ࡱ>     q` 0bjbjqPqP: ::h`V\V\V\V\^|^J ~~~~9;;;;;;$,hR__~~d~~99I ~^ `t?V\U:9z0:zzt88v=TDՀE__ == Androgen Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a  HYPERLINK "http://en.wikipedia.org/wiki/Steroid_hormone" steroid hormone, that stimulates or controls the development and maintenance of male characteristics in  HYPERLINK "http://en.wikipedia.org/wiki/Vertebrate" \o "Vertebrate" vertebrates by binding to  HYPERLINK "http://en.wikipedia.org/wiki/Androgen_receptor" \o "Androgen receptor" androgen receptors. This includes the activity of the accessory  HYPERLINK "http://en.wikipedia.org/wiki/Male" male  HYPERLINK "http://en.wikipedia.org/wiki/Sex_organ" \o "Sex organ" sex organs and development of male  HYPERLINK "http://en.wikipedia.org/wiki/Secondary_sex_characteristic" \o "Secondary sex characteristic" secondary sex characteristics. Androgens were first discovered in 1936. Androgens are also the original  HYPERLINK "http://en.wikipedia.org/wiki/Anabolic_steroid" \o "Anabolic steroid" anabolic steroids and the precursor of all  HYPERLINK "http://en.wikipedia.org/wiki/Estrogen" \o "Estrogen" estrogens, the  HYPERLINK "http://en.wikipedia.org/wiki/Female" female sex hormones. The primary and most well-known androgen is  HYPERLINK "http://en.wikipedia.org/wiki/Testosterone" testosterone. Types HYPERLINK "http://en.wikipedia.org/wiki/File:Steroidogenesis.svg"   HYPERLINK "http://en.wikipedia.org/wiki/File:Steroidogenesis.svg" \o "Enlarge"   HYPERLINK "http://en.wikipedia.org/wiki/Steroidogenesis" \o "Steroidogenesis" Steroidogenesis, showing the relation between several androgens at bottom left. (Estrone and estradiol, in contrast, are  HYPERLINK "http://en.wikipedia.org/wiki/Estrogens" \o "Estrogens" estrogens. A subset of androgens, adrenal androgens, includes any of the 19-carbon steroids synthesized by the  HYPERLINK "http://en.wikipedia.org/wiki/Adrenal_cortex" adrenal cortex, the outer portion of the  HYPERLINK "http://en.wikipedia.org/wiki/Adrenal_gland" adrenal gland (zonula reticularisinnermost region of the adrenal cortex), that function as weak steroids or steroid precursors, including  HYPERLINK "http://en.wikipedia.org/wiki/Dehydroepiandrosterone" dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione. Besides testosterone, other androgens include:  HYPERLINK "http://en.wikipedia.org/wiki/Dehydroepiandrosterone" Dehydroepiandrosterone (DHEA): a steroid hormone produced in the  HYPERLINK "http://en.wikipedia.org/wiki/Adrenal_cortex" adrenal cortex from  HYPERLINK "http://en.wikipedia.org/wiki/Cholesterol" cholesterol. It is the primary precursor of natural  HYPERLINK "http://en.wikipedia.org/wiki/Estrogen" \o "Estrogen" estrogens.  HYPERLINK "http://en.wikipedia.org/wiki/Dehydroepiandrosterone" \o "Dehydroepiandrosterone" DHEA is also called  HYPERLINK "http://en.wikipedia.org/wiki/Dehydroisoandrosterone" \o "Dehydroisoandrosterone" dehydroisoandrosterone or  HYPERLINK "http://en.wikipedia.org/wiki/Dehydroandrosterone" \o "Dehydroandrosterone" dehydroandrosterone.  HYPERLINK "http://en.wikipedia.org/wiki/Androstenedione" Androstenedione (Andro): an androgenic steroid produced by the  HYPERLINK "http://en.wikipedia.org/wiki/Testes" \o "Testes" testes,  HYPERLINK "http://en.wikipedia.org/wiki/Adrenal_cortex" adrenal cortex, and  HYPERLINK "http://en.wikipedia.org/wiki/Ovaries" \o "Ovaries" ovaries. While  HYPERLINK "http://en.wikipedia.org/wiki/Androstenedione" \o "Androstenedione" androstenediones are converted metabolically to  HYPERLINK "http://en.wikipedia.org/wiki/Testosterone" testosterone and other androgens, they are also the parent structure of  HYPERLINK "http://en.wikipedia.org/wiki/Estrone" estrone. Use of androstenedione as an athletic or body building  HYPERLINK "http://en.wikipedia.org/wiki/Bodybuilding_supplement" \o "Bodybuilding supplement" supplement has been banned by the  HYPERLINK "http://en.wikipedia.org/wiki/International_Olympic_Committee" International Olympic Committee as well as other sporting organizations.  HYPERLINK "http://en.wikipedia.org/wiki/Androstenediol" Androstenediol: the steroid  HYPERLINK "http://en.wikipedia.org/wiki/Metabolite" metabolite that is thought to act as the main regulator of  HYPERLINK "http://en.wikipedia.org/wiki/Gonadotropin" gonadotropin secretion.  HYPERLINK "http://en.wikipedia.org/wiki/Androsterone" Androsterone: a chemical by-product created during the breakdown of androgens, or derived from  HYPERLINK "http://en.wikipedia.org/wiki/Progesterone" progesterone, that also exerts minor masculinising effects, but with one-seventh the intensity of testosterone. It is found in approximately equal amounts in the  HYPERLINK "http://en.wikipedia.org/wiki/Blood_plasma" \o "Blood plasma" plasma and  HYPERLINK "http://en.wikipedia.org/wiki/Urine" urine of both males and females.  HYPERLINK "http://en.wikipedia.org/wiki/Dihydrotestosterone" Dihydrotestosterone (DHT): a  HYPERLINK "http://en.wikipedia.org/wiki/Metabolite" metabolite of  HYPERLINK "http://en.wikipedia.org/wiki/Testosterone" testosterone, and a more potent androgen than  HYPERLINK "http://en.wikipedia.org/wiki/Testosterone" testosterone in that it binds more strongly to  HYPERLINK "http://en.wikipedia.org/wiki/Androgen_receptor" \o "Androgen receptor" androgen receptors. It is produced in the  HYPERLINK "http://en.wikipedia.org/wiki/Adrenal_cortex" adrenal cortex. Functions Development of the male Testes formation During mammalian development, the gonads are at first capable of becoming either  HYPERLINK "http://en.wikipedia.org/wiki/Ovary" \o "Ovary" ovaries or testes. HYPERLINK "http://en.wikipedia.org/wiki/Androgen" \l "cite_note-0#cite_note-0" [1] In humans, starting at about week 4 the gonadal rudiments are present within the  HYPERLINK "http://en.wikipedia.org/wiki/Intermediate_mesoderm" intermediate mesoderm adjacent to the developing kidneys. At about week 6, epithelial  HYPERLINK "http://en.wikipedia.org/wiki/Sex_cords" \o "Sex cords" sex cords develop within the forming testes and incorporate the  HYPERLINK "http://en.wikipedia.org/wiki/Germ_cell" \o "Germ cell" germ cells as they migrate into the gonads. In males, certain  HYPERLINK "http://en.wikipedia.org/wiki/Y_chromosome" Y chromosome genes, particularly  HYPERLINK "http://en.wikipedia.org/wiki/SRY" SRY, control development of the male phenotype, including conversion of the early bipotential gonad into testes. In males, the sex cords fully invade the developing gonads. Androgen production The mesoderm-derived  HYPERLINK "http://en.wikipedia.org/wiki/Epithelium" \o "Epithelium" epithelial cells of the sex cords in developing testes become the Sertoli cells which will function to support sperm cell formation. A minor population of non-epithelial cells appear between the tubules by week 8 of human fetal development. These are Leydig cells. Soon after they differentiate, Leydig cells begin to produce androgens. Androgen effects The androgens function as  HYPERLINK "http://en.wikipedia.org/wiki/Paracrine_signalling" \o "Paracrine signalling" paracrine  HYPERLINK "http://en.wikipedia.org/wiki/Hormone" \o "Hormone" hormones required by the Sertoli cells in order to support sperm production. They are also required for masculinization of the developing male fetus (including penis and scrotum formation). Under the influence of androgens, remnants of the  HYPERLINK "http://en.wikipedia.org/wiki/Mesonephron" \o "Mesonephron" mesonephron, the  HYPERLINK "http://en.wikipedia.org/wiki/Wolffian_ducts" \o "Wolffian ducts" Wolffian ducts, develop into the  HYPERLINK "http://en.wikipedia.org/wiki/Epididymis" epididymis,  HYPERLINK "http://en.wikipedia.org/wiki/Vas_deferens" vas deferens and  HYPERLINK "http://en.wikipedia.org/wiki/Seminal_vesicles" \o "Seminal vesicles" seminal vesicles. This action of androgens is supported by a hormone from Sertoli cells, MIH (Mllerian inhibitory hormone), which prevents the embryonic Mllerian ducts from developing into fallopian tubes and other female reproductive tract tissues in male embryos. MIH and androgens cooperate to allow for the normal movement of testes into the scrotum. Early regulation Before the production of the pituitary hormone  HYPERLINK "http://en.wikipedia.org/wiki/Luteinizing_hormone" luteinizing hormone (LH) by the embryo starting at about weeks 1112,  HYPERLINK "http://en.wikipedia.org/wiki/Human_chorionic_gonadotrophin" \o "Human chorionic gonadotrophin" human chorionic gonadotrophin (hCG) promotes the differentiation of Leydig cells and their production of androgens at week 8. Androgen action in target tissues often involves conversion of testosterone to 5-dihydrotestosterone ( HYPERLINK "http://en.wikipedia.org/wiki/Dihydrotestosterone" \o "Dihydrotestosterone" DHT). Spermatogenesis During puberty, androgen,  HYPERLINK "http://en.wikipedia.org/wiki/Luteinising_hormone" \o "Luteinising hormone" LH and  HYPERLINK "http://en.wikipedia.org/wiki/Follicle_stimulating_hormone" \o "Follicle stimulating hormone" FSH production increase and the sex cords hollow out, forming the seminiferous tubules, and the germ cells start to differentiate into sperm. Throughout adulthood, androgens and  HYPERLINK "http://en.wikipedia.org/wiki/FSH" FSH cooperatively act on Sertoli cells in the testes to support sperm production. HYPERLINK "http://en.wikipedia.org/wiki/Androgen" \l "cite_note-1#cite_note-1" [2] Exogenous androgen supplements can be used as a  HYPERLINK "http://en.wikipedia.org/wiki/Male_contraceptive" male contraceptive. Elevated androgen levels caused by use of androgen supplements can inhibit production of LH and block production of endogenous androgens by Leydig cells. Without the locally high levels of androgens in testes due to androgen production by Leydig cells, the seminiferous tubules can degenerate resulting in infertility. For this reason, many transdermal androgen patches are applied to the scrotum. Inhibition of fat deposition Males typically have less  HYPERLINK "http://en.wikipedia.org/wiki/Adipose_tissue" adipose tissue than females. Recent results indicate that androgens inhibit the ability of some fat cells to store lipids by blocking a signal transduction pathway that normally supports adipocyte function. HYPERLINK "http://en.wikipedia.org/wiki/Androgen" \l "cite_note-Singh_R.2C_Artaza_JN.2C_Taylor_WE.2C_et_al._2006_141.E2.80.9354-2#cite_note-Singh_R.2C_Artaza_JN.2C_Taylor_WE.2C_et_al._2006_141.E2.80.9354-2" [3] Also, androgens, but not estrogens, increase beta  HYPERLINK "http://en.wikipedia.org/wiki/Adrenergic_receptor" \o "Adrenergic receptor" adrenergic receptors while decreasing alpha adrenergic receptors- which results in increased levels of epinephrine/ norepinephrine due to lack of alpha-2 receptor negative feedback and decreased fat accumulation due to epinephrine/ norepinephrine then acting on lipolysis-inducing beta receptors. Muscle mass Males typically have more  HYPERLINK "http://en.wikipedia.org/wiki/Skeletal_muscle" skeletal muscle mass than females. Androgens promote the enlargement of skeletal muscle cells and probably act in a coordinated manner to function by acting on several cell types in skeletal muscle tissue. HYPERLINK "http://en.wikipedia.org/wiki/Androgen" \l "cite_note-3#cite_note-3" [4] One type of cell that conveys hormone signals to generating muscle is the  HYPERLINK "http://en.wikipedia.org/wiki/Myoblast" myoblast. Higher androgen levels lead to increased expression of androgen receptor. Fusion of  HYPERLINK "http://en.wikipedia.org/wiki/Myoblasts" \o "Myoblasts" myoblasts generates  HYPERLINK "http://en.wikipedia.org/w/index.php?title=Myotubes&action=edit&redlink=1" \o "Myotubes (page does not exist)" myotubes, in a process that is linked to androgen receptor levels. HYPERLINK "http://en.wikipedia.org/wiki/Androgen" \l "cite_note-pmid15623502-4#cite_note-pmid15623502-4" [5] Brain Circulating levels of androgens can influence human behavior because some  HYPERLINK "http://en.wikipedia.org/wiki/Neuron" \o "Neuron" neurons are sensitive to steroid hormones. Androgen levels have been implicated in the regulation of human  HYPERLINK "http://en.wikipedia.org/wiki/Aggression" aggression HYPERLINK "http://en.wikipedia.org/wiki/Androgen" \l "cite_note-Singh_R.2C_Artaza_JN.2C_Taylor_WE.2C_et_al._2006_141.E2.80.9354-2#cite_note-Singh_R.2C_Artaza_JN.2C_Taylor_WE.2C_et_al._2006_141.E2.80.9354-2" [3] and libido. Indeed, androgens are capable of altering the structure of the brain in several species, including mice, rats, and primates, producing  HYPERLINK "http://en.wikipedia.org/wiki/Sex_differences" \o "Sex differences" sex differences. HYPERLINK "http://en.wikipedia.org/wiki/Androgen" \l "cite_note-5#cite_note-5" [6] Numerous reports have outlined that androgens alone are capable of altering the structure of the brain, HYPERLINK "http://en.wikipedia.org/wiki/Androgen" \l "cite_note-6#cite_note-6" [7] however it is difficult to identify which alterations in neuroanatomy stem from androgens or estrogens, because of their potential for conversion. Insensitivity to androgen Reduced ability of a  HYPERLINK "http://en.wikipedia.org/wiki/Sex_chromosome" \o "Sex chromosome" XY  HYPERLINK "http://en.wikipedia.org/wiki/Karyotype" karyotype fetus to respond to androgens can result in one of several conditions, including infertility and several forms of  HYPERLINK "http://en.wikipedia.org/wiki/Intersex" intersex conditions. Antiandrogen An antiandrogen, or androgen antagonist, is any of a group of  HYPERLINK "http://en.wikipedia.org/wiki/Hormone" hormone  HYPERLINK "http://en.wikipedia.org/wiki/Receptor_antagonist" receptor antagonist compounds that are capable of preventing or inhibiting the biologic effects of  HYPERLINK "http://en.wikipedia.org/wiki/Androgen" \o "Androgen" androgens, HYPERLINK "http://en.wikipedia.org/wiki/Antiandrogen" \l "cite_note-0#cite_note-0" [1]  HYPERLINK "http://en.wikipedia.org/wiki/Male" male sex  HYPERLINK "http://en.wikipedia.org/wiki/Hormone" \o "Hormone" hormones, on normally responsive tissues in the body. Antiandrogens usually work by blocking the appropriate  HYPERLINK "http://en.wikipedia.org/wiki/Receptor_(biochemistry)" \o "Receptor (biochemistry)" receptors, competing for binding sites on the  HYPERLINK "http://en.wikipedia.org/wiki/Cell_(biology)" \o "Cell (biology)" cell's surface, obstructing the androgens' pathway. Indications Antiandrogens are often indicated to treat severe male sexual disorders, such as  HYPERLINK "http://en.wikipedia.org/wiki/Hypersexuality" hypersexuality (excessive  HYPERLINK "http://en.wikipedia.org/wiki/Sexual_desire" \o "Sexual desire" sexual desire) and  HYPERLINK "http://en.wikipedia.org/wiki/Sexual_deviation" \o "Sexual deviation" sexual deviation such as  HYPERLINK "http://en.wikipedia.org/wiki/Paraphilia" \o "Paraphilia" paraphilias, as well as use as an  HYPERLINK "http://en.wikipedia.org/wiki/Antineoplastic" antineoplastic agent and  HYPERLINK "http://en.wikipedia.org/wiki/Palliative" \o "Palliative" palliative,  HYPERLINK "http://en.wikipedia.org/wiki/Adjuvant" adjuvant or  HYPERLINK "http://en.wikipedia.org/wiki/Neoadjuvant" \o "Neoadjuvant" neoadjuvant  HYPERLINK "http://en.wikipedia.org/wiki/Hormone_therapy" \o "Hormone therapy" hormonal therapy in  HYPERLINK "http://en.wikipedia.org/wiki/Prostate_cancer" prostate cancer. Antiandrogens can also be used for treatment of  HYPERLINK "http://en.wikipedia.org/wiki/Benign_prostatic_hyperplasia" benign prostatic hyperplasia (prostate enlargement),  HYPERLINK "http://en.wikipedia.org/wiki/Acne_vulgaris" acne vulgaris, androgenetic alopecia ( HYPERLINK "http://en.wikipedia.org/wiki/Male_pattern_baldness" \o "Male pattern baldness" male pattern baldness), and  HYPERLINK "http://en.wikipedia.org/wiki/Hirsutism" hirsutism (excessive  HYPERLINK "http://en.wikipedia.org/wiki/Hair" \o "Hair" hairiness). On occasion, they are also used as a  HYPERLINK "http://en.wikipedia.org/wiki/Male_contraceptive" male contraceptive agent, to purposefully prevent or counteract masculinisation in the case of  HYPERLINK "http://en.wikipedia.org/wiki/Transwomen" \o "Transwomen" transsexual women undergoing  HYPERLINK "http://en.wikipedia.org/wiki/Sex_reassignment_therapy" sex reassignment therapy, and to prevent the symptoms associated with reduced  HYPERLINK "http://en.wikipedia.org/wiki/Testosterone" testosterone, such as  HYPERLINK "http://en.wikipedia.org/wiki/Hot_flash" \o "Hot flash" hot flashes, following  HYPERLINK "http://en.wikipedia.org/wiki/Castration" castration. They can also be used for the treatment of  HYPERLINK "http://en.wikipedia.org/wiki/Polycystic_ovarian_syndrome" \o "Polycystic ovarian syndrome" polycystic ovarian syndrome (PCOS). The administration of antiandrogens in males can result in slowed or halted development or reversal of male  HYPERLINK "http://en.wikipedia.org/wiki/Secondary_sex_characteristic" \o "Secondary sex characteristic" secondary sex characteristics, reduced activity or function of the accessory male  HYPERLINK "http://en.wikipedia.org/wiki/Sex_organs" \o "Sex organs" sex organs, and hyposexuality (diminished  HYPERLINK "http://en.wikipedia.org/wiki/Sexual_desire" \o "Sexual desire" sexual desire or  HYPERLINK "http://en.wikipedia.org/wiki/Libido" libido). Sometimes as a part of a program for registered sex offenders recently released from prisons, the offender is administered antiandrogen drugs to reduce the likelihood of repeat offending by reducing sexual drive, etc. Examples Currently available antiandrogen drugs (brand names, which may include other active ingredients, in parentheses) include:  HYPERLINK "http://en.wikipedia.org/wiki/Spironolactone" Spironolactone (Aldactone, Spiritone), a synthetic 17-spirolactone  HYPERLINK "http://en.wikipedia.org/wiki/Corticosteroid" corticosteroid, which is a renal competitive  HYPERLINK "http://en.wikipedia.org/wiki/Aldosterone" aldosterone antagonist in a class of  HYPERLINK "http://en.wikipedia.org/wiki/Pharmaceutical" \o "Pharmaceutical" pharmaceuticals called  HYPERLINK "http://en.wikipedia.org/wiki/Potassium" potassium-sparing  HYPERLINK "http://en.wikipedia.org/wiki/Diuretic" \o "Diuretic" diuretics, used primarily to treat low- HYPERLINK "http://en.wikipedia.org/wiki/Renin" renin  HYPERLINK "http://en.wikipedia.org/wiki/Hypertension" hypertension,  HYPERLINK "http://en.wikipedia.org/wiki/Hypokalemia" hypokalemia, and  HYPERLINK "http://en.wikipedia.org/wiki/Conn%27s_syndrome" \o "Conn's syndrome" Conn's syndrome.  HYPERLINK "http://en.wikipedia.org/wiki/Cyproterone_acetate" \o "Cyproterone acetate" Cyproterone acetate (Androcur, Climen, Diane 35, Ginette 35), a  HYPERLINK "http://en.wikipedia.org/wiki/Chemical_synthesis" \o "Chemical synthesis" synthetic  HYPERLINK "http://en.wikipedia.org/wiki/Steroid" steroid, a potent antiandrogen that also possesses  HYPERLINK "http://en.wikipedia.org/wiki/Progestagen" \o "Progestagen" progestational properties.  HYPERLINK "http://en.wikipedia.org/wiki/Flutamide" Flutamide (Eulexin),  HYPERLINK "http://en.wikipedia.org/wiki/Nilutamide" nilutamide (Anandron, Nilandron) and  HYPERLINK "http://en.wikipedia.org/wiki/Bicalutamide" bicalutamide (Casodex), nonsteroidal, pure antiandrogens. Flutamide is the oldest and has more unwanted side-effects than the others. Bicalutamide is the newest and has the least side-effects.  HYPERLINK "http://en.wikipedia.org/wiki/Ketoconazole" Ketoconazole (Nizoral), an  HYPERLINK "http://en.wikipedia.org/wiki/Imidazole" imidazole derivative used as a  HYPERLINK "http://en.wikipedia.org/wiki/Broad-spectrum" \o "Broad-spectrum" broad-spectrum antifungal agent effective against a variety of fungal infections; side-effects include serious  HYPERLINK "http://en.wikipedia.org/wiki/Liver" liver damage and reduced levels of androgen from both the  HYPERLINK "http://en.wikipedia.org/wiki/Testicle" \o "Testicle" testicles and  HYPERLINK "http://en.wikipedia.org/wiki/Adrenal_gland" \o "Adrenal gland" adrenal glands. Ketoconazole is a relatively weak antiandrogen.  HYPERLINK "http://en.wikipedia.org/wiki/Finasteride" Finasteride (Proscar, Propecia) and  HYPERLINK "http://en.wikipedia.org/wiki/Dutasteride" dutasteride (Avodart), inhibitors of the  HYPERLINK "http://en.wikipedia.org/wiki/5-alpha_reductase" \o "5-alpha reductase" 5--reductase  HYPERLINK "http://en.wikipedia.org/wiki/Enzyme" enzyme that prevent the conversion of testosterone into  HYPERLINK "http://en.wikipedia.org/wiki/Dihydrotestosterone" dihydrotestosterone (DHT). Finasteride blocks only 5--reductase type II, dutasteride also blocks type I. They are not general antiandrogens in that they do not counteract the effects or production of other androgens other than DHT; however, DHT is 3-5 times more potent than testosterone or other androgens (except in skeletal muscle tissue, where testosterone is the main androgen).There are a number of in vivo and in vitro plant/herbal  HYPERLINK "http://en.wikipedia.org/wiki/5-alpha_reductase_inhibitor" \o "5-alpha reductase inhibitor" inhibitors of the 5-alpha reductase  HYPERLINK "http://en.wikipedia.org/wiki/Dichlorodiphenyldichloroethylene" \o "Dichlorodiphenyldichloroethylene" DDE The metabolite of  HYPERLINK "http://en.wikipedia.org/wiki/DDT" DDT is DDE, which acts as a weak antiandrogen.  HYPERLINK "http://en.wikipedia.org/wiki/Bexlosteride" Bexlosteride  HYPERLINK "http://en.wikipedia.org/wiki/Izonsteride" Izonsteride  HYPERLINK "http://en.wikipedia.org/w/index.php?title=Epristeride&action=edit&redlink=1" \o "Epristeride (page does not exist)" Epristeride  HYPERLINK "http://en.wikipedia.org/wiki/Turosteride" Turosteride Antiandrogen herbs The best known plant-derived anti-androgen is  HYPERLINK "http://en.wikipedia.org/wiki/3,3%27-Diindolylmethane" 3,3'-Diindolylmethane(DIM) HYPERLINK "http://en.wikipedia.org/wiki/Antiandrogen" \l "cite_note-example_web_reference-1#cite_note-example_web_reference-1" ] Spearmint tea has antiandrogenic properties in females with hirsutism.  HYPERLINK "http://en.wikipedia.org/wiki/Scutellaria_baicalensis" Scutellaria baicalensis may also have antiandrogenic properties The compound N-butylbenzene-sulfonamide (NBBS) isolated from  HYPERLINK "http://en.wikipedia.org/wiki/Pygeum_africanum" \o "Pygeum africanum" Pygeum africanum is a specific  HYPERLINK "http://en.wikipedia.org/wiki/Androgen_antagonist" \o "Androgen antagonist" androgen antagonist.  HYPERLINK "http://en.wikipedia.org/wiki/Glycyrrhiza_glabra" \o "Glycyrrhiza glabra" Glycyrrhiza glabra has shown antiandrogenic activity in male rats A herbal formula (termed KMKKT) containing Korean  HYPERLINK "http://en.wikipedia.org/wiki/Angelica_gigas" Angelica gigas Nakai (AGN) root and nine other oriental herbs has shown in vitro anti-androgen activity.  HYPERLINK "http://en.wikipedia.org/wiki/Pygeum_africanum" \o "Pygeum africanum" Pygeum africanum contains an antiandrogenic compound atraric acid Duke's data base lists several more Human chorionic gonadotropin Human chorionic gonadotropin or human chorionic gonadotrophin (hCG) is a  HYPERLINK "http://en.wikipedia.org/wiki/Glycoprotein" glycoprotein  HYPERLINK "http://en.wikipedia.org/wiki/Hormone" hormone produced during  HYPERLINK "http://en.wikipedia.org/wiki/Pregnancy" pregnancy that is made by the developing  HYPERLINK "http://en.wikipedia.org/wiki/Embryo" embryo after  HYPERLINK "http://en.wikipedia.org/wiki/Conception_(biology)" \o "Conception (biology)" conception and later by the  HYPERLINK "http://en.wikipedia.org/wiki/Syncytiotrophoblast" syncytiotrophoblast (part of the  HYPERLINK "http://en.wikipedia.org/wiki/Placenta" placenta). but it is not known whether this production is a contributing cause or an effect of  HYPERLINK "http://en.wikipedia.org/wiki/Tumorigenesis" \o "Tumorigenesis" tumorigenesis. hCG is also produced in the  HYPERLINK "http://en.wikipedia.org/wiki/Pituitary_gland" pituitary gland of males and females of all ages Structure Human chorionic gonadotropin is a  HYPERLINK "http://en.wikipedia.org/wiki/Glycoprotein" glycoprotein composed of 244  HYPERLINK "http://en.wikipedia.org/wiki/Amino_acid" \o "Amino acid" amino acids with a  HYPERLINK "http://en.wikipedia.org/wiki/Molecular_mass" molecular mass of 36.7  HYPERLINK "http://en.wikipedia.org/wiki/KDa" \o "KDa" kDa. Its total dimensions are 753530  HYPERLINK "http://en.wikipedia.org/wiki/%C3%85ngstr%C3%B6m" \o "ngstrm" ngstrms (7.53.53  HYPERLINK "http://en.wikipedia.org/wiki/Nanometer" \o "Nanometer" nanometers). It is  HYPERLINK "http://en.wikipedia.org/wiki/Heterodimer" \o "Heterodimer" heterodimeric, with an  (alpha)  HYPERLINK "http://en.wikipedia.org/wiki/Protein_subunit" \o "Protein subunit" subunit identical to that of  HYPERLINK "http://en.wikipedia.org/wiki/Luteinizing_hormone" luteinizing hormone (LH),  HYPERLINK "http://en.wikipedia.org/wiki/Follicle-stimulating_hormone" follicle-stimulating hormone (FSH),  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid-stimulating_hormone" thyroid-stimulating hormone (TSH), and  (beta) subunit that is unique to hCG. The  HYPERLINK "http://en.wikipedia.org/wiki/Chorionic_gonadotropin_alpha" \o "Chorionic gonadotropin alpha"  (alpha)  HYPERLINK "http://en.wikipedia.org/wiki/Protein_subunit" \o "Protein subunit" subunit is 92 amino acids long and has dimensions 602515 ngstrms (62.51.5nm). The -subunit of hCG gonadotropin contains 145 amino acids and has dimensions 6.52.52nm, encoded by six highly-homologous  HYPERLINK "http://en.wikipedia.org/wiki/Gene" \o "Gene" genes that are arranged in tandem and inverted pairs on  HYPERLINK "http://en.wikipedia.org/wiki/Chromosome_19" \o "Chromosome 19" chromosome 19q13.3 - CGB ( HYPERLINK "http://en.wikipedia.org/wiki/CGB1" \o "CGB1" 1,  HYPERLINK "http://en.wikipedia.org/wiki/CGB2_(gene)" \o "CGB2 (gene)" 2,  HYPERLINK "http://en.wikipedia.org/w/index.php?title=CGB3&action=edit&redlink=1" \o "CGB3 (page does not exist)" 3,  HYPERLINK "http://en.wikipedia.org/w/index.php?title=CGB5&action=edit&redlink=1" \o "CGB5 (page does not exist)" 5,  HYPERLINK "http://en.wikipedia.org/wiki/CGB7" \o "CGB7" 7,  HYPERLINK "http://en.wikipedia.org/w/index.php?title=CGB8&action=edit&redlink=1" \o "CGB8 (page does not exist)" 8). The two subunits create a small  HYPERLINK "http://en.wikipedia.org/wiki/Hydrophobic" \o "Hydrophobic" hydrophobic core surrounded by a high surface area-to-volume ratio: 2.8 times that of a sphere. The vast majority of the outer amino acids are  HYPERLINK "http://en.wikipedia.org/wiki/Hydrophilic" \o "Hydrophilic" hydrophilic. Function Human chorionic gonadotropin interacts with the  HYPERLINK "http://en.wikipedia.org/wiki/LHCG_receptor" \o "LHCG receptor" LHCG receptor and promotes the maintenance of the  HYPERLINK "http://en.wikipedia.org/wiki/Corpus_luteum" corpus luteum during the beginning of  HYPERLINK "http://en.wikipedia.org/wiki/Pregnancy" pregnancy, causing it to secrete the hormone  HYPERLINK "http://en.wikipedia.org/wiki/Progesterone" progesterone. Progesterone enriches the  HYPERLINK "http://en.wikipedia.org/wiki/Uterus" uterus with a thick  HYPERLINK "http://en.wikipedia.org/wiki/Uterine_lining" \o "Uterine lining" lining of  HYPERLINK "http://en.wikipedia.org/wiki/Blood_vessel" \o "Blood vessel" blood vessels and  HYPERLINK "http://en.wikipedia.org/wiki/Capillary" \o "Capillary" capillaries so that it can sustain the growing  HYPERLINK "http://en.wikipedia.org/wiki/Fetus" fetus. Due to its highly-negative charge, hCG may repel the immune cells of the mother, protecting the fetus during the first trimester. It has also been hypothesized that hCG may be a placental link for the development of local maternal immunotolerance. For example, hCG-treated endometrial cells induce an increase in T cell apoptosis (dissolution of T-cells). These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance, and may facilitate the trophoblast invasion, which is known to expedite fetal development in the endometrium. It has also been suggested that hCG levels are linked to the severity of  HYPERLINK "http://en.wikipedia.org/wiki/Morning_sickness" morning sickness in pregnant women. Because of its similarity to  HYPERLINK "http://en.wikipedia.org/wiki/Luteinizing_hormone" \o "Luteinizing hormone" LH, hCG can also be used clinically to induce  HYPERLINK "http://en.wikipedia.org/wiki/Ovulation" ovulation in the  HYPERLINK "http://en.wikipedia.org/wiki/Ovary" \o "Ovary" ovaries as well as  HYPERLINK "http://en.wikipedia.org/wiki/Testosterone" testosterone production in the  HYPERLINK "http://en.wikipedia.org/wiki/Testes" \o "Testes" testes. As the most abundant biological source is women who are presently pregnant, some organizations collect urine from pregnant women to extract hCG for use in  HYPERLINK "http://en.wikipedia.org/wiki/Assisted_reproductive_technology" \o "Assisted reproductive technology" fertility treatment. HYPERLINK "http://en.wikipedia.org/wiki/Human_chorionic_gonadotropin" \l "cite_note-5#cite_note-5" [6] Human chorionic gonadotropin also plays a role in  HYPERLINK "http://en.wikipedia.org/wiki/Cellular_differentiation" cellular differentiation/proliferation and may activate  HYPERLINK "http://en.wikipedia.org/wiki/Apoptosis" apoptosis. HYPERLINK "http://en.wikipedia.org/wiki/Human_chorionic_gonadotropin" \l "cite_note-Michels-6#cite_note-Michels-6" [7] Production Like other  HYPERLINK "http://en.wikipedia.org/wiki/Gonadotropin" \o "Gonadotropin" gonadotropins, hCG can be extracted from urine or by genetic modification. Pregnyl, Follutein, Profasi, Choragon and Novarel use the former method, derived from the urine of pregnant women.  HYPERLINK "http://en.wikipedia.org/wiki/Ovidrel" \o "Ovidrel" Ovidrel, on the other hand, is a product of  HYPERLINK "http://en.wikipedia.org/wiki/Recombinant_DNA" recombinant DNA. hCG is produced from the syncytiotrophoblast cell layer. Testing Levels of hCG may be measured in the  HYPERLINK "http://en.wikipedia.org/wiki/Blood" blood or  HYPERLINK "http://en.wikipedia.org/wiki/Urine" urine. Most commonly, this is done as a  HYPERLINK "http://en.wikipedia.org/wiki/Pregnancy_test" pregnancy test, intended to indicate the presence or absence of an implanted  HYPERLINK "http://en.wikipedia.org/wiki/Mammalian_embryogenesis" \o "Mammalian embryogenesis" embryo. Testing for hCG may also be done when diagnosing or monitoring  HYPERLINK "http://en.wikipedia.org/wiki/Germ_cell_tumor" \o "Germ cell tumor" germ cell tumors and  HYPERLINK "http://en.wikipedia.org/wiki/Gestational_trophoblastic_disease" gestational trophoblastic disease. Most tests employ a monoclonal antibody, which is specific to the -subunit of hCG (-hCG). This procedure is employed to ensure that tests do not make  HYPERLINK "http://en.wikipedia.org/wiki/Type_I_and_type_II_errors" \o "Type I and type II errors" false positives by confusing hCG with LH and FSH. (The latter two are always present at varying levels in the body, whereas the presence of hCG almost always indicates pregnancy.) The  HYPERLINK "http://en.wikipedia.org/wiki/Urine_test" \o "Urine test" urine test may be a chromatographic  HYPERLINK "http://en.wikipedia.org/wiki/Immunoassay" immunoassay or any of several other test formats, home-, physician's office-, or laboratory-based. Published detection thresholds range from 20 to 100 mIU/ml, depending on the brand of test Early in pregnancy, more accurate results may be obtained by using the first urine of the morning (when hCG levels are highest). When the urine is dilute ( HYPERLINK "http://en.wikipedia.org/wiki/Specific_gravity" specific gravity less than 1.015), the hCG concentration may not be representative of the blood concentration, and the test may be falsely negative. The  HYPERLINK "http://en.wikipedia.org/wiki/Blood_plasma" \o "Blood plasma" serum test, using 2-4 mL of venous blood, is typically a chemiluminescent or fluorimetric immunoassay HYPERLINK "http://en.wikipedia.org/wiki/Human_chorionic_gonadotropin" \l "cite_note-henry-7#cite_note-henry-7" ] that can detect hCG levels as low as 5 mIU/ml and allows quantification of the hCG concentration. The ability to quantitate the hCG level is useful in the monitoring  HYPERLINK "http://en.wikipedia.org/wiki/Germ_cell_tumor" \o "Germ cell tumor" germ cell and  HYPERLINK "http://en.wikipedia.org/wiki/Gestational_trophoblastic_disease" \o "Gestational trophoblastic disease" trophoblastic tumors, followup care after  HYPERLINK "http://en.wikipedia.org/wiki/Miscarriage" miscarriage, and in diagnosis of and follow-up care after treatment of  HYPERLINK "http://en.wikipedia.org/wiki/Ectopic_pregnancy" ectopic pregnancy. The lack of a visible fetus on vaginal  HYPERLINK "http://en.wikipedia.org/wiki/Ultrasound" ultrasound after the hCG levels have reached 1500 mIU/ml is strongly indicative of an ectopic pregnancy. As pregnancy tests, quantitative blood tests and the most sensitive urine tests usually detect hCG between 6 to 12 days after  HYPERLINK "http://en.wikipedia.org/wiki/Ovulation" ovulation However, it must be taken into account that total hCG levels may vary in a very wide range within the first 4 weeks of gestation, leading to false results during this period of time. Gestational trophoblastic disease like  HYPERLINK "http://en.wikipedia.org/wiki/Hydatidiform_mole" \o "Hydatidiform mole" Hydatidiform moles ("molar pregnancy") or Choriocarcinoma may produce high levels of hCG (due to the presence of syncytialtrophoblasts- part of the villi that make up the placenta) despite the absence of an embryo. This, as well as several other conditions, can lead to elevated hCG readings in the absence of pregnancy. hCG levels are also a component of the  HYPERLINK "http://en.wikipedia.org/wiki/Triple_test" triple test, a screening test for certain fetal chromosomal abnormalities/birth defects. Hypothyroidism Hypothyroidism (pronounced  HYPERLINK "http://en.wikipedia.org/wiki/Wikipedia:IPA_for_English" \o "Wikipedia:IPA for English" /hajpuajrTjdjzYm/) is a deficiency of  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid_hormone" thyroid hormone.  HYPERLINK "http://en.wikipedia.org/wiki/Iodine_deficiency" Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by any number of other causes such as several conditions of the the  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid_gland" \o "Thyroid gland" thyroid gland, or less commonly, the  HYPERLINK "http://en.wikipedia.org/wiki/Pituitary_gland" pituitary gland or  HYPERLINK "http://en.wikipedia.org/wiki/Hypothalamus" hypothalamus It can result from a lack of a thyroid gland. It can also be due to  HYPERLINK "http://en.wikipedia.org/wiki/Iodine-131" iodine-131 used to treat thyroid cancer,  HYPERLINK "http://en.wikipedia.org/wiki/Thyroidectomy" \o "Thyroidectomy" its surgical removal.  HYPERLINK "http://en.wikipedia.org/wiki/Cretinism" Cretinism is a  HYPERLINK "http://en.wikipedia.org/wiki/Congenital_hypothyroidism" \o "Congenital hypothyroidism" form of hypothyroidism found in infants. Hypothyroidism is highly underdiagnosed, especially in women, to the tune of 13,000,000 Americans HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-2#cite_note-2" ] and 200,000,000 people worldwide Signs and symptoms Early hypothyroidism has often very mild and unspecific symptoms. Hypothyroidism can be associated with the following symptoms Early Poor muscle tone ( HYPERLINK "http://en.wikipedia.org/wiki/Muscle_hypotonia" \o "Muscle hypotonia" muscle hypotonia)  HYPERLINK "http://en.wikipedia.org/wiki/Fatigue_(medical)" \o "Fatigue (medical)" Fatigue Any form of menstrual irregularity and fertility problems  HYPERLINK "http://en.wikipedia.org/wiki/Hyperprolactinemia" \o "Hyperprolactinemia" Hyperprolactinemia and  HYPERLINK "http://en.wikipedia.org/wiki/Galactorrhea" galactorrhea  HYPERLINK "http://en.wikipedia.org/wiki/Elevated_serum_cholesterol" \o "Elevated serum cholesterol" Elevated serum cholesterol  HYPERLINK "http://en.wikipedia.org/wiki/Cold_intolerance" \o "Cold intolerance" Cold intolerance, increased sensitivity to cold  HYPERLINK "http://en.wikipedia.org/wiki/Constipation" Constipation Rapid thoughts Color sensitivity  HYPERLINK "http://en.wikipedia.org/wiki/Depression_(mood)" \o "Depression (mood)" Depression  HYPERLINK "http://en.wikipedia.org/wiki/Muscle_cramps" \o "Muscle cramps" Muscle cramps and  HYPERLINK "http://en.wikipedia.org/wiki/Joint_pain" \o "Joint pain" joint pain Thin,  HYPERLINK "http://en.wikipedia.org/wiki/Brittle_fingernails" \o "Brittle fingernails" brittle fingernails Coarse hair  HYPERLINK "http://en.wikipedia.org/wiki/Paleness" \o "Paleness" Paleness Decreased sweating Dry, itchy skin  HYPERLINK "http://en.wikipedia.org/wiki/Weight_gain" Weight gain and  HYPERLINK "http://en.wikipedia.org/wiki/Water_retention_(medicine)" \o "Water retention (medicine)" water retention HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-7#cite_note-7" [8] HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-8#cite_note-8" [9] HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-9#cite_note-9" [10]  HYPERLINK "http://en.wikipedia.org/wiki/Bradycardia" Bradycardia (low heart rate fewer than sixty beats per minute) Late  HYPERLINK "http://en.wikipedia.org/wiki/Goiter" \o "Goiter" Goiter Slow speech and a  HYPERLINK "http://en.wikipedia.org/wiki/Hoarse" \o "Hoarse" hoarse, breaking voice deepening of the voice can also be noticed, caused by  HYPERLINK "http://en.wikipedia.org/wiki/Reinke%27s_Edema" \o "Reinke's Edema" Reinke's Edema. Dry puffy skin, especially on the face Thinning of the outer third of the eyebrows ( HYPERLINK "http://en.wikipedia.org/wiki/Sign_of_Hertoghe" sign of Hertoghe) Abnormal  HYPERLINK "http://en.wikipedia.org/wiki/Menstrual_cycles" \o "Menstrual cycles" menstrual cycles Low  HYPERLINK "http://en.wikipedia.org/wiki/Basal_body_temperature" basal body temperature Thyroid-Related Depression Uncommon Impaired  HYPERLINK "http://en.wikipedia.org/wiki/Memory" memory Impaired cognitive function (brain fog) and inattentivenessA  HYPERLINK "http://en.wikipedia.org/wiki/Bradycardia" \o "Bradycardia" slow heart rate with  HYPERLINK "http://en.wikipedia.org/wiki/ECG" \o "ECG" ECG changes including low voltage signals. Diminished cardiac output and decreased contractility  HYPERLINK "http://en.wikipedia.org/wiki/Reactive_hypoglycemia" \o "Reactive hypoglycemia" Reactive (or post-prandial) hypoglycemia HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-pmid5086042-12#cite_note-pmid5086042-12" [13] Sluggish  HYPERLINK "http://en.wikipedia.org/wiki/Reflex_action" \o "Reflex action" reflexes  HYPERLINK "http://en.wikipedia.org/wiki/Hair_loss" \o "Hair loss" Hair loss  HYPERLINK "http://en.wikipedia.org/wiki/Anemia" Anemia caused by impaired haemoglobin synthesis (decreased  HYPERLINK "http://en.wikipedia.org/wiki/Erythropoietin" \o "Erythropoietin" EPO levels), impaired intestinal iron and  HYPERLINK "http://en.wikipedia.org/wiki/Folate" \o "Folate" folate absorption or B12 deficiency from  HYPERLINK "http://en.wikipedia.org/wiki/Pernicious_anemia" pernicious anemia  HYPERLINK "http://en.wikipedia.org/wiki/Difficulty_swallowing" \o "Difficulty swallowing" Difficulty swallowing  HYPERLINK "http://en.wikipedia.org/wiki/Shortness_of_breath" \o "Shortness of breath" Shortness of breath with a shallow and slow respiratory pattern Increased need for sleep  HYPERLINK "http://en.wikipedia.org/wiki/Irritability" Irritability and mood instability Yellowing of the skin due to impaired conversion of  HYPERLINK "http://en.wikipedia.org/wiki/Beta-carotene" \o "Beta-carotene" beta-carotene HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-14#cite_note-14" ] to vitamin A (carotoderma) Impaired renal function with decreased  HYPERLINK "http://en.wikipedia.org/wiki/Glomerular_filtration_rate" \o "Glomerular filtration rate" glomerular filtration rate Acute psychosis ( HYPERLINK "http://en.wikipedia.org/wiki/Myxedema_madness" \o "Myxedema madness" myxedema madness) (a rare presentation of hypothyroidism)  HYPERLINK "http://en.wikipedia.org/w/index.php?title=Decreased_libido_in_men&action=edit&redlink=1" \o "Decreased libido in men (page does not exist)" Decreased libido in men HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-15#cite_note-15" ] due to impairment of testicular testosterone synthesis Decreased sense of taste and smell ( HYPERLINK "http://en.wikipedia.org/wiki/Anosmia" anosmia) Puffy face, hands and feet (late, less common symptoms)  HYPERLINK "http://en.wikipedia.org/wiki/Gynecomastia" Gynecomastia  HYPERLINK "http://en.wikipedia.org/wiki/Deafness" \o "Deafness" Deafness HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-16#cite_note-16" [17] Causes About three percent of the general population has hypothyroidism. Iodine deficiency is the most common cause of hypothyroidism worldwide In iodine-replete individuals hypothyroidism is frequently caused by  HYPERLINK "http://en.wikipedia.org/wiki/Hashimoto%27s_thyroiditis" Hashimoto's thyroiditis, or otherwise as a result of either an absent  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid" thyroid gland or a deficiency in stimulating hormones from the  HYPERLINK "http://en.wikipedia.org/wiki/Hypothalamus" hypothalamus or  HYPERLINK "http://en.wikipedia.org/wiki/Pituitary" \o "Pituitary" pituitary. Factors such as  HYPERLINK "http://en.wikipedia.org/wiki/Iodine_deficiency" iodine deficiency or exposure to  HYPERLINK "http://en.wikipedia.org/wiki/Iodine-131" iodine-131 from  HYPERLINK "http://en.wikipedia.org/wiki/Nuclear_fallout" nuclear fallout, which is absorbed by the thyroid gland like regular iodide and destroys its cells, can increase the risk. Congenital hypothyroidism is very rare accounting for approximately 0.2 and can have several causes such as thyroid aplasia or defects in the hormone metabolism. Thyroid hormone insensitivity (most often T3 receptor defect) also falls into this category although in this condition the levels of thyroid hormones may be normal or even markedly elevated. Hypothyroidism can result from  HYPERLINK "http://en.wikipedia.org/wiki/Postpartum_thyroiditis" postpartum thyroiditis, a condition that affects about 5% of all women within a year of giving birth] The first phase is typically  HYPERLINK "http://en.wikipedia.org/wiki/Hyperthyroidism" hyperthyroidism; the thyroid then 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 result from  HYPERLINK "http://en.wikipedia.org/wiki/De_Quervain%27s_thyroiditis" de Quervain's thyroiditis, which, in turn, is often caused by having a bad flu that enters and destroys part, or all, the  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid" thyroid. Hypothyroidism can also result from sporadic inheritance, sometimes  HYPERLINK "http://en.wikipedia.org/wiki/Autosome" \o "Autosome" autosomal recessive Hypothyroidism is also a relatively common disease in domestic dogs, with some specific breeds having a definite predisposition. Temporary hypothyroidism can be due to the  HYPERLINK "http://en.wikipedia.org/wiki/Wolff-Chaikoff_effect" \o "Wolff-Chaikoff effect" Wolff-Chaikoff effect. A very high intake of iodine can be used to temporarily treat hyperthyroidism, especially in an emergency situation. Although iodide is a substrate for thyroid hormones, high levels reduce iodide  HYPERLINK "http://en.wikipedia.org/wiki/Organification" organification in the thyroid gland, decreasing hormone production. The  HYPERLINK "http://en.wikipedia.org/wiki/Antiarrhythmic_agent" antiarrhythmic agent  HYPERLINK "http://en.wikipedia.org/wiki/Amiodarone" amiodarone can cause hyper- or hypothyroidism due to its high iodine content. Hypothyroidism can be caused by  HYPERLINK "http://en.wikipedia.org/wiki/Lithium_pharmacology" \o "Lithium pharmacology" lithium-based  HYPERLINK "http://en.wikipedia.org/wiki/Mood_stabilizer" \o "Mood stabilizer" mood stabilizers, usually used to treat  HYPERLINK "http://en.wikipedia.org/wiki/Bipolar_disorder" bipolar disorder (previously known as manic depression). HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-causes-0#cite_note-causes-0" [1] In fact, lithium has occasionally been used to treat hyperthyroidism. HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-20#cite_note-20" [21] Other drugs that may produce hypothyroidism include  HYPERLINK "http://en.wikipedia.org/wiki/Interferon_alpha" \o "Interferon alpha" interferon alpha,  HYPERLINK "http://en.wikipedia.org/wiki/Interleukin-2" \o "Interleukin-2" interleukin-2, and  HYPERLINK "http://en.wikipedia.org/wiki/Thalidomide" thalidomide Hypothyroidism is often classified by association with the indicated organ dysfunction (see below Diagnosis To diagnose primary hypothyroidism, many doctors simply measure the amount of  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid-stimulating_hormone" thyroid-stimulating hormone (TSH) being produced by the pituitary gland. High levels of TSH indicate that the thyroid is not producing sufficient levels of  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid_hormone" thyroid hormone (mainly as  HYPERLINK "http://en.wikipedia.org/wiki/Thyroxine" thyroxine (T4) and smaller amounts of triiodothyronine (T3)). However, measuring just TSH fails to diagnose secondary and tertiary hypothyroidism, thus leading to the following suggested blood testing if the TSH is normal and hypothyroidism is still suspected: Free triiodothyronine (fT3) Free  HYPERLINK "http://en.wikipedia.org/wiki/Levothyroxine" levothyroxine (fT4) Total T3 Total T4 Additionally, the following measurements may be needed: 24-Hour urine-free T3 Antithyroid  HYPERLINK "http://en.wikipedia.org/wiki/Antibodies" \o "Antibodies" antibodies for evidence of  HYPERLINK "http://en.wikipedia.org/wiki/Autoimmune_disease" \o "Autoimmune disease" autoimmune diseases that may be damaging the thyroid gland Serum cholesterol which may be elevated in hypothyroidism  HYPERLINK "http://en.wikipedia.org/wiki/Prolactin" Prolactin as a widely available test of pituitary function Testing for anemia, including  HYPERLINK "http://en.wikipedia.org/wiki/Ferritin" ferritin Basal body temperature Thyroid related depression treatment Talk Therapy Depression Medication Treatment Main article:  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid_hormone" \l "Medical_use_of_thyroid_hormones" \o "Thyroid hormone" Medical use of thyroid hormones Hypothyroidism is treated with the levorotatory forms of  HYPERLINK "http://en.wikipedia.org/wiki/Thyroxine" thyroxine ( HYPERLINK "http://en.wikipedia.org/wiki/Levothyroxine" levothyroxine) (L-T4) and  HYPERLINK "http://en.wikipedia.org/wiki/Triiodothyronine" triiodothyronine (liothyronine) (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. Levothyroxine is best taken 3060 minutes before breakfast, as some food can diminish absorption. Compared to water, coffee reduces absorption of levothyroxine by about 30 percent. Some patients might appear to be resistant to levothyroxine, when in fact they do not properly absorb the tablets - a problem which is solved by pulverizing the medication 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 T4 and T3 in combination This treatment protocol involves administering both synthetic L-T4 and L-T3 simultaneously in combination. Desiccated thyroid extract  HYPERLINK "http://en.wikipedia.org/wiki/Desiccated_thyroid_extract" Desiccated thyroid extract is an animal-based thyroid extract, most commonly from a  HYPERLINK "http://en.wikipedia.org/wiki/Pig" \o "Pig" porcine source. It is also a combination therapy, containing natural forms of L-T4 and L-T3. Treatment controversy Some patients remain symptomatic despite treatment with levothyroxine (T4) and normal TSH. These remaining symptoms have raised the question whether some patients might benefit from substitution of some T3 for T4. This has been investigated in more than a dozen studies, ost of which conclude that a combination therapy of T4 and T3 does not appear to be superior to monotherapy. However, a 2009 study suggests that it's possible that a subgroup of patients with a polymorphism in the type 2 deiodinase might benefit from combined therapy. Above that, the available data, such as a study demonstrating pre- and post-T3 levels in thyroidectomized patients, do not rule out that thyroidectomized patients (with no residual endogenous T3 production) might benefit from the addition of T3. A 2005 study compared patients treated with T4 and healthy patients (taking no thyroid hormones) with similar TSH levels, and found significant lower T3 levels in the thyroid patients. HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-50#cite_note-50" ] A study with rats, whose thyroids where removed, found that only the combined treatment with T4 and T3 ensured euthyroidism in all tissues of the thyroidectomized rats. There is 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. HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-pmid17479444-52#cite_note-pmid17479444-52" ] Slow release T3 may avoid this, but this has not yet been combined with T4 or compared to T4 monotreatment. Subclinical hypothyroidism Subclinical hypothyroidism occurs when thyrotropin (TSH) levels are elevated but thyroxine (T4) and triiodothyronine (T3) levels are normal Prevalence estimates range 38%, increasing with age; incidence is more common in women than in men. HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-pmid19121255-54#cite_note-pmid19121255-54" ] In primary hypothyroidism, TSH levels are high and T4 and T3 levels are low. TSH usually increases when T4 and T3 levels drop. TSH prompts the thyroid gland to make more hormone. In subclinical hypothyroidism, TSH is elevated but below the limit representing overt hypothyroidism. The levels of the active hormones will be within the laboratory reference ranges. There is a range of opinion on the biochemical and symptomatic point at which to treat with levothyroxine, the typical treatment for overt hypothyroidism. Reference ranges have been debated as well. The American Association of Clinical Endocrinologists (ACEE) considers 0.454.5 HYPERLINK "http://en.wikipedia.org/wiki/International_unit" \o "International unit" mIU/L, with the ranges down to 0.1 and up to 10mIU/L requiring monitoring but not necessarily treatment There is always the risk of  HYPERLINK "http://en.wikipedia.org/wiki/Overtreatment" \o "Overtreatment" overtreatment and hyperthyroidism. Some studies have suggested that subclinical hypothyroidism does not need to be treated. A  HYPERLINK "http://en.wikipedia.org/wiki/Meta-analysis" meta-analysis by the  HYPERLINK "http://en.wikipedia.org/wiki/Cochrane_Collaboration" Cochrane Collaboration found no benefit of thyroid-hormone replacement except "some parameters of lipid profiles and left-ventricular function A more recent meta-nalysis looking into whether subclinical hypothyroidism may increase the risk of cardiovascular disease, as has been previously suggested, HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" \l "cite_note-57#cite_note-57" ] found a possible modest increase and suggested further studies be undertaken with coronary-heart disease as an end point "before current recommendations are updated." Alternative treatments Alternative practitioners may combine conventional serum tests with less conventional tests to assess thyroid-hormone function, or simply look at symptoms] Compounded slow-release T3 has been suggested for use in combination with T4, which proponents argue will mitigate many of the symptoms of functional hypothyroidism and improve  HYPERLINK "http://en.wikipedia.org/wiki/Quality_of_life" quality of life. This is still controversial and is rejected by the  HYPERLINK "http://en.wikipedia.org/wiki/Scientific_consensus" \o "Scientific consensus" conventional medical establishment Hypothyroidism and Diet This condition affects the immune system and metabolism. There are a number of supplementary vitamins and minerals specifically designed to support deficiencies in both and sufferers can mistakenly take them believing them to be beneficial. However it is important that these should never be self-prescribed since they can directly impact the effectiveness of thyroxine (usually through preventing its absorbtion). These are: Calcium Soya Iron (includes Iron rich foods such as Broccoli) Iodine (includes Kelp tablets) Selenium (includes natural sources such as sea food) Magnesium Zinc Caffeine Hyperthyrodism Hyperthyroidism (rarely hypothyreosis) is the term for overactive tissue within the  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid" thyroid gland causing an overproduction of thyroid  HYPERLINK "http://en.wikipedia.org/wiki/Hormone" \o "Hormone" hormones ( HYPERLINK "http://en.wikipedia.org/wiki/Thyroxine" thyroxine or "T4" and/or  HYPERLINK "http://en.wikipedia.org/wiki/Triiodothyronine" triiodothyronine or "T3"). Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. It is important to note that hyperthyroidism and thyrotoxicosis are not synonymous. For instance, thyrotoxicosis could instead be caused by ingestion of  HYPERLINK "http://en.wikipedia.org/wiki/Exogenous" \o "Exogenous" exogenous thyroid hormone or inflammation of the thyroid gland, causing it to release its stores of thyroid hormonesHyperthyroidism may be asymptomatic, but when it is not, symptoms are due to an excess of thyroid hormone. Thyroid hormone is important at a cellular level, affecting nearly every type of tissue in the body. Thyroid hormone functions as a controller of the pace of all of the processes in the body. This pace is called the metabolic rate (see  HYPERLINK "http://en.wikipedia.org/wiki/Metabolism" metabolism). If there is too much thyroid hormone, every function of the body tends to speed up. Therefore, some of the symptoms of hyperthyroidism are nervousness, irritability, increased perspiration, heart racing, hand tremors, anxiety, difficulty sleeping, thinning of the skin, fine brittle hair, and muscular weaknessespecially in the upper arms and thighs. More frequent bowel movements may occur, but diarrhea is uncommon. Weight loss, sometimes significant, despite a good appetite may occur, vomiting, and, for women, menstrual flow may lighten and menstrual periods may occur less often Thyroid hormone is critical to normal function of cells. In excess, it both overstimulates metabolism and exacerbates the effect of the  HYPERLINK "http://en.wikipedia.org/wiki/Sympathetic_nervous_system" sympathetic nervous system, causing "speeding up" of various body systems and symptoms resembling an overdose of  HYPERLINK "http://en.wikipedia.org/wiki/Epinephrine" epinephrine (adrenaline). These include fast heart beat and symptoms of  HYPERLINK "http://en.wikipedia.org/wiki/Palpitation" \o "Palpitation" palpitations, nervous system  HYPERLINK "http://en.wikipedia.org/wiki/Tremor" tremor such as of the hands and  HYPERLINK "http://en.wikipedia.org/wiki/Anxiety" anxiety symptoms, digestive system hypermotility, unintended weight loss, and (in "lipid panel" blood tests) a lower and sometimes unusually low serum  HYPERLINK "http://en.wikipedia.org/wiki/Cholesterol" cholesterol. Hyperthyroidism usually begins slowly. At first, the symptoms may be mistaken for simple nervousness due to stress. If one has been trying to lose weight by dieting, one may be pleased with weight loss success until the hyperthyroidism, which has quickened the weight loss, causes other problems. In  HYPERLINK "http://en.wikipedia.org/wiki/Graves_disease" \o "Graves disease" Graves disease, which is the most common form or cause of hyperthyroidism, the eyes may look enlarged because the eye muscles swell and push the eye forward. This can only be resolved surgically by orbital decompression. Sometimes, one or both eyes may bulge. Some patients have swelling of the front of the neck from an enlarged thyroid gland (a goiter). Because hyperthyroidism, especially Graves disease, may run in families, examinations of the members of a family may reveal other individuals with thyroid problems. A lack of functioning thyroid tissue results in a symptomatic lack of thyroid hormone, termed  HYPERLINK "http://en.wikipedia.org/wiki/Hypothyroidism" hypothyroidism. Hyperthyroidism due to certain types of  HYPERLINK "http://en.wikipedia.org/wiki/Hashimoto%27s_thyroiditis" \o "Hashimoto's thyroiditis" thryroiditis can eventually lead to hypothyroidism, as the thyroid gland is damaged. Also,  HYPERLINK "http://en.wikipedia.org/wiki/Radioiodine" \o "Radioiodine" radioiodine treatment of  HYPERLINK "http://en.wikipedia.org/wiki/Grave%27s_disease" \o "Grave's disease" Grave's disease often eventually leads to hypothyroidism. Such hypothyroidism may be avoided by regular thyroid hormone testing and oral thyroid hormone supplementation. Major clinical signs include  HYPERLINK "http://en.wikipedia.org/wiki/Weight_loss" weight loss (often accompanied by an increased  HYPERLINK "http://en.wikipedia.org/wiki/Appetite" appetite),  HYPERLINK "http://en.wikipedia.org/wiki/Anxiety" anxiety, intolerance to  HYPERLINK "http://en.wikipedia.org/wiki/Heat" heat, hair loss, muscle aches, weakness, fatigue, hyperactivity, irritability,  HYPERLINK "http://en.wikipedia.org/wiki/Hypoglycemia" hypoglycemia,  HYPERLINK "http://en.wikipedia.org/wiki/Apathy" apathy,  HYPERLINK "http://en.wikipedia.org/wiki/Polyuria" polyuria,  HYPERLINK "http://en.wikipedia.org/wiki/Polydipsia" polydipsia,  HYPERLINK "http://en.wikipedia.org/wiki/Delirium" delirium,  HYPERLINK "http://en.wikipedia.org/wiki/Tremor" tremor,  HYPERLINK "http://en.wikipedia.org/wiki/Pretibial_myxedema" pretibial myxedema, and sweating. In addition, patients may present with a variety of symptoms such as  HYPERLINK "http://en.wikipedia.org/wiki/Palpitations" \o "Palpitations" palpitations and  HYPERLINK "http://en.wikipedia.org/wiki/Arrhythmia" \o "Arrhythmia" arrhythmias (the notable ones being  HYPERLINK "http://en.wikipedia.org/wiki/Atrial_fibrillation" atrial fibrillation), shortness of breath ( HYPERLINK "http://en.wikipedia.org/wiki/Dyspnea" dyspnea), loss of  HYPERLINK "http://en.wikipedia.org/wiki/Libido" libido,  HYPERLINK "http://en.wikipedia.org/wiki/Amenorrhea" \o "Amenorrhea" amenorrhea,  HYPERLINK "http://en.wikipedia.org/wiki/Nausea" nausea,  HYPERLINK "http://en.wikipedia.org/wiki/Vomiting" vomiting,  HYPERLINK "http://en.wikipedia.org/wiki/Diarrhea" diarrhea,  HYPERLINK "http://en.wikipedia.org/wiki/Gynaecomastia" \o "Gynaecomastia" gynaecomastia and  HYPERLINK "http://en.wikipedia.org/wiki/Feminization" feminization. Long term untreated hyperthyroidism can lead to  HYPERLINK "http://en.wikipedia.org/wiki/Osteoporosis" osteoporosis. These classical symptoms may not be present often in the elderly.[ HYPERLINK "http://en.wikipedia.org/wiki/Wikipedia:Citation_needed" \o "Wikipedia:Citation needed" citation needed] Neurological manifestations can include  HYPERLINK "http://en.wikipedia.org/wiki/Tremor" \o "Tremor" tremors,  HYPERLINK "http://en.wikipedia.org/wiki/Chorea_(disease)" \o "Chorea (disease)" chorea,  HYPERLINK "http://en.wikipedia.org/wiki/Myopathy" myopathy, and in some susceptible individuals (in particular of Asian descent)  HYPERLINK "http://en.wikipedia.org/wiki/Thyrotoxic_periodic_paralysis" \o "Thyrotoxic periodic paralysis" periodic paralysis. An association between thyroid disease and  HYPERLINK "http://en.wikipedia.org/wiki/Myasthenia_gravis" myasthenia gravis has been recognized. The thyroid disease, in this condition, is autoimmune in nature and approximately 5% of patients with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is not well understoodMinor ocular (eye) signs, which may be present in any type of hyperthyroidism, are eyelid retraction ("stare"), extra-ocular muscle weakness, and lid-lag.[] In hyperthyroid stare ( HYPERLINK "http://en.wikipedia.org/wiki/Dalrymple_sign" \o "Dalrymple sign" Dalrymple sign) the eyelids are retracted upward more than normal (the normal position is at the superior corneoscleral limbus, where the "white" of the eye begins at the upper border of the iris). Extra-ocular muscle weakness may present with double vision. In lid-lag ( HYPERLINK "http://en.wikipedia.org/wiki/Von_Graefe%27s_sign" von Graefe's sign), when the patient tracks an object downward with their eyes, the eyelid fails to follow the downward moving iris, and the same type of upper globe exposure which is seen with lid retraction occurs, temporarily. These signs disappear with treatment of the hyperthyroidism] Neither of these ocular signs should be confused with  HYPERLINK "http://en.wikipedia.org/wiki/Exophthalmos" exophthalmos (protrusion of the eyeball), which occurs specifically and uniquely in hyperthyroidism caused by  HYPERLINK "http://en.wikipedia.org/wiki/Graves%27_disease" Graves' disease (note that not all exopthalmos is caused by Graves' disease, but when present with hyperthyroidism is diagnostic of Graves' disease). This forward protrusion of the eyes is due to immune-mediated inflammation in the retro-orbital (eye socket) fat. Exophthalmos, when present, may exacerbate hyperthyroid lid-lag and stare Thyrotoxic crisis (or thyroid storm) is a rare but severe complication of hyperthyroidism, which may occur when a thyrotoxic patient becomes very sick or physically stressed. Its symptoms can include: an increase in body temperature to over 40 degrees Celsius (104 degrees Fahrenheit), tachycardia, arrhythmia, vomiting, diarrhea, dehydration, coma, and death]Thyroid storm requires emergency treatment and hospitalization. The main treatment is to decrease the circulating thyroid hormone levels and decrease their formation.  HYPERLINK "http://en.wikipedia.org/wiki/Propylthiouracil" Propylthiouracil and  HYPERLINK "http://en.wikipedia.org/wiki/Methimazole" methimazole are two agents that decrease thyroid hormone synthesis and are usually prescribed in fairly high doses. To inhibit thyroid hormone release from the thyroid gland, sodium iodide, potassium iodide, and/or Lugol's solution can be given. Beta blockers such as propranolol (Inderal, Inderal LA, Innopran XL) can help to control the heart rate, and intravenous steroids may be used to help support the circulation. Earlier in this century, the mortality of thyroid storm approached 100%. However, now, with the use of aggressive therapy as described above, the death rate from thyroid storm is less than 20%. Causes There are several causes of hyperthyroidism. Most often, the entire gland is overproducing thyroid hormone. This is called  HYPERLINK "http://en.wikipedia.org/wiki/Graves%27_disease" Graves' disease. Less commonly, a single nodule is responsible for the excess hormone secretion, called a "hot" nodule. Thyroiditis (inflammation of the thyroid) can also cause hyperthyroidism. Functional thyroid tissue producing an excess of thyroid hormone occurs in a number of clinical conditions. The major causes in humans are: Graves' disease an autoimmune disease (usually, the most common etiology with 50-80% worldwide, although this varies substantially with location - i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981). Thought to be due to varying Iodine in the diet.  HYPERLINK "http://en.wikipedia.org/wiki/Toxic_thyroid_adenoma" \o "Toxic thyroid adenoma" Toxic thyroid adenoma (the most common etiology in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country  HYPERLINK "http://en.wikipedia.org/wiki/Toxic_multinodular_goitre" \o "Toxic multinodular goitre" Toxic multinodular goitre High blood levels of thyroid hormones (most accurately termed  HYPERLINK "http://en.wikipedia.org/wiki/Hyperthyroxinemia" hyperthyroxinemia) can occur for a number of other reasons:  HYPERLINK "http://en.wikipedia.org/wiki/Inflammation" Inflammation of the thyroid is called  HYPERLINK "http://en.wikipedia.org/wiki/Thyroiditis" thyroiditis. There are several different kinds of thyroiditis including  HYPERLINK "http://en.wikipedia.org/wiki/Hashimoto%27s_thyroiditis" Hashimoto's thyroiditis (immune-mediated), and  HYPERLINK "http://en.wikipedia.org/wiki/Subacute_thyroiditis" subacute thyroiditis (DeQuervain's). These may be initially associated with secretion of excess thyroid hormone, but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism. Oral consumption of excess thyroid hormone tablets is possible, as is the rare event of consumption of ground beef contaminated with thyroid tissue, and thus thyroid hormone (termed "hamburger hyperthyroidism").  HYPERLINK "http://en.wikipedia.org/wiki/Amiodarone" Amiodarone, an anti-arrhythmic drug is structurally similar to thyroxine and may cause either under- or overactivity of the thyroid.  HYPERLINK "http://en.wikipedia.org/wiki/Postpartum_thyroiditis" Postpartum thyroiditis (PPT) occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. This form of hyperthyroidism usually corrects itself within weeks or months without the need for treatment. Hypersecretion of  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid_stimulating_hormone" \o "Thyroid stimulating hormone" thyroid stimulating hormone (TSH), which in turn is almost always caused by a pituitary adenoma, accounts for much less than 1 percent of hyperthyroidism cases. Diagnosis Measuring the level of  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid-stimulating_hormone" thyroid-stimulating hormone (TSH), produced by the pituitary gland (which in turn is also regulated by the hypothalamus's TSH Releasing Hormone) in the blood is typically the initial test for suspected hyperthyroidism. A low TSH level typically indicates that the pituitary gland is being inhibited or "instructed" by the brain to cut back on stimulating the thyroid gland, having sensed increased levels of T4 and/or T3 in the blood. In rare circumstances, a low TSH indicates primary failure of the pituitary, or temporary inhibition of the pituitary due to another illness ( HYPERLINK "http://en.wikipedia.org/wiki/Euthyroid_sick_syndrome" euthyroid sick syndrome) and so checking the T4 and T3 is still clinically useful. Measuring specific  HYPERLINK "http://en.wikipedia.org/wiki/Antibody" \o "Antibody" antibodies, such as anti-TSH-receptor antibodies in Graves' disease, or anti-thyroid-peroxidase in Hashimoto's thyroiditisa common cause of HYPOthyroidismmay also contribute to the diagnosis. The diagnosis of hyperthyroidism is confirmed by blood tests that show a decreased thyroid-stimulating hormone (TSH) level and elevated T4 and T3 levels. TSH is a hormone made by the pituitary gland in the brain that tells the thyroid gland how much hormone to make. When there is too much thyroid hormone, the TSH will be low. A radioactive iodine uptake test and thyroid scan together characterizes or enables radiologists and doctors to determine the cause of hyperthyroidism. The uptake test uses radioactive iodine injected or taken orally on an empty stomach to measure the amount of iodine absorbed by the thyroid gland. Persons with hyperthyroidism absorb too much iodine. A thyroid scan producing images is typically conducted in connection with the uptake test to allow visual examination of the over-functioning gland. Thyroid  HYPERLINK "http://en.wikipedia.org/wiki/Scintigraphy" scintigraphy is a useful test to characterize (distinguish between causes of) hyperthyroidism, and this entity from thyroiditis. This test procedure typically involves two tests performed in connection with each other: an iodine uptake test and a scan (imaging) with a  HYPERLINK "http://en.wikipedia.org/wiki/Gamma_camera" gamma camera. The uptake test involves administering a dose of radioactive iodine (radioiodine), typically  HYPERLINK "http://en.wikipedia.org/wiki/Iodine-123" Iodine-123 or 123I, which is the most suitable isotope of iodine for the diagnostic study of thyroid diseases. I-123 is an almost ideal isotope of iodine for imaging thyroid tissue and thyroid cancer metastasis. Typical administration involves a pill containing sodium iodide (NaI) taken orally, which contains a small amount of  HYPERLINK "http://en.wikipedia.org/wiki/Iodine-123" iodine-123, amounting to perhaps less than a grain of salt. A 2-hour fast of no food prior to and for 1 hour after ingesting the pill is required. This low dose of radioiodine is typically tolerated by individuals otherwise allergic to iodine (such as those unable to tolerate contrast mediums containing larger doses of iodine such as used in  HYPERLINK "http://en.wikipedia.org/wiki/X-ray_computed_tomography" \o "X-ray computed tomography" CT scan,  HYPERLINK "http://en.wikipedia.org/wiki/Intravenous_pyelogram" intravenous pyelogram (IVP), and similar imaging diagnostic procedures). Excess radioiodine that does not get absorbed into the thyroid gland is eliminated by the body in urine. Some patients may experience a slight allergic reaction to the diagnostic radioiodine, and may be given an  HYPERLINK "http://en.wikipedia.org/wiki/Antihistamine" \o "Antihistamine" antihistamine. The patient returns 24 hours later to have the level of radioiodine "uptake" (absorbed by the thyroid gland) measured by a device with a metal bar placed against the neck, which measures the radioactivity emitting from the thyroid. This test takes about 4minutes while the uptake% is accumulated (calculated) by the machine software. A scan is also performed, wherein images (typically a center, left and right angle) are taken of the contrasted thyroid gland with a  HYPERLINK "http://en.wikipedia.org/wiki/Gamma_camera" gamma camera; a  HYPERLINK "http://en.wikipedia.org/wiki/Radiologist" \o "Radiologist" radiologist will read and prepare a report indicating the uptake% and comments after examining the images. Hyperthyroid patients will typically "take up" higher than normal levels of radioiodine. Normal ranges for RAI uptake are from 10-30%. In addition to testing the TSH levels, many doctors test for T3, Free T3, T4, and/or Free T4 for more detailed results. Typical adult limits for these hormones are: TSH (units): 0.45 - 4.50 uIU/mL; T4 Free/Direct (nanograms): 0.82 - 1.77ng/dl; and T3 (nanograms): 71 - 180ng/dl. Persons with hyperthyroidism can easily exhibit levels many times these upper limits for T4 and/or T3. See a complete table of normal range limits for thyroid function at the  HYPERLINK "http://en.wikipedia.org/wiki/Thyroid_gland" \o "Thyroid gland" thyroid gland article. Treatment The large and generally accepted modalities for treatment of hyperthyroidism in humans involve initial temporary use of suppressive thyrostatics medication (antithyroid drugs), and possibly later use of permanent surgical or radioisotope therapy. All approaches may cause under active thyroid function (hypothyroidism) which is easily managed with  HYPERLINK "http://en.wikipedia.org/wiki/Levothyroxine" levothyroxine supplementation. Temporary medical therapy Thyrostatics (antithyroid drugs) Thyrostatics are drugs that inhibit the production of thyroid hormones, such as  HYPERLINK "http://en.wikipedia.org/wiki/Carbimazole" carbimazole (used in UK) and  HYPERLINK "http://en.wikipedia.org/wiki/Methimazole" methimazole (used in US), and  HYPERLINK "http://en.wikipedia.org/wiki/Propylthiouracil" propylthiouracil. Thyrostatics are believed to work by inhibiting the iodination of thyroglobulin by thyroperoxidase, and, thus, the formation of tetra-iodothyronine (T4). Propylthiouracil also works outside the thyroid gland, preventing conversion of (mostly inactive) T4 to the active form T3. Because thyroid tissue usually contains a substantial reserve of thyroid hormone, thyrostatics can take weeks to become effective, and the dose often needs to be carefully titrated over a period of months, with regular doctor visits and blood tests to monitor results. A very high dose is often needed early in treatment, but, if too high a dose is used persistently, patients can develop symptoms of hypothyroidism. This titrating of the dose is difficult to do accurately, and so sometimes a "block and replace" attitude is taken. In block and replace treatments thyrostatics are taken in sufficient quantities to completely block thyroid hormones, the patient treated as though they have complete hypothyroidism. Beta-blockers Many of the common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety are mediated by increases in beta adrenergic receptors on cell surfaces.  HYPERLINK "http://en.wikipedia.org/wiki/Beta_blockers" \o "Beta blockers" Beta blockers, typically used to treat high blood pressure, are a class of drugs that offset this effect, reducing rapid pulse associated with the sensation of palpitations, and decreasing tremor and anxiety. Thus, a patient suffering from hyperthyroidism can often obtain immediate temporary relief until the hyperthyroidism can be characterized with the Radioiodine test noted above and more permanent treatment take place. Note that these drugs do not treat hyperthyroidism or any of its long-term effects if left untreated, but, rather, they treat or reduce only symptoms of the condition. Some minimal effect on thyroid hormone production however also comes with Propranolol - which has two roles in the treatment of hyperthyroidism, determined by the different isomers of propranolol. L-propranolol causes beta-blockade, thus treating the symptoms associated with hyperthyroidism such as tremor, palpitations, anxiety, and heat intolerance. D-propranolol inhibits Thyroxine deiodinase, thereby blocking the conversion of T4 to T3, providing some though minimal therapeutic effect. Other beta blockers are used to treat only the symptoms associated with hyperthyroidism.  HYPERLINK "http://en.wikipedia.org/wiki/Propranolol" Propranolol in the US, and  HYPERLINK "http://en.wikipedia.org/wiki/Metoprolol" Metoprolol in the UK, are most frequently used to augment treatment for hyperthyroid patients. Permanent treatments Surgery as an option predates the use of the less invasive radioisotope therapy (radioiodine 131 thyroid ablation), but is still required in cases where the thyroid gland is enlarged and causing compression to the neck structures, or the underlying cause of the hyperthyroidism may be cancerous in origin. Some patients suffering from the related condition of thyroid eye disease leading to  HYPERLINK "http://en.wikipedia.org/wiki/Diplopia" diplopia because this condition can be worsened by radiotherapy treatment. Surgery  HYPERLINK "http://en.wikipedia.org/wiki/Surgery" Surgery (to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method, and because there is a risk of also removing the  HYPERLINK "http://en.wikipedia.org/wiki/Parathyroid_glands" \o "Parathyroid glands" parathyroid glands, and of cutting the  HYPERLINK "http://en.wikipedia.org/wiki/Recurrent_laryngeal_nerve" recurrent laryngeal nerve, making swallowing difficult, and even simply generalized staph infection as with any major surgery. Some Graves' disease patients, however, that cannot tolerate medicines for one reason or another, patients that are allergic to iodine, or patients that refuse radioiodine may opt for surgical intervention. Also, some surgeons believe that radioiodine treatment is unsafe in patients with unusually large gland, or those whose eyes have begun to bulge from their sockets, fearing that the massive dose of radioiodine 131 needed will only exacerbate the patient's symptoms. Radioiodine In  HYPERLINK "http://en.wikipedia.org/wiki/Iodine-131" iodine-131 (radioiodine)  HYPERLINK "http://en.wikipedia.org/wiki/Radiation_therapy" \l "Radioisotope_Therapy_.28RIT.29" \o "Radiation therapy" radioisotope therapy, which was first pioneered by Dr.  HYPERLINK "http://en.wikipedia.org/wiki/Saul_Hertz" Saul Hertz, HYPERLINK "http://en.wikipedia.org/wiki/Hyperthyroidism" \l "cite_note-Vignette-12#cite_note-Vignette-12" [13] radioactive iodine-131 is given orally (either by pill or liquid) on a one-time basis, to severely restrict, or altogether destroy the function of a hyperactive thyroid gland. This isotope of radioactive iodine used for ablative treatment is more potent than diagnostic radioiodine (iodine-123), which has a biological half life from 813 hours. Iodine-131, which also emits beta particles that are far more damaging to tissues at short range, has a half-life of approximately 8 days. Patients not responding sufficiently to the first dose are sometimes given an additional radioiodine treatment, at a larger dose. Iodine-131 in this treatment is picked up by the active cells in the thyroid and destroys them, rendering the thyroid gland mostly or completely inactive. Since iodine is picked more readily (though not exclusively) by thyroid cells, and (more important) is picked up even more readily by over-active thyroid cells, the destruction is local, and there are no widespread side-effects with this therapy. Radioiodine ablation has been used for over 50 years, and the only major reasons for not using it are pregnancy and breast-feeding (breast tissue also picks up and concentrates iodine). Once the thyroid function is reduced, replacement hormone therapy taken orally each day may easily provide the required amount of thyroid hormone the body needs. There is, however, a contrasting study noting increased cancer incidence after radioiodine treatment for hyperthyroidismThe principal advantage of radioiodine treatment for hyperthyroidism is that it tends to have a much higher success rate than medications. Depending on the dose of radioiodine chosen, and the disease under treatment (Grave's vs. toxic goiter, vs. hot nodule etc.), success rate in achieving definitive resolution of the hyperthyroidism may vary from 75-100%. A major expected side-effect of radioiodine in patients with Graves' disease is the development of lifelong hypothyroidism, requiring daily treatment with thyroid hormone. Also, there are some indications that patients suffering from related eye disease experience a worsening of this condition, and for this reason some patients elect to have a surgical solution. On occasion, some patients may require more than one radioactive treatment, depending on the type of disease present, the size of the thyroid, and the initial dose administered. Many patients are initially unhappy at the thought of having to take a thyroid hormone pill for the rest of their lives. Nevertheless, as thyroid hormone is safe, inexpensive, and easy to take, and is identical to the thyroid hormone normally made by the thyroid, this therapy is, in general, extremely safe and very well tolerated by the vast majority of patients As radioactive iodine treatment results in destruction of thyroid tissue, there is often a transient period of several days to weeks when the symptoms of hyperthyroidism may actually worsen following radioactive iodine therapy. In general, this happens as a result of thyroid hormone's being released into the blood following the radioactive iodine-mediated destruction of thyroid cells that contain thyroid hormone. In some patients, treatment with medications such as beta blockers (propranolol, atenolol, etc.) may be useful during this period of time. Many patients are able to tolerate the initial few weeks without any problem whatsoever. Most patients do not experience any difficulty after the radioactive iodine treatment, usually given as a small pill. On occasion, neck tenderness or a sore throat may become apparent after a few days, if moderate inflammation in the thyroid develops and produces discomfort in the neck or throat area. This is usually transient, and not associated with a fever, etc. Women breastfeeding should discontinue breastfeeding for at least a week, and likely longer, following radioactive iodine treatment, as small amounts of radioactive iodine may be found in breast milk even several weeks after the radioactive iodine treatment. A common outcome following radioiodine is a swing from hyperthyroidism to the easily treatable hypothyroidism, which occurs in 78% of those treated for Graves' thyrotoxicosis and in 40% of those with toxic multinodular goiter or solitary toxic adenoma Use of higher doses of radioiodine reduces the incidence of treatment failure, with penalty for higher response to treatment consisting mostly of higher rates of eventual hypothyroidism which requires hormone treatment for life. There is increased sensitivity to radioiodine therapy in thyroids appearing on  HYPERLINK "http://en.wikipedia.org/wiki/Medical_ultrasonography" \o "Medical ultrasonography" ultrasound scans as more uniform (hypoechogenic), due to densely packed large cells, with 81% later becoming hypothyroid, compared to just 37% in those with more normal scan appearances (normoechogenic Thyroid storm Thyroid storm presents with extreme symptoms of hyperthyroidism. It is treated aggressively with  HYPERLINK "http://en.wikipedia.org/wiki/Resuscitation" \o "Resuscitation" resuscitation measure along with a combination of the above modalities including: an intravenous beta blockers such as  HYPERLINK "http://en.wikipedia.org/wiki/Propranolol" propranolol, followed by a  HYPERLINK "http://en.wikipedia.org/wiki/Thionamide" \o "Thionamide" thionamide such as  HYPERLINK "http://en.wikipedia.org/wiki/Methimazole" methimazole, an iodinated radiocontrast agent or an iodine solution if the radiocontrast agent is not available, and an intravenous  HYPERLINK "http://en.wikipedia.org/wiki/Steroid" steroid such as hydrocortisone In other animals Cats In veterinary medicine, hyperthyroidism is one of the most common endocrine conditions affecting older domesticated felines (cats). Some veterinarians estimate that it occurs in up to 2% of cats over the age of 10. HYPERLINK "http://en.wikipedia.org/wiki/Hyperthyroidism" \l "cite_note-19#cite_note-19" ] The disease has become significantly more common since the first reports of feline hyperthyroidism in the 1970s. In cats, one cause of hyperthyroidism tends to be benign tumors, but the reason those cats develop such tumors continues to be researched. However, recent research published in Environmental Science & Technology, a publication of the American Chemical Society, suggests that many cases of feline hyperthyroidism are associated with exposure to environmental contaminants called  HYPERLINK "http://en.wikipedia.org/wiki/Polybrominated_diphenyl_ethers" polybrominated diphenyl ethers (PBDEs), which are present in flame retardants in many household products, in particular, furniture and some electronic products. The study from which the report was based was conducted jointly by researchers at the EPA's National Health and Environmental Effects Laboratory and Indiana University. In the study, which involved 23 pet cats with feline hyperthyroidism, PDBE blood levels were three times as high as those in younger, non-hyperthyroid cats. In ideal circumstances, PBDE and related endocrine disruptors that seriously damage health would not be present in the blood of any animals or humans. Mutations of the thyroid-stimulating hormone receptor that cause a constitutive activation of the thyroid gland cells have been discovered recently. Many other factors may play a role in the pathogenesis of the disease such as goitrogens (isoflavones such as genistein, daidzein, and quercertin) and iodine and selenium content in the diet. The most common presenting symptoms are: rapid  HYPERLINK "http://en.wikipedia.org/wiki/Weight_loss" weight loss,  HYPERLINK "http://en.wikipedia.org/wiki/Tachycardia" tachycardia (rapid heart rate),  HYPERLINK "http://en.wikipedia.org/wiki/Vomiting" vomiting,  HYPERLINK "http://en.wikipedia.org/wiki/Diarrhea" diarrhea, increased consumption of fluids ( HYPERLINK "http://en.wikipedia.org/wiki/Polydipsia" polydipsia ( ) n o z { ! P Q U V W X * + H I   U V _ ` f g վվվվվվվվվվվվվվվվվվ&hxhAt5>*B*\mH phsH ,jhxhAt5B*U\mH phsH #hxhAt5B*\mH phsH /h LShAt5B*CJ0KH$\aJ0mH phsH 8 # o >-&Den$ & FddA$[$\$gdAt$ & FddA$[$\$gdAt$ & FddA$[$\$gdAt$ & FddA$[$\$gdAt$A$gdAt$dd@&A$[$\$gd LS$ddA$[$\$gdAt$dd@&A$[$\$a$gd LS    ! # ( ) l n o p #$CD}~no樒{{{{{{g{{{g{{{g{{{g{{&hxhAt5>*B*\mH phsH ,jhxhAt5B*U\mH phsH +hxhAt5B*CJ$\aJ$mH phsH #hxhAt5B*\mH phsH ,hxhAt56>*B*\]mH phsH )hxhAt56B*\]mH phsH 2jhxhAt56B*U\]mH phsH (o>?  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+hxhAt5B*CJ\aJmH phsH 3`BBBBBRDSDDDDDDDEEEEEESFTFfFgF|F}FFFFF*I+I`IaIkIlI{I|IIIJ J,J-JbJcJmJnJoJpJ/jhxhAt5B*H*U\mH phsH &hxhAt5>*B*\mH phsH ,jhxhAt5B*U\mH phsH +hxhAt5B*CJ\aJmH phsH #hxhx5B*\mH phsH #hxhAt5B*\mH phsH 0DI'IU'XYZ|\]^``a2cef@hH$dd@&A$[$\$gdAt$dd@&A$[$\$gdAt$ddA$[$\$gdx$dd@&A$[$\$gdAt$ddA$[$\$gdAtpJJJJJz\{\\\+],]<]=]]^g^h^^^^^,_-_c_d_o_p_________`ԿԭpZppp+hxhAt5B*CJ\aJmH phsH &hxhAt5>*B*\mH phsH ,jhxhAt5B*U\mH phsH #hxhx5B*\mH phsH #hxhAt5B*\mH phsH )hxhAt5>*B*H*\mH phsH /jhxhAt5B*H*U\mH phsH &hxhAt5B*H*\mH phsH #````````````aaa2b3b4b5b!d"dkdldddohphhhhhhhhíkV)hxhAt5>*B*H*\mH phsH &hxhAt5B*H*\mH phsH /jhxhAt5B*H*U\mH phsH +hxhAt5B*CJ\aJmH phsH +hxhAt5B*CJ\aJmH phsH #hxhAt5B*\mH phsH &hxhAt5>*B*\mH phsH ,jhxhAt5B*U\mH phsH !hhhhiiBiCiKiLiNiOiiiiiiiiiii,-`aij@ANO  FGXë×&hxhAt5B*H*\mH phsH +hxhAt5B*CJ\aJmH phsH U#hxhAt5B*\mH phsH &hxhAt5>*B*\mH phsH ,jhxhAt5B*U\mH phsH ;) and food, and increased urine production ( HYPERLINK "http://en.wikipedia.org/wiki/Polyuria" polyuria). Other symptoms include hyperactivity, possible aggression,  HYPERLINK "http://en.wikipedia.org/wiki/Heart_murmurs" \o "Heart murmurs" heart murmurs, a  HYPERLINK "http://en.wikipedia.org/wiki/Gallop_rhythm" gallop rhythm, an unkempt appearance, and large, thick nails. About 70% of afflicted cats also have enlarged thyroid glands ( HYPERLINK "http://en.wikipedia.org/wiki/Goiter" \o "Goiter" goiter). The same three treatments used with humans are also options in treating feline hyperthyroidism (surgery, radioiodine treatment, and anti-thyroid drugs). Drugs must be given to cats for the remainder of their lives, but may be the least expensive option, especially for very old cats. Radioiodine treatment and surgery often cure hyperthyroidism. Some veterinarians prefer radioiodine treatment over surgery because it does not carry the risks associated with  HYPERLINK "http://en.wikipedia.org/wiki/Anesthesia" anesthesia. Radioiodine treatment, however, is not available in all areas for cats. The reason is that this treatment requires nuclear radiological expertise and facilities, since the animal's urine, sweat, saliva, and stool are radioactive for several days after the treatment, requiring special inpatient handling and facilities usually for a total of 3 weeks (first week in total isolation and the next two weeks in close confinement The guidelines for radiation levels vary from state to state; some states such as Massachusetts allow hospitalization for as little as two days before the animal is sent home with care instructions. Surgery tends to be done only when just one of the thyroid glands is affected (unilateral disease); however, following surgery, the remaining gland may become over-active. As in people, one of the most common complications of the surgery is hypothyroidism. Dogs Hyperthyroidism is very rare in canines (dogs) (occurring in less than 1 or 2% of dogs), who instead tend to have the opposite problem: hypothyroidism, which can manifest itself in a unhealthy-appearing coat and fertility problems in females. When hyperthyroidism does appear in dogs, it tends to be due to over-supplementation of the thyroid hormone during treatment for hypothyroidismm. Symptoms usually disappear when the dose is adjusted] On occasion, dogs will have functional carcinoma in the thyroid; more often (about 90% of the time), this is a very aggressive tumor that is invasive and easily metastasizes or spreads to other tissues (esp. the  HYPERLINK "http://en.wikipedia.org/wiki/Lungs" \o "Lungs" lungs), making prognosis very poor. While surgery is possible, it is often very difficult due to the invasiveness of the mass in surrounding tissue including the  HYPERLINK "http://en.wikipedia.org/wiki/Arteries" \o "Arteries" arteries, the  HYPERLINK "http://en.wikipedia.org/wiki/Esophagus" esophagus, and  HYPERLINK "http://en.wikipedia.org/wiki/Windpipe" \o "Windpipe" windpipe. It may only be possible to reduce the size of the mass, thus relieving symptoms and also allowing time for other treatments to work] If a dog does have a benign functional carcinoma (appears in 10% of the cases), treatment and prognosis are no different from those of the cat. The only real difference is that dogs tend to appear to be asymptomatic, with the exception of having an enlarged thyroid gland appearing as a lump on the neck] XY^_>?GHNOefïïÜ%hxhG5B*Z\_Ho(ph&hxhAt5B*H*\mH phsH #hxhAt5B*\mH phsH &hxhAt5>*B*\mH phsH ,jhxhAt5B*U\mH phsH Hg$$ddA$[$\$gdx81h:p. 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