1. Endocrinology Thyroid Function Tests Case F Tu Nguyen Tuan Tran Thi Trang

2. Patient Information Ms FF, aged in her late thirties, presSents with history of weight gain, tiredness, neck discomfort and goitre. Initial TFT results were as follows: TestsResults Recommended Range FT4 10 pmol/L 10 – 25 pmol/L FT3 4.2 pmol/L 3 – 8 pmol/L TSH 45 mU/L 3 – 9 mU/L

3. Questions Do these results reflect the diagnosis of Hashimoto’s thyroiditis. Is Ms FF hypothyroid? Explain whether measurements of all her initial TFTs were warranted? Describe the approaches to measurement of autoantibodies in the evaluation of thyroid function and the application of these results in the diagnosis of thyroid dysfunction.

4. What is Hashimoto’s Thyroiditis? Discovered by Dr Hakaru Hashimoto in 1912 Thyroiditis is inflammation of the thyroid gland Hashimoto thyroiditis is the most common form of thyroiditis It is an autoimmune disorder resulting in gradual destruction of thyroid gland

5. Common Symptoms of Hashimoto’s Thyroiditis Patients may be asymptomatic but may complain of: fatigue muscle weakness weight gain enlarged thyroid = goitre

6. Common Clinical Findings Definitive indicator of Hashimoto’s thyroiditis is the presence of thyroid – specific autoantibodies in the serum TFTs can be normal but presence of high antimicrosomal and less commonly antithyroglobulin in serum TFTs abnormal (eg elevated TSH) with presence of autoantibodies

7. Common Clinical Findings Do these results reflect the diagnosis of Hashimoto’s thyroiditis? YES Is Ms FF hypothyroid? YES

8. Were the measurements of all the initial TFTs warranted?

9. Thyroid Stimulating Hormone (TSH) TSH is the most valuable thyroid function test (according to the American Association of Clinical Endocrinologists) Detect primary and central hypothyroidism and hyperthyroidism in neonatal screening

10. Free Thyroxine (FT4) Gives a more accurate measure of thyroid function when the thyroid function status is rapidly changing Hypothyroidism is detected by low to normal FT4 with elevated TSH levels Hyperthyroidism is detected by elevated FT4 with low TSH levels

11. Free Triiodothyronine (FT3) Gives a measure of thyroid function Used in diagnosis of hyperthyroidism Hyperthyroidism is detected by elevated FT3 with low TSH levels

12. Diagnosis of Thyroid Function The first diagnostic test is the measure of TSH If TSH is low, further tests of FT4 and FT3 are required if FT4 or FT3 is elevated then the diagnosis is hyperthyroidism Hyperthyroidism TSH FT4 FT3

13. Diagnosis of Thyroid Function If TSH is elevated, further test of FT4 is required if FT4 is low to normal then the diagnosis is primary hypothyroidism (Hashimoto’s Thyroiditis) Primary Hypothyroidism TSH FT4

14. Diagnosis of Thyroid Function If TSH is normal or low and FT4 is low then diagnosis is secondary hypothyroidism (due to pituitary or hypothalamic disease) Secondary Hypothyroidism TSH FT4

15. Diagnosis for Mrs FF Mrs FF has elevated TSH Therefore need to test for FT4 Mrs FF also has normal FT4 Therefore Mrs FF was diagnosed with Hashimoto’s thyroiditis (primary hypothyroidism) Therefore only TSH and FT4 tests would be needed to warrant Mrs FF’s diagnosis of Hashimoto’s Thyroiditis TestsResults Recommended Range FT4 10 pmol/L 10 – 25 pmol/L FT3 4.2 pmol/L 3 – 8 pmol/L TSH 45 mU/L 3 – 9 mU/L

16. Describe approaches to the measurement of thyroid autoantibodies in the evaluation of thyroid function and the application of these results in diagnosis of the nature of the thyroid function

17. Screening for thyroid autoimmunity Determination of thyroid peroxidase antibodies (TPOAb) Determination of thyroglobulin antibodies (TgAb) Are measure to confirm or rule out autoimmune disease

18. Screening for thyroid autoimmunity TPOAb and TgAb determination helps to distinguish individuals with thyroid autoimmunity from patients with non- thyroid autoimmune diseases such as: Addison’s disease Grave’s disease Hashimoto’s thyroiditis Type 1 diabetes

19. Differential diagnosis Presence of thyroid peroxidase Ab associate with: Thyroid autoimmune disease Focal thyroiditis Presence of thyroid peroxide Ab + elevated TSH in autoimmune thyroiditis suggest: Progression of overt hypothyroidism

20. Differential diagnosis Autoantibodies to thyroid peroxidase and, less commonly, to thyroglobulin are present in almost all patients with Hashimoto’s thydoiditis Thyroid peroxidase autoantibodies are usually detected in patients with Grave’s disease

21. Hashimoto’s thyroiditis: an example In Hashimoto’s thyroiditis (i.e. chronic inflammation of thyroid caused by autoimmune factors) Lab findings early in the disease consists of normal T4 & TSH levels and high titers of thyroid peroxidase antibodies and less commonly anti-thyroglobulin antibodies

22. Screening for thyroid autoimmunity Thyroid Ab measurement is not useful in differentiating between autoimmune thyroiditis and thyroid malignancies Both these Ab are commonly measured by RIA, ELISA or IRMA techniques

23. Measurement of thyroid autoantibodies Thyroid peroxidase autoantibody test has replaced the older tanned red cell agglutination test for thyroid anti-microsomal autoantibodies Reasons for replacement of new immunoassay methods because they are more sensitive, can be easily automated and quantitative Disadvantages: wide variability in sensitivity and specificity

24. Clinical Significance Thyroid autoantibodies are usually present in the serum of patient with autoimmune thyroid disease E.g. TSH receptor autoantibody are present in most patients with Grave’s disease Aging is also associated with the presence of thyroid autoantibodies

25. Clinical Significance Because TSH receptor autoantibody has the ability to pass through the placenta, its presence during pregnancy can complicate fetal functions Studies suggest that thyroid peroxidase Ab may contribute to future thyroid dysfunction Thyroid peroxidase Ab is also involved in the development of autoimmune complications from treatment of other drugs

26. Clinical Significance Changes in autoantibody conc. will result in changes in thyroid autoimmune disease activities However, thyroid autoantibody measurements are not used for the treatment of autoimmune thyroid disease Because treatment is intended to correct the thyroid dysfunction & not the autoimmunity part of the disease