Hypothyroidism
65845
225907674
2008-07-15T23:28:56Z
64.161.160.194
/* Causes */
{{Infobox_Disease |
Name = Hypothyroidism |
Image = Thyroxine-2D-skeletal.png |
Caption = [[Thyroxine]] (T4) normally produced in 20:1 ratio to [[triiodothyronine]] (T3) |
DiseasesDB = 6558 |
ICD10 = {{ICD10|E|03|9|e|00}} |
ICD9 = {{ICD9|244.9}} |
ICDO = |
OMIM = |
MedlinePlus = |
eMedicineSubj = med |
eMedicineTopic = 1145 |
MeshID = 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.
==Causes==
About three percent of the general population is hypothyroid.<ref name=“Auburn University”>{{cite book |author=Jack DeRuiter |title=Thyroid Pathology |year=2002 |pages=30 |url= http://www.auburn.edu/~deruija/endp_thyroidpathol.pdf |format=PDF}}</ref> Factors such as iodine deficiency or exposure to Iodine-131 ([[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 [[autosome|autosomal]] recessive.
Hypothyroidism is also a relatively common hormone disease in domestic dogs, with some specific breeds having a definite predisposition.<ref>{{cite web |author=Brooks W |title=Hypothyroidism in Dogs |url=http://www.veterinarypartner.com/Content.plx?P=A&A=461 |work=The Pet Health Library |date=01/06/2008 |publisher=VetinaryPartner.com |accessdate=2008-02-28}}</ref>
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:<ref>{{cite web |author=Simon H |title=Hypothyroidism |url=http://www.umm.edu/patiented/articles/what_causes_hypothyroidism_000038_2.htm |date=2006-04-19 |publisher=University of Maryland Medical Center |accessdate=2008-02-28}}</ref><ref>{{cite web |author=Department of Pathology |title=Pituitary Gland -- Diseases/Syndromes |url=http://www.pathology.vcu.edu/education/endocrine/endocrine/pituitary/diseases.html |date=[[June 13]], [[2005]] |publisher=Virginia Commonwealth University (VCU) |accessdate=2008-02-28}}</ref>
{| class="wikitable"
| '''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.<ref name="ATA">{{cite book |author=American Thyroid Association (ATA) |title=Hypothyroidism Booklet |year=2003 |pages=6 |url=http://www.thyroid.org/patients/brochures/Hypothyroidism%20_web_booklet.pdf#search=%22hypothyroidism%22 |format=PDF}}</ref>
|-
| ''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.''
|}
===General psychological associations===
Hypothyroidism can be caused by [[Lithium pharmacology|lithium]]-based [[mood stabilizer]]s, usually used to treat [[bipolar disorder]] (previously known as manic depression).
In addition, patients with hypothyroidism and psychiatric symptoms may be diagnosed with:<ref>{{cite journal |author=Heinrich TW, Grahm G |title=Hypothyroidism Presenting as Psychosis: Myxedema Madness Revisited |journal= |volume=5 |issue=6 |pages=260–266 |year=2003 |pmid=15213796 |doi=}}</ref><!-- this seems a broken link, or is subscription required:<ref name="Identifying hypothyroidism’s psychiatric presentations">Current Psychiatry Online, [http://www.currentpsychiatry.com/article_pages.asp?AID=4545&UID=29961]</ref> -->
* atypical [[Clinical depression|depression]] (which may present as [[dysthymia]])
* bipolar spectrum syndrome (including bipolar I or bipolar II disorder, [[cyclothymia]], or [[premenstrual syndrome]])
* [[ADHD predominantly inattentive|inattentive ADHD]] or [[sluggish cognitive tempo]]
In adults, hypothyroidism is associated with the following symptoms:<ref name="ATA">{{cite book |author=American Thyroid Association (ATA) |title=Hypothyroidism Booklet |year=2003 |pages=6 |url=http://www.thyroid.org/patients/brochures/Hypothyroidism%20_web_booklet.pdf#search=%22hypothyroidism%22 |format=PDF}}</ref><ref name=nlm>{{MedlinePlus|000367|Hypothyroidism - primary}} - see list of Symptoms</ref><ref>[http://health.nytimes.com/health/guides/disease/hypothyroidism/print.html "Hypothyroidism - In-Depth Report." ''The New York Times.'' Copyright 2008]</ref>
====Early symptoms====
* Poor muscle tone ([[muscle hypotonia]])
* [[Fatigue (medical)|Fatigue]]
* [[Cold intolerance]], increased sensitivity to cold
* [[Depression (mood)|Depression]]
* [[Constipation]]
* [[Muscle cramps]] and [[joint pain]]
* [[Arthritis]]
* [[Goiter]]
* Thin, [[brittle fingernails]]
* Thin, brittle hair
* [[Paleness]]
* Dry, itchy skin
* [[Weight gain]] and [[water retention]].<ref>{{cite web |title=Hypothyroidism |url=http://www.aace.com/pub/thyroidbrochures/pdfs/Hypothyroidism.pdf |format=PDF |publisher=American Association of Clinical Endocrinologists}}</ref><ref>{{cite journal |author=Yeum CH, Kim SW, Kim NH, Choi KC, Lee J |title=Increased expression of aquaporin water channels in hypothyroid rat kidney |journal=Pharmacol. Res. |volume=46 |issue=1 |pages=85–8 |year=2002 |month=July |pmid=12208125 |doi= |url=}}</ref>
* [[Bradycardia]] (low heart rate: less than sixty beats per minutes)
====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]]
====Less common symptoms====
* Heat intolerance, increased sensitivity to heat
* Impaired [[memory]]
* Impaired cognitive function ([[brain fog]]) and inattentiveness
* [[Urticaria]] (hives)
* [[Migraine]] headache
* A [[bradycardia|slow heart rate]] with [[ECG]] changes including low voltage signals. Diminished cardiac output and decreased contractility.
* [[Reactive hypoglycemia|Reactive (or post-prandial) hypoglycemia]]<ref name="pmid5086042">{{cite journal |author=Hofeldt FD, Dippe S, Forsham PH |title=Diagnosis and classification of reactive hypoglycemia based on hormonal changes in response to oral and intravenous glucose administration |journal=Am. J. Clin. Nutr. |volume=25 |issue=11 |pages=1193–201 |year=1972 |pmid=5086042 |doi= |url=http://www.ajcn.org/cgi/reprint/25/11/1193.pdf |format=PDF}}</ref>
* [[Pericardial effusion]]s may occur.
* Sluggish [[reflex action|reflexes]]
* [[Hair loss]]
* [[Anemia]] caused by impaired hemoglobin synthesis (decreased [[Erythropoietin|EPO]] levels), impaired intestinal iron and [[folate]] absorption or B12 deficiency from [[pernicious anemia]]
* [[Anxiety]]/panic attacks
* [[Difficulty swallowing]]
* [[Shortness of breath]] with a shallow and slow respiratory pattern.
* Impaired ventilatory responses to [[hypercapnia]] and [[Hypoxia (medical)|hypoxia]].
* Increased need for sleep
* [[Osteopenia]] or [[Osteoporosis]]
* [[Irritability]] and mood instability
* Yellowing of the skin due to impaired conversion of [[beta-carotene]] to vitamin A
* Impaired renal function with decreased [[Glomerular filtration rate|GFR]].
* Thin, fragile or absent [[eponychium|cuticles]]
* [[Elevated serum cholesterol]]
* Acute psychosis ([[myxedema madness]]) is a rare presentation of hypothyroidism
* [[Decreased libido]]
* Decreased sense of taste and smell (late, less common symptoms)
* Puffy face, hands and feet (late, less common symptoms)
* Depression
===Pediatric===
Hypothyroidism in [[Pediatrics|pediatric]] patients was previously classified as ''[[Cretinism]]'', and can cause the following symptoms:
* [[short stature]]
* [[mental retardation]] if present at birth, and untreated.
===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]].
==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]] (T<sub>4</sub>) and smaller amounts of triiodothyronine (T<sub>3</sub>)). 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 (fT<sub>3</sub>)
* free levothyroxine (fT<sub>4</sub>)
* total T<sub>3</sub>
* total T<sub>4</sub>
Additionally, the following measurements may be needed:
* 24 hour urine free T<sub>3</sub> <ref name="24hurine">Baisier W. Hertoghe J. Eeckhaut W. Thyroid insufficiency. Is TSH the only diagnostic tool? J Nutr Environ ed. 2000;10:105-113. [http://www.ingentaconnect.com/content/routledg/cjne/2000/00000010/00000002/art00002"Thyroid insufficiency. Is TSH the only diagnostic tool?"]</ref>
* antithyroid [[antibodies]] - for evidence of [[autoimmune disease]]s 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
==Treatment==
{{main|Thyroid hormone#Medical use of thyroid hormones|l1=Medical use of thyroid hormones}}
Hypothyroidism is treated with the levorotatory forms of [[thyroxine]] (L-T<sub>4</sub>) and [[triiodothyronine]] (L-T<sub>3</sub>). 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:
;T<sub>4</sub> Only: This treatment protocol involves supplementation of levothyroxine alone, in a synthetic form. It is currently the standard treatment in mainstream medicine.<ref name=AACE-guidelines2002>{{cite journal |author=American Association of Clinical Endocrinologists |title=Medical Guidelines For Clinical Practice For The Evaluation And Treatment Of Hyperthyroidism And Hypothyroidism |journal=Endocrine Practice |volume=8 |issue=6 |year=2002 |month=November/December |pages=457–469 |url=http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf |format=PDF}}</ref>
;T<sub>4</sub> and T<sub>3</sub> in Combination: This treatment protocol involves administering both synthetic L-T<sub>4</sub> and L-T<sub>3</sub> simultaneously in combination.<ref name="pmid9971866">{{cite journal |author=Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ |title=Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism |journal=N. Engl. J. Med. |volume=340 |issue=6 |pages=424–9 |year=1999 |month=February |pmid=9971866 |doi= |url=http://content.nejm.org/cgi/content/full/340/6/424}}</ref>
;Desiccated Thyroid Extract: [[Desiccated thyroid extract]] is an animal based thyroid extract, most commonly from a [[Pig|porcine]] source. It is also a combination therapy, containing natural forms of L-T<sub>4</sub> and L-T<sub>3</sub>.<ref name=Baisier2001>{{cite journal |author=Baisier, W.V.; Hertoghe, J.; Eeckhaut, W. |title= Thyroid Insufficiency. Is Thyroxine the Only Valuable Drug? |journal=Journal of Nutritional and Environmental Medicine |volume=11 |issue=3 |year=2001 |month=September|pages=159–66 |url= |doi=10.1080/13590840120083376}} - [http://www.ingentaconnect.com/content/routledg/cjne/2001/00000011/00000003/art00002 Abstract]</ref>
===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.<ref name=AACE-guidelines2002/> 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.
<ref name="prange2000">{{cite journal |author=Robertas Bunevicius, Arthur J. Prange Jr. |title=Mental improvement after replacement therapy with thyroxine plus triiodothyronine: relationship to cause of hypothyroidism |journal=The International Journal of Neuropsychopharmacology |volume=3 |issue=2 |pages=167-174 |year=2000 |month=June |pmid= |doi=doi:10.1017/S1461145700001826 |url=http://journals.cambridge.org/action/displayAbstract?aid=52289}}</ref>
<ref name="pmid9971866"/>. 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.<ref name=Baisier2001/>
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.<ref name="pmid15163340">{{cite journal |author=Siegmund W, Spieker K, Weike AI, ''et al'' |title=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 |journal=Clin. Endocrinol. (Oxf) |volume=60 |issue=6 |pages=750–7 |year=2004 |month=June |pmid=15163340 |doi=10.1111/j.1365-2265.2004.02050.x |url=}}</ref> And, a 2007 metaanalysis of the nine controlled studies so far published found no significant difference in the effect on psychiatric symptoms.<ref name="pmid17878495">{{cite journal |author=Joffe RT, Brimacombe M, Levitt AJ, Stagnaro-Green A |title=Treatment of clinical hypothyroidism with thyroxine and triiodothyronine: a literature review and metaanalysis |journal=Psychosomatics |volume=48 |issue=5 |pages=379–84 |year=2007 |pmid=17878495 |doi=10.1176/appi.psy.48.5.379 |url=}}</ref>
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.<ref name="pmid17479444">{{cite journal |author=Saravanan P, Siddique H, Simmons DJ, Greenwood R, Dayan CM |title=Twenty-four hour hormone profiles of TSH, Free T3 and free T4 in hypothyroid patients on combined T3/T4 therapy |journal=Exp. Clin. Endocrinol. Diabetes |volume=115 |issue=4 |pages=261–7 |year=2007 |month=April |pmid=17479444 |doi=10.1055/s-2007-973071 |url=}}</ref>
===Subclinical hypothyroidism===
Subclinical hypothyroidism occurs when thyrotropin (TSH) levels are elevated but thyroxine (T<sub>4</sub>) and triiodothyronine (T<sub>3</sub>) levels are normal.<ref name="Auburn University">{{cite book |author=Jack DeRuiter |title=Endocrine Module (PYPP 5260) |chapter=Thyroid pathology |chapterurl=http://www.auburn.edu/~deruija/endp_thyroidpathol.pdf |format=PDF |year=2002 |pages=pp30 |publisher=Auburn University School of Pharmacy}}</ref> In primary hypothyroidism, TSH levels are high and T<sub>4</sub> and T<sub>3</sub> levels are low. Endocrinologists are puzzled because TSH usually increases when T<sub>4</sub> and T<sub>3</sub> 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.<ref>{{cite web |title=Subclinical Thyroid Disease |url=http://www.aace.com/pub/positionstatements/subclinical.php |work=Guidelines & Position Statements |date=[[July 11]], [[2007]] |publisher=The American Association of Clinical Endocrinologists |accessdate=2008-06-08}}</ref> 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".<ref name="pmid17636722">{{cite journal |author=Villar H, Saconato H, Valente O, Atallah A |title=Thyroid hormone replacement for subclinical hypothyroidism |journal=Cochrane database of systematic reviews (Online) |volume= |issue=3 |pages=CD003419 |year=2007 |pmid=17636722 |doi=10.1002/14651858.CD003419.pub2}}</ref>
A more recent metanalysis looking into whether subclinical hypothyroidism may increase the risk of cardiovascular disease, as has been previously suggested,<ref>{{cite journal |author=Biondi B, Palmieri EA, Lombardi G, Fazio S |title=Effects of subclinical thyroid dysfunction on the heart |journal=Ann. Intern. Med. |volume=137 |issue=11 |pages=904–14 |year=2002 |month=December |pmid=12458990 |doi= |url=}}</ref> found a possible modest increase and suggested further studies be undertaken with coronary heart disease as a end point "before current recommendations are updated".<ref>{{cite journal |author=Ochs N, Auer R, Bauer DC, ''et al'' |title=Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality |journal=Ann. Intern. Med. |volume=148 |issue=11 |pages=832–45 |year=2008 |month=June |pmid=18490668 |doi= |url=http://www.annals.org/cgi/content/full/148/11/832}}</ref>
==References==
{{Reflist|2}}
== External links ==
www.thyroiduk.org [ThyroidUK]
*[http://www.hormone.org/public/thyroid.cfm Thyroid Section] of [[The Hormone Foundation]]
*[http://www.thyroidscience.com/ Thyroid Science journal]
*[http://www.endo-society.org The Endocrine Society]
*[http://www.aace.com/ American Association of Clinical Endocrinologists]
*[http://thyroidfoundation.org/ American Foundation of Thyroid Patients]
*[http://www.allthyroid.org/ Thyroid Foundation of America]
*[http://www.thyroid.org.au/ Thyroid Australia]
*[http://www.mayoclinic.com/health/hypothyroidism/DS00353 Mayo Clinic: Hypothyroidism]
*[http://www.ahsta.com AHSTA: Hypothyroidism in Thyroid Autoimmunity]
{{Endocrine pathology}}
[[Category:Thyroid disease]]
[[bs:Hipotireoidizam]]
[[bg:Хипотиреоидизъм]]
[[de:Hypothyreose]]
[[es:Hipotiroidismo]]
[[fr:Myxœdème]]
[[it:Ipotiroidismo]]
[[nl:Hypothyreoïdie]]
[[ja:甲状腺機能低下症]]
[[no:Hypotyreose]]
[[pl:Niedoczynność tarczycy]]
[[pt:Hipotiroidismo]]
[[ru:Гипотиреоз]]
[[fi:Kilpirauhasen vajaatoiminta]]
[[sv:Hypotyreos]]
[[vi:Suy giáp]]
[[tr:Hipotiroidi]]