Hypothyroidism

Infobox_Disease
Name = Hypothyroidism

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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.cite book |author=Jack DeRuiter |title=Thyroid Pathology |year=2002 |pages=30 |url= http://www.auburn.edu/~deruija/endp_thyroidpathol.pdf |format=PDF] 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. [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]

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: [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] [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]

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: [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=]
* atypical depression (which may present as dysthymia)
* bipolar spectrum syndrome (including bipolar I or bipolar II disorder, cyclothymia, or premenstrual syndrome)
* inattentive ADHD or sluggish cognitive tempo

ymptoms

In adults, hypothyroidism is associated with the following symptoms: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] MedlinePlus|000367|Hypothyroidism — primary — see list of Symptoms] [ [http://health.nytimes.com/health/guides/disease/hypothyroidism/print.html "Hypothyroidism — In-Depth Report." "The New York Times." Copyright 2008] ]

Early symptoms

* Poor muscle tone (muscle hypotonia)
* Fatigue
* Cold intolerance, increased sensitivity to cold
* Depression
* Muscle cramps and joint pain
* Arthritis
* Goiter
* Thin, brittle fingernails
* Thin, brittle hair
* Paleness
* Dry, itchy skin
* Weight gain and water retention. [cite web |title=Hypothyroidism |url=http://www.aace.com/pub/thyroidbrochures/pdfs/Hypothyroidism.pdf |format=PDF |publisher=American Association of Clinical Endocrinologists] [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=]
* Bradycardia (low heart rate: less than sixty beats per minute)
* Constipation

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

* Migraine headache
* Impaired memory
* Anxiety/panic attacks
* Urticaria (hives)
* Impaired cognitive function (brain fog) and inattentiveness
* A slow heart rate with ECG changes including low voltage signals. Diminished cardiac output and decreased contractility.
* Reactive (or post-prandial) hypoglycemiacite 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]
* Pericardial effusions may occur.
* Sluggish reflexes
* Hair loss
* Early greying of the hair
* Anemia caused by impaired hemoglobin synthesis (decreased EPO levels), impaired intestinal iron and folate absorption or B12 deficiency from pernicious anemia

* Difficulty swallowing
* Shortness of breath with a shallow and slow respiratory pattern.
* Impaired ventilatory responses to hypercapnia and 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 GFR.
* Thin, fragile or absent 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
* Premature wrinkling on the face

Pediatric

Hypothyroidism in pediatric patients was previously classified as "Cretinism", and can cause the following symptoms:
* short stature
* mental retardation if present at birth, and untreated.

everity

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 cardiovascular 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 (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;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?"] ]
* 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.

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.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]

;T₄ and T₃ in Combination: This treatment protocol involves administering both synthetic L-T₄ and L-T₃ simultaneously in combination.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]

;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.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] ]

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. 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. 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] . 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.

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.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=] And, a 2007 metaanalysis of the nine controlled studies so far published found no significant difference in the effect on psychiatric symptoms.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=]

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.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=]

ubclinical hypothyroidism

Subclinical hypothyroidism occurs when thyrotropin (TSH) levels are elevated but thyroxine (T₄) and triiodothyronine (T₃) levels are normal.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] 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. [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] 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".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] A more recent metanalysis looking into whether subclinical hypothyroidism may increase the risk of cardiovascular disease, as has been previously suggested, [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=] found a possible modest increase and suggested further studies be undertaken with coronary heart disease as a end point "before current recommendations are updated". [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]

References

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.icarecafe.com/?page_id=1107&group_id=6/ icarecafe Hypothyroid Patient Group]
* [http://www.ahsta.com Alternative Health Solutions for Thyroid Autoimmunity]
* [http://www.elaine-moore.com Elaine Moore Graves' and Autoimmune Disease Education]