Thyroid Disease

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Thyroid Disease

  1. 1. The Physician's Guide to Laboratory Test Selection and Interpretation Thyroid Disease Clinical Background Thyroid disease frequently arises from autoimmune processes that stimulate overproduction of hormones or cause gland destruction that subsequently leads to underproduction of hormones. Epidemiology • Incidence • Hypothyroidism • 4-6% of the population • Increases with age (1 of 4 nursing home patients has hypothyroidism) • Primary congenital hypothyroidism – 1/3,000 infants • Hyperthyroidism • 1-2% of the population • In pregnant females – 2/1,000 pregnancies • Age – onset is 40s-50s for both hypo- and hyperthyroidism • Sex – M<F, 1:5-8 for both types Hypothyroidism • Caused by underproduction of hormones Etiologies • Autoimmunity – Graves disease • Iatrogenic (treatment of hyperthyroidism) • Iodine deficiency most common cause worldwide • Drugs – amiodarone, androgens, aspirin, cholestyramine, estrogens, furosemide, glucocorticoids, levodopa, lithium, neuroleptics, phenytoin, propranolol Clinical Presentation • Insidious onset is common • Fatigue, depression, cold intolerance, weight gain, bradycardia, constipation, hair loss, alopecia, carpal tunnel syndrome, dry/coarse skin, skin thickening (myxedema) • Most serious manifestation is myxedema coma • Congenital disease • Growth retardation • Developmental delay/mental retardation Treatment • Pregnant patients with hypothyroid may require increase of replacement therapy Hyperthyroidism (Thyrotoxicosis) • Caused by overproduction of thyroid hormones Etiologies • Graves disease accounts for 60-80% of cases • Autoimmune – thyroid stimulating immune globulins (TSI IgG) bind to thyrotropin receptors on the thyroid gland • Toxic multinodular (Plummer disease) or uninodular goiter • Secrete hormone autonomously • Thyroiditis ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Thyroid Disease - p. 1 of 8
  2. 2. The Physician's Guide to Laboratory Test Selection and Interpretation • Postpartum • Subacute • Other – thyroid stimulating hormone (TSH) secreting tumors (rare); ingestion of T3, T4, drug-induced (amiodarone) Clinical Presentation • Hyperactivity, heat intolerance, fatigue, weakness, diarrhea, tachycardia, tremor, goiter, weight loss • Diffuse nontender enlargement of the gland • Ophthalmopathy – occurs in 30% of patients and consists of protrusion of the eyes and periorbital swelling Treatment • Usually required Pregnancy-related thyroid disorders Pathophysiology • Thyroid binding globulin levels (TBG) are elevated as estrogen increases • Increased TBG causes a shift in T3 and T4 reference ranges 1.5 times the nonpregnant state; always use trimester specific reference values • Reference intervals for free T4 have not been well established in pregnant patients – some authors advocate use of total T4 in place of free T4 during pregnancy • TSH falls and may be below the lower adult reference limit in 20% of pregnancies • Hypothyroidism • 0.3-0.7% of pregnancies • Associated with infertility, low birth weight, low fetal IQ, fetal demise, hypertension, placenta abruptio and postpartum hemorrhage (fetus may be unaffected) • Symptoms – low energy, inappropriate weight gain, constipation, goiter, cold intolerance and bradycardia • Most common cause – chronic autoimmune thyroiditis • Hyperthyroidism • 0.2% of pregnancies • Associated with spontaneous abortions, infertility, still births, low birth weight, pre-term delivery, fetal or neonatal hyperthyroidism, congestive heart failure in mother • In 2% of pregnancies, T4 is supranormal around 10-12 weeks because hCG is at its peak and TSH is at its nadir • Symptoms – weight loss, goiter, muscle weakness, palpitations, onycholysis, tachycardia and eye changes • Causes • Gestational transient thyrotoxicosis – frequently associated with hyperemesis gravidarum in first trimester • Hyperemesis gravidarum • Trophoblastic tumors such as choriocarcinoma • TSH receptor mutations • Euthyroid sick syndrome • Low levels of thyroid hormone in clinically euthyroid patients who have systemic illnesses • Diagnosis – TSH normal; T3, T4 may be low ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Thyroid Disease - p. 2 of 8
  3. 3. The Physician's Guide to Laboratory Test Selection and Interpretation Diagnosis Indications for Testing • Symptoms of hyper- or hypothyroidism, family history of autoimmune thyroiditis Laboratory Testing • Hypothyroidism • Initial evaluation should include thyroid stimulating hormone (TSH) (increased) followed by Free T4 (FT4) (decreased), thyroid antibodies • Hypothyroidism during pregnancy may cause fetal demise and low IQ in liveborn (endemic cretinism) infants • Order TSH and TPO antibody testing for patients who have a prior diagnosis of or family history of hypothyroidism • Elevated TPO antibodies associated with post-partum thyroiditis • Subclinical disease • TSH minimally elevated with normal T4, T3 • Presence of symptoms or experiencing infertility, consider testing for hypothyroidism • Hyperthyroidism • Initial evaluation involves TSH measurement (decreased), Free T4 (increased) • Further evaluation may include thyroid antibody evaluation, radioiodine uptake of the thyroid gland Differential Diagnosis • Hyperthyroidism • Drug-induced (amiodarone) • Thyrotoxicosis factitia • Trophoblastic tumors • Anxiety • Sepsis • Hypothyroidism • Depression • Cushing disease • Obesity • Polycystic ovarian syndrome (PCOS) • Metabolic syndrome Screening • Hypothyroidism • Neonatal – 24 hours using TSH • Abnormal tests must be followed up with T4 • Pregnancy – not recommended to screen all pregnant women; however, women at risk (previous hypothyroidism, pregestational diabetes mellitus, previous thyroid disease) and women who are symptomatic should be screened using TSH Monitoring • Hyperthyroidism • Initial monitoring of TSH and T4 – 6 weeks after initiation of therapy until euthyroid • Patients eventually develop hypothyroidism in autoimmune disease as the gland burns out • Monitor TSH and T4 every year ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Thyroid Disease - p. 3 of 8
  4. 4. The Physician's Guide to Laboratory Test Selection and Interpretation • Hypothyroidism – TSH and T4 are useful in monitoring thyroid replacement therapy • Monitor TSH in pregnant women to assess adequacy of therapy screening Lab Tests Indications for Laboratory Testing Tests generally appear in the order most useful for common clinical situations. For test-specific information, refer to the test number in the ARUP Laboratory Test Directory on the ARUP Web site at www.aruplab.com. Test Name and Number Recommended Use Limitations Follow Up Thyroid Stimulating Initial screening test for suspected If elevated or Hormone hypothyroidism and hyperthyroidism depressed, order Free 0070145 Functional sensitivity of assay is T4 or T4 Method: <0.02 mU/L Electrochemiluminescent Immunoassay Thyroxine, Free (Free T4) First line test 0070138 Most reliable marker of thyroid Method: function when illness is suspected Electrochemiluminescent Immunoassay Thyroxine Some authors advocate using 0070140 total T4 in place of free T4 during pregnancy (adjusting the reference Method: interval upward by 1.5 times) Electrochemiluminescent Immunoassay Thyroid Stimulating Detect thyroid antibodies for Immunoglobulin diagnosing autoimmune disease 0099430 (Graves disease) Method: Bioassay/ Chemiluminescence Thyroid Peroxidase (TPO) Detect antibodies for diagnosing Antibody autoimmune disease 0050075 Method: Chemiluminescent Immunoassay Thyroid Stimulating Detect antibodies for diagnosing Hormone Receptor autoimmune disease Antibody (TRAb) 2002734 Method: Electrochemiluminescent Immunoassay ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Thyroid Disease - p. 4 of 8
  5. 5. The Physician's Guide to Laboratory Test Selection and Interpretation Thyroid Antibodies Detect antibodies for diagnosing 0050645 autoimmune disease Method: Test includes thyroid peroxidase Chemiluminescent (TPO) and thyroglobulin antibodies Immunoassay Thyroglobulin Antibody Detect antibodies for diagnosing 0050105 autoimmune disease Method: Test is part of thyroid antibody panel Chemiluminescent Immunoassay Additional Tests Available Test Name and Number Comments Thyroid Stimulating Hormone 3rd Generation 0070225 Method: Electrochemiluminescent Immunoassay Thyroxine, Free by Equilibrium Dialysis/HPLC-Tandem Mass Spectrometry 0093244 Method: Equilibrium Dialysis/High Performance Liquid Chromatography-Tandem Mass Spectrometry Triiodothyronine, Reverse 0070188 Method: Radioimmunoassay Triiodothyronine, Total (Total T3) 0070474 Method: Electrochemiluminescent Immunoassay Triiodothyronine, Free by Equilibrium Dialysis/HPLC-Tandem Mass Spectrometry 0093243 Method: Equilibrium Dialysis/High Performance Liquid Chromatography-Tandem Mass Spectrometry Thyroxine Binding Globulin 0070410 Method: Chemiluminescent Immunoassay Triiodothyronine, Free (Free T3) Not preferred test for hypothyroidism 0070133 Confirm diagnosis of hyperthyroidism with a Method: normal Free T4 or total thyroxine (T4) Electrochemiluminescent Immunoassay ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Thyroid Disease - p. 5 of 8
  6. 6. The Physician's Guide to Laboratory Test Selection and Interpretation T3 Uptake 0070135 Method: Electrochemiluminescent Immunoassay Iodine, 24 Hour, Urine 0092487 Method: Inductively Coupled Plasma/Mass Spectrometry Thyroid Panel T3 uptake, a component test, is obsolete 0070141 FT4 (Free Thyroxine) has emerged as a more Method: commonly ordered replacement for this panel over Electrochemiluminescent Immunoassay the past decade T3 Uptake Obsolete test 0070135 Thyroxine, Free (Free T4) is the preferred test Method: alternative for T3 uptake and Free Thyroxine Index Electrochemiluminescent Immunoassay tests Guidelines ACOG Committee Opinion No. 381: Subclinical hypothyroidism in pregnancy.Obstet Gynecol. 2007; 110 (4) :959-960. ACR Appropriateness Criteria® neuroendocrine imaging. American College of Radiology - Medical Specialty Society. 1999 (Revised 2008). Demers Laurence M, Spencer Carol A. LABORATORY MEDICINE PRACTICE GUIDELINES Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease. The National Academy of Clinical Biochemistry. [Accessed: 22 Jul 2009] Cited References Dominguez LJ, Bevilacqua M, Dibella G, Barbagallo M. Diagnosing and managing thyroid disease in the nursing home.J Am Med Dir Assoc. 2008; 9 (1) :9-17. General References Arrigo T, Wasniewska M, Crisafulli G, Lombardo F, Messina MF, Rulli I, Salzano G, Valenzise M, Zirilli G, De Luca F. Subclinical hypothyroidism: the state of the art.J Endocrinol Invest. 2008; 31 (1) :79-84. Balestrieri GP. Primary or secondary hypothyroidism?.J Am Geriatr Soc. 2008; 56 (7) :1377-. Brent GA. Clinical practice. Graves' disease.N Engl J Med. 2008; 358 (24) :2594-2605. Casey BM, Leveno KJ. Thyroid disease in pregnancy.Obstet Gynecol. 2006; 108 (5) :1283-1292. Cook A. Subclinical hypothyroidism: Let's identify research questions.BMJ. 2008; 337 :a1259-. DeBoer MD, Lafranchi SH. Pediatric thyroid testing issues.Pediatr Endocrinol Rev. 2007; 5 Suppl 1 :570-577. Downs H, Meyer AA, Flake D, Solbrig R. Clinical inquiries: How useful are autoantibodies in diagnosing thyroid disorders?.J Fam Pract. 2008; 57 (9) :615-616. Fatourechi V. Subclinical hypothyroidism: an update for primary care physicians.Mayo Clin Proc. 2009; 84 (1) :65-71. Gyamfi C, Wapner RJ, D'Alton ME. Thyroid dysfunction in pregnancy: the basic science and clinical evidence surrounding the controversy in management.Obstet Gynecol. 2009; 113 (3) :702-707. ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Thyroid Disease - p. 6 of 8
  7. 7. The Physician's Guide to Laboratory Test Selection and Interpretation Herrick B. Subclinical hypothyroidism.Am Fam Physician. 2008; 77 (7) :953-955. Jayakumar RV. Hypothyroidism.J Indian Med Assoc. 2006; 104 (10) :557-60, 562. Kwaku MP, Burman KD. Myxedema coma.J Intensive Care Med. 2007; 22 (4) :224-231. Lynn WR, Lynn JA. Hypothyroidism is easily overlooked.Practitioner. 2007; 251 (1699) :61-5, 67. Marx H, Amin P, Lazarus JH. Hyperthyroidism and pregnancy.BMJ. 2008; 336 (7645) :663-667. Nayak B, Hodak SP. Hyperthyroidism.Endocrinol Metab Clin North Am. 2007; 36 (3) :617-56, v. Nygaard B. Hyperthyroidism.Am Fam Physician. 2007; 76 (7) :1014-1016. Pezzino V, Sipione C, Vigneri R. Improving the diagnosis of central hypothyroidism.J Endocrinol Invest. 2008; 31 (10) :939-. Sahai I, Marsden D. Newborn screening.Crit Rev Clin Lab Sci. 2009; 46 (2) :55-82. Wartofsky L. Myxedema coma.Endocrinol Metab Clin North Am. 2006; 35 (4) :687-viii. Wilcken B, Wiley V. Newborn screening.Pathology. 2008; 40 (2) :104-115. References from the ARUP Institute for Clinical and Experimental Pathology® Baloch ZW, Cibas ES, Clark DP, Layfield LJ, Ljung BM, Pitman MB, Abati A. The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation.Cytojournal. 2008; 5 :6-. La'ulu SL, Roberts WL. Second-trimester reference intervals for thyroid tests: the role of ethnicity.Clin Chem. 2007; 53 (9) :1658-1664. Layfield LJ, Abrams J, Cochand-Priollet B, Evans D, Gharib H, Greenspan F, Henry M, LiVolsi V, Merino M, Michael CW, Wang H, Wells SA. Post-thyroid FNA testing and treatment options: a synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference.Diagn Cytopathol. 2008; 36 (6) :442-448. Lockwood CM, Grenache DG, Gronowski AM. Serum human chorionic gonadotropin concentrations greater than 400,000 IU/L are invariably associated with suppressed serum thyrotropin concentrations.Thyroid. 2009; 19 (8) :863-868. Lyon JL, Alder SC, Stone MB, Scholl A, Reading JC, Holubkov R, Sheng X, White GL Jr, Hegmann KT, Anspaugh L, Hoffman FO, Simon SL, Thomas B, Carroll R, Meikle AW. Thyroid disease associated with exposure to the Nevada nuclear weapons test site radiation: a reevaluation based on corrected dosimetry and examination data.Epidemiology. 2006; 17 (6) :604-614. McDonald SD, Walker MC, Ohlsson A, Murphy KE, Beyene J, Perkins SL. The effect of tobacco exposure on maternal and fetal thyroid function.Eur J Obstet Gynecol Reprod Biol. 2008; 140 (1) :38-42. Rawlins ML, Roberts WL. Performance characteristics of six third-generation assays for thyroid-stimulating hormone.Clin Chem. 2004; 50 (12) :2338-2344. Roberts RF, La'ulu SL, Roberts WL. Performance characteristics of seven automated thyroxine and T-uptake methods.Clin Chim Acta. 2007; 377 (1-2) :248-255. Sandrock T, Terry A, Martin JC, Erdogan E, Meikle WA. Detection of thyroid-stimulating immunoglobulins by use of enzyme-fragment complementation.Clin Chem. 2008; 54 (8) :1401-1402. Silvio R, Swapp KJ, La'ulu SL, Hansen-Suchy K, Roberts WL. Method specific second-trimester reference intervals for thyroid-stimulating hormone and free thyroxine.Clin Biochem. 2009; 42 (7-8) :750-753. Yue B, Rockwood AL, Sandrock T, La'ulu SL, Kushnir MM, Meikle AW. Free thyroid hormones in serum by direct equilibrium dialysis and online solid-phase extraction--liquid chromatography/tandem mass spectrometry.Clin Chem. 2008; 54 (4) :642-651. Reviewed by Meikle, A. Wayne, MD. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Thyroid Disease - p. 7 of 8
  8. 8. The Physician's Guide to Laboratory Test Selection and Interpretation Roberts, William L., MD, PhD. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor of Pathology, University of Utah Diagnostic Algorithm(s) PDF algorithm(s) available at www.arupconsult.com. Thyroid Disorders Testing Algorithm Thyroid Nodules Testing Algorithm Related Content Autoimmune Thyroid Disease - Thyroiditis Gestational Trophoblastic Disease Hypopituitarism Osteoporosis Thyroid Cancer Comprehensive Review: September 2009 Last Update: August 2009 ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com © 2006–2010 ARUP Laboratories. All Rights Reserved. Thyroid Disease - p. 8 of 8

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