Autoimmune Thyroid Disorders

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What is AITD?
Autoimmune thyroid disease (AITD) is a common organ specific autoimmune disorder seen mostly in women between 30-50 yrs of age.

Forms of AITD
Hyperthyroid Graves disease (GD) Hashimotos (goitrous) thyroiditis Atrophic autoimmune hypothyroidism Postpartum thyroiditis (PPT) Thyroid associated orbitopathy (TAO)

Hashimotos thyroiditis (HT) and Graves disease (GD) are the commonest type and share many features immunologically
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Prevalence of AITD
About 2 to 4 percent of women and up to 1% of men are affected worldwide, and the prevalence rate increases with advancing age. Prevalence rate of autoimmune mediated hypothyroidism is about 0.8 per 100 and 95% among them are women. Graves disease is about one tenth as common as hypothyroidism and tends to occur more in younger individuals.

Scenario in India
The true prevalence and incidence in India of thyroid disorders is difficult to estimate. 7.5% prevalence of autoimmune thyroiditis was demonstrable by fine needle aspiration biopsy among female goitrous students. As India is now predominantly iodine sufficient we are nearing the peak prevalence of the autoimmune epidemic.

Thyroid Autoantibody Prevalence and Association with Hypothyroidism

(NHANES III. 2002;J Clin Endocrinol Metab 2002,87:489-99)

Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html 3

Etiology Multifactorial

Genetic HLA complex (HLA DR-3) [HLAA10, B8 and DQw2 is seen in India] T cell regulatory gene (CTLA 4) Environmental

Source: Thyroid 2003 Mary Ann Liebert, Inc

Pathogenesis of AITD
The development of antibodies to thyroid peroxidase (TPO), thyroglobulin (TG) and thyroid stimulating hormone receptor (TSHR) is the main hallmark of AITD

Source: Clin Endocrinol 2004 Blackwell Publishing

Diagnosis of AITD: Indian Thyroid Guidelines 2011

Tests for antibodies against: Thyroid peroxidase (TPOAb), Thyroglobulin (TgAb) and TSH receptors (TRAb) are used in the diagnosis of autoimmune thyroid disorders.

Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html

Characterization of Thyroid Disorders According to Results of Thyroid Function Tests

Clinical Use of TPOAb Tests

TPOAb Found in
1. 70-80 % of patients with Graves disease 2. Virtually all patients with Hashimotos, atrophic thyroiditis or post-partum thyroiditis 3. Reproductive complications (such as miscarriage, infertility, IVF failure, fetal death, pre-eclampsia, preterm delivery and postpartum thyroiditis and depression)

Recommendations
Detectable level of TPOAb typically precedes the development of an elevated TSH and is therefore a risk factor for hypothyroidism. Although the appearance of TPOAb usually precedes the development of thyroid dysfunction, recent studies suggest that a hypoechoic ultrasound pattern may precede a biochemical TPOAb abnormality. Although changes in autoantibody concentrations often reflect a change in disease activity, serial thyroid autoantibody measurements are not recommended for monitoring treatment for AITD.

Futuristic Perspective
May be used as a prognostic indicator for thyroid dysfunction.
Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html

Clinical Use of TgAb

Recommendations
Auto antibodies against Tg are encountered in autoimmune thyroid conditions, usually in association with TPOAb.

However, the recent NHANES III study found that 3 % of subjects with no risk factors for thyroid disease had detectable TgAb without TPOAb. In these subjects with only TgAb detected, no association with TSH abnormalities was found so that the clinical significance of an isolated TgAb abnormality remains to be established. This suggests that it is unnecessary to measure both TPOAb and TgAb for a routine evaluation of thyroid autoimmunity.

According to the current guidelines, all sera should be pre-screened for TgAb by a sensitive immunoassay method prior to Tg testing. Therefore, TgAb is primarily used as an adjunct test for serum Tg estimation.

Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html

TRAb & Its Classes

(a) thyroid stimulating autoantibodies (TSAb) cause Graves hyperthyroidism (a) thyroid stimulation-blocking antibodies (TBAb) block receptor binding of TSH

Clinical Use of TRAb Tests

TBII (Thyrotrophin Binding Inhibiting Immunoglobulin) assays have comparable diagnostic sensitivity to TSAb bioassays (70-95%) for diagnosing Graves hyperthyroidism or detecting a relapse or response to therapy. TBII tests are important for evaluating pregnant patients with a history of autoimmune thyroid disease, in whom there is a risk of transplacental passage of TRAb to the infant . Since TRAb and other thyroid antibodies levels increase acutely significantly after radioiodine therapy, a TRAb measurement prior to radioiodine therapy may be useful to predict risk of TAO (Thyroid-Associated Orbitopathy).

Each class of TRAb (TSAb and TBAb) may be detected alone or in combination. The relative concentrations of the two classes of TRAb may modulate the severity of Graves hyperthyroidism and may change in response to therapy or pregnancy.

Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html 10

Postpartum thyroiditis (PPT)

PPT is destructive thyroiditis during the first 12 month postpartum. It occurs in 5-9% of unselected postpartum women, with 3 fold increase risk of PPT in women with type 1 diabetes. It may also occur after loss of pregnancy at 520 wk gestation.

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Guidelines for PPT

TSH estimation at 3 and 6 months in women known to be TPOAb positive & for women with type 1 diabetes mellitus (PPT 3-fold greater). Women with a history of PPT have a markedly heightened risk of developing permanent primary hypothyroidism within 5 to 10 years, should undergo annual TSH assessments. Asymptomatic women with PPT who have a TSH above the reference range but less than 10mU/ml and who are not planning a subsequent pregnancy do not necessarily require intervention but should, if untreated, be re-monitored in 48 weeks. Symptomatic women and women with a TSH above normal and who are attempting pregnancy should be treated with levothyroxine. Women with postpartum depression should be screened for hypothyroidism and appropriately treated.

Clinical Decision Tree

Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html 12

Guidelines of the American Thyroid Association (2011) for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum
Euthyroid women (not receiving LT4) who are TAb+ require monitoring for hypothyroidism during pregnancy. Serum TSH should be evaluated every 4 weeks during the first half of pregnancy and at least once between 26 and 32 weeks gestation. Selenium supplementation is not recommended for TPOAb+ women during pregnancy. In the presence of a suppressed serum TSH in the first trimester (TSH <0.1 mIU/L), a history and physical examination are indicated. FT4 measurements should be obtained in all patients. Measurement of TT3 and TRAb may be helpful in establishing a diagnosis of hyperthyroidism. If the patient has a past or present history of Graves' disease, a maternal serum determination of TRAb should be obtained at 2024 weeks gestation. Fetal surveillance with serial ultrasounds should be performed in women who have uncontrolled hyperthyroidism and/or women with high TRAb levels (greater than three times the upper limit of normal). A consultation with an experienced obstetrician or maternalfetal medicine specialist is optimal. Such monitoring may include ultrasound for heart rate, growth, amniotic fluid volume, and fetal goiter Women with postpartum depression should have TSH, FT4, and TPOAb tests performed. Treatment of TAb+ euthyroid pregnant woman with either LT4 or iodine to prevent PPT is ineffective and is not recommended. Serum TSH values should be obtained early in pregnancy in women with TPOAb positivity at high risk for overt hypothyroidism.
Source: ATA Guidelines 2011

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Case Study
A female, 62 years of age, suffers from pernicious anaemia for which she has received 1 (one) mg cyanocobalamine intramuscularly every 3 month for the last 10 years. At a routine visit the patient is found with a puffy swollen face due to a non-pitting oedema. Her skin is dry and cold, the heart rate is 55 beats per min, her hair is sparse, and she complains of constipation and fatigue. A series of blood tests reveals the following: High levels of microsomal autoantibodies against the thyroid gland and autoantibodies against her parietal cells. The TSH concentration in the plasma is high, whereas the T4 is low. The haematological variables are satisfying. 1. What is the probable diagnosis? 2. What are the treatment? 3. Is there any connection between pernicious anaemia and the other condition?

Interpretation
1.Hashimotos thyroiditis is a probable diagnosis, because the microsomal auto-antibodies have caused atrophy of the thyroid and hypothyroidism (myxoedema). A high TSH level and a low total or fT4 in plasma confirms the diagnosis primary hypothyroidism. Hypercholesterolaemia is typical as is increased concentrations of liver and muscle enzymes (aspartate transferase, creatine kinase) in the plasma. 2.Thyroid hormone in the form of levo-thyroxine is the treatment of choice. The initial dose to old patients has to be cautiously low such as 50 mg orally once or twice a week, since any overdose elicits cardiac arrhythmia or failure. 3. A patient with one organ-specific autoimmune disorder (here pernicious anaemia) is prone to get another (Hashimotos thyroiditis with atrophy and myxoedema).

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Tests Done in SRL

Test Rational Thyroid Panel (TSH3G UL If abnormal then FT3 & FT4) Thyroid Autoantibodies Panel (Thyroid Peroxidase (also known as Anti Microsomal Ab) & Thyroglobulin Ab) Thyroid Panel II (FT3, FT4, TSH3G UL) Thyroid Panel IV (T3, T4, TSH) Thyroid Screening Panel (FT4, TSH3G UL & TPO) TSH Receptor Ab TBG Method Chemiluminescence Chemiluminescence Code 1499RTP 1016

Chemiluminescence Chemiluminescence Chemiluminescence RIA Chemiluminescence

1499 TPC TSP 3254I 3238

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Thank You

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