Hypothyroidism

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

Contents

[edit] Causes

About three percent of the general population is hypothyroid.[1] Factors such as iodine deficiency or exposure to I-131 can increase that risk. There are a number of causes for overt 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

The ability of hypothyroidism to mimic a number of medical conditions originates in the vast functions of the thyroid hormones, which are reduced or absent in this case. The functions of thyroid hormones include modulation of carbohydrate, protein and fat metabolism, vitamin utilization, mitochondrial function, digestive process, muscle and nerve activity, blood flow, oxygen utilization, hormone secretion and sexual and reproductive health[7] to mention a few. Thus, when the thyroid hormone content gets out of balance, systems covering the whole body are affected. This is why hypothyroidism can look like other diseases. Conversely, sometimes other conditions can be mistaken for hypothyroidism.

[edit] Adults

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

[edit] Early symptoms

[edit] Late symptoms

  • Slowed 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] Pediatric

Hypothyroidism in pediatric patients was previously classified as Cretinism, and can cause the following symptoms:

[edit] Severity

The severity of hypothyroidism varies widely. Some have few overt symptoms, others with moderate symptoms can be mistaken for having other diseases and states. Advanced hypothyroidism may cause severe complications including cardiovasular and psychiatric myxedema.

[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 [10]
  • 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

[edit] Treatment

Main article: Medical use of thyroid hormones

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 protocol involves supplementation of levothyroxine alone, in a synthetic form. It is currently the standard treatment in mainstream medicine.[11]
T4 and T3 in Combination
This treatment protocol involves administering both synthetic L-T4 and L-T3 simultaneously in combination.[12]
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.[13]

[edit] Treatment Controversy

Though the current standard treatment in thyroid therapy is levothyroxine only, there exists some controversy about which treatment protocol is most effective. Some publications have challenged the status quo, stating that combination therapies can be more effective.[12][13] 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.[11]

Some studies have shown no improvement in mood or mental abilities for those on combination therapy, and possibly impaired well-being from subclinical hyperthyroidism.[14] 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.[15] A 2007 metaanalysis of the nine controlled studies so far published found no significant difference in the effect on psychiatric symptoms.[16]

[edit] Subclinical hypothyroidism

Subclinical hypothyroidism occurs when thyrotropin (TSH) levels are elevated but thyroxine (T4) and triiodothyronine (T3) levels are normal.[17] 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.[18] 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".[19]

[edit] References

  1. ^ Jack DeRuiter (2002). Thyroid Pathology (PDF), 30. 
  2. ^ Brooks W (01/06/2008). Hypothyroidism in Dogs. The Pet Health Library. VetinaryPartner.com. Retrieved on 2008-02-28.
  3. ^ Simon H (4/19/2006). Hypothyroidism. University of Maryland Medical Center. Retrieved on 2008-02-28.
  4. ^ Department of Pathology (June 13, 2005). Pituitary Gland -- Diseases/Syndromes. Virginia Commonwealth University (VCU). Retrieved on 2008-02-28.
  5. ^ a b American Thyroid Association (ATA) (2003). Hypothyroidism Booklet (PDF), 6. 
  6. ^ Heinrich TW, Grahm G (2003). "Hypothyroidism Presenting as Psychosis: Myxedema Madness Revisited" 5 (6): 260-266. PMID 15213796. 
  7. ^ Comprehensive Thyroid Assessment. Geneva Diagnostics. Retrieved on 2007-05-21.
  8. ^ MedlinePlus Encyclopedia Hypothyroidism - primary - see list of Symptoms
  9. ^ 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. 
  10. ^ 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?"
  11. ^ 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. 
  12. ^ 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. PMID 9971866. 
  13. ^ 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
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ Jack DeRuiter (2002). "Thyroid pathology", Endocrine Module (PYPP 5260) (PDF), Auburn University School of Pharmacy, pp30. 
  18. ^ Subclinical Thyroid Disease. Guidelines & Position Statements. The American Association of Clinical Endocrinologists (July 11, 2007). Retrieved on 2008-06-08.
  19. ^ 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. 

[edit] External links

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Endocrine pathology: endocrine diseases (E00-35, 240-259)
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