A highly spiced dish consisting of roasted game birds minced and stewed in wine. [French salmis, short for salmigondis, salmagundi; see J, Wagar G, et al. Spontaneous hypothyroidism after antithyroid treatment of hyperthyroid Graves' disease. J Endocrinol Invest 1981;4:399-402. 11. Leary AC, Grealy G, Higgens TM, et al. Long-term outcomes of treatment of hyperthyroidism in Ireland. Ir J Med Sci 1999:168:47-52. 12. Tamai H, Kasagi K, Takaishi Y, et al. Development of spontaneous hypothyroidism in patients with Graves' disease treated with antithyroid drugs: clinical, immunological and histological findings in 26 patients. J Clin Endocrinol Metab 1989;69:49-53. 13. Wayne E. The assessment of thyroid function. Br J Surg 1965;52:717-721. 14. Sgarbi JA, Villaca FG, Garbeline B, et al. The effects of early antithyroid therapy for endogenous subclinical subclinical /sub·clin·i·cal/ (sub-klin´i-k'l) without clinical manifestations. sub·clin·i·cal adj. Not manifesting characteristic clinical symptoms. Used of a disease or condition. hyperthyroid in clinical and heart abnormalities, J Clin Endocrinol Metab 2003;88:1672-1677. 15. Werner SC. Modification of the classification of the eye changes of Graves' disease: recommendations of the committee of the Ad Hoc Committee ad hoc committee A committee formed with the purpose of addressing a specific issue or issues, which theoretically is disbanded once its raison d'etre is finished of the American Thyroid Association. J Clin Endocrinol Metab 1977;44:203-204. 16. Escobar-Jimenez F, Fernadez-Soto ML, Luna-Lopes V, et al. Trends in diagnostic and therapeutic criteria in Graves' disease in the last 10 years. Postgrad Med J 2000;76:340-344. 17. Romaldini JH, Bromberg N, Werner RS, et al. Comparison of effects of high and low dosage regimens of antithyroid drugs in the management of Graves' hyperthyroidism. J Clin Endocrinol Metab 1983;57:563-570. 18. Werner RS, Romaldini JH, Farah CS, et al. Serum thyroid stimulating antibody, thyroglobulin thyroglobulin /thy·ro·glob·u·lin/ (thi?ro-glob´u-lin) an iodine-containing glycoprotein of high molecular weight, occurring in the colloid of the follicles of the thyroid gland; the iodinated tyrosine moieties of thyroglobulin form the levels and thyroid suppressibility measurement as predicted of outcome of combined methimazole and triiodothyronine triiodothyronine /tri·io·do·thy·ro·nine/ (tri?i-o?do-thi´ro-nen) one of the thyroid hormones, an organic iodine-containing compound liberated from thyroglobulin by hydrolysis. It has several times the biological activity of thyroxine. therapy in Graves' disease. Thyroid 1991;1:293-299. 19. Tamai H, Hirota Y, Kasagi K, et al. The mechanism of spontaneous hypothyroidism in patients with Graves' disease after antithyroid drug treatment. J Clin Endocrinol Metab 1987;64:718-722. 20. Shiguemasa C, Mitani Y, Tanigushi S, et al. Development of post partum spontaneously resolving transient Graves' hyperthyroidism followed immediately by transient hypothyroidism. J Intern Med 1990;228:23-28. 21. Tamai H, Kasagi K, Hara T, et al. Follow-up study of thyroid stimulating blocking antibodies in hypothyroid patients. Clin Endocrinol 1990;33:699-707. 22. Buchanan WW, Koutras DA, Crooks J, et al. The clinical significance of the complement fixation test Noun 1. complement fixation test - a blood test in which a sample of serum is exposed to a particular antigen and complement in order to determine whether or not antibodies to that particular antigen are present; used as a diagnostic test in thyrotoxicosis. J Endocrinol 1962;24:115-125. 23. Fatourechi V, McConahey WM, Woolner LB. Hyperthyroidism associated with histological Hashimoto's thyrotoxicosis. Mayo Clin Proc 1971;46:682-689. 24. Hirota Y, Tamai H, Hayashi Y, et al. Thyroid function and histology in forty-five patients with hyperthyroid Graves" disease in clinical remission more then 10 years after thionamide drug treatment. J Clin Endocrinol Metab 1986;62:165-169. 25. Paschke R, Vogg M, Swillens S, et al. Correlation of microsomal microsomal pertaining to or emanating from microsome. antibodies with the intensity of the intrathyroidal autoimmune process in Graves' disease. J Clin Endocrinol Metab 1993;77:939-943. 26. Mariotti S, Caturegli P, Piccolo piccolo, small transverse flute pitched an octave higher than the standard flute. Its tone is bright and shrill, and it can produce the highest notes in the orchestral range. The piccolo is used in orchestras and especially in military bands. See fife. P, et al. Antithyroid peroxidase antibodies in thyroid disease. J Clin Endocrinol Metab 1990;71:661-669. 27. Prentice LM, Phillips DI, Sarsero D, et al. Geographical distribution of subclinical autoimmune thyroid disease in Britain: a study using highly sensitive assays for autoantibodies to thyroglobulin and thyroid peroxidase. Acta Endocrinol (Copenh) 1990;123:493-498. 28. Palmer KT. A prospective study into thyroid disease in a geriatric unit. N Z Med J 1977;86:323-324. 29. Chueire VB, Silva ET, Perrotta E, et al. High serum TSH levels are associated with depression in the elderly. Arch Gerontol Geriatr 2003;36:281-288. 30. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Wickham Survey. Clin Endocrinol (Oxf) 1995;43:55-68. 31. Hollowell JG, Staehlyng NW, Flanders WD, et al. Serum TSH, T4, and thyroid antibodies in United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489-499. 32. Kraiem Z, Baron E, Kahana L, et al. Changes in stimulating and blocking TSH receptor antibodies in a patient undergoing tree cycles of transition from hypo hypo: see sodium thiosulfate. to hyperthyroidism and back to hypothyroidism. Clin Endocrinol (Oxf) 1992;36:211-214. 33. Ueta Y, Fukui H, Murakami H, et al. Development of primary hypothyroidism with the appearance of blocking-type antibody to thyrotropin receptor in Graves' disease in late pregnancy. Thyroid 1999;2:179-182. 34. Chiovato L, Marcocci C, Mariotti S, et al. L-thyroxine therapy induces a fall of thyroid microsomal and thyroglobulin antibody in idiopathic mixedema and in hypothyroid but not in euthyroid Hashimotos thyroiditis. J Endocrinol Invest 1986;9:299-305. Adriana V.C. De Moraes, MD, Ana Beatriz P. Pedro, MD, and Joao H. Romaldini, MD, PhD From the Service of Endocrinology, Hospital Servidor Publico Estadual, Iamspe, Sao Paulo, Brazil. Reprint requests to Joao H. Romaldini, Av. Indianapolis, 530, 04062-000 Sao Paulo, SP Brazil. Email: jhroma@netpoint.com.br Part of this work was presented at 70th Annual Meeting of the American Thyroid Association, 1997, Colorado Springs, CO, USA Accepted June 21, 2006. RELATED ARTICLE: Key Points * Spontaneous hypothyroidism was noted in 9.3% of 139 patients in remission after antithyroid drug therapy for Graves hyperthyroidism. * An incidence rate of 2.3% per year of observation (17.5 years, 6-25 years) was also reported. * The increase in thyroid peroxidase antibody titers was related to spontaneous hypothyroidism.
Table. Treatment regimen for Graves disease and the development of
spontaneous hypothyroidism
Spontaneous
Regimen Number Dosage (a) hypothyroidism
Methimazole 17 10 mg daily 2 (11.8%)
Methimazole plus 68 45-60 mg daily 5 (7.2%)
L-triiodothyronine (b)
Propylthiouracil 19 100-200 mg daily 2 (10.5%)
Propylthiouracil plus 35 500-600 mg daily 4 (11.4%)
L-triiodothyronine
Chi-square 0.642, P = 0.88
(a) As daily maintenance dose
(b) Antithyroid drugs were associated with L-triiodothyronine (50 to 75
ug daily) in order to keep the serum T4 concentrations below the lower
limit of normal range and serum TSH concentration nearly always in the
normal range.
B COLLINS (Member): 5/26/2009 1:29 PM
I sure wish this article would talk more abuot the Blocking TRab (TSBab) since I feel that the rise in TPOabs are probably due to a higher level of TSH receptor autoimmunity when ATD therapy is cut short (aka, before TRab antibodies have been fully put into remission).<br><br>Personally, I've seen surge in TRab antibodies when my dose of ATD is cut too low (ie; 2.5 mg) and I seem to notice studies like these use doses of 5mg or higher - never less than 5mg. I wonder if the normal designed doses (5mg) have a better effect on autoimmune modulation? <br><br>If so, then why don't more doctors add supplemental hormone to the ATD therapy when the lowest 5mg dose is starting to cause too much thyroid suppression, while also knowing the therapy needs to continue? |
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