ORIGINAL ARTICLE Does Iodine Excess Lead to Hypothyroidism? Evidence from a Case-Control Study in India Atul Kotwal, a Jyoti Kotwal, b Rajat Prakash, a and Narendra Kotwal a a Office of Director General, b Sir Gangaram Hospital Professor and Head, Department of Haematology, New Delhi, India Received for publication March 15, 2015; accepted July 28, 2015 (ARCMED-D-15-00174). Background. Iodine deficiency disorders have been known to mankind since antiquity and various researchers elucidated the role of iodine in its causation. However, recent ev- idence shows that the entire control program ignored multi-causality and association of increased iodine intake with hypothyroidism. This study was conducted to assess differ- ences of iodine intake as measured by urinary iodine excretion (UIE) between cases of hypothyroidism and healthy controls. Methods. A case-control study was conducted with three groups (cases, hospital controls and community controls) in two cities of India. Patients with overt hypothyroidism were cases (n 5 150) and were compared with age, sex and socioeconomic status-matched hospital (n 5 154) and community (n 5 488) controls. Thyroid function tests (T3, T4, TSH) were used as diagnostic and inclusion criteria. TPOAb and UIE estimation were carried out for all study participants. Results. Mean values of TPOAb and UIE were higher in cases as compared to hospital controls as well as community controls ( p !0.05). With a cut off of 34 IU/mL for TPOAb, more cases had an anti-TPO level O34 as compared to hospital controls ( p !0.001) as well as community controls ( p !0.001); OR, 0.06 (95% CI, 0.03, 0.12) and 0.08 (0.05, 0.12), respectively. For UIE cut-off of 300 mg/L, more cases than hospital controls ( p 5 0.090) and community controls ( p 5 0.001) had higher levels; OR, 0.671, (0.422, 1.066) and 0.509, (0.348, 0.744), respectively. Conclusion. The study has clearly shown that cases of hypothyroidism are associated with excess iodine intake. Cohort studies to generate further evidence and an eco- social epidemiological approach have been suggested as the way forward. Ó 2015 IMSS. Published by Elsevier Inc. Key Words: Iodine deficiency disorders, Case-control study, Hypothyroidism, Salt iodization, Autoimmune thyroiditis, Urinary iodine excretion. Introduction Goiter and other iodine deficiency disorders (IDDs) have been known for a long time with the existence of endemic goiter in an extensive belt along the southern slopes of the Himalayas, Alps and Andes. The early pioneers in the study of endemic goiter pointed to the complex etiology of goiter and commented on various causative factors (1e3). Later, the role of iodine in the causation of goiter was elucidated by various researchers working in these areas and results of few studies formed the basis of control and prevention ac- tivities of goiter (4,5). Worldwide, some countries have re- sorted to universalization of iodized salt (USI), whereas others have not done so and instead focused on making it available as a choice for the communities. The scientific backbone of universal iodination has been challenged due to weaknesses in the science and politics of the intervention to control IDDs. Few papers have also challenged the research forming the basis of information on the magnitude of the problem and effectiveness of the intervention (6,7). According to available evidence, the issues related to IDDs Address reprint requests to: Atul Kotwal, Department of Comm Med, Commandant 153 Gen Hospital, Formerly-Director AFMS (Med Research), O/o DGAFMS, Min of Def and Professor and Head, ACMS, Delhi Cantt, New Delhi, India; Phone: 00918860438811; FAX: 911123092088; E-mail: dratulkotwal@gmail.com 0188-4409/$ - see front matter. Copyright Ó 2015 IMSS. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.arcmed.2015.07.005 Archives of Medical Research 46 (2015) 490e494