Subclinical hypothyroidism

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

Prognosis

"Subclinical hypothyroidism is associated with an increased risk of congenital heart disease (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 U.S. 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

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