Androgen insensitivity syndrome natural history, complications and prognosis: Difference between revisions
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==Overview== | ==Overview== | ||
The symptoms of androgen insensitivity syndrome usually develop in the fetal developmental stage and start with non-androgenic aspects of male development such as formation of testes, production of testosterone and [[anti-müllerian hormone]] (AMH) by the testes which prevents the [[uterus]] and upper [[vagina]] from forming, and [[prostate]] and other internal male genital ducts fail to form because of lack of testosterone action. Childhood growth is normal and the karyotypic incongruity remains unsuspected unless an inguinal lump is discovered to be a testis during surgical repair of an [[inguinal hernia]], [[appendectomy]], or other coincidental surgery. Complications such as Infertility, psychological and social issues, osteoporosis and cancers show somatic alterations in AR whcih lead to cancers of the male breast, larynx, liver, testes and bladder. Prognosis is good after orchidectomy at the proper time. For incomplete AIS patients, it depends on the presence and severity of ambiguous genitalia. | The symptoms of androgen insensitivity syndrome usually develop in the fetal developmental stage and start with non-androgenic aspects of male development such as formation of [[testes]], production of [[testosterone]] and [[anti-müllerian hormone]] (AMH) by the testes which prevents the [[uterus]] and upper [[vagina]] from forming, and [[prostate]] and other internal male genital ducts fail to form because of lack of [[testosterone]] action. Childhood growth is normal and the karyotypic incongruity remains unsuspected unless an inguinal lump is discovered to be a [[testis]] during surgical repair of an [[inguinal hernia]], [[appendectomy]], or other coincidental surgery. Complications such as [[Infertility]], psychological and social issues, [[osteoporosis]] and cancers show somatic alterations in [[androgen receptor]] (AR) whcih lead to cancers of the male breast, larynx, liver, testes and bladder. Prognosis is good after [[orchidectomy]] at the proper time. For incomplete AIS patients, it depends on the presence and severity of ambiguous genitalia. | ||
==Natural History== | ==Natural History== | ||
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*If a 46,XY fetus cannot respond to testosterone or [[DHT]], only the non-androgenic aspects of male development begin to take place: formation of testes, production of testosterone and [[anti-müllerian hormone]] (AMH) by the testes, and suppression of [[müllerian ducts]]. | *If a 46,XY fetus cannot respond to testosterone or [[DHT]], only the non-androgenic aspects of male development begin to take place: formation of testes, production of testosterone and [[anti-müllerian hormone]] (AMH) by the testes, and suppression of [[müllerian ducts]]. | ||
*The testes usually remain in the abdomen, or occasionally move into the [[inguinal canal]]s but can go no further because there is no [[scrotum]]. | *The testes usually remain in the abdomen, or occasionally move into the [[inguinal canal]]s but can go no further because there is no [[scrotum]]. | ||
*AMH prevents the [[uterus]] and upper [[vagina]] from forming. The testes make male amounts of testosterone and [[DHT]] but no androgenic [[sexual differentiation]] occurs. Most of the [[prostate]] and other internal male genital ducts fail to form because of lack of testosterone action. A shallow vagina forms, surrounded by normally-formed labia. Phallic tissue remains small and becomes a [[clitoris]]. At birth, a child with CAIS appears to be a typical girl, with no reason to suspect an incongruous karyotype and testosterone level, or lack of uterus. | *AMH prevents the [[uterus]] and upper [[vagina]] from forming. The testes make male amounts of testosterone and [[DHT]] but no androgenic [[sexual differentiation]] occurs. Most of the [[prostate]] and other internal male genital ducts fail to form because of lack of testosterone action. A shallow vagina forms, surrounded by normally-formed labia. Phallic tissue remains small and becomes a [[clitoris]]. At birth, a child with CAIS appears to be a typical girl, with no reason to suspect an incongruous karyotype and [[testosterone]] level, or lack of [[uterus]]. | ||
*Childhood growth is normal and the karyotypic incongruity remains unsuspected unless an inguinal lump is discovered to be a testis during surgical repair of an [[inguinal hernia]], [[appendectomy]], or other coincidental surgery. | *Childhood growth is normal and the karyotypic incongruity remains unsuspected unless an inguinal lump is discovered to be a testis during surgical repair of an [[inguinal hernia]], [[appendectomy]], or other coincidental surgery. | ||
*[[Puberty]] tends to begin slightly later than the average for girls. As the [[hypothalamus]] and [[pituitary]] signal the testes to produce testosterone, amounts more often associated with boys begin to appear in the blood. Some of the testosterone is converted into [[estradiol]], which begins to induce normal [[breast]] development. Normal reshaping of the pelvis and redistribution of body [[adipose|fat]] occurs as in other girls. Little or no pubic hair or other androgenic hair appears, sometimes a source of worry or shame. Acne is rare. | *[[Puberty]] tends to begin slightly later than the average for girls. As the [[hypothalamus]] and [[pituitary]] signal the testes to produce [[testosterone]], amounts more often associated with boys begin to appear in the blood. Some of the [[testosterone]] is converted into [[estradiol]], which begins to induce normal [[breast]] development. Normal reshaping of the pelvis and redistribution of body [[adipose|fat]] occurs as in other girls. Little or no pubic hair or other androgenic hair appears, sometimes a source of worry or shame. Acne is rare. | ||
*As menarche typically occurs about two years after breast development begins, no one usually worries about lack of menstrual periods until a girl reaches 14 or 15 years of age. At that point, an astute physician may suspect the diagnosis just from the breast/hair discrepancy. Diagnosis of complete AIS is confirmed by discovering an adult male testosterone level, 46,XY karotype, and a shallow vagina with no [[cervix]] or uterus. | *As [[menarche]] typically occurs about two years after breast development begins, no one usually worries about lack of [[menstrual]] periods until a girl reaches 14 or 15 years of age. At that point, an astute physician may suspect the diagnosis just from the breast/hair discrepancy. Diagnosis of complete AIS is confirmed by discovering an adult male testosterone level, 46,XY karotype, and a shallow vagina with no [[cervix]] or uterus. | ||
*Hormone measurements in pubertal girls and women with CAIS and PAIS are similar, and are characterized by total testosterone levels in the upper male rather than female range, estradiol levels mildly elevated above the female range, mildly elevated [[luteinizing hormone|LH]] levels, normal [[follicle stimulating hormone|FSH]] levels, [[sex hormone binding globulin]] levels in the female range, and possibly mild elevation of [[anti-müllerian hormone|AMH]]. [[DHT]] levels are in the normal male range in CAIS but reportedly in the lower male range in PAIS. Interpretation of hormone levels in infancy is more complex and cannot be as easily summarized for this article. Androgen receptor testing has become available commercially but is rarely needed for diagnosis of CAIS and PAIS. | *Hormone measurements in pubertal girls and women with CAIS and PAIS are similar, and are characterized by total testosterone levels in the upper male rather than female range, [[estradiol]] levels mildly elevated above the female range, mildly elevated [[luteinizing hormone|LH]] levels, normal [[follicle stimulating hormone|FSH]] levels, [[sex hormone binding globulin]] levels in the female range, and possibly mild elevation of [[anti-müllerian hormone|AMH]]. [[DHT]] levels are in the normal male range in CAIS but reportedly in the lower male range in PAIS. Interpretation of hormone levels in infancy is more complex and cannot be as easily summarized for this article. Androgen receptor testing has become available commercially but is rarely needed for diagnosis of CAIS and PAIS. | ||
*Adult women with CAIS tend to be taller than average, primarily because of their later timing of puberty. Breast development is said to be average to above average. Lack of responsiveness to androgen prevents some usual female adult hair development, including pubic, axillary, upper lip. In contrast, head hair remains fuller than average, without recession of scalp or thinning with age. Shallowness of the vagina varies and may or may not lead to mechanical difficulties during [[coitus]]. Although the testes develop fairly unexceptionally before puberty if not removed, the testes in adults with CAIS become increasingly distinctive, with unusual spermatogenic cells and no [[spermatogenesis]]. | *Adult women with CAIS tend to be taller than average, primarily because of their later timing of puberty. Breast development is said to be average to above average. Lack of responsiveness to androgen prevents some usual female adult hair development, including [[pubic]], [[axillary]], upper lip. In contrast, head hair remains fuller than average, without recession of scalp or thinning with age. Shallowness of the vagina varies and may or may not lead to mechanical difficulties during [[coitus]]. Although the testes develop fairly unexceptionally before puberty if not removed, the testes in adults with CAIS become increasingly distinctive, with unusual spermatogenic cells and no [[spermatogenesis]]. | ||
*By clinical reports and information from support groups, women with CAIS are at least as likely as other women to have a female gender identity and to be attracted sexually to men. | *By clinical reports and information from support groups, women with CAIS are at least as likely as other women to have a female gender identity and to be attracted sexually to men. | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
The symptoms of androgen insensitivity syndrome usually develop in the fetal developmental stage and start with non-androgenic aspects of male development such as formation of testes, production of testosterone and anti-müllerian hormone (AMH) by the testes which prevents the uterus and upper vagina from forming, and prostate and other internal male genital ducts fail to form because of lack of testosterone action. Childhood growth is normal and the karyotypic incongruity remains unsuspected unless an inguinal lump is discovered to be a testis during surgical repair of an inguinal hernia, appendectomy, or other coincidental surgery. Complications such as Infertility, psychological and social issues, osteoporosis and cancers show somatic alterations in androgen receptor (AR) whcih lead to cancers of the male breast, larynx, liver, testes and bladder. Prognosis is good after orchidectomy at the proper time. For incomplete AIS patients, it depends on the presence and severity of ambiguous genitalia.
Natural History
1. Natural history of CAIS
- If a 46,XY fetus cannot respond to testosterone or DHT, only the non-androgenic aspects of male development begin to take place: formation of testes, production of testosterone and anti-müllerian hormone (AMH) by the testes, and suppression of müllerian ducts.
- The testes usually remain in the abdomen, or occasionally move into the inguinal canals but can go no further because there is no scrotum.
- AMH prevents the uterus and upper vagina from forming. The testes make male amounts of testosterone and DHT but no androgenic sexual differentiation occurs. Most of the prostate and other internal male genital ducts fail to form because of lack of testosterone action. A shallow vagina forms, surrounded by normally-formed labia. Phallic tissue remains small and becomes a clitoris. At birth, a child with CAIS appears to be a typical girl, with no reason to suspect an incongruous karyotype and testosterone level, or lack of uterus.
- Childhood growth is normal and the karyotypic incongruity remains unsuspected unless an inguinal lump is discovered to be a testis during surgical repair of an inguinal hernia, appendectomy, or other coincidental surgery.
- Puberty tends to begin slightly later than the average for girls. As the hypothalamus and pituitary signal the testes to produce testosterone, amounts more often associated with boys begin to appear in the blood. Some of the testosterone is converted into estradiol, which begins to induce normal breast development. Normal reshaping of the pelvis and redistribution of body fat occurs as in other girls. Little or no pubic hair or other androgenic hair appears, sometimes a source of worry or shame. Acne is rare.
- As menarche typically occurs about two years after breast development begins, no one usually worries about lack of menstrual periods until a girl reaches 14 or 15 years of age. At that point, an astute physician may suspect the diagnosis just from the breast/hair discrepancy. Diagnosis of complete AIS is confirmed by discovering an adult male testosterone level, 46,XY karotype, and a shallow vagina with no cervix or uterus.
- Hormone measurements in pubertal girls and women with CAIS and PAIS are similar, and are characterized by total testosterone levels in the upper male rather than female range, estradiol levels mildly elevated above the female range, mildly elevated LH levels, normal FSH levels, sex hormone binding globulin levels in the female range, and possibly mild elevation of AMH. DHT levels are in the normal male range in CAIS but reportedly in the lower male range in PAIS. Interpretation of hormone levels in infancy is more complex and cannot be as easily summarized for this article. Androgen receptor testing has become available commercially but is rarely needed for diagnosis of CAIS and PAIS.
- Adult women with CAIS tend to be taller than average, primarily because of their later timing of puberty. Breast development is said to be average to above average. Lack of responsiveness to androgen prevents some usual female adult hair development, including pubic, axillary, upper lip. In contrast, head hair remains fuller than average, without recession of scalp or thinning with age. Shallowness of the vagina varies and may or may not lead to mechanical difficulties during coitus. Although the testes develop fairly unexceptionally before puberty if not removed, the testes in adults with CAIS become increasingly distinctive, with unusual spermatogenic cells and no spermatogenesis.
- By clinical reports and information from support groups, women with CAIS are at least as likely as other women to have a female gender identity and to be attracted sexually to men.
2. Reifenstein syndrome
Puberty can produce secondary sex characteristics of both sexes, though not fertility as the spermatogenic tissue requires androgen support as well as scrotal location. The amounts of androgenic body hair and breast development are variable.
Complications
- Infertility
- Psychological and social issues
- Osteoporosis: Reduced Bone mineral density (BMD) at the spine and hip in subjects with CAIS. There has been no relationship found between age of gonadectomy and BMD, and also no drop in BMD in subjects followed up after gonadectomy. [1]
- Some cancers show somatic alterations in Androgen receptor (AR) gene. These, however, appear to result in a gain of function rather than the loss of function seen in AIS. Cancers include the following : [2]
Prognosis
For patients with complete androgen insensitivity syndrome, prognosis is good after orchidectomy at the proper time. For incomplete androgen insensitivity syndrome patients, it depends on the presence and severity of ambiguous genitalia.
References
- ↑ King TFJ, Wat WZM, Creighton SM, Conway GS (2017). "Bone mineral density in complete androgen insensitivity syndrome and the timing of gonadectomy". Clin Endocrinol (Oxf). doi:10.1111/cen.13368. PMID 28493277.
- ↑ Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean L, Bird TD, Ledbetter N, Mefford HC, Smith R, Stephens K, Gottlieb B, Trifiro MA. PMID 20301602. Vancouver style error: initials (help); Missing or empty
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