Subclinical hypothyroidism

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In medicine, subclinical hypothyroidism is an elevated thyrotropin (TSH) concentration can maintain a normal or near normal thyroxine (T4) concentration.[1][2]

Prognosis

"Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater" according to a individual patient data meta-analysis. [3]

Thyrotropin level

Evolution of thyrotropin values over 5 years.[4]
  Follow-up TSH value
TSH > 10 TSH < 10
TSH > 10 35% 64%
TSH 5.5 - 10 3% 97%

The thyrotropin level helps predict progression to overt hypothyroidism.[4]

Antithyroid peroxidase antibodies

Antithyroid peroxidase (also called antithyroid microsomal) antibodies my help predict progression to overt hypothyroidism.[5][6][7]

Diagnostic accuracy for predicting over hypothyroidism has been reported.

Diez et al found that among patients with TSH > 5, antibodies > 20 U/ml were significant predictors of hypothyrodism after 3.5 years of follow-up in which 26% developed overt hypothyroidism, but not after controlling for initial thyrotropin level.[7]

  • Sensitivity 93%
  • Specificity 30%
  • Positive predictive value 32%
  • Negative predictive value 92%

Walsh et al found that among patients with TSH> 4, antibodies > 35 U/ml were significant predictors of hypothyrodism after 13 years of follow-up in which 31% developed overt hypothyroidism, but not after controlling for initial thyrotropin level.[5]

  • Sensitivity 84%
  • Specificity 30%
  • Positive predictive value 60%
  • Negative predictive value 60%

Treatment

"In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity" according to a meta-analysis by the Cochrane Collaboration. [8]

Subsequent randomized controlled trials have been positive using 100 microg T4 orally per day[9] and negative using 25 microg T4 orally per day[10].

Subsequent observational studies have[11] and have not[12] shown a relationship between untreated subclinical hypothyroidism and ischemic heart disease.

Clinical practice guidelines guide management.[13]

Prior consensus statements conflict with some recommending[14][15][16] and others not[1] recommending treatment.[17]

Screening

The US Preventive Services Task Force states:[18]

"t is uncertain whether treatment will improve quality of life in otherwise healthy patients who have abnormal TSH levels and normal free thyroxine levels."

The Institute of Medicine recommends against screening.[19]

References

  1. 1.0 1.1 Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH et al. (2004). "Subclinical thyroid disease: scientific review and guidelines for diagnosis and management.". JAMA 291 (2): 228-38. DOI:10.1001/jama.291.2.228. PMID 14722150. Research Blogging.
  2. Cooper DS, Biondi B (2012). "Subclinical thyroid disease.". Lancet 379 (9821): 1142-54. DOI:10.1016/S0140-6736(11)60276-6. PMID 22273398. Research Blogging.
  3. Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP et al. (2010). "Subclinical hypothyroidism and the risk of coronary heart disease and mortality.". JAMA 304 (12): 1365-74. DOI:10.1001/jama.2010.1361. PMID 20858880. Research Blogging. Review in: Evid Based Med. 2011 Feb;16(1):31-2
  4. 4.0 4.1 Meyerovitch J, Rotman-Pikielny P, Sherf M, Battat E, Levy Y, Surks MI (2007). "Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians.". Arch Intern Med 167 (14): 1533-8. DOI:10.1001/archinte.167.14.1533. PMID 17646608. Research Blogging.
  5. 5.0 5.1 Walsh JP, Bremner AP, Feddema P, Leedman PJ, Brown SJ, O'Leary P (2010). "Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a community-based cohort using current immunoassay techniques.". J Clin Endocrinol Metab 95 (3): 1095-104. DOI:10.1210/jc.2009-1977. PMID 20097710. Research Blogging.
  6. Li Y, Teng D, Shan Z, Teng X, Guan H, Yu X et al. (2008). "Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes.". J Clin Endocrinol Metab 93 (5): 1751-7. DOI:10.1210/jc.2007-2368. PMID 18270254. Research Blogging.
  7. 7.0 7.1 Díez JJ, Iglesias P (2004). "Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure.". J Clin Endocrinol Metab 89 (10): 4890-7. DOI:10.1210/jc.2003-032061. PMID 15472181. Research Blogging.
  8. Villar HC, Saconato H, Valente O, Atallah AN (2007). "Thyroid hormone replacement for subclinical hypothyroidism.". Cochrane Database Syst Rev (3): CD003419. DOI:10.1002/14651858.CD003419.pub2. PMID 17636722. Research Blogging. Review in: ACP J Club. 2008 Jan-Feb;148(1):7 Review in: ACP J Club. 2008 Jan-Feb;148(1):6 Review in: Evid Based Med. 2008 Feb;13(1):22
  9. Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU (2007). "The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial.". J Clin Endocrinol Metab 92 (5): 1715-23. DOI:10.1210/jc.2006-1869. PMID 17299073. Research Blogging.
  10. Parle J, Roberts L, Wilson S, Pattison H, Roalfe A, Haque MS et al. (2010). "A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham Elderly Thyroid study.". J Clin Endocrinol Metab 95 (8): 3623-32. DOI:10.1210/jc.2009-2571. PMID 20501682. Research Blogging.
  11. Razvi S, Weaver JU, Butler TJ, Pearce SH (2012). "Levothyroxine Treatment of Subclinical Hypothyroidism, Fatal and Nonfatal Cardiovascular Events, and Mortality.". Arch Intern Med. DOI:10.1001/archinternmed.2012.1159. PMID 22529180. Research Blogging.
  12. Razvi S, Weaver JU, Vanderpump MP, Pearce SH (2010). "The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: reanalysis of the Whickham Survey cohort.". J Clin Endocrinol Metab 95 (4): 1734-40. DOI:10.1210/jc.2009-1749. PMID 20150579. Research Blogging.
  13. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI et al. (2012). "Clinical Practice Guidelines for Hypothyroidism in Adults: Co-sponsored by American Association of Clinical Endocrinologists and the American Thyroid Association.". Endocr Pract: 1-207. DOI:10.4158/EP12280.GL. PMID 22967432. Research Blogging.
  14. Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT et al. (2005). "Consensus Statement #1: Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and The Endocrine Society.". Thyroid 15 (1): 24-8; response 32-3. DOI:10.1089/thy.2005.15.24. PMID 15687817. Research Blogging.
  15. Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT et al. (2004). "Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society.". Endocr Pract 10 (6): 497-501. PMID 16033723[e]
  16. Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT (2005). "Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society.". J Clin Endocrinol Metab 90 (1): 581-5; discussion 586-7. DOI:10.1210/jc.2004-1231. PMID 15643019. Research Blogging.
  17. Ringel MD, Mazzaferri EL (2005). "Subclinical thyroid dysfunction--can there be a consensus about the consensus?". J Clin Endocrinol Metab 90 (1): 588-90. DOI:10.1210/jc.2004-2173. PMID 15643021. Research Blogging.
  18. Helfand M, U.S. Preventive Services Task Force (2004). "Screening for subclinical thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force.". Ann Intern Med 140 (2): 128-41. PMID 14734337[e]
  19. Institute of Medicine (2003). Medicare Coverage of Routine Screening for Thyroid Dysfunction