Which tests to order and when

In clinical practice, three basic scenarios indicate a need for laboratory evaluation of thyroid function: (1) suspicion of thyroid disease based on clinical signs and symptoms,1-4 (2) screening for thyroid disease,1-6 and (3) evaluation of treatment for thyroid disease.1,4,7,8

Working up symptomatic patients: When clinical signs and symptoms of hypothyroidism or hyperthyroidism (Table 3) are present, evaluation of a serum TSH and FTI or FT4 is indicated.1,4 Because thyroid dysfunction may develop insidiously over a long period, consideration of subclinical thyroid disorders is crucial in the presence of abnormal test results regardless of clinical presentation. Subclinical hyperthyroidism and subclinical hypothyroidism are exclusively laboratory diagnoses.7,8 Subclinical hypothyroidism should be suspected when the serum TSH is increased above the upper limit of the reference range (>5.0 mU/L) in combination with a normal T4.1,5,7,8 Conversely, subclinical hyperthyroidism is likely when TSH is decreased below the lower limit of the reference range (<0.10 mU/L) in the presence of a normal T4 (Table 1).1,5,7,8

Screening: Patients not previously diagnosed or treated for thyroid disease should be screened if they are older than 60 years or if they have a personal history of surgery or irradiation of the thyroid or neck, any family history of autoimmune disease, or an existing thyroid nodule or goiter.3,6 Screening is also indicated for those patients who are currently using or who have a history of long-term use of amiodarone or lithium.3,6 Newborns are screened to detect hypothyroidism in infancy by performing a serum T4 level on the blood spot collected shortly after birth; hypothyroidism that is detected early can be treated and mental retardation or cretinism prevented.2-4

Subclinical hyperthyroidism is estimated to occur in 2% of the adult population.1,5,7,8 The condition may be due to TSH suppression from an exogenous source or to endogenous production of thyroid hormone that suppresses pituitary TSH production and keeps FT4 and T3 levels normal.1,2,7,8 Such circumstances may represent the early stages of clinical hyperthyroidism and should be considered a risk factor for the development of osteoporosis and adverse cardiac manifestations, such as atrial fibrillation.1,2 Once the suppressed TSH is detected, repeat evaluation is needed to document that the low level is persistent. The American Academy of Clinical Endocrinologists (AACE) recommends that TSH, FT4, and T3 determinations be repeated two to four months after the initial discovery of low TSH.1,2 While treatment guidelines for subclinical hyperthyroidism have not been established, patients who have persistently low TSH levels should be re-evaluated at six-month intervals thereafter.1

Subclinical hypothyroidism occurs in about 5% of the adult population, but prevalence may be as high as 20% in women older than 60 years.1,5,7,8 Approximately 5% of patients with subclinical hypothyroidism will progress to clinical hypothyroidism each year.5,8 Subclinical hypothyroidism increases the risks for hyperlipidemia, atherosclerosis, and possibly neurobehavioral disorders.2,5,7,8 Patients with subclinical hypothyroidism (TSH >5.0 mU/L) should be re-evaluated within three months and then every six months.8

Treatment monitoring: The same tests that are used for diagnosis of thyroid disease can be used to follow treatment. Hypothyroid patients who are started on levothyroxine should have their TSH measured every six to eight weeks to guide dose adjustments.2,4 Dosing is considered therapeutic once TSH levels reach normal ranges and the patient is no longer symptomatic.1-4

Female patients who become pregnant while taking levothyroxine should have a TSH level assessed immediately after pregnancy is diagnosed, since the replacement dose of levothyroxine will typically increase during pregnancy.1-4  These patients will also need TSH assessment at regular intervals throughout the pregnancy and postpartum period even if they had stable TSH levels prior to pregnancy.1-4 Left untreated, maternal hypothyroidism can cause defects of the fetal neural development.

Patients with low TSH who are treated for Graves’ disease, thyroid nodules, and thyroiditis may also be monitored using TSH and T4 levels at four-week intervals during treatment.1-4 Monitoring of such patients should continue until thyroid levels normalize and symptoms resolve.

Dr. Gunder and Ms. Haddow are assistant professors in the School of Allied Health Sciences at the Medical College of Georgia in Augusta.

References

1. Ladenson P, Kim M. The thyroid. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa.: Saunders; 2007: chap 244.
2. Baskin HJ, Cobin RH, Duick DS, et al; American Association of Clinical Endocrinologists Thyroid Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002;8:457-469.
3. American Academy of Family Physicians (AAFP). Summary of recommendations for clinical preventive services. Revision 6.8. Leawood, Kan.: American Academy of Family Physicians (AAFP); October 2009.
4. Wu A, ed. Teitz Clinical Guide to Laboratory Tests. 4th ed. Philadelphia, Pa.: Saunders; 2006. 
5. U.S. Preventive Services Task Force. Screening for thyroid disease: recommendation statement. Ann Intern Med. 2004;140:125-127.
6. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow up of the Wickham Survey. Clin Endocrinol (Oxf). 1995;43:55-68.
7. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291:228-238.
8. Wilson GR, Curry RW. Subclinical thyroid disease. Am Fam Physician. 2005;72:1517-1524.

All electronic documents accessed November 19, 2009.