2. Evaluation of Thyroid Nodules and Abnormal TFT’s Michael L. Tuggy, MD Swedish Family Medicine, Seattle, WA

3. Case 1 42 y.o. male with no active medical problems. During your routine physical, note a thyroid nodule. Told by ENT last year not to worry about it. PE: 1 x 2cm R lower pole nodule. What information do you want from the patient?

4. Age as a Risk Factor Age –young patients (<20 years of age) –thyroid nodules are much more likely to be malignant (40-50%). –elderly (>60 years of age) -higher risk, especially of more aggressive thyroid tumors.

5. Gender and Thyroid Nodules Gender –male -higher risk if nodule present –females have many more nodules less likely to be malignant. still have majority of thyroid cancers

6. Other major risks Radiation to head and neck. –40% risk of thyroid cancer usually 25 years later. –Exposed populations- Polynesian studies Family History of MEN II, Gardner’s Syndrome, Cowden’s disease.

7. Historical Red Flags Recent growth Soft tissue swelling Vocal changes Dysphagia Signs of thyroid dysfunction

8. Case 2 26 y.o. Eritrean female with a 2-3 year history of goiter. No symptoms but noted enlargement on right for 1 year. P.E.: 3x4 cm Right sided thyroid mass, firm, adherent to soft tissue. What physical findings are worrisome? How can you best clarify the nature of the nodule?

9. Physical Exam of the Thyroid Use both hands simultaneously to evaluate for symmetry Patient upright - screening exam Patient supine with neck in extension- detailed exam. Swallowing assists in elevating gland. Evaluation of other neck structures. Voice changes (recurrent laryngeal nerve).

11. Exam while sitting

12. Supine Exam

13. Thyroid Scans Purpose –Determine function of the gland and/or a nodule within the gland Hot nodules - usually independently functioning nodules –Rarely, rarely malignant Cold nodules - either adenoma or maligancy –15% chance of malignancy in adults.

14. Thyroid Ultrasound Can identify presence of nodules. May be able to characterize follicular vs. solid. Not able to rule our malignant nodule Aid in biopsy. Thyroid

15. Case 3 30 y.o. WF with enlarging cold benign thyroid adenoma (diagnosis from previous FNA biopsy). PE: 4 x 5 cm mass on Right What do you do now?

16. Fine-Needle Aspiration Best tool for determining pathology other than surgical excision. Can be as high as 80 % sensitive and 95% specific. Operator dependent in obtaining adequate amount of tissue. 25 gauge needle is optimal. Should not be relied on if negative in patient with previous neck irradiation. –Multifocal tumors common.

17. Interpreting the Biopsy Report What you get: –benign (low probability) –indeterminate –suspicious (high probability) –inadequate specimen What it means: –benign - 90-95% likelihood it is benign –indeterminate- who knows? –suspicious- it’s malignant. –inadequate specimen - do it again (and again)

18. Thyroid Malignancies- Papillary Most common 30% have node metastasis at diagnosis Radiation related Histologically, psammoma bodies distinguish from benign adenoma.

19. Thyroid Malignancies-Follicular 20 % of malignancies Distinguished from normal follicular adenomas by invasion of capsule or blood vessels. May be difficult to determine on FNA

20. Thyroid Malignancies- Medullary 5-10% of cases arise from the C cells which produce calcitonin diagnosis based on elevated thyrocalcitonin levels and thyroid nodule (cold)

21. Thyroid Malignancies- Anaplastic < 10% Highly aggressive with local extension at time of diagnosis. No suitable therapy Prognosis < 1 yr from diagnosis

22. Treatment For all malignancies, excision of the the lobe (or if post-radiation the entire gland). XRT- very specific and well tolerated- I 131 therapy. Anaplastic tumors - palliative radiation and XRT. F/U after Rx: TSH antibody scan, I 131 scan or newer tagged antibody test to look for metastasis.

23. What about those benign nodules? No specific treatment is needed. Thyroid suppression may shrink size of adenomas Not proven to be effective or necessary May hide malignancies - ? Periodic biopsies or scans.

24. Outcomes Case 1. - Papillary cancer - 3 (+) nodes –no metastasis at 5 year. Case 2. - Follicular cancer - 5 (+) nodes –lost to follow-up, negative at 1 year. Case 3. - Large adenoma with incidental 1 cm papillary carcinoma superior to nodule. –Negative I 131 scan one year out.

25. Summary: Solitary Nodule Evaluation Do I scan first or FNA first?- –high risk - scan and FNA Is the nodule cold or hot? Cold - FNA biopsy –low risk - FNA if indeterminate- scan and re-biopsy or just re-biopsy. Can I believe the results of the biopsy? –Review results with pathologist and patient. Don’t suppress undiagnosed nodules - you need a diagnosis first.

27. Never assume a solitary thyroid nodule is benign. Prove it.

28. Evaluation of Abnormal Thyroid Function Tests Part duex...

29. Case A. 19 y.o. BF with 3 month history of fatigue, weight loss, jitteriness and difficulty sleeping. Exam: diffusely enlarged, non- tender thyroid. No nodules. TSH: 0.1 T4- 28!

30. What ya get... TSH- new assays very sensitive to thyroid state. (Tells you what the brain sees) Free T4, T3 levels - highly accurate (tells you what the body sees) T3-RU, total T3, T4 - no longer needed with new assays for free T3 and T4.

31. Hyperthyroid States Suppresses TSH Elevated T4, T3 (one or both) DDx: –Graves, –acute thyroiditis –early pregnancy, molar pregnancy –exogenous hormone ingestion. –Toxic goiter –? Congenital TSH deficiency (hypothyroid)

32. Hypothyroid States Elevated TSH (usually > 20), decrease T3, T4. DDx –Primary –severe illness –TSH tumor (pituitary) –Panhypopituitarism (low TSH)

33. Case B. 29 y.o. trekker with complaint of fatigue for the past 2 weeks while hiking at 12-15,000 ft., sore throat for the past 7 days Exam: mild erythema of lower neck Tender thyroid. Dx: Acute thyroiditis - De Quervain’s. (Type 1) Prognosis: good, self-limited. RX: ASA ii p.o. TID x 14 days.

34. Thyroiditis Type 1 Autoimmune Thyroiditis (Hashimoto's Disease Type 1) –1A Goitrous –1B Nongoitrous –Status Euthyroid with normal TSH level. Autoantibodies to Tg and TPO usually present.

35. Thyroiditis Type 2 Autoimmune Thyroiditis (Hashimoto's Disease Type 2) –2A Goitrous (classic Hashimoto's disease) –2B Nongoitrous (primary myxedema, atrophic thyroiditis) Status Persistent hypothyroidism with increased TSH levels. Autoantibodies to Tg and TPO usually present. Some type 2B is associated with blocking- type TSH receptor autoantibodies.

36. Thyroiditis –2C Transient aggravation of thyroiditis Status May start as transient thyrotoxicosis (increased serum thyroid hormones with low thyroidal radioactive iodine uptake). Often followed by transient hypothyroidism. However, patients may show transient hypothyroidism without the preceding thyrotoxicosis. Autoantibodies to Tg and TPO present. Example: postpartum thyroiditis.

37. Thyroiditis Type 3 Autoimmune Thyroiditis (Graves' Disease) –3A Hyperthyroid Graves' disease –3B Euthyroid Graves' disease Status Hyperthyroid or euthyroid with suppressed TSH. Stimulatory autoantibodies to the TSH receptor are present. Autoantibodies to Tg and TPO are also usually present.

38. Thyroiditis –3C Hypothyroid Graves' disease Status Orbitopathy with hypothyroidism. Diagnostic levels of autoantibodies to the TSH receptor of the blocking or stimulating variety may be detected. Autoantibodies to Tg and TPO are usually present.

39. Grave’s Management PTU or methimazole –PTU in pregnancy at lowest possible doses Beta-blockade: Propranolol 20-80mg q 8 or atenolol 50-100mg q day. Iodine (I 131 therapy Dexamethasone 2mg q 6

40. Goiters Diffuse or multi-nodular enlargement Clinical trials suppressing TSH down to 0.5 to 1.0 show 58% had significant reduction in size compared to placebo (5%). I 131 treatment will reduce size also but 25- 40% will become hypothyroid over 5 years.

41. Summary Newest tests for TSH and T4/T3 levels allow for better diagnosis Auto-antibody testing less useful due to extensive overlap in thyroiditis. Many forms of thyroiditis are self-limited but should be followed q 3 months until resolved. Options for therapy for Grave’s disease.