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Classification and external resources
Thyroxine (T4) normally produced in 20:1 ratio to triiodothyronine (T3)
ICD-10 E03.9
ICD-9 244.9
DiseasesDB 6558
eMedicine med/1145 
MeSH D007037

Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants.


[edit] Causes

About three percent of the general population is hypothyroid.[1] Factors such as iodine deficiency or exposure to Iodine-131 (I-131) can increase that risk. There are a number of causes for hypothyroidism. Historically, and still in many developing countries, iodine deficiency is the most common cause of hypothyroidism worldwide. In iodine-replete individuals, hypothyroidism is mostly caused by Hashimoto's thyroiditis, or by a lack of the thyroid gland or a deficiency of hormones from either the hypothalamus or the pituitary.

Hypothyroidism can result from postpartum thyroiditis, a condition that affects about 5% of all women within a year after giving birth. The first phase is typically hyperthyroidism. Then, the thyroid either returns to normal or a woman develops hypothyroidism. Of those women who experience hypothyroidism associated with postpartum thyroiditis, one in five will develop permanent hypothyroidism requiring life-long treatment.

Hypothyroidism can also result from sporadic inheritance, sometimes autosomal recessive.

Hypothyroidism is also a relatively common hormone disease in domestic dogs, with some specific breeds having a definite predisposition.[2]

Temporary hypothyroidism can be due to the Wolff-Chaikoff effect. A very high intake of iodine can be used to temporarily treat hyperthyroidism, especially in an emergency situation. Although iodine is substrate for thyroid hormones, high levels prompt the thyroid gland to take in less of the iodine that is eaten, reducing hormone production.

Hypothyroidism is often classified by the organ of origin:[3][4]

Type Origin Description
Primary thyroid gland The most common forms include Hashimoto's thyroiditis (an autoimmune disease) and radioiodine therapy for hyperthyroidism.
Secondary pituitary gland Occurs if the pituitary gland does not create enough thyroid stimulating hormone (TSH) to induce the thyroid gland to produce enough thyroxine and triiodothyronine. Although not every case of secondary hypothyroidism has a clear-cut cause, it is usually caused by damage to the pituitary gland, as by a tumor, radiation, or surgery.[5]
Tertiary hypothalamus Results when the hypothalamus fails to produce sufficient thyrotropin-releasing hormone (TRH). TRH prompts the pituitary gland to produce thyrotropin (TSH). Hence may also be termed hypothalamic-pituitary-axis hypothyroidism.

[edit] General psychological associations

Hypothyroidism can be caused by lithium-based mood stabilizers, usually used to treat bipolar disorder (previously known as manic depression).

In addition, patients with hypothyroidism and psychiatric symptoms may be diagnosed with:[6]

[edit] Symptoms

In adults, hypothyroidism is associated with the following symptoms:[5][7][8]

[edit] Early symptoms

[edit] Late symptoms

  • slow speech and a hoarse, breaking voice. Deepening of the voice can also be noticed.
  • Dry puffy skin, especially on the face
  • Thinning of the outer third of the eyebrows.
  • Abnormal menstrual cycles
  • Low basal body temperature

[edit] Less common symptoms

[edit] Diagnostic testing

To diagnose primary hypothyroidism, many doctors simply measure the amount of Thyroid-stimulating hormone (TSH) being produced by the pituitary gland. High levels of TSH indicate that the thyroid is not producing sufficient levels of Thyroid hormone (mainly as thyroxine (T4) and smaller amounts of triiodothyronine (T3)). However, measuring just TSH fails to diagnose secondary and tertiary forms of hypothyroidism, thus leading to the following suggested blood testing if the TSH is normal and hypothyroidism is still suspected:

  • free triiodothyronine (fT3)
  • free levothyroxine (fT4)
  • total T3
  • total T4

Additionally, the following measurements may be needed:

  • 24 hour urine free T3;[13]
  • antithyroid antibodies — for evidence of autoimmune diseases that may be damaging the thyroid gland
  • serum cholesterol — which may be elevated in hypothyroidism
  • prolactin — as a widely available test of pituitary function
  • testing for anemia, including ferritin
  • basal body temperature

[edit] Treatment

Hypothyroidism is treated with the levorotatory forms of thyroxine (L-T4) and triiodothyronine (L-T3). Both synthetic and animal-derived thyroid tablets are available and can be prescribed for patients in need of additional thyroid hormone. Thyroid hormone is taken daily, and doctors can monitor blood levels to help assure proper dosing. There are several different treatment protocols in thyroid replacement therapy:

T4 Only
This treatment involves supplementation of levothyroxine alone, in a synthetic form. It is currently the standard treatment in mainstream medicine.[14]
T4 and T3 in Combination
This treatment protocol involves administering both synthetic L-T4 and L-T3 simultaneously in combination.[15]
Desiccated Thyroid Extract
Desiccated thyroid extract is an animal based thyroid extract, most commonly from a porcine source. It is also a combination therapy, containing natural forms of L-T4 and L-T3.[16]

[edit] Treatment controversy

The current standard treatment in thyroid therapy is levothyroxine only, and the American Association of Clinical Endocrinologists (AACE) states that desiccated thyroid hormone, combinations of thyroid hormone, or triiodothyronine should not generally be used for replacement therapy.[14] Nevertheless, there exists some controversy about whether this treatment protocol is optimal, and recent studies have given conflicting results.

Two recent studies comparing synthetic T4 versus synthetic T4 + T3 have shown "clear improvements in both cognition and mood" from combination therapy.[17] [15] Another study comparing synthetic T4 and desiccated thyroid extract showed marked improvements in virtually all symptom categories when certain patients were switched from synthetic T4 to desiccated thyroid extract.[16]

However, other studies have shown no improvement in mood or mental abilities for those on combination therapy, and possibly impaired well-being from subclinical hyperthyroidism.[18] Also, a 2007 metaanalysis of the nine controlled studies so far published found no significant difference in the effect on psychiatric symptoms.[19]

There is also concern among some practitioners about the use of T3 due to its short half life. T3 when used on its own as a treatment results in wide fluctuations across the course of a day in the thyroid hormone levels, and with combined T3/T4 therapy there continues to be wide variation throughout each day.[20]

[edit] Subclinical hypothyroidism

Subclinical hypothyroidism occurs when thyrotropin (TSH) levels are elevated but thyroxine (T4) and triiodothyronine (T3) levels are normal.[1] In primary hypothyroidism, TSH levels are high and T4 and T3 levels are low. Endocrinologists are puzzled because TSH usually increases when T4 and T3 levels drop. TSH prompts the thyroid gland to make more hormone. Endocrinologists are unsure how subclinical hypothyroidism affects cellular metabolic rates (and ultimately the body's organs) because the levels of the active hormones are adequate. Some have proposed treating subclinical hypothyroidism with levothyroxine, the typical treatment for overt hypothyroidism, but the benefits and the risks are unclear. Reference ranges have been debated as well. The American Association of Clinical Endocrinologists (ACEE) supports a narrower TSH range, especially when the person has clinical signs of thyroid disease. This reference range may reduce the risks of goiter, thyroid nodules, thyroid cancer, and overt hypothyroidism, but remains controversial.[21] There is always the risk of overtreatment and hyperthyroidism. Some studies have suggested that subclinical hypothyroidism does not need to be treated. A meta-analysis by the Cochrane Collaboration found no benefit of thyroid hormone replacement except "some parameters of lipid profiles and left ventricular function".[22] A more recent metanalysis looking into whether subclinical hypothyroidism may increase the risk of cardiovascular disease, as has been previously suggested,[23] found a possible modest increase and suggested further studies be undertaken with coronary heart disease as a end point "before current recommendations are updated".[24]

[edit] Sub-laboratory hypothyroidism

"Sub-laboratory" hypothyroidism occurs when blood levels of thyroid hormones and thyrotropin (TSH) are within reference ranges, yet hypothyroid symptoms are present and resolve with thyroid therapy. [25] This type of hypothyroidism is thought not to be another form of the disease, but instead simply illuminates the failure of blood tests to fully reflect the health of the hypothalamic-pituitary-thyroid axis. The lack of correlation between hypothyroid symptoms and serum thyrotropin (TSH) and T4, has been pointed out by several researchers[13].

[edit] References

  1. ^ a b Jack DeRuiter (2002) (PDF). Thyroid Pathology. pp. 30. http://www.auburn.edu/~deruija/endp_thyroidpathol.pdf. 
  2. ^ Brooks W (01/06/2008). "Hypothyroidism in Dogs". The Pet Health Library. VetinaryPartner.com. http://www.veterinarypartner.com/Content.plx?P=A&A=461. Retrieved on 2008-02-28. 
  3. ^ Simon H (2006-04-19). "Hypothyroidism". University of Maryland Medical Center. http://www.umm.edu/patiented/articles/what_causes_hypothyroidism_000038_2.htm. Retrieved on 2008-02-28. 
  4. ^ Department of Pathology (June 13, 2005). "Pituitary Gland -- Diseases/Syndromes". Virginia Commonwealth University (VCU). http://www.pathology.vcu.edu/education/endocrine/endocrine/pituitary/diseases.html. Retrieved on 2008-02-28. 
  5. ^ a b American Thyroid Association (ATA) (2003) (PDF). Hypothyroidism Booklet. pp. 6. http://www.thyroid.org/patients/brochures/Hypothyroidism%20_web_booklet.pdf#search=%22hypothyroidism%22. 
  6. ^ Heinrich TW, Grahm G (2003). Hypothyroidism Presenting as Psychosis: Myxedema Madness Revisited. 5. pp. 260–266. PMID 15213796. 
  7. ^ MedlinePlus Encyclopedia Hypothyroidism — primary — see list of Symptoms
  8. ^ "Hypothyroidism — In-Depth Report." The New York Times. Copyright 2008
  9. ^ "Hypothyroidism" (PDF). American Association of Clinical Endocrinologists. http://www.aace.com/pub/thyroidbrochures/pdfs/Hypothyroidism.pdf. 
  10. ^ Yeum CH, Kim SW, Kim NH, Choi KC, Lee J (July 2002). "Increased expression of aquaporin water channels in hypothyroid rat kidney". Pharmacol. Res. 46 (1): 85–8. doi:10.1016/S1043-6618(02)00036-1. PMID 12208125. 
  11. ^ Thyroid and Weight. The American Thyroid Association
  12. ^ Hofeldt FD, Dippe S, Forsham PH (1972). "Diagnosis and classification of reactive hypoglycemia based on hormonal changes in response to oral and intravenous glucose administration" (PDF). Am. J. Clin. Nutr. 25 (11): 1193–201. PMID 5086042. http://www.ajcn.org/cgi/reprint/25/11/1193.pdf. 
  13. ^ a b Baisier W. Hertoghe J. Eeckhaut W. Thyroid insufficiency. Is TSH the only diagnostic tool? J Nutr Environ ed. 2000;10:105–113. "Thyroid insufficiency. Is TSH the only diagnostic tool?"
  14. ^ a b American Association of Clinical Endocrinologists (November/December 2002). "Medical Guidelines For Clinical Practice For The Evaluation And Treatment Of Hyperthyroidism And Hypothyroidism" (PDF). Endocrine Practice 8 (6): 457–469. http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf. 
  15. ^ a b Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ (February 1999). "Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism". N. Engl. J. Med. 340 (6): 424–9. doi:10.1056/NEJM199902113400603. PMID 9971866. http://content.nejm.org/cgi/content/full/340/6/424. 
  16. ^ a b Baisier, W.V.; Hertoghe, J.; Eeckhaut, W. (September 2001). "Thyroid Insufficiency. Is Thyroxine the Only Valuable Drug?". Journal of Nutritional and Environmental Medicine 11 (3): 159–66. doi:10.1080/13590840120083376. Abstract
  17. ^ Robertas Bunevicius, Arthur J. Prange Jr. (June 2000). "Mental improvement after replacement therapy with thyroxine plus triiodothyronine: relationship to cause of hypothyroidism". The International Journal of Neuropsychopharmacology 3 (2): 167–174. doi:10.1017/S1461145700001826. http://journals.cambridge.org/action/displayAbstract?aid=52289. 
  18. ^ Siegmund W, Spieker K, Weike AI, et al (June 2004). "Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14 : 1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism". Clin. Endocrinol. (Oxf) 60 (6): 750–7. doi:10.1111/j.1365-2265.2004.02050.x. PMID 15163340. 
  19. ^ Joffe RT, Brimacombe M, Levitt AJ, Stagnaro-Green A (2007). "Treatment of clinical hypothyroidism with thyroxine and triiodothyronine: a literature review and metaanalysis". Psychosomatics 48 (5): 379–84. doi:10.1176/appi.psy.48.5.379. PMID 17878495. 
  20. ^ Saravanan P, Siddique H, Simmons DJ, Greenwood R, Dayan CM (April 2007). "Twenty-four hour hormone profiles of TSH, Free T3 and free T4 in hypothyroid patients on combined T3/T4 therapy". Exp. Clin. Endocrinol. Diabetes 115 (4): 261–7. doi:10.1055/s-2007-973071. PMID 17479444. 
  21. ^ "Subclinical Thyroid Disease". Guidelines & Position Statements. The American Association of Clinical Endocrinologists. July 11, 2007. http://www.aace.com/pub/positionstatements/subclinical.php. Retrieved on 2008-06-08. 
  22. ^ Villar H, Saconato H, Valente O, Atallah A (2007). "Thyroid hormone replacement for subclinical hypothyroidism". Cochrane database of systematic reviews (Online) (3): CD003419. doi:10.1002/14651858.CD003419.pub2. PMID 17636722. 
  23. ^ Biondi B, Palmieri EA, Lombardi G, Fazio S (December 2002). "Effects of subclinical thyroid dysfunction on the heart". Ann. Intern. Med. 137 (11): 904–14. PMID 12458990. 
  24. ^ Ochs N, Auer R, Bauer DC, et al (June 2008). "Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality". Ann. Intern. Med. 148 (11): 832–45. PMID 18490668. http://www.annals.org/cgi/content/full/148/11/832. 
  25. ^ Alan Gaby (2004). ""Sub-laboratory" Hypothyroidism and the Empirical use of Armour Thyroid" (PDF). Alternative Medicine Review 9 (2): 157–179. http://www.thorne.com/media/hypothyroidism9-2.pdf. 

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