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| ==Overview==
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| '''Hypothyroidism''' is the disease state in human and animals caused by insufficient production of [[thyroid hormone]] by the [[thyroid gland]]. It affects about 5% of the United Kingdom population over 60 years of age. As of 2006, more than 1% of the United Kingdom population were receiving T<sub>4</sub> ([[Thyroxine]]) replacement therapy for hypothyroidism.<ref name="tjcemjul06">{{cite journal |author=Grozinsky-Glasberg S, Fraser A, Nahshoni E, Weizman A, Leibovici L |title=Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials |journal=J. Clin. Endocrinol. Metab. |volume=91 |issue=7 |pages=2592-9 |year=2006 |month=July |pmid=16670166 |doi=10.1210/jc.2006-0448}}</ref>
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| ==Causes== | | ==[[Hypothyroidism overview|Overview]]== |
| There are several distinct causes for chronic hypothyroidism. Historically and, still, in many developing countries [[iodine deficiency]] is the most common cause of hypothyroidism world-wide. In present day developed countries, however, 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.
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| 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.
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| Hypothyroidism can also result from sporadic inheritance, sometimes [[autosome|autosomal]] recessive.
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| Temporary hypothyroidism can be due to the [[Wolff-Chaikoff effect]].
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| Hypothyroidism is often classified by the organ of origin:<ref>http://www.umm.edu/patiented/articles/what_causes_hypothyroidism_000038_2.htm</ref><ref>http://www.pathology.vcu.edu/education/endocrine/endocrine/pituitary/diseases.html</ref>
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| {| class="wikitable"
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| | '''Type''' || '''Origin''' || '''Description'''
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| | ''Primary hypothyroidism'' || [[thyroid gland]] || The most common forms include [[Hashimoto's thyroiditis]] (an [[autoimmune]] disease) and [[radioiodine]] therapy for [[hyperthyroidism]].
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| | ''Secondary hypothyroidism'' || [[pituitary gland]] || Occurs if the pituitary gland does not create enough [[thyroid stimulating hormone]] (TSH, [[Thyrotropin]]) to induce the thyroid gland to create a sufficient quantity of [[thyroxine]]. Although not every case of secondary hypothyroidism has a clear-cut cause, it is usually caused when the pituitary is damaged by a tumor, radiation, or surgery so that it is no longer able to instruct the thyroid to make enough hormone<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>
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| | ''Tertiary hypothyroidism'', also called ''hypothalamic-pituitary-axis hypothyroidism'' || [[hypothalamus]] || Results when the hypothalamus fails to produce sufficient [[TRH]].
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| |}
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| === Complete Differential Diagnosis of Causes of Hypothyroidism===
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| * [[Amyloidosis]]
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| * Antithyroid drugs
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| * [[Cystinosis]]
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| * [[Dermatosclerosis]]
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| * [[Drugs]]
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| * [[Hashimoto's Thyroiditis]]
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| * Head and neck surgery
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| * [[Hemochromatosis]]
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| * Iodine deficiency
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| * [[Neoplastic]]
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| * Peripheral thyroid gland disorder resistance
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| * [[Radiation]] therapy to head neck or chest area
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| * Radioactive iodine therapy
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| * [[Reidel's Thyroiditis]]
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| * [[Sarcoidosis]], granulomatous disease
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| * [[Scleroderma]]
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| * Secondary hypothyroidism
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| * Silent [[thyroiditis]]
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| * Subacute [[thyroiditis]]
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| * Subtotal thyroidectomy
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| * Supprative [[thyroiditis]]
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| * Thyreostatic therapy
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| * Thyroid agenesis, dysgenesis, ectopy
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| * [[TSH]] (thyroid stimulating hormone) deficiency
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| ===General psychological associations===
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| Hypothyroidism can be caused by [[Lithium pharmacology|lithium]]-based [[mood stabilizer]]s, usually used to treat [[bipolar disorder]] (previously known as manic depression).
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| 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> -->
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| * atypical [[Clinical depression|depression]] (which may present as [[dysthymia]])
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| * bipolar spectrum syndrome (including bipolar I or bipolar II disorder, [[cyclothymia]], or [[premenstrual syndrome]])
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| * [[borderline personality disorder]]
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| * a [[psychotic disorder]] (typically, paranoid [[schizophrenia]])
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| * [[ADHD predominantly inattentive|inattentive ADHD]] or [[sluggish cognitive tempo]]
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| ==Symptoms==
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| 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.
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| 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<ref name="Geneva Diagnostics">{{cite web |title=Comprehensive Thyroid Assessment |url=http://www.gdx.net/home/assessments/thyroid/ |publsiher=Geneva Diagnostics}}</ref> to mention a few. Thus, when the thyroid hormone content gets out of balance, systems covering the whole body are affected, and that's why hypothyroidism can look like other diseases. Conversely, sometimes other conditions can be mistaken for hypothyroidism.
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| ===Adults===
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| In adults, hypothyroidism is associated with the following symptoms:<ref name="ATA"/>
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| ====Early symptoms====
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| * Poor muscle tone ([[muscle hypotonia]])
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| * [[Fatigue (medical)|Fatigue]]
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| * Cold intolerance, increased sensitivity to cold
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| * [[Constipation]]
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| * [[Weight gain]]
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| * [[Muscle cramps]] and [[joint pain]]
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| * Thin, [[Brittle fingernails]]
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| * Thin, brittle hair
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| * [[Paleness]]<ref name=nlm> [http://www.nlm.nih.gov/medlineplus/ency/article/000367.htm#Symptoms NLM] </ref>
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| ====Late symptoms====
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| * Slowed speech and a [[hoarse]], breaking voice. Deepening of the voice can also be noticed.
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| * Dry puffy skin, especially on the face
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| * Thinning of the outer third of the eyebrows
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| * Abnormal [[menstrual cycles]]
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| * Low [[basal body temperature]]<ref name=nlm/>
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| ====Less common symptoms====
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| * Heat intolerance, increased sensitivity to heat
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| * Impaired [[memory]]
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| * Impaired cognitive function (brain fog) and inattentiveness
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| * [[Urticaria]] (hives)
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| * [[Migraine]] headache
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| * A [[bradycardia|slow heart rate]] with [[ECG]] changes including low voltage signals. Diminished cardiac output and decreased contractility.
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| * [[Reactive hypoglycemia|Reactive (or post-prandial) hypoglycemia]]<ref name="hypoglycemia"> Fred D.Hofdelt, Stephen Dippe, Peter H. Forshman "Diagnosis and classification of reactive hypoglycemia based on hormonal changes in response to oral and intravenous glucose administration" ''The American Journal of Clinical Nutrition''[http://www.ajcn.org/cgi/reprint/25/11/1193.pdf]</ref>
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| * [[Pericardial effusion]]s may occur.
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| * Sluggish [[reflex action|reflexes]]
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| * [[hair loss]]
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| * [[Anemia]] caused by impaired hemoglobin synthesis (decreased [[Erythropoietin|EPO]] levels), impaired intestinal iron and [[folate]] absorption or B12 deficiency from [[pernicious anemia]]
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| * [[anxiety]]/panic attacks
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| * [[difficulty swallowing]]
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| * [[Shortness of breath]] with a shallow and slow respiratory pattern.
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| * Impaired ventilatory responses to [[hypercapnia]] and [[Hypoxia (medical)|hypoxia]].
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| * Increased need for sleep
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| * [[Osteopenia]] or [[Osteoporosis]]
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| * [[Irritability]] and mood instability
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| * Yellowing of the skin due to impaired conversion of [[beta-carotene]] to vitamin A
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| * Impaired renal function with decreased [[Glomerular filtration rate|GFR]].
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| * Thin, fragile or absent [[eponychium|cuticles]]
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| * [[Elevated serum cholesterol]]
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| * Acute psychosis ([[myxedema madness]]) is a rare presentation of hypothyroidism
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| * [[Decreased libido]]
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| * Decreased sense of taste and smell (late, less common symptoms)
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| * Puffy face, hands and feet (late, less common symptoms)
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| ===Pediatric===
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| Hypothyroidism in pediatric patients can cause the following additional symptoms: | |
| * [[short stature]]
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| * [[mental retardation]] if present at birth, and untreated.
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| ===Severity===
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| 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]].
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| ==Diagnostic testing==
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| To diagnose primary hypothyroidism, many doctors simply measure the amount of [[Thyroid-stimulating hormone]] (TSH) being produced. 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 (fT3)). 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:
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| * [[thyroid-stimulating hormone]] ([[TSH]])
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| * [[free triiodothyronine]] ([[fT3]])
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| * [[free levothyroxine]] ([[fT4]])
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| * [[total T3]]
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| * [[total T4]]
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| Additionally, the following measurements may be needed:
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| * antithyroid [[antibodies]] - for evidence of [[autoimmune disease]]s that may be damaging the [[thyroid gland]]
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| * serum [[cholesterol]] - which may be elevated in [[hypothyroidism]]
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| * [[prolactin]] - as a widely available test of pituitary function
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| * testing for [[anemia]], including [[ferritin]]
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| ==Treatment==
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| {{main|Thyroid hormone#Medical use of thyroid hormones|l1=Medical use of thyroid hormones}}
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| 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 dosaging.
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| The American Thyroid Association cautions against taking herbal remedies, and warns that taking too much iodine can actually worsen hypothyroidism.<ref name="ATA"> </ref>
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| Some researchers would suggest that there is no benefit to treatment with the T<sub>4</sub> - T<sub>3</sub> combination therapy over the T<sub>4</sub> monotherapy. A [[meta-analysis]] of 11 [[randomized controlled trials]] found no advantage with the T<sub>4</sub> - T<sub>3</sub> combination therapy over the T<sub>4</sub> monotherapy.<ref name="tjcemjul06"/>
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| However, many of the studies involved in this meta-analysis were not properly designed. They tested the medication's effectiveness by providing the same dose of thyroid medication to each patient and by utilizing the TSH test as a measure of treatment effectiveness. Thyroid medication must be individualized to the patient, carefully observing free T4 and free T3 (not TSH, which is a diagnostic tool but not a treatment tool). Beneficial effects would not expect to be seen at doses not tailored to the individual's needs. Clinically, most physicians prescribing T3 as part or all of a hypothyroid patient's treatment find that most patients receiving T3 in fact must be on a larger dose than was administered in these studies. The meta-analysis results ought to be held in question, therefore; and the knowledgeable physician will administer T3 medication for the hypothyroid patient who continues to present with symptoms and whose free T3 level is low, or low in the range.
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| ===Subclinical hypothyroidism===
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| A [[meta-analysis]] by the [[Cochrane Collaboration]] found no benefit 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>
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| == External links == | | == External links == |
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| *[http://www.thyroid.org.au/ Thyroid Australia] | | *[http://www.thyroid.org.au/ Thyroid Australia] |
| *[http://www.mayoclinic.com/health/hypothyroidism/DS00353 Mayo Clinic: Hypothyroidism] | | *[http://www.mayoclinic.com/health/hypothyroidism/DS00353 Mayo Clinic: Hypothyroidism] |
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| ==References==
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| {{Reflist|2}}
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| <br>
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| {{Endocrine pathology}} | | {{Endocrine pathology}} |
