Thyroid-stimulating Hormone (TSH)

Overview:

Thyroid function test. Investigation of low thyroxine (T4) result; the differential diagnosis of primary hypothyroidism from normal, and the differential diagnosis of primary hypothyroidism from pituitary/hypothalamic hypothyroidism. TSH is high in primary hypothyroidism. Low TSH occurs in hyperthyroidism. Evaluation of therapy in hypothyroid patients receiving various thyroid hormone preparations: Low values are found in states of excessive thyroid replacement. Normal result on a sensitive TSH assay is acceptable evidence of adequate thyroid replacement.

Follow-up of patients who have had hyperthyroidism treated with radioiodine or surgery. Follow-up low T4 newborn results.

This third-generation TSH assay can be considered a test for thyroid disease. A result within the accepted reference interval provides strong evidence for euthyroidism.

Spurious increase from antibovine TSH antibodies by double-antibody technique has been reported.2 TSH may be affected by glucocorticoids, dopamine, and by severe illness,3 and these remain limitations even for the new, sensitive TSH assays. TSH suppression in hypothyroidism with severe illness has been reported with TSH increase with recovery.4 Normal TSH levels in the presence of hypothyroidism have been reported with head injury.5 Iopanoic acid, ipodate, and an antiarrhythmic drug, amiodarone, cause changes in thyroid test results including increases in T4, free T4, and TSH and decreases of T3.6 TSH is not elevated in secondary hypothyroidism.

Probably no single test, even the sensitive immunoassays, can be expected to adequately reflect thyroid status under all circumstances. Among possible problems are the recovery phase of nonthyroidal illness, states of resistance to thyroid hormone, thyrotropin-producing tumors, thyroid status in acute psychiatric illness, early in thyrotoxicosis and in subacute thyroiditis.7

The consequences of subclinical thyroid disease (serum TSH 0.1−0.45 μIU/mL or 4.5−10.0 μIU/mL) are minimal and current guidelines recommend against routine treatment of patients with TSH levels in these ranges, but thyroid function tests should be repeated at 6- to 12-month intervals to monitor TSH levels;8 however, treatment of subclinical hypothyroidism is indicated in patients with TSH levels >10.0 μIU/mL or in patients with TSH levels <10.0 μIU/mL in conjunction with goiter or positive for antithyroid peroxidase antibodies (or both).9 In patients who are receiving replacement therapy, the dose should be adjusted so serum TSH values range from 0.3−3.0 μIU/mL. An exception is thyroid hormone replacement treatment after thyroidectomy for differentiated thyroid cancer, in which case, a mildly to moderately suppressed TSH level is generally desirable.10 It is reasonable to consider serum TSH measurement for pregnant women or women planning to become pregnant with a family history of thyroid disease, prior thyroid dysfunction, symptoms or physical findings suggestive of hypo- or hyperthyroidism, an abnormal thyroid gland on examination, type 1 diabetes mellitus, or a personal history of autoimmune disorder.11 Suggested upper limit for the TSH reference range for pregnant women and preconception is: first trimester − <2.5 μIU/mL, and 3.0 μIU/mL in the second and third trimesters.10

Unsuspected increase in the level of serum TSH is not uncommon in elderly subjects. A study by Sawin et al found that 22 of 344 (5.9%) healthy persons older than age 60 had a TSH level >10 μIU/mL; 10 of the 22 had low T4 and FT4 index. Elderly hypothyroid individuals may have minimal recognizable clinical symptoms of thyroid deficiency.11 TSH is the single most sensitive test for primary hypothyroidism. If there is clear evidence for hypothyroidism and the TSH is not elevated, hypopituitarism should be considered (secondary hypothyroidism).

TSH levels have been elevated or inappropriately detectable for high thyroid hormone levels in some patients with thyrotropin-secreting pituitary adenomas. Delay in diagnosis of these tumors may lead to visual compromise. The effects of such neoplasms can be misdiagnosed as those of primary hyperthyroidism.

Until the late 1980s, TSH assays were not sufficiently sensitive to distinguish hyperthyroidism from euthyroid (normal) subjects. The new generation of ultrasensitive TSH immunoassays have provided a far more effective diagnostic separation of thyrotoxicosis from euthyroidism.

This assay has a sensitivity of 0.004 μIU/mL and meets all criteria as a third-generation TSH assay.

1. Reference Intervals for Children and Adults.Elecsys Thyroid Test. Roche Diagnostics; May 2005. PubMed 8595709

2. Sain A, Sham R, Singh A, et al. Erroneous thyroid-stimulating hormone radioimmunoassay results due to interfering antibovine thyroid-stimulating hormone antibodies. Am J Clin Pathol. 1979; 71(5):540-542. PubMed 377939

3. Chopra IJ, Hershman JM, Pardridge MD, et al. Thyroid function in nonthyroidal illnesses. Ann Intern Med.. 1983; 98(6):946-957. PubMed 6407376

4. Morley JE, Slag MF, Elson MK, et al. The interpretation of thyroid function tests in hospitalized patients. JAMA. 1983; 249(17):2377-2379. PubMed 6403725

5. Slag MF, Morley JE, Elson MK, et al. Free thyroxine levels in critically ill patients. A comparison of currently available assays. JAMA. 1981; 246(23):2702-2706. PubMed 6796703

6. Borst GC, Eil G, Burman KD. Euthyroid hyperthyroxinemia. Ann Intern Med. 1983; 98(3):366-378 (review). PubMed 6187257 7. Ehrmann DA, Sarne DH. Serum thyrotropin and the assessment of thyroid status. Ann Intern Med. 1989; 110(3):179-181. PubMed 2643378

8. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: Scientific review and guidelines for diagnosis and management. JAMA. 2004; 291(2):228-238. PubMed 14722150

9. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002 Nov-Dec; 8(6):457-469. PubMed 15260011

10. Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011; 21(10):1081-1125. PubMed 21787128

11. Sawin CT, Chopra D, Azizi F, et al. The aging thyroid. Increased prevalence of elevated serum thyrotropin levels in the elderly. JAMA. 1979; 242(3):247-250. PubMed 448912

Baskin HJ. Endocrinologic evaluation of impotence. South Med J. 1989; 82(4):446-449. PubMed 2495570

Brennan MD, Klee GG, Preissner CM, et al. Heterophilic serum antibodies: A cause for falsely elevated serum thyrotropin levels. Mayo Clin Proc. 1987; 62(10):894-898. PubMed 3657306

Clark PM, Clark JD, Holder R, et al. Pulsatile secretion of TSH in healthy subjects. Ann Clin Biochem. 1987; 24(Pt 5):470-476. PubMed 3310836

Cooper DS. Thyroid hormone treatment: New insights into an old therapy. JAMA. 1989; 261(18):2694-2695. PubMed 2709547

Ericsson UB, Fernlund P, Thorell JI. Evaluation of the usefulness of a sensitive immunoradiometric assay for thyroid-stimulating hormone as a first-line thyroid function test in an unselected patient population.