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THYROID DISORDERS Too Hot, Too Cold or Just Right

THYROID DISORDERS Too Hot, Too Cold or Just Right. Uzma Khan, MD. Associate Professor of Clinical Internal Medicine University of Missouri-Columbia ACP 2012. On her show, Oprah Winfrey admitted a thyroid problem was the cause of her tiredness. Simple case.

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THYROID DISORDERS Too Hot, Too Cold or Just Right

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  1. THYROID DISORDERSToo Hot, Too Cold or Just Right Uzma Khan, MD. Associate Professor of Clinical Internal Medicine University of Missouri-Columbia ACP 2012

  2. On her show, Oprah Winfrey admitted a thyroid problem was the cause of her tiredness

  3. Simple case • 45 year old lady, mother of two teenagers, works at Wal-Mart pharmacy • Presents with tiredness, sleepy all the time, weight gain of 10 lbs. over the last 5 years, skin and hair is dry • Her hair dresser advised her to get her thyroid checked

  4. History- Questions to ask • No history of radiation to head and neck • No personal history of thyroid problems • During pregnancy? • No family history of thyroid problems --“ goiter”

  5. Work up • Lab tests • TSH • Free T4 • Total T4 • Free T3 • Total T3 • TPO antibodies • Thyroglobulin • Thyroglobulin Antibodies • Imaging studies • Thyroid uptake and scan • Thyroid ultrasound • CT scan of neck • PET scan • Fine needle aspiration

  6. Endocrine Review, 2008

  7. The percentage of subjects with an elevated TSH level by sex and decade of age. Percentages of hypothyroidism ranged from 4% to 21% in women and from 3% to 16% in men. Canaris et al, The Colorado Thyroid Disease Prevalence Study, 2000

  8. The percentage of euthyroid subjects compared with those with an elevated TSH level who reported each symptom.

  9. The proportions of elevated, normal, or low lipid levels according to thyroid function status.

  10. Levothyroxine (T4) • Medical situations where T4 medication may be affected. • Estrogen: Pregnancy, OCP, HRT • Drugs that interfere with T4 absorption • Iron, Calcium • Cholestyramine (cholesterol resin Rx) • At least 4h between T4 and these drugs! • Increase TBG: estrogen, heroin, methadone • Decrease TBG: depakote, dilantin, androgens

  11. T3/T4 Combos • Thyrolar, Armour thyroid • Combo pill of T3 and T4 • Ratio of T4:T3 = 4:1 (not 14:1) • T3 still not slow release • Few small studies showing benefit • 1999 NEJM study 33 patients • Benefit: mood & cognitive function • Cytomel is only T3………..limited use • Only check a TSH…do not check T4 or T3

  12. Complex Case • 42 year old female presents with left thyroid nodule detected during annual physical exam • She is a country singer , has no medical problems, takes no medications, and has a healthy 2 year old son • There is no history of head and neck irradiation, her mother has hypothyroidism, there is no family history of thyroid cancer • She denies dysphagia, ROS is negative, and states” I did not even know it was there”

  13. Thyroid Incidentaloma Palpable: 5% women 1% men Ultrasound: 19-67%

  14. Thyroid Nodules PrevalenceAutopsy Data • Autopsy data from 821 patients at the Mayo clinic with “normal” thyroids on clinical examination • 49% had thyroid nodules • 12 % had single nodule • 37% had multiple nodules • 35.5% of these nodules were >2 cm Mortensen et al. J Clin Endocrinology, 1955

  15. Common Varieties of Thyroid Nodules

  16. TechniqueThe location of the thyroid is identified by inspection. Using the anterior or posterior approach, palpate the thyroid to identify nodules Note the size and number of nodules. Note the consistency of the nodule. Palpate regional lymph nodes for consistency and mobility. • Posterior approach • Anterior approach

  17. The Pemberton sign Wallace C , Siminoski K Ann Intern Med 1996;125:568-569

  18. Work up • Lab tests • TSH • Free T4 • Total T4 • Free T3 • Total T3 • TPO antibodies • Thyroglobulin • Thyroglobulin Antibodies • Imaging studies • Thyroid uptake and scan • Thyroid ultrasound • CT scan of neck • PET scan • Fine needle aspiration

  19. Work up- Next step • Lab tests • TSH: 0.2 mIU/L • Free T4: Normal • Total T4 • Total T3 • Free T3 • TPO antibodies • Thyroglobulin • Thyroglobulin Antibodies • Imaging studies • Thyroid uptake and scan • Thyroid ultrasound • CT scan of neck • PET scan • Fine needle aspiration

  20. Work up- Next step • Lab tests • TSH: 0.2 mIU/L • Total T4 • Free T4 • Total T3 • Free T3 • TPO antibodies • Thyroglobulin • Thyroglobulin Antibodies • Imaging studies • Thyroid uptake and scan ? Toxic multinodular goiter? • Thyroid ultrasound • CT scan of neck • PET scan • Fine needle aspiration

  21. Work up- Next step • Lab tests • TSH: 0.2 mIU/L • Total T4 • Free T4 • Total T3 • Free T3 • TPO antibodies • Thyroglobulin • Thyroglobulin Antibodies • Imaging studies • Thyroid uptake and scan ? Toxic multinodular goiter? • Thyroid ultrasound • Multiple thyroid nodules with concerning features in left thyroid nodule • CT scan of neck • PET scan • Fine needle aspiration

  22. Work up- Next step • Lab tests • TSH: 0.2 mIU/L • Total T4 • Free T4 • Total T3 • Free T3 • TPO antibodies • Thyroglobulin • Thyroglobulin Antibodies • Imaging studies • Thyroid uptake and scan ? Toxic multinodular goiter? • Thyroid ultrasound • Multiple thyroid nodules with concerning features in left thyroid nodule • CT scan of neck • PET scan • Fine needle aspiration • Indeterminate!

  23. Genetic medicine Era…New tools!! • She declines surgery, wants to know if we can be more “sure” about cancer • The endocrinologist says “ will assess the cells for mutations”……?

  24. Work up- Next step • Lab tests • TSH: 0.2 mIU/L • Total T4 • Free T4 • Total T3 • Free T3 • TPO antibodies • Thyroglobulin • Thyroglobulin Antibodies • Imaging studies • Thyroid uptake and scan ? Toxic multinodular goiter? • Thyroid ultrasound • Multiple thyroid nodules with concerning features in left thyroid nodule • CT scan of neck • PET scan • Fine needle aspiration • Indeterminate!

  25. Work up- Next step • Lab tests • TSH: 0.2 mIU/L • Total T4 • Free T4 • Total T3 • Free T3 • TPO antibodies • Thyroglobulin • Thyroglobulin Antibodies • Imaging studies • Thyroid uptake and scan ? Toxic multinodular goiter? • Thyroid ultrasound • Multiple thyroid nodules with concerning features in left thyroid nodule • CT scan of neck • PET scan • Fine needle aspiration • Indeterminate!

  26. Thyroid Cancer Incidence and Mortality, 1973-2002 • 10th leading cancer type in women • 22590 new cases/year • 2400 deaths/year • 50% increase in incidence in 25 years Davies, L. et al. JAMA 2006;295:2164-2167.

  27. Trends in Incidence of Thyroid Cancer (1973-2002) and Papillary Tumors by Size (1988-2002) in the United States Davies, L. et al. JAMA 2006;295:2164-2167.

  28. Risk of Malignancy • A study of 317 thyroid incidentalomas by Nam-Goong et al in 2004 Nam-Goong et al. Clinical Endocrinolog. 2004

  29. Radioactive iodine management • Consensus: • Fine needle aspiration---if shows malignancy • Total thyroidectomy • Ablative doses of radioiodine • Suppressive treatment • Periodic follow up with thyroglobulin and imaging with radioiodine scans

  30. Close follow up

  31. rhTSH • recombinant form of human TSH • Thyrogen® (thyrotropin alfa for injection) is a highly purified • Thyrotropin alfa is synthesized in a genetically modified Chinese hamster ovary cell line • Can be used for • Remnant ablation • Follow up WBS/thyroglobulin

  32. Scheduling of rhTSH Doses and Diagnostic Procedures • Recommended dose: 0.9mg IM q24 hr x 2 doses • Serum Tg protocol is identical for both Tg alone testing and when combined with WBS • 4 mCi 131I should be used for scans; which should be acquired for  30 minutes and/ or  140,000 counts

  33. Maximum Percent Change from Baseline in the Sum of the Longest Diameters (SLD) of Target Lesions Motesanib Diphosphate in Progressive Differentiated Thyroid Cancer Sherman S et al, NEJM, July 2008

  34. Know the thyroid well!! You may need it as the next White House Physician

  35. TSH: 6.1 mIU/ l ( 0.40-4.5) • TSH : first line test • 2nd generation: good immunometric, sandwich assays: up to 0.1 • 3rd generation: ? Varying sensitivity immunochemiluminometric Assays: up to 0.01 • TSH: normal range: 0.40 -4.5 m IU/L • <0.1: Hyperthyroidism • 0.1 – 0.3: subclinical hyperthyroidism • 0.32-5.6: normal vs central hypothyroidism • 6-10: subclinical hypothyroidism • > 10: primary hypothyroidism

  36. Know what you are “fishing for”……………………………………………..

  37. T4 or T3 • T4 • Free T4 : good • Total T4: make sure you know about TBG • T3 • FT3: very minute amounts • TT3: helpful in T3 thyrotoxicosis, remember TBG! • Free T4 : normal

  38. Thyroid Function T4 Protein* binding + 0.03% free T4 80% (peripheral) T3 Protein* binding + 0.3% free T3 20% * Thyroid hormone Binding: TBG 75% Transthyretin 15% Albumin 10% Ratio of T4:T3 -stored in thyroglobulin: 15:1 -secreted in blood: 10:1 Increased production due to any reason Leads to an increase in T3

  39. Serum TSH range in the US population Not a Gaussian curve…………… Tail Hollowel et all, NHANES III survey, JCEM 2002

  40. Thyroid tests • Antibodies • 10% of general population • TPO> Hashimotos • TSI > Graves • Tg> non specific • Remember PGAs • Thyroglobulin • Large glycoprotein • Only source: thyroid follicular cell • Assay limitation: • Tg Ab • >variability 25% • Know why you are doing it • Thyroid cancer • Exogenous TH?

  41. Utility of Radioactive Iodine Uptake (RAIU)

  42. Your Interpretation 24 hour RAIU = 25%. TSH 0.2 mU/L. Thyroid palpably “cobblestone” texture.

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