Facts About Iodine and Autoimmune Thyroiditis

Facts About Iodine and Autoimmune Thyroiditis...

Facts About Iodine and Autoimmune Thyroiditis

Guy E. Abraham, M.D.

In 1912, pathologist H. Hashimoto published in the German language and in a German medical journal (1), his histological findings in four thyroid glands removed at surgery: numerous lymphoid follicles; extensive connective tissue formation; diffuse round cell infiltration; and significant changes of the acinar epithelium. He called this pathology of the thyroid "struma lymphomatosa", but it became popular under the name "Hashimoto Thyroiditis". At the time of Hashimoto’s publication, autoimmune thyroiditis was not observed in the U.S. population until the iodization of salt. Hashimoto’s thyroiditis is now classified as goitrous autoimmune thyroiditis AIT because the gland is enlarged, in distinction to atrophic autoimmune thyroiditis where atrophy and fibrosis are predominant. Both conditions are chronic, progressing over time to hypothyroidism in a significant percentage of Patients (2).

In several communities worldwide, an increased incidence of AIT was reported following implementation of iodization of sodium chloride (3). In areas of the United States where this relationship has been studied, mainly in the Great Lakes Region, a similar trend was reported. In 1966 and 1968 Weaver et al (4,5) from Ann Arbor Michigan reported: "The salient histopathological feature of the thyroid glands, removed at operation in a five-year period before iodine prophylaxis (1915 to 1920), was the paucity of lymphocytes in their parenchyma, and, more importantly, the absence of thyroiditis of any form" "It should be emphasized that the thyroid glands prior to the use of iodized salt were devoid of lymphocytes, and nodular colloid goiters with dense lymphocytic infiltrates were found after the introduction of iodized salt in 1924″.

Furszyfer et al (6), from the Mayo Clinic, studied the average annual incidence of Hashimoto’s thyroiditis among women of Olmsted County, Minnesota during 3 consecutive periods covering 33 years of observation, from 1935 to 1967. They found the incidence to be higher in women 40 years and older versus women 39 years and less. However, in both groups, there was a progressive increase in the incidence of Hashimoto’s thyroiditis over time. During the 3 periods evaluated, that is 1935-1944; 1945-1954; 1955-1967; the average annual incidence of Hashimoto’s per 100,000 population were 2.1; 17.9; and 54.1 for women 39 years and less. For women 40 years and older, the average annual incidence over the same 3 periods were: 16.4; 27.4; and 94.1.

It is important to point out that the Mayo Clinic study started 10-15 years after implementation of iodization of salt in the area. Therefore,even during the first decade of observation, the prevalence of autoimmune thyroiditis was already significant. Again, it must be emphasized that prior to the implementation of iodized salt as observed by Weaver, et al,(4.5) this pathology of the thyroid gland was not reported in the US, even though the Lugol solution and potassium iodide were used extensively in medical practice at that time in daily amount two orders of magnitude greater than the average intake of iodide from table salt.

It is of interest to note that prior to iodization of salt, AIT was almost non-existent in the USA, although Lugol solution and potassium iodide were used extensively in medical practice in amounts 2 orders of magnitude greater than the average daily amount ingested from iodized salt (2). This suggests that inadequate iodide intake aggravated by goitrogens, not excess iodide, was the cause of this condition. To be discussed later, AIT cannot be induced by inorganic iodide in laboratory animals unless combined with goitrogens, therefore inducing iodine deficiency.

The pathophysiology of AIT is poorly understood. Experimentally induced autoimmune thyroiditis in laboratory animals by acutely administered iodide required the use of antithyroid drugs, essentially goitrogens, to produce these effects (7-10). These goitrogens induced thyroid hyperplasia and iodide deficiency. Antioxydants either reduced or prevented the acute iodide-induced thyroiditis in chicks (11) and mice (12). Bagchi et al (11) and Many et al (12) proposed that the thyroid injury induced by the combined use of iodide and goitrogens occurs through the generation of reactive oxygen species.

We have previously proposed a mechanism for the oxidative damage caused by low levels of iodide combined with antithyroid drugs (2): Inadequate iodide supply to the thyroid gland, aggravated by goitrogens, activates the thyroid peroxydase (TPO) system through elevated TSH, low levels of iodinated lipids, and high cytosolic free calcium, resulting in excess production of H2O2. The excess H2O2 production is evidenced by the fact that antioxidants used in Bagchi’s experiments did not interfere with the oxidation and organification of iodide and therefore neutralized only the excess oxydant (11). This H2O2 production is above normal due to a deficient feedback system caused by high cytosolic calcium due to magnesium deficiency and low levels of iodinated lipids which requires for their synthesis iodide levels 2 orders of magnitude greater than the RDA for iodine (2). Once the low iodide supply is depleted, TPO in the presence of H2O2 Molar and organic substrate reverts to its peroxydase function which is the primary function of haloperoxydases, causing oxidative damage to molecules nearest to the site of action: TPO and the substrate thyroglobulin (Tg). Oxydized TPO and Tg elicit an autoimmune reaction with production of antibodies against these altered proteins with subsequent damage to the apical membrane of the thyroid cells, resulting in the lymphocytic infiltration and in the clinical manifestations of Hashimoto’s thyroiditis. Eventually, the oxidative damage to the TPO results in deficient H2O2 production.

Hypothyroidism occurs in AIT when oxidation and organification of iodide in the thyroid gland become deficient enough to affect synthesis of thyroid hormones.

In vitro studies with purified fractions of calf thyroid glands by De Groot et al (13) gave compelling evidence that iodide at 10-5 Molar confers protection to TPO against oxidative damage. To achieve peripheral levels of 10-5 Molar iodide, a human adult needs a daily amount of 50 to 100 mg. DeGroot’s findings can be summarized as follows:

1. TPO is inactivated by H2O2.

2. KI at 10-5 Molar protects TPO from oxidative damage.

3. Potassium Bromide and Potassium Fluoride do not share this protective
effect of KI.

4. The protective effect of KI is not due to the covalent binding of iodine
to TPO but due to the presence of KI itself in the incubation media.

Based on the above facts, it is obvious that iodine deficiency, not excess, is the cause of AIT.


1) Hashimoto, H., Zur Kenntniss der lymphomatosen Veranderung der Schilddruse (Struma lymphomatosa). Arch. Klin. Chir., 97:219-248, 1912.

2) Abraham, G.E., The safe and effective implementation of orthoiodosupplementation in medical practice. The Original Internist, 11:17-36, 2004.

3) Gaitan, E., Nelson, N.C., Poole, G.V., Endemic Goiter and Endemic Thyroid Disorders. World J. Surg., 15:205-215, 1991. (Autoimmune Thyroiditis)

4) Weaver, D.K., Batsakis, J.G., Nishiyama, R.H., Relationship of Iodine to "Lymphocytic Goiters". Arch. Surg., 98:183-186, 1968. (Autoimmune Thyroiditis)

5) Weaver, D.K., Nishiyama, R.H., Burton, W.D., et al, Surgical Thyroid Disease. Arch. Surg., 92:796-801, 1966. (Autoimmune Thyroiditis)

6) Furszyfer, J., Kurland, L.T., Woolner, L.B., et al, Hashimoto’s Thyroiditis in Olmsted County, Minnesota, 1935 through 1967. Mayo Clin. Proc., 45:586-596, 1970. (Autoimmune Thyroiditis)

7) Weetman, A.P., Chronic Autoimmune Thyroiditis. In Werner & Ingbar’s The Thyroid – Braverman LE and Utiger RD Editors, Lippincott Williams & Wilkins, 721-732, 2000. (Autoimmune Thyroiditis)

8 ) Follis, R.H., Further observations on thyroiditis and colloid accumulation in hyperplastic thyroid glands of hamsters receiving excess iodine. Lab Invest., 13:1590-1599, 1964. (Goiter)

9) Belshaw, B.E., Becker, D.V., Necrosis of Follicular Cells and Discharge of Thyroidal Iodine Induced by Administering Iodide to Iodine-Deficient Dogs. J. Clin. Endocr. Metab., 13:466-474, 1973. (Goiter)

10) Mahmoud, I., Colin, I., Many, M.C., et al, Direct toxic effect of iodine in excess on iodine-deficient thyroid gland: epithelial necrosis and inflammation associated with lipofuscin accumulation. Exp. Mol. Pathol., 44:259-271, 1986.

11) Bagchi, N., Brown, T.R., Sundick, R.S., Thyroid Cell Injury Is an Initial Event in the Induction of Autoimmune Thyroiditis by Iodine in Obese Strain Chickens. Endocrinology, 136:5054-5060, 1995. (Autoimmune Thyroiditis)

12) Many, M.C., Papadopoulaous, J., Martic, C., et al, Iodine induced cell damage in mouse hyperplastic thyroid is associated to lipid peroxidation. In: Gordon A, Gross J, Hennenian G (eds) Progress in Thyroid Research. Proceedings of the 10th International Thyroid Conference. Balkema, Rotterdam, 635-638, 1991.

13) DeGroot Leslie J., et al, Studies on an Iodinating Enzyme from Calf Thyroid. Endocrinology Vol. 76 p.632-645,1965.

14) Okerlund, M.D., The Clinical Utility of Fluorescent Scanning of the Thyroid. In Medical Applications of Fluorescent Excitation Analysis, Editors Kaufman and Price, CRC Press, Boca Raton Florida, pg 149-160, 1979.

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