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Thyroid Diseases. Scott Urquhart, PA-C Clinical Instruct., George Washington Univ. PA Program Adjunct Clinical Prof., James Madison Univ. PA Program Diabetes and Thyroid Associates. Fredericksburg, Virginia. Q1: The most common thyroid function disorder is?. 1) Graves’ disease

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    1. Thyroid Diseases Scott Urquhart, PA-C Clinical Instruct., George Washington Univ. PA Program Adjunct Clinical Prof., James Madison Univ. PA Program Diabetes and Thyroid Associates. Fredericksburg, Virginia

    2. Q1: The most common thyroid function disorder is? • 1) Graves’ disease • 2) Hypothyroidism • 3) Sub-acute thyroiditis • 4) Thyroid cancer

    3. Q2: The most sensitive test for thyroid function is? • 1) Free T4 • 2) Free T3 • 3) TSH • 4) Thyroid ultra sound

    4. Q3: The best assay to confirm that a patient’s hypothyroidism is autoimmune in nature? • 1) Thyroid stimulating immunoglobulins • 2) Anti-nuclear antibody • 3) TSH • 4) Thyroid peroxidase antibodies

    5. Q4: The best assay to confirm that a patient’s hyperthyroidism is autoimmune in nature? • 1) Thyroid stimulating immunoglobulins • 2) Anti-nuclear antibody • 3) TSH • 4) Thyroid peroxidase antibodies

    6. Q5: Which is the best study to confirm the etiology of a patient’s thyrotoxicosis? • 1) I123 thyroid scan/uptake • 2) Neck CT or MRI • 3) Thyroid ultrasound • 4) Fine needle aspiration of the thyroid

    7. Q6: Which is the best study to make the initial evaluation for thyroid nodules discovered on routine physical exam? • 1) I123 thyroid scan/uptake • 2) Neck CT or MRI • 3) Thyroid ultrasound • 4) Fine needle aspiration of the thyroid

    8. Q7: Patient has a thyroid U/S showing a solid dominant (>10mm) nodule and normal thyroid function, what is your next step? • 1) Re-check thyroid U/S in 1 year • 2) Fine needle aspiration of the thyroid • 2) Neck CT or MRI • 4) I123 thyroid scan/uptake

    9. Q8: Thyroid U/S shows homogeneous increased radiotracer uptake, the diagnosis is? • 1) Metastatic thyroid cancer • 2) Graves’ disease • 3) Toxic multi-nodular goiter • 4) Toxic thyroid nodule

    10. Q9: Methimazole or propylthiouracil and used to treat hypothyroidism? • 1) True • 2) False

    11. Q10: Which in not an appropriate treatment for Graves’ disease? • 1) Thyroidectomy • 2) Anti-thyroid medications such as propylthiouracil or methimazole • 3) Levothyroxine sodium • 4) I131 radioactive iodine

    12. OBJECTIVES • Order and interpret appropriate labs and studies necessary for the diagnosis of the thyroid disorders discussed in this lecture. • Describe the common signs and symptoms of hyper/hypothyroidism, work-up, treatment, and follow-up. • Provide a practical approach to the work-up and diagnosis of thyroid nodules. • Know when to refer.

    13. Thyroid Diseases Scott Urquhart, PA-C Clinical Instruct., George Washington Univ. PA Program Adjunct Clinical Prof., James Madison Univ. PA Program Diabetes and Thyroid Associates. Fredericksburg, Virginia

    14. Major Thyroid Abnormalities Functional / Biochemical Structural / Anatomy • Thyroid • Goiter • Nodules • Cold • Warm or Hot • Cysts • Malignancies • Hypothyroidism • Hyperthyroidism

    15. At Risk Population for Thyroid Dysfunction • Women, elderly, postpartum 4-8 months. • FamHx of Hashimoto’s or Graves’ dz. • PMHx or FamHX autoimmune diseases – SLE, RA, DM1, Addison’s, vitiligo, pernicious anemia. • Type 1 DM: ~20% increase risk for thyroid dysfunction, mainly hypothyroid. • Patients treated with amiodarone, lithium, others. Am. Thyroid Association, postpartum thyroiditis, accessed 6/4/2011 AACE Thyroid Guidelines, Endocr Pract. 2002;8(No. 6) Basic and Clinical Endocrinology, Lange Series, 7th edition

    16. HYPOTHALAMIC / PITUITARY THYROID AXIS • TRH: stimulate anterior pituitary to release TSH. • TSH:stimulate thyroid for synthesis and release of T4 and T3. • Low T4, Low T3: stimulate TSH and TRH. • High T4, High T3: inhibit TSH and TRH. Basic and Clinical Endocrinology, Lange Series, 7th edition

    17. THYROID HORMONES • T4 to T3 secretion ratio of 10:1. • T3 is 4X more biologically active than T4. • T1/2: T4 = 7days, T3 = 1 day. • T4,T3: 99% bound to protein, i.e. metabolically inactive. • From thyroid: 100% - T4, 20% - T3 remainder of T3 is from T4 to T3 conversion in peripheral tissues. Basic and Clinical Endocrinology, Lange Series, 7th edition

    18. THYROID TESTINGBiochemical 1) TSH - highly sensitive, best test for thyroid function. • Free T4 (FT4)- biologically active. • Free T3 (FT3) - biologically active. - rarely need to check unless, TSH is low or undetectable with a normal FT4.

    19. THYROID TESTING(more specific) • Thyroid Peroxidase Antibodies (TPO-Ab’s) - Hashimotos Thyroiditis • Thyroid Stimulating Immunoglobulins (TSI’s) or TSH receptor antibodies (TRAb). - Unique to Graves’ disease • I-123 RAIU (Radio Active Iodine Uptake) evaluation for thyrotoxicosis, shape, size. Don’t use to confirm hypothyroidism.

    20. DON’T FORGET THE BASICS • History of present illnessand ROS. • PMHx – postpartum • Past Hx of thyroid pain/tenderness/nodule/ enlargement or goiter • H/O autoimmune diseases • FamHX – thyroid dysfunction, thyroid cancer, Autoimmune diseases. • Medications • Systematic physical exam

    21. Hypothyroidism

    22. HYPOTHYROIDISM • Prevalence: 4 - 8% general population. • Mean age of Dx: 5th decade of life • Female to male ratio: 10:1 Endocrine Secrets. McDermott, 4rd Edition

    23. PRIMARY HYPOTHYROIDISM • Identification on clinical basis can be challenging. • Symptoms generally vague. • Frequently goes unnoticed, confused as other health problems. • Insidious onset + poor index of suspicion = misdiagnosis

    24. ETIOLOGY • Autoimmune: - Chronic lymphocytic thyroiditis = Hashimoto’s - positive TPO-Ab’s - remember postpartum thyroiditis • Iatrogenic: I-131 RAI, total/subtotal thyroidectomy, neck irradiation. • Congenital: agenesis, dysgenesis. • Drug induced: lithium, amiodarone, chemotherapy, others. Endocrine Secrets. McDermott, 4rd Edition Basic and Clinical Endocrinology, Lange Series, 7th edition

    25. Clinical Symptoms of Hypothyroidism • Fatigue • Lethargy • Cold intolerance • Constipation • Decreased memory • Depression • Mental Impairment • Arthralgias • Hoarseness • Heavy menstrual flow • Paresthesias • Sleepiness • Weight gain ,edema • Muscle cramps AACE Thyroid Guidelines, Endocr Pract. 2002;8(No. 6) Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.

    26. Clinical Signs of Hypothyroidism • Bradycardia • Coarse hair, hair loss • Delayed relaxation phase of deep tendon reflexes • Dry, cool, pale skin • Goiter • Hoarseness • Non-pitting edema (myxedema) • Puffy eyes and face • Slow movements • Slow speech • Thinning lateral third of eyebrows AACE Thyroid Guidelines, Endocr Pract. 2002;8(No. 6) Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clin. Text. 8th ed. 2000.

    27. Example of Clinical Manifestationsof Hypothyroidism • Patient example • Fatigue (“no energy”), cold intolerance, constipation, weight gain, fatigue, problems with concentration (“mental clouding”), dry skin

    28. CLINICALMANIFESTATONSEXAM • NECK: thyroid may be normal, enlarged, symmetric/asymm., smooth or lumpy. • HEART: bradycardia. • EXTREMS: pretibial/ankle edema, dry cool skin, brittle nails. • NEURO: DTR’s with delayed relaxation phases • HEENT: periorbital puffiness, loss of lateral eyebrows, coarse/thinning hair.

    29. LABORATORY EVALUATION • TSH - high • Free T4 - low • Check both if new diagnosis to make sure PITUITARY-THYROID AXIS intact. • Consider TPO-Ab

    30. Levothyroxine Sodium (LT4 ) • Exogenously administered LT4 hormone • Indistinguishable from endogenous T4, both in its physiologic effects and its quantification as measured in blood • LT4 is the treatment of choice as replacement or supplemental hormone therapy • Branded preparations are preferred Levothyroxine Bioequivalence Briefing Document. Available at: http://www.fda.gov/ohrms/dockets/ac/03/briefing/3926B1_02_A-abbott.pdf

    31. TREATMENT • Levothyroxine (LT4), narrow therapeutic range • 0.3 – 3.0 IU/mL, caution in lower range TSH. • Brand vs. generic vs. T4 + T3 combination. • Lifelong treatment, most cases • Dosing: 1.6 mcg/kg/day = ~100 - 125 mcg/day. • Compliance, empty stomach, competing agents for absorption (Iron, Calcium ) • Check TSH no sooner than 6 weeks after initial start of LT4 or any adjustment. AACE Thyroid Guidelines, Endocr Pract. 2002;8(No. 6)

    32. Therapy Monitoring • Clinical and laboratory monitoring enable • Evaluation of the clinical response • Assessment of patient compliance • Assessment of drug interactions, if applicable • Adjustment of dosage, as needed • Clinical and laboratory evaluations should be performed • At 6- to 8-week intervals while titrating • Annually once a euthyroid state is established

    33. Factors That May Reduce Levothyroxine Effectiveness • Malabsorption Syndromes • Post jejunoileal bypass surgery • Short bowel syndrome • Celiac disease • Reduced Absorption • Colestipol hydrochloride • Sucralfate • Ferrous sulfate • Food (eg, soybean formula) • Aluminum hydroxide • Cholestyramine • Sodium polystyrene sulfonate • Drugs That Increase Clearance • Rifampin • Carbamazepine • Phenytoin • Factors That Reduced T4 to T3 Clearance • Amiodarone • Selenium deficiency • Other Mechanisms • Lovastatin • Sertraline Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text. 8th ed. 2000. Synthroid® [package insert]. Abbott Laboratories; 2003.

    34. Thyroid Hormone TherapySpecial Treatment Populations • Patients 50 years of age or with underlying cardiac disease • Initial dose of LT4 - 25 to 50 mcg/d • Elderly patients with cardiac disease • Initial dose of LT4 - 12.5 to 25 mcg/d • Patients with heart failure • Both hypo- and hyperthyroidism can worsen heart failure Levothyroxine Bioequivalence Briefing Document. Available at: http://www.fda.gov/ohrms/dockets/ac/03/briefing/3926B1_02_A-Abbott.pdf

    35. Treating Hypothyroidism Before and During Pregnancy • Encourage adherence with LT4 replacement therapy before conception • Monitor TSH levels before conception and during first trimester • Consider increase of LT4 dosage in athyreotic patients by 25% - 50% when pregnancy is confirmed • Monitor TSH levels every 6 to 8 weeks throughout pregnancy • Reinstate pre-pregnancy LT4 dosage immediately following delivery Gharib H, et al. Endocr Pract. 1999;5:367-368. Mandel SJ, et al. N Engl J Med. 1990;323:91-96.

    36. Over-Replacement Risks • Switching a narrow therapeutic index drug, such as LT4, without retesting and re-titrating can cause inconsistent TSH control, resulting in over-replacement • Over-replacement risks (TSH <0.5 IU/mL) • Iatrogenic thyrotoxic state • Increased heart rate and myocardial contractility • For cardiac patients, increased risk of angina and MI • Reduced bone density/osteoporosis • Psychiatric symptoms, such as anxiety, sleep disturbance, irritability, and fatigue Synthroid® [package insert]. Abbott Laboratories; 2003. Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. Felicetta JV. Consultant. 2002;1597-1606. Available at: www.consultantlive.com. Accessed July 1, 2003.

    37. Case 1 46 y.o. female presents with a 3 - 4 month history of heavier than usual menstrual cycles, fatigue, “feeling sleepy all of the time”, depressed, constipation, problems concentrating, cold intolerance. • PMHx: unremarkeable • FAMHx: Adopted.

    38. Case 1 continued • P.E. : DTR’s show delayed relaxation phases of biceps and brachioradialis, non tender symmetric goiter @ 2 times normal size without nodules. • LABS : TSH 77.02 (0.45-4.50) Free T4 0.38 (0.8 – 1.50) TPO-Ab 267 reactive greater 40.

    39. Case 1 continued • Dx: Hashimoto’s Thyroiditis • Tx: 100 mcg qd, non-generic LT-4 Follow-up in 6 weeks and recheck TSH • F/U: Feeling “90% better” TSH 7.62 Increase to 112mcg qd. Follow-up in 2 months. • 2 months later TSH – 2.11 (0.50 - 3.00). Plan: follow and adjust LT-4 based on TSH

    40. SUBCLINICAL HYPOTHYROIDISM • Very difficult to diagnose clinically • High index of suspicion, may be asymptomatic • 4 -15% of general population* • 20% of pts. over 60 y.o. (esp. women)** • LABS: TSH - minimally high (6 - 10 IU/mL) Free T4 – low normal • TREATMENT: controversial, consider if symptoms, lipid abnormality, if TPO-Ab positive • Low dose LT-4 vs. surveillance, education. *US Endocrinology Volume 4 Issue 1 *www.aace.com accessed 6/4/2011

    41. Mild Thyroid Failure and Neurobehavioral Abnormalities • Conditions reported to occur more frequently in patients with mild thyroid failure • Depression • Anxiety • Somatic complaints • Cognitive abnormalities Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. Cooper DS. N Engl J Med. 2001;345:260-264.

    42. Rationale for Treating Mild Thyroid Failure • Potential benefits from treatment • Prevent progression to overt hypothyroidism • Improve serum lipid profile, which may reduce the risk of death from cardiovascular causes • Reduce symptoms, including psychiatric and cognitive abnormalities Cooper DS. N Engl J Med. 2001;345:260-264.

    43. Case 2 • Hx: 32 y.o. women referred for mildly increased TSH 8.69 (0.46-4.68) • Symtoms: mild fatigue, dry skin, “not feeling my usual self” • PMHx: no H/O thyroid disorders, or recent of remote thyroid pain/tender. • FAMHx: Mother, two maternal aunts with hyperthyroidism.

    44. Case 2 continued • P.E. : Thyroid minimally enlarged and non-tender, no nodules. remainder of exam unremarkable. • Labs: TSH 7.5 (.46 – 4.68) FREE T4 0.82 (0.80-1.50). TPO-Ab 317 reactive greater than 40

    45. Case 2 continued • DX:Subclinical Hypothyroidism • Hashimotos thyroiditis • Tx: “Brand LT4” 25 mcg q.d. Follow-up and TSH in 2 months. • Follow-up: patient feeling better without complaints TSH 1.89 (0.5 – 3.0) Education, need to follow

    46. Hyperthyroidism

    47. HYPERTHYROIDISMETIOLOGY • Graves’ disease ( autoimmune ). • Toxic multi-nodular goiter ( toxic MNG ). • Toxic nodule (hot or warm nodule)

    48. Common Symptoms and Signs of Thyrotoxicosis Symptoms • Nervous / shaky • Fatigue • Muscle weakness • Increased perspiration • Heat intolerance • Tremor • Palpitations • Appetite/weight changes • Menstrual disturbances Signs • Goiter • Hyperactivity • Tachycardia / arrhythmia • Systolic hypertension • Warm, moist, or smooth skin • Stare and eyelid retraction • Tremor • Hyper-reflexia Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.

    49. GRAVES’ Dz • ~75% of cases of hyperthyroidism. • Thyroid Stimulating Immunoglobulins (TSI’s) and / or TSH receptor antibodies (TRAb) levels usually increased • Incidence 2nd – 4th decade of life. • ~5 times more likely in women. Basic and Clinical Endocrinology, Lange Series, 7th edition

    50. Thyrotoxicosis - work-up • Labs- demonstrate thyrotoxicosis. • TSH - Low or undetectable • Free T4 and/or Free T3 – Increased I123 thyroid scan / uptake • Uptake is increased. • 4 hour: normal ref. (5 – 15%) • 24 hour: normal ref. (6 - 30%) • Scan (anatomical findings via radiotracer uptake) • Homogeneous ( Graves’ Dz) • multiple areas (Toxic MNG) • single area (Hot or warm nodule) Hyperthyroidism Management Guidelines, Endocr Pract. 2011;17(No. 3)