Reifenstein syndrome is a type of androgen insufficiency. Reifenstein syndrome occurs in men when their body is unable to appropriately respond to androgens and testosterone. It is characterized by ambiguous external genitalia, gynecomastia, and infertility due to sclerosis of the seminal tubules.
Males with Reifenstein syndrome have partial androgen insensitivity; they are born with external male sex features. Affected men often present for clinical workup at the time of puberty, with the following physical characteristics and/or complaints  :
- Small and/or abnormal male genitals (e.g., small penis, small scrotum, incompletely closed or undescended testicles) 
- Sparse facial hair and difficulty growing a beard (normal amount of pubic and axillary hair)
- Complaints of sexual dysfunction
- Inability to impregnate female partner due to infertility
It is important to note a contrast of presenting symptoms between men with Reifenstein syndrome (partial androgen insensitivity) to those with complete androgen insensitivity. Men with complete androgen insensitivity often present with external female sex characteristics (without a uterus), internal male sex characteristics (e.g., undescended testes), and absent or very little pubic or axillary hair.
Entire Body System
Klinefelter syndrome XXY gonadal dysgenesis An inherited condition caused by an extra complete–most commonly–or partial X chromosome; it is the most common cause of 1º hypogonadism Clinical Often asymptomatic; may first come to medical attention for infertility [medical-dictionary.thefreedictionary.com]
Infants, young children, and asymptomatic young adults can be evaluated with simple urine testing on an outpatient basis. Medical therapy is used to ameliorate the rate of pigment deposition. [scrigroup.com]
- Small Scrotum
Symptoms Abnormal male genitals Hypospadias Small penis Small scrotum, with a line down the middle (bifid) or incompletely closed Undescended testicles Breast development in males at time of puberty Decreased body hair and beard, but normal pubic and [coordinatedhealth.com]
These may include: Abnormal male genitals, such as the urethra being on the underside of the penis, small penis, small scrotum (with a line down the middle or incompletely closed), or undescended testicles. [account.allinahealth.org]
Symptoms Return to top Abnormal male genitals Hypospadias Small penis Small scrotum, with a line down the middle (bifid) or incompletely closed Undescended testicles Breast development in males at time of puberty Decreased body hair and beard, but normal [pacificschoolserver.org]
Symptoms Abnormal male genitals, including undescended testes; a small scrotum, with a line down the middle (bifid) or incompletely closed; a small penis; and hypospadias (the urethra exits the body on the side of the penis, not the tip) Breast development [medical-dictionary-search-engines.com]
Diagnosis of Reifenstein syndrome consists of a history, physical findings, blood tests, genetic tests, sperm count, and less often a testicular biopsy. Physical findings include varying degrees of ambiguous external genitalia, small penis and scrotum, undescended testes, space facial hair, and gynecomastia. Affected individuals may also have partially developed female sex organs, a small or missing vas deferens.
Blood tests for various sex hormones (testosterone and its derivatives, anti-müllerian hormone, sex hormone-binding globulin, luteinizing hormone) are often performed. Prior to puberty, laboratory tests will reflect normal levels of testosterone, dihydrotestosterone, and luteinizing hormone. Following puberty, there may be normal or elevated testosterone with elevated levels of luteinizing hormone. Additionally, either during the first year of life or the following puberty, men will often have elevated levels of anti-müllerian hormone .
An abdomen/pelvic ultrasound is the most useful radiological test. Findings commonly demonstrate the absence of a uterus, impaired development of prostate and Wolffian duct derivatives, and undescended testes   . In rare instances where there is a palpable mass or otherwise clinically indicated, a magnetic resonance imaging may be used to visualize the pelvic anatomy.
Genetic analysis will show a normal 46 XY chromosomal pattern. Genetic defects in the androgen receptor (AR) gene cause androgen insensitivity syndrome by preventing the androgen receptors from functioning correctly. A mutation of the AR gene causes cells to be less responsive or refractory to androgens. Androgens and androgen receptors also play a role in hair growth and libido. Depending on the degree of mutation of the AR gene, an affected individual's sex characteristics can vary from mostly female to mostly male    . A DNA analysis of the androgen receptor gene will detect any mutations in the AR gene. The number of CAG repeats in exon 1 of the AR gene have been shown to be inversely proportional to the transcriptional activity of the androgen target gene; in other words, the greater the number of trinucleotide CAG repeats, the greater the degree of androgen insensitivity.
Treatment with testosterone suppressed serum luteinizing hormone levels and promoted mild virilizing effects. [ncbi.nlm.nih.gov]
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. [pacificschoolserver.org]
CLOSE Medical Disclaimer The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. [crm.diseaseinfosearch.org]
After puberty: normal or elevated testosterone, elevated LH. 46,XY karyotype DNA analysis of the androgen receptor gene Treatment of Androgen Insensitivity Syndromes Treatment of the Mild Androgen Insensitivity Syndrome (MAIS) Causal treatment of MAIS [urology-textbook.com]
Testosterone treatment that is started early may prevent some infertility. [coordinatedhealth.com]
Support Groups Androgen Insensitivity Syndrome Support Group (AISSG) — www.aissg.org Intersex Society of North America (ISNA) — www.isna.org Expectations (prognosis) Androgens are most important during early development in the womb. [coordinatedhealth.com]
Tests may include: Blood tests to check levels of male and female hormones Genetic tests such as karyotyping to check chromosomes Sperm count Testicular biopsy Pelvic ultrasound to check if female reproductive organs are present Outlook (Prognosis) Androgens [account.allinahealth.org]
Support Groups Androgen Insensitivity Syndrome Support Group (AISSG) -- www.aissg.org Intersex Society of North America (ISNA) -- www.isna.org Expectations (prognosis) Androgens are most important during early development in the womb. [indiatoday.in]
Support Groups Return to top Androgen Insensitivity Syndrome Support Group (AISSG) -- www.medhelp.org/www/ais/ Intersex Society of North America (ISNA) -- www.isna.org Outlook (Prognosis) Return to top Androgens are most important during early development [pacificschoolserver.org]
Expectations (prognosis) Androgens are most important during early development in the womb. [medical-dictionary-search-engines.com]
Reifenstein syndrome has been shown to have a heterogenous etiology, with some patients demonstrating a decreased number of normal receptors and others having receptors that are defective, as evidenced by their decreased affinity for dihydroterststerone [medigoo.com]
Etiology (Causes) of the Androgen Insensitivity Syndrome Different mutations of the androgen receptor gene, located on the X chromosome, lead to a reduced (partial) androgen response or complete lack of androgen response (PAIS or CAIS). [urology-textbook.com]
[…] hormone replacement therapy (HRT) and psychological support. [5, 7, 8] For individuals with androgen insensitivity syndrome, the standard of care is an orchidectomy to prevent possible malignant degeneration of the testes.  Pathophysiology The basic etiology [emedicine.medscape.com]
Etiology of nondisjunction in humans. Environ Mol Mutagen 1995; 25(Suppl 26):38-47.  Carotheres AD, Fillippi G. Klinefelter’s syndrome in Sardinia and Scotland: comparative studies of parental age and other aetiological factors in 47,XXY. [hawaii.edu]
Endocrine epidemiology of male breast cancer. Anticancer Res. 8, 845–850 (1988). 3 Thomas, D.B. et al. Breast cancer in men: risk factors with hormonal implications. Am. J. Epidemiol. 135, 734–748 (1992). 4 Rosenblatt, K.A. et al. [nature.com]
Epidemiology Incidence 1:20000 to 1:60000 Mild Androgen Insensitivity Syndrome (MAIS) Patients with a minimal androgen insensitivity syndrome (MAIS) are phenotypically male; the most common symptom is infertility. [urology-textbook.com]
Additional Contributors Arlan L Rosenbloom, MD Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida College of Medicine; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology Arlan [emedicine.medscape.com]
[…] syndrome (AIS) has 2 aspects: hormone replacement therapy (HRT) and psychological support. [5, 7, 8] For individuals with androgen insensitivity syndrome, the standard of care is an orchidectomy to prevent possible malignant degeneration of the testes.  Pathophysiology [emedicine.medscape.com]
This review focuses on the clinical features and molecular pathophysiology of AIS and explores the relationship of the molecular defects in the AR gene to their clinical expression. [hormones.gr]
Morris suggested the term testicular feminization, and by 1963 most of the essential pathophysiology of complete AIS was suspected. [t-vox.org]
In addition, the defective androgen receptor might have prevented suppressive effects of androgens on the Leydig cells. [ncbi.nlm.nih.gov]
Rapidly find the answers you need with separate sections on diseases and disorders, differential diagnosis, clinical algorithms, laboratory results, and clinical preventive services, plus an at-a-glance format that uses cross-references, outlines, bullets [books.google.de]
Prevention Prenatal testing is available. People with a family history of these conditions should consider genetic counseling. Testosterone treatment that is started early may prevent some infertility. [coordinatedhealth.com]
Prevention Prenatal testing is available. People with a family history of these conditions should consider genetic counseling. Testosterone treatment that is started early may prevent some infertility. References Donohoue P. [indiatoday.in]
Prevention Return to top Prenatal testing is available. People with a family history of these conditions should consider genetic counseling. Testosterone treatment that is started early may prevent some infertility. [pacificschoolserver.org]
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- Chen MJ, Vu BM, Axelrad M, et al. Androgen Insensitivity Syndrome: Management Considerations from Infancy to Adulthood. Pediatr Endocrinol Rev. 2015;12:373-87.
- Gottlieb B, Pinsky L, Beitel LK, Trifiro M. Androgen insensitivity. Am J Med Genet. 1999;89:210-7.
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