Thyroid Disease

  • Diagnosis
  • Algorithms
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Symptoms of hyper- or hypothyroidism
  • Family history of autoimmune thyroiditis
  • Goiter on physical exam

Laboratory Testing

  • Initial evaluation for thyroid disease – thyroid stimulating hormone (Choosing Wisely: 5 Things Physicians and Patients Should Question, 2015; American Society for Clinical Pathology)
    • Thyroid stimulating hormone (TSH) and T4 normal – thyroid disease unlikely
    • TSH elevated – suggests hypothyroidism
      • Order free T4 (thyroxine)
        • Low – hypothyroidism confirmed
          • Consider thyroid antibody testing
        • Normal – consider T3 (triiodothyronine) testing
          • Low T3 – hypothyroidism confirmed
          • Normal T3 – hypothyroidism unlikely, but if indicated by clinical presentation, could be subclinical hypothyroidism
    • TSH low – suggests hyperthyroidism
      • Order free T4
        • High – hyperthyroidism confirmed
        • Normal – consider T3 testing
          • Normal T3 – if TSH levels 0.1-0.4, subclinical hyperthyroidism
          • High T3 – hyperthyroidism
        • Low – central hypothyroidism or severe illness
  • Hypothyroidism during pregnancy may cause fetal demise and low IQ in liveborn infants (endemic cretinism)
    • Different reference ranges based on trimester
    • Order TSH and thyroid peroxidase (TPO) antibody testing for patients who have a prior diagnosis or family history of hypothyroidism
    • Elevated TPO antibodies associated with postpartum thyroiditis
  • Euthyroid sick syndrome
    • Low levels of thyroid hormone in clinically euthyroid patients who have systemic illnesses
    • Diagnosis – TSH variable; free T3, T4 may be low

Imaging Studies

  • Only order ultrasound in patients with abnormal thyroid function tests if palpable abnormality is present (ASCP's Pathology-Related Choosing Wisely Recommendations, 2015; The Endocrine Society, American Association of Clinical Endocrinologists)

Differential Diagnosis

Thyroid Disorders Testing Algorithm

Thyroid Nodules Testing Algorithm

  • At-large population screening for thyroid disfunction not recommended in nonpregnant, asymptomatic adults (USPSTF, 2015; AAFP, 2015)
    • The American Thyroid Association and American Association of Clinical Endocrinologists (Garber, 2012) recommend consideration of screening patients >60 years and “aggressive” case findings
  • Neonatal – TSH at 24 hours of age
    • Abnormal tests must be followed up with T4 test
  • Pregnancy
    • Universal screening is not recommended (ACOG, 2015; AACE, 2012; Endocrine Society, 2012)
    • Women at risk should be screened using TSH (Endocrine Society Guidelines, 2007; ACOG, 2007)
    • Risk factors include the following
      • Personal or family history of thyroid disease
      • Pregestational diabetes mellitus or other known autoimmune diseases
      • Prior head and neck irradiation
      • Previous infertility
      • History of miscarriage or preterm delivery
      • Women who are symptomatic
  • Hyperthyroidism
    • Initial monitoring – TSH and free T4 testing 6 weeks after initiation of therapy until euthyroid
    • Patients eventually develop hypothyroidism in autoimmune disease as the gland burns out
    • Monitor TSH and free T4 every year
    • Pregnancy-related hyperthyroidism – check TSH 6 weeks postpartum
  • Hypothyroidism – TSH and free T4 useful in monitoring thyroid replacement therapy
    • Monitor TSH in pregnant women to assess adequacy of therapy screening

Thyroid disease frequently arises from autoimmune processes that stimulate overproduction of hormones (hyperthyroidism) or causes gland destruction that subsequently leads to underproduction of hormones (hypothyroidism).

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
      • 2-3% of the population
      • 2/1,000 pregnancies
  • Age – onset is 40s-50s for both hypo- and hyperthyroidism
  • Sex – M<F, 1:5-8 for both types

Disorders

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

Thyroxine 0070140
Method: Quantitative Electrochemiluminescent Immunoassay

Limitations

May not be useful in monitoring treatment in individuals receiving T4 replacement therapy

Thyroid Stimulating Immunoglobulin 0099430
Method: Quantitative Bioassay/Quantitative Chemiluminescent Immunoassay

Limitations

Blocking antibodies specific to TSHR may decrease TSI antibody levels; net response is most likely physiologic

TSH serum levels ≥6 mU/L may cause a false-positive result

Thyroid Stimulating Hormone Receptor Antibody (TRAb) 2002734
Method: Quantitative Electrochemiluminescent Immunoassay

Thyroid Peroxidase (TPO) Antibody 0050075
Method: Quantitative Chemiluminescent Immunoassay

Thyroglobulin Antibody 0050105
Method: Quantitative Chemiluminescent Immunoassay

Thyroid Antibodies 0050645
Method: Chemiluminescent Immunoassay

Additional Tests Available

Triiodothyronine, Total (Total T3) 0070474
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Not recommended for routine thyroid screening

Indications for ordering are rare cases of suppressed serum thyroid stimulating hormone (TSH) with normal free thyroxine (FT4) (eg, suspected T3 toxicosis, subclinical T3 hyperthyroidism, rare pituitary conditions)

Thyroid Stimulating Hormone 0070145
Method: Quantitative Chemiluminescent Immunoassay

Comments

Preferred test for screening and monitoring thyroid function, but does not include T4 reflex testing.

Aid in the diagnosis of primary hyperthyroidism and differential diagnosis of hypothyroidism

Monitor individuals on thyroid hormone replacement therapy

Confirm suppression during thyroxine therapy for thyroid carcinoma

Thyroxine, Free (Free T4) 0070138
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Not the preferred initial thyroid disorder screening test

Order following abnormal thyroid stimulating hormone (TSH) result 

Order in conjunction with TSH if pituitary (secondary) hypothyroidism is suspected

Assess thyroid status in pregnant women or those on estrogen supplementation, phenytoin, or salicylates

Monitor thyroid hormone replacement therapy during pregnancy and treatment of secondary hypothyroidism

Thyroxine, Free by Equilibrium Dialysis/HPLC-Tandem Mass Spectrometry 0093244
Method: Quantitative Equilibrium Dialysis/High Performance Liquid Chromatography-Tandem Mass Spectrometry

Comments

Not recommended for routine evaluation of thyroid disorders; order free T4 instead

Triiodothyronine, Reverse by Tandem Mass Spectrometry 2007918
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Comments

Generally not recommended for routine evaluation of thyroid disorders, although may be considered in pregnant women

Triiodothyronine (T3), Free by Equilibrium Dialysis/LC-MS/MS 2011793
Method: Quantitative Equilibrium Dialysis/High Performance Liquid Chromatography-Tandem Mass Spectrometry

Thyroxine Binding Globulin 0070410
Method: Quantitative Chemiluminescent Immunoassay

Comments

Not recommended for routine thyroid screening

Aid in interpreting T3 and T4 levels that do not correlate with clinical findings

Triiodothyronine, Free (Free T3) 0070133
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Not recommended for routine thyroid screening

Indications for ordering are rare cases of suppressed serum thyroid stimulating hormone (TSH) with normal free thyroxine (FT4) (eg, suspected T3 toxicosis, subclinical T3 hyperthyroidism, rare pituitary conditions)

Second-line test in evaluating individuals during pregnancy, those receiving steroids, or individuals with dysalbuminemia

Do not order for individuals with abnormal total T3 values

False positives may result from thyrotoxicosis or excess replacement therapy

Thyroid Panel 0070141
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Not recommended for routine thyroid screening

Total T4, T3 uptake, and estimation of free thyroxine (FT4) index have limited clinical utility

Replaced by the combination of more sensitive TSH and FT4 tests that provide direct measurements

T3 Uptake 0070135
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Not recommended for routine thyroid screening

Replaced by the combination of more sensitive TSH and FT4 tests that provide direct measurements

Little clinical value as stand-alone test

Guidelines

American College of Obstetricians and Gynecologists. Practice Bulletin No. 148: Thyroid disease in pregnancy. Obstet Gynecol. 2015; 125(4): 996-1005. PubMed

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

American Society for Clinical Pathology. Choosing Wisely - Pathology-Related Choosing Wisely Recommendations. An initiative of the ABIM Foundation. [Initial posting Feb 2015; Accessed: Nov 2015]

Bahn R, Burch H, Cooper D, Garber J, Greenlee C, Klein I, Laurberg P, McDougall R, Montori V, Rivkees S, Ross D, Sosa J, Stan M, American Thyroid Association, American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011; 17(3): 456-520. PubMed

Clinical Preventive Service Recommendation - Thyroid. Am Fam Physician. Leawood, KS [Accessed: Jun 2015]

Committee on Patient Safety and Quality Improvement, Committee on Professional Liability. ACOG Committee Opinion No. 381: Subclinical hypothyroidism in pregnancy. Obstet Gynecol. 2007; 110(4): 959-60. PubMed

De Groot L, Abalovich M, Alexander E, Amino N, Barbour L, Cobin R, Eastman C, Lazarus J, Luton D, Mandel S, Mestman J, Rovet J, Sullivan S. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012; 97(8): 2543-65. PubMed

Endocrine Society. Five Things Physicians and Patients Should Question. Endocrine Society. [Accessed: Jan 2016]

Garber J, Cobin R, Gharib H, Hennessey J, Klein I, Mechanick J, Pessah-Pollack R, Singer P, Woeber K, American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012; 18(6): 988-1028. PubMed

LeFevre M, U.S. Preventive Services Task Force. Screening for thyroid dysfunction: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015; 162(9): 641-50. PubMed

Routine Thyroid Screening Not Recommended for Pregnant Women. News release. American College of Obstetricians and Gynecologists. [Accessed: Sep 2011]

Rugge B, Bougatsos C, Chou R. Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015; 162(1): 35-45. PubMed

General References

Almandoz J, Gharib H. Hypothyroidism: etiology, diagnosis, and management. Med Clin North Am. 2012; 96(2): 203-21. PubMed

Carney L, Quinlan J, West J. Thyroid disease in pregnancy. Am Fam Physician. 2014; 89(4): 273-8. PubMed

Casey B, de Veciana M. Thyroid screening in pregnancy. Am J Obstet Gynecol. 2014; 211(4): 351-353.e1. PubMed

DeBoer M, LaFranchi S. Pediatric thyroid testing issues. Pediatr Endocrinol Rev. 2007; 5 Suppl 1: 570-7. PubMed

Franklyn J, Boelaert K. Thyrotoxicosis. Lancet. 2012; 379(9821): 1155-66. PubMed

Kundra P, Burman K. The effect of medications on thyroid function tests. Med Clin North Am. 2012; 96(2): 283-95. PubMed

LaFranchi S. Approach to the diagnosis and treatment of neonatal hypothyroidism. J Clin Endocrinol Metab. 2011; 96(10): 2959-67. PubMed

Menconi F, Marcocci C, Marinò M. Diagnosis and classification of Graves' disease. Autoimmun Rev. 2014; 13(4-5): 398-402. PubMed

Negro R, Mestman J. Thyroid disease in pregnancy. Best Pract Res Clin Endocrinol Metab. 2011; 25(6): 927-43. PubMed

Samuels M. Subacute, silent, and postpartum thyroiditis. Med Clin North Am. 2012; 96(2): 223-33. PubMed

Seigel S, Hodak S. Thyrotoxicosis. Med Clin North Am. 2012; 96(2): 175-201. PubMed

Shih J, Agus M. Thyroid function in the critically ill newborn and child. Curr Opin Pediatr. 2009; 21(4): 536-40. PubMed

Sweeney L, Stewart C, Gaitonde D. Thyroiditis: an integrated approach. Am Fam Physician. 2014; 90(6): 389-96. PubMed

Vaidya B, Pearce S. Diagnosis and management of thyrotoxicosis. BMJ. 2014; 349: g5128. PubMed

Wilcken B, Wiley V. Newborn screening. Pathology. 2008; 40(2): 104-15. PubMed

Yazbeck C, Sullivan S. Thyroid disorders during pregnancy. Med Clin North Am. 2012; 96(2): 235-56. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Baloch Z, Cibas E, Clark D, Layfield L, Ljung B, Pitman M, Abati A. The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation. Cytojournal. 2008; 5: 6. PubMed

La'ulu S, Roberts W. Second-trimester reference intervals for thyroid tests: the role of ethnicity. Clin Chem. 2007; 53(9): 1658-64. PubMed

Layfield L, Abrams J, Cochand-Priollet B, Evans D, Gharib H, Greenspan F, Henry M, LiVolsi V, Merino M, Michael C, Wang H, Wells S. 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): 442-8. PubMed

Lockwood C, Grenache D, Gronowski A. Serum human chorionic gonadotropin concentrations greater than 400,000 IU/L are invariably associated with suppressed serum thyrotropin concentrations. Thyroid. 2009; 19(8): 863-8. PubMed

Lyon J, Alder S, Stone M, Scholl A, Reading J, Holubkov R, Sheng X, White G, Hegmann K, Anspaugh L, Hoffman O, Simon S, Thomas B, Carroll R, Meikle W. 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): 604-14. PubMed

McDonald S, Walker M, Ohlsson A, Murphy K, Beyene J, Perkins S. The effect of tobacco exposure on maternal and fetal thyroid function. Eur J Obstet Gynecol Reprod Biol. 2008; 140(1): 38-42. PubMed

Pierce M, Sandrock R, Gillespie G, Meikle A. Measurement of thyroid stimulating immunoglobulins using a novel thyroid stimulating hormone receptor-guanine nucleotide-binding protein, (GNAS) fusion bioassay. Clin Exp Immunol. 2012; 170(2): 115-21. PubMed

Rawlins M, Roberts W. Performance characteristics of six third-generation assays for thyroid-stimulating hormone. Clin Chem. 2004; 50(12): 2338-44. PubMed

Roberts R, La'ulu S, Roberts W. Performance characteristics of seven automated thyroxine and T-uptake methods. Clin Chim Acta. 2007; 377(1-2): 248-55. PubMed

Sandrock T, Terry A, Martin J, Erdogan E, Meikle W. Detection of thyroid-stimulating immunoglobulins by use of enzyme-fragment complementation. Clin Chem. 2008; 54(8): 1401-2. PubMed

Silvio R, Swapp K, La'ulu S, Hansen-Suchy K, Roberts W. Method specific second-trimester reference intervals for thyroid-stimulating hormone and free thyroxine. Clin Biochem. 2009; 42(7-8): 750-3. PubMed

Yue B, Rockwood A, Sandrock T, La'ulu S, Kushnir M, Meikle W. Free thyroid hormones in serum by direct equilibrium dialysis and online solid-phase extraction--liquid chromatography/tandem mass spectrometry. Clin Chem. 2008; 54(4): 642-51. PubMed

Medical Reviewers

Last Update: January 2016