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Continuous Methimazole or Radioiodine Treatment for Hyperthyroidism

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Continuous Methimazole or Radioiodine Treatment for Hyperthyroidism

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  1. Born in 1942, in Tehran, the capital city of Iran, Fereidoun Azizi obtained his MD from Tehran University, School of Medicine in 1966, Dr. Azizi then completed his internal medicine speciality, endocrinology and methabolism subspeciality and nuclear medicine speciality from Tufts University, School of Medicine, Boston, USA and obtained three American Boards of Internal Medicine, Endocrinology and Metabolism, and Nuclear Medicine in 1972, 1973 and 1974, respectively. He was appointed assistant professor of medicine at Tufts University, and Chief of Endocrinology and acting-chief of Nuclear Medicine at St. Elizabeth’s Hospital of Boston, Tufts Medical School from 1974 until 1979, when he returned to Iran. He began his affilation with Beheshti University, and has since served as associate professor in 1979 and as professor of medicine and endocrinology since 1985. His appointements have been Dean of the medical school, Chancellor of Shahid Beheshti University of Medical Sciences, Head of the medical group of Supreme Council for Educational Programming and Director of Medical Commission of Council for Scientific Research in the Islamic Republic of Iran. He has served as President of Iranian College of Internal Medicine and is currently the president of the Iran Endocrine Society. Professor Azizi has been the Leading Professor and Director of Endocrine Division at Taleghani Medical center, Shahid Beheshti University of Medical Sciences since 1989 and Director of Endocrine Research Center since 1994. He has had a large endocrine practice since 1979. Professor Azizi’s many research contributions have been in various fields of endocrinology and metabolism, in particular the hypothalamic-pituitary-thyroid axis. He began his work with Professor L.E. Braverman in Boston and continued his interest in thyroid pathophysiology in Iran. He focused many of his research projects in 80’s in iodine deficiency in Iran, presented the results to the Minister of Health of Iran in 1988 and initiated the first national IDD survey, which led to the formation of National Council for Control of Iodine Deficiency Disorders in Iran in 1989;

  2. in order to ensure sustained elimination of iodine deficiency in the last 20 years in Iran. He also directed the national research project of Tehran Lipid and Glucose Study in the last 14 years. Professot Azizi was the Regional Coordinator for the Middle East and North Africa of Internaltional Council for Control of Iodine Deficiency Disorders (ICCIDD) and has served as consultant and advisor to WHO and UNICEF on multiple occasions. He is the Editor-in-Chief of the International Journal of Endocrinology and Metabolism. Professor Azizi has 1040 publications including 486 peer reviewed international paper and 524 scientific papers in Iranian medical Journals and 30 full text or chapters in scientific books. He is an invited reviewer for more than 26 scientific medical journals. He has received many awards including five awards from presidents of I.R. Iran for “Distinguished Professor”, “Research Excellence”, “Kharazmi Feitival”, “Distinguished Research Center”and “Health Promition” in 1992, 1994, 1997, 2002 and 2008; State of Kwait Prize for excellence in diabetes in Eastern Mediterranean Region in 2007 and Nagataki Prize from Asia-Oceania Congress of Endocrinology in 2009. He was selected, as Distinguished Scienctist of the Year by Iranian Academy of Medical Sciences in 2011.

  3. Continuous Methimazole or Radioiodine Treatment for Hyperthyroidism F.Azizi, V.Yousefi, A.Bahreynian , F.Sheikholeslam, M.Tohidi, Y.Mehrabi Research Institute for Endocrine Sciences Shahid Beheshti University of Med Sci Tehran, I.R.Iran 10th Asia and Oceania Thyroid Assocition Congress 21-24 Oct. 2012, Bali, Indonesia

  4. INTRODUCTION Reasons for increased reliance in radioiodine treatment: • ↑ Atrial fibrillation due to hyperthyroidism • ↑ Cardiovascular and cerebrovascular morbidity • High relapse after discontinuation of antithyroids • Ease, effectiveness and low cost of RAI

  5. Long Term Consequences of RAI Therapy: Thyroid failures 50-70% to 90-100% ↑ Morbidity from vascular causes (? Due to hyperthyroidism itself) ↑ Cancer incidence and mortality Dependency on thyroxine therapy

  6. Patients on levothyroxine replacement: * 30-40% abnormal TSH concentration (subclinical hypo-and hyperthyroidism) due to: → Variable potency, uniformity & reproducibility of thyroxine preparations → Lack of patiens’ compliance

  7. “In patients with recurrent hyperthyroidism after disontinution of antithyroid drugs, long term (mean 10 years) continuous treatment with methimazole (MMI) was safe, and had comparable expense and complications with radioiodine treatment” Azizi F, et al. Europ J Endocrinol 2005; 152: 695

  8. PATIENTS AND METHODS • Clinical trial • Between march 1989 and July 2009 • Mean follow up 14 ±3 (range 5-20) years • Patients with diffuse toxic goiter • Tehran; area of iodine sufficiency • 59 patients on continuous MMI and 73 on levothyroxine treated radioiodine induced hypothyroidism • Followed every 3-6 months with TFT’s for mean of 14 years

  9. Patients with recurrent hyperthyroidism (104) Randomization Radiiodine therapy (51) MMI treatment (34) Excluded (29) LFU (10) LFU (6 ) Hyper (1) Hypothyroid (25) Hypo (1) Euthyroid (16) Euthyroid(26) Thyroxine treated Euthyroid (25) Non Randomized (135) MMI R% Euthyroid (33) RAI R% Hypothroid on T4 R% (48) RAI (73) MMI (59) Euthyroid (32) LFU (22)

  10. Measurements at final visit • Weight, height, BMI • LRC questionnaire for physical activity • Grades of goiter • Thyroid function tests • TPOAb and TRAb • Serum lipids and lipoproteins • Bone mineral density • Echochardiography

  11. Health Status and Neuro-psychology Tests

  12. Age, BMI and physical activity in methimazole and radioiodine treated patients at final visit

  13. Serum lipids and lipoproteines concentrations in methimazole and radioiodine treated patients † * † * * p<0.001, † p<0.02

  14. Findings of echocardiography in methimazole and radioiodine treated patients P<0.001 P<0.02

  15. Occurrence of abnormal serum TSH in methimazole and radioiodine treated patients during mean 15 years follow up P<0.001 P<0.04

  16. Summary statistics and p values for neuro-psychologic tests

  17. The relative risk and confidence interval of the drangements in TSH secretion and the rates of occurrence of goiter elevated, TPOAb and TRAs and dislipidemia in the continues MMI – treated, compared to radioiodine- treat patients Variable Relative risk (95% CI) P Value During follow up At final visit

  18. The relative risk and confidence interval of the rate of occurrence of bone mineral density <-1 SD Zscore and é velocity <12 and 16.8 cm and early diastolic E/é ratio <6.7 in continuous MMI- treated, compared to radioiodine-treated patients Relative risk (95% CI) P Value Variable At final visit

  19. CONCLUSIONS (1) Long-term continuous MMI tratement: • Effective • Safe, rare side effects • High treatment compliance • Comparable expense with RAI therapy

  20. CONCLUSIONS (2) Long-term continuous MMI tratement compared to thyroxine-treated RAI-induced hypothyroidism: • More physical activity • More goiter • Better lipid profile • Higher TPOAb titers • Better memory, mood and IQ • Less psychotic • Less subclinical hypo-and hyperthyroidism

  21. CONCLUSIONS (3) Continuous methimazole treatment should be considered as an optional approach to long – term treatment of patients with diffuse toxic goiter, in particular those with recurrent hyperthyroidism.

  22. Algorithm for the Use of Antithyroid Drugs among Patients with thyrotoxicosis Small or moderately enlarged thyroid; children or pregnant or lactating women; patients with severe eye disease Very large diffuse goiter, multinodular goiter, toxic adenoma Radioiodine therapy ? surgery Antithyroid drug therapy Discontinue drug therapy after 18 mo Normalization of thyroid function With antithyroid drugs before therapy in elderly patients and those with heart disease Monitor thyroid function Relapse Remission Monitor thyroid function every 12 mo indefinitely Definitive radioiodine therapy Second course of antithyroid drug therapy in children and adolescents Continuous MMI therapy

  23. The relative risk and confidence interval of the drangements in TSH secretion and the rates of occurrence of goiter elevated, TPOAb and TRAs and dislipidemia in the continues MMI – treated, compared to radioiodine- treat patients Variable Relative risk (95% CI) P Value During follow up At final visit é é é

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