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Lancet (London, England) Oct 2012Androgen insensitivity syndrome in its complete form is a disorder of hormone resistance characterised by a female phenotype in an individual with an XY karyotype and... (Review)
Review
Androgen insensitivity syndrome in its complete form is a disorder of hormone resistance characterised by a female phenotype in an individual with an XY karyotype and testes producing age-appropriate normal concentrations of androgens. Pathogenesis is the result of mutations in the X-linked androgen receptor gene, which encodes for the ligand-activated androgen receptor--a transcription factor and member of the nuclear receptor superfamily. This Seminar describes the clinical manifestations of androgen insensitivity syndrome from infancy to adulthood, reviews the mechanism of androgen action, and shows examples of how mutations of the androgen receptor gene cause the syndrome. Management of androgen insensitivity syndrome should be undertaken by a multidisciplinary team and include gonadectomy to avoid gonad tumours in later life, appropriate sex-hormone replacement at puberty and beyond, and an emphasis on openness in disclosure.
Topics: Androgen-Insensitivity Syndrome; Androgens; Diagnosis, Differential; Female; Humans; Male; Mutation; Zinc Fingers
PubMed: 22698698
DOI: 10.1016/S0140-6736(12)60071-3 -
European Review For Medical and... Jun 2018We provide a review of the literature about the Androgen Insensitivity Syndrome (AIS), its onset and associated developmental anomalies and the genetic alterations... (Review)
Review
OBJECTIVE
We provide a review of the literature about the Androgen Insensitivity Syndrome (AIS), its onset and associated developmental anomalies and the genetic alterations causing it.
MATERIALS AND METHODS
We searched PubMed with a larger emphasis on the physiology, genetics and current management of AIS.
RESULTS
AIS is an X-linked recessive Disorder of Sex Development (DSD). It is caused by mutations of the Androgen Receptor, and their large amount and heterogeneity (missense and nonsense mutations, splicing variants, deletions, and insertions) are responsible for the wide spectrum of possible phenotypes of patients, divided into Partial AIS (PAIS) and Complete AIS (CAIS). Once the clinical and laboratory investigations have laid the foundation for a diagnostic hypothesis, it is important to identify the actual karyotype of the individual and search for the mutation in the Androgen Receptor to diagnose with certainty the syndrome. Alternatively, in the absence of such evidence, the diagnosis should more properly be an AIS-like condition, which we describe as well in our report.
CONCLUSIONS
The management of this DSD is based on pharmacotherapies, surgery and psychological support: all of them must be directed to facilitate the patient's life, considering his/her sexual identity.
Topics: Androgen-Insensitivity Syndrome; Humans; Male; Mutation; Receptors, Androgen
PubMed: 29949163
DOI: 10.26355/eurrev_201806_15272 -
Archives of Endocrinology and Metabolism 2018Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen... (Review)
Review
Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype - phenotype correlation in this syndrome. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. Treatment depends on the phenotype and social sex of the individual. Open issues in the management of androgen insensitivity syndromes includes decisions on sex assignment, timing of gonadectomy, fertility, physcological outcomes and genetic counseling.
Topics: Androgen-Insensitivity Syndrome; Female; Hormone Replacement Therapy; Humans; Male; Phenotype
PubMed: 29768628
DOI: 10.20945/2359-3997000000031 -
International Journal of Molecular... Jan 2021Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY... (Review)
Review
Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS.
Topics: Androgen-Insensitivity Syndrome; Androgens; Chromosomes, Human, X; Female; Gonads; Hormone Replacement Therapy; Humans; Karyotype; Male; Mutation; Receptors, Androgen
PubMed: 33514065
DOI: 10.3390/ijms22031264 -
Journal of Neuroendocrinology Feb 2022Widespread sex differences in human brain structure and function have been reported. Research on animal models has demonstrated that sex differences in brain and... (Review)
Review
Widespread sex differences in human brain structure and function have been reported. Research on animal models has demonstrated that sex differences in brain and behavior are induced by steroid hormones during specific, hormone sensitive, developmental periods. It was shown that typical male neural and behavioral characteristics develop under the influence of testosterone, mostly acting during perinatal development. By contrast, typical female neural and behavioral characteristics may actually develop under the influence of estradiol during a specific prepubertal period. This review provides an overview of our current knowledge on the role of steroid hormones in the sexual differentiation of the human brain. Both clinical and neuroimaging data obtained in patients with altered androgen levels/actions (i.e., congenital adrenal hyperplasia or complete androgen insensitivity syndrome [CAIS]), point to an important role of (prenatal) androgens in inducing typical male neural and psychosexual characteristics in humans. In contrast to rodents, there appears to be no obvious role for estrogens in masculinizing the human brain. Furthermore, data from CAIS also suggest a contribution of sex chromosome genes to the development of the human brain. The final part of this review is dedicated to a brief discussion of gender incongruence, also known as gender dysphoria, which has been associated with an altered or less pronounced sexual differentiation of the brain.
Topics: Androgen-Insensitivity Syndrome; Androgens; Animals; Brain; Female; Gonadal Steroid Hormones; Humans; Male; Pregnancy; Sex Differentiation; Steroids
PubMed: 34708466
DOI: 10.1111/jne.13050 -
Italian Journal of Pediatrics Sep 2021In healthy adolescents, delayed pubarche is generally a benign condition that is caused by a physiological discrepancy between gonadarche and adrenarche. In presence of... (Review)
Review
In healthy adolescents, delayed pubarche is generally a benign condition that is caused by a physiological discrepancy between gonadarche and adrenarche. In presence of other clinical signs and symptoms, delayed pubarche can be caused by single or multiple hormones deficiency (such as adrenal insufficiency, panhypopituitarism and hypothyroidism) and/or genetic conditions (Turner syndrome, androgen insensitivity syndrome). Exposition to endocrine disruptors has also been described as a possible cause of delay of pubic hair development. Basic blood tests, karyotype and first level imaging studies are helpful in the differential diagnosis.
Topics: Addison Disease; Adolescent; Adrenal Insufficiency; Androgen-Insensitivity Syndrome; Endocrine Disruptors; Environmental Exposure; Female; Humans; Hypothyroidism; Male; Puberty, Delayed; Turner Syndrome
PubMed: 34488834
DOI: 10.1186/s13052-021-01134-0 -
Internal Medicine (Tokyo, Japan) May 2004Coregulators are a group of proteins, which modulate the nuclear receptor transactivation function. In this study, a new "coregulator disease" concept was proposed from... (Comparative Study)
Comparative Study Review
Coregulators are a group of proteins, which modulate the nuclear receptor transactivation function. In this study, a new "coregulator disease" concept was proposed from observations of a case of androgen insensitivity syndrome (AIS) and cases involving Rubinstein-Taybi syndrome and X-linked dementia and hypothyroidism syndrome. In addition, coregulators are thought to be closely associated with the pathogenesis of several diseases such as hormone-dependent cancers and leukemia. Based on these observations, the clinical disorders associated with some coregulator abnormalities were reviewed.
Topics: Androgen-Insensitivity Syndrome; DNA-Binding Proteins; Female; Humans; Male; Receptors, Androgen; Rubinstein-Taybi Syndrome; Sensitivity and Specificity; Thyroid Hormone Resistance Syndrome; Trans-Activators; Transcriptional Activation
PubMed: 15206547
DOI: 10.2169/internalmedicine.43.368 -
Obstetrics and Gynecology Nov 2016Disorders (differences) of sexual development encompass a variety of conditions with atypical development of chromosomal, gonadal, or anatomic sex. Three of the most... (Review)
Review
Disorders (differences) of sexual development encompass a variety of conditions with atypical development of chromosomal, gonadal, or anatomic sex. Three of the most common differences of sex development conditions include congenital adrenal hyperplasia, complete androgen insensitivity, and Turner syndrome. Obstetrician-gynecologists who care for affected individuals in their practice must be familiar with the genetic, endocrine, and anatomic considerations of the most common conditions to provide optimal care. As women with these conditions transition to adult care, the gynecologist needs to assess the patient's understanding and educate her regarding her diagnosis and ongoing medical care. All of these conditions may affect self-perception, mental health, fertility, sexual function, and bone and cardiovascular health. Women with congenital adrenal hyperplasia need lifelong endocrine management and require genetic counseling before pregnancy. Women with androgen insensitivity syndrome require counseling regarding gonadectomy and hormone replacement therapy and may require vaginal elongation for intercourse. Most women with Turner syndrome experience premature ovarian insufficiency and require long-term estrogen replacement. Women with Turner syndrome often have congenital anomalies and autoimmune disorders, which require regular monitoring and care during adulthood. The purpose of this review is to provide the obstetrician-gynecologist who cares for adult women with the most common disorders (differences) of sexual development conditions an outline of the current recommendations for screening and ongoing health care with particular emphasis on the underlying genetics, management of subfertility, infertility and sexual concerns, approach to hypogonadism, and understanding of associated comorbidities.
Topics: Adrenal Insufficiency; Adult; Androgen-Insensitivity Syndrome; Disorders of Sex Development; Female; Genetic Diseases, X-Linked; Humans; Hypoadrenocorticism, Familial; Male; Turner Syndrome
PubMed: 27741188
DOI: 10.1097/AOG.0000000000001672