Thyroid Disease

1. Thyroid Disease Common Problems in Family Practice

2. Thyroid Disease • Hypothyroidism • Hyperthyroidism • Thyroid Nodules • Thyroiditis

3. Thyroid Testing • TSH • Free T4 • T3 - Resin Uptake • Antithyroid Antibodies

4. Thyroid Tests • Thyroid Imaging • Radionuclide Scans • Ultrasound • Thyroid Uptake • FNA

5. Serum TSH • Radioimmunoassay • normal range 0.5 - 5.0 mU/L • detection limit of 1.0 mU/L • Immunometric assay • detection limit of 0.1 mU/L • better for screening purposes • Chemiluminometric assay • detection limit of 0.01 mU/L

6. Serum free T4 and T3 • Measures unbound hormone • Helpful when binding proteins may fluctuate due to illness or drug therapy

7. T3-Resin Uptake • Used to calculate the free hormone index • Value is the percentage of resin bound tracer compared to the whole • Varies inversely with the number of free binding sites for T3 (determined by both binding protein levels and endogenous hormone production) • Distinguishes TBG excess and deficiency from hyper and hypothyroidism

8. Screening for thyroid dysfunction • Serum TSH normal - no further testing • Serum TSH high - add free T4 • Serum TSH low - add free T4 and T3 • If pituitary disease suspected • measure TSH and free T4 • Serum TSH normal but symptomatic • measure free T4

9. Screening inpatients • Thyroid function testing not recommended due to changes in thyroid hormones, binding proteins and TSH concentrations • low concentrations of binding proteins • increased free fatty acids displacing hormone from binding proteins • acquired central hypothyroidism • medications affecting thyroid function

10. Monitoring thyroid therapy • Serum free T4 very insensitive (useful in monitoring dosage in secondary hypothyroidism due to pituitary or hypothalamic disease) • Free T4 level in this situation maintained in the upper 50 percent of the normal range

11. Monitoring suppressive therapy • Used to prevent recurrence of thyroid CA or goiter • Measure serum TSH • TSH normal - increase levothyroxine dose • TSH value 0.06 - 0.5 mU/L - appropriate level for suppression • TSH value <0.05 mU/L - check free T4 to assess potentially excessive therapy, adjust if indicated

12. T3 therapy (Cytomel) • Not recommended for treating hypothyroidism in general • Consider for patients who are still symptomatic on levothyroxine • Measure both serum T3 and TSH to assess therapy in this case

13. Monitoring hyperthyroidism therapy • Serum TSH unable to distinguish degree of illness • Serum T3 disproportionately higher than T4 • During treatment, TSH may remain subnormal for several weeks to months • Need to rely on T4 and T3 for efficacy of treatment with antithyroid drugs, radioiodine or surgery

14. Patterns of Thyroid Function Tests • See handout

15. Drugs affecting thyroid function or function tests • Drugs causing hypothyroidism • lithium, perchlorate, interferon, interleukin, iodine , radiographic agents, expectorants, kelp tablets, potassium iodine solutions, Betadine douches, topical antiseptics

16. Drugs affecting thyroid function or function tests • Drugs causing hyperthyroidism • iodine, amiodarone, interferon, interleukin

17. Drugs affecting thyroid function or function tests • Drugs causing abnormal test results without thyroid dysfunction • low serum TBG - androgens, danazol, glucocorticoids, niacin • high serum TBG - estrogens, tamoxifen, raloxifene, methadone, 5FU, clofibrate, heroin • decreased T4 binding to TBG - salicylates, salsalate, furosemide, heparin, some NSAIDs

18. Drugs affecting thyroid function or function tests • Drugs causing abnormal test results without thyroid dysfunction • Increased T4 clearance - phenytoin, carbamazepine, rifampin, phenobarbital • Suppression of TSH secretion - dopamine, dobutamine, glucocorticoids, octreotide • Impaired conversion of T4 to T3 - amiodarone, glucocorticoids, contrast for OCG, propylthiouracil, beta blockers

19. Thyroid antibodies • Graves Disease • LATS (long acting thyroid stimulator) IgG immunoglobulin • inhibits binding of TSH, stimulates thyroid hormone production • levels drop after treatment for hyperthyroidism (radioiodine, surgery) but usually rise transiently before dropping

20. Thyroid antibodies • Additional autoantibodies are found in Graves Disease • to thyroglobulin • to thyroid peroxidase • usually lower levels than in chronic autoimmune thyroiditis

21. Thyroid antibodies • Chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) • lymphocytic infiltration of thyroid occurs in both this and Graves Disease • progression from Graves to Hashimoto’s and vice/versa can occur • can be hyperthyroid one year and hypothyroid the next

22. Thyroid antibodies • Antibodies present in Hashimoto’s • to thyroglobulin • to thyroid peroxidase • to TSH receptors, (becomes an inhibitor instead of stimulator as in Grave’s), specific to Grave’s or Hashimoto’s • to sodium-iodide symporter

23. Thyroid imaging • Thyroid radioiodine uptake and scan • used to confirm Graves’ hyperthyroidism and exclude other causes, (particularly subacute lymphocytic (painless) thyroiditis • radioiodine or technetium scans used to evaluate thyroid nodules (radioiodine preferred as more sensitive in picking up cold nodules

24. Thyroid imaging • Thyroid scan • indeterminate nodules can be assessed by suppression scanning • giving exogenous thyroid hormone to suppress TSH production will accentuate an autonomously functioning nodule • may need to measure TSH, if result still ambiguous, to insure suppression

25. Thyroid imaging • Pituitary MRI • CT of the sella turcica • both used if suspicious of mass or hypothalamic disorder causing low or high TSH levels, not explained by endogenous thyroid disease

26. Thyroid imaging • Ultrasound • used to provide anatomic information rather than functional (confirm physical findings) • primarily used to distinguish thyroid nodules and guide fine needle aspirations • solitary solid nodules, 1.0 cm or greater, which are cold on scan are more likely to be cancer, particularly if they have microcalcifications, irregular borders or central blood flow

27. Thyroid imaging • Ultrasound • cystic nodules found on ultrasound are less likely to be cancer • should be aspirated for cytology to insure that no cancer is present

28. Fine needle aspiration • Office procedure • Procedure outcomes improved when using ultrasound guided FNA but expensive • nondiagnostic • benign • suspicious or indeterminate • malignant

29. Case 1 • 34 year old woman, asymptomatic • on physical exam, mildly enlarged thyroid with possible nodule in right lobe • What tests would you use to evaluate this?

30. Case 2 • 26 year old woman with complaints of palpitations, sweats, weight loss • Physical exam shows mild lid lag, tachycardia, mild tremor and mild goiter • What tests would you do?

31. Case 3 • 55 year old male with complaints of fatigue, constipation, weight gain of 15 pounds in past 3 months • Physical exam shows mild bradycardia of 55, slowed DTRs, coarse hair and skin • What tests would you do?

32. Case 4 • 55 year old woman gets screening TSH which comes back at 6.5 mU/L, patient is asymptomatic • What tests, if any, do you do in addition?