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 [1] [2]:

• Small and/or abnormal male genitals (e.g., small penis, small scrotum, incompletely closed or undescended testicles) [3]
• Gynecomastia
• 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.

• Infertility

  The patient was diagnosed with infertility due to oligonecrosprmia. [garj.org]

  […] syn·drome ( rī'fĕn-stīn ), [MIM*312300 and MIM*313700] partial androgen sensitivity; a familial form of male pseudohermaphroditism characterized by varying degrees of ambiguous genitalia or hypospadias, postpubertal development of gynecomastia, and infertility [medical-dictionary.thefreedictionary.com]

  It can be difficult for men with the gene to pass it on, since they are often infertile. [allthingsvagina.com]

  A male with Reifenstein syndrome can have a normal lifespan and be totally healthy, with the exception of infertility and possible psychological problems related to gender identity. [medical-dictionary-search-engines.com]

• Virilization

  Some authors recommend early bilateral orchiectomy to avoid further virilization at puberty. [urology-textbook.com]

  Defects of the androgen receptor in 46,XY individuals cause aberrant virilization that varies from a female phenotype to men with minor defects. [ncbi.nlm.nih.gov]

• Falling

  It should be emphasized that the disorders of androgen sensitivity represent a spectrum rather than 6 discrete diseases, and some affected persons will have features that fall between the phenotypes described. 1. [t-vox.org]

  But the condition can quickly progress to shock, which is marked by falling blood pressure and body temperature, confusion, clotting abnormalities and bleeding into the skin. Blood poisoning is a medical emergency and can be fatal if left untreated. [naturallivingcenter.net]

  […] kiss for the first time later.. .attempt initial intercourse later and actually perform it later.. .Furthermore they have intercourse with a second partner later.. .and the number of their coital partners is fewer.. .chromatin positive men belatedly fall [hawaii.edu]

  The corresponding false positive rates for a detection rate of 85% fall to 1.8% and 4.2% if the triple test replaces the quadruple test, and to 2.4% and 5.1% if the double test is used. [scrigroup.com]

• Tall Stature

  Clinically, the syndrome is characterized by findings of small, firm testes and symptoms of androgen deficiency but they may also present with azoospermia, tall stature and bilateral painless gynecomastia. [sciepub.com]

  […] endocrine disorder E34.4 Constitutional tall stature E34.5 Androgen insensitivity syndrome E34.51 Complete androgen insensitivity syndrome E34.52 Partial androgen insensitivity syndrome E34.8 Other specified endocrine disorders E34.9 Endocrine disorder [icd10data.com]

  A condition in which a person has one Y-chromosome and two (or more) X-chromosomes, usually characterized by low testosterone levels, small testicles, tall stature and long limbs, sparse body hair, and infertility. [medical-dictionary.thefreedictionary.com]

• Trisomy 21

  Risk of trisomy 21 in offspring of patients with Klinefelter’s syndrome. Lancet 357: 2104, 2001. PubMed CrossRef Google Scholar 51. Morel F, Bernicot I, Herry A, Le Bris MJ, Amice V, De Braekeleer M. [link.springer.com]

  […] positive correlation between maternal age and maternal meiotic I errors only.14 That maternal and paternal errors of gametogenesis were almost equally responsible for causing the 47,XXY karyotype contrasts with most cases of autosomal aneuploidy (ie, trisomy [jamanetwork.com]

• Heart Disease

  Mortality from ischemic heart disease, however, was reduced. Evaluate and optimize control of diabetes mellitus if necessary. Assess for long-term complications of diabetes (atherosclerosis, renal disease). [accessanesthesiology.mhmedical.com]

  Avoid sudden or prolonged exposure to extreme temperatures in baths, wraps, saunas, or other forms of hydrotherapy, particularly with heart disease, lung disease, or if pregnant. [naturallivingcenter.net]

  Treatment There is no cure for this disease. [scrigroup.com]

• Hypertension

  Failure to menstruate or to develop secondary sexual traits such as breasts or body hair, hypertension, and hypokalemia are characteristics. 3-Beta Hydroxysteroid Dehydrogenase Deficiency (3-Beta-HSD): Presents clinically at birth and leads to death within [accessanesthesiology.mhmedical.com]

  Munich MARCELLA RIETSCHEL 1898 Department of Psychiatry 1899 SOPHIE NICOLE Germany 1901 ALFRIED KOHLSCHÜTTER 1918 GIORA Z FEUERSTEIN Department of Dermatology Venerology and Allergy University Hospital SchleswigHolstein 1925 Division of Nephrology and Hypertension [books.google.de]

  Patients should avoid obesity because it increases already high risks of hypertension and insulin resistance. Patients with short stature require fewer calories than those of normal height. [scrigroup.com]

• Osteoporosis

  Lifestyle changes Leading a healthy lifestyle, including eating a healthy diet and exercising regularly, can help reduce your chances of getting conditions like type 2 diabetes, osteoporosis, and cardiovascular disease. [nhs.uk]

  They are at high risk for osteoporosis and so should take estrogen replacement therapy. The gene for the syndrome is on the X chromosome in band Xq11-q12. The gene codes for the androgen receptor (also called the dihydrotestosterone receptor). [rxlist.com]

  Osteoporosis may lead to vertebral collapse and even scoliosis. Unless treated with exogenous testosterone starting at puberty, patients can become obese and develop diabetes mellitus. [accessanesthesiology.mhmedical.com]

• Fracture

  Vertebral body fractures can result in decreased mobility of spine and/or compression of nerves or spinal cord. Any neurologic abnormalities should be documented preoperatively. Cervical spine mobility should be evaluated. [accessanesthesiology.mhmedical.com]

  らを実験台にして死亡 Celsus ケルスス Celsus kerion ケルスス禿瘡 Cerenkov チェレンコフ Cerenkov radiation チェレンコフ放射 Chaddock チャドック Chaddock reflex チャドック反射 Chagas シャーガス Chagas' disease シャーガス病 CarlosJustiniano Ribeiro Chagas （1879 - 1934） a Brazilian physician Chance チャンス Chance fracture [jams.med.or.jp]

  […] mass.18,56 Testosterone replacement treatment before the age of 20 years can improve bone mass to normal values, whereas testosterone replacement therapy begun later produces no significant increase but may help prevent further bone loss and possibly fractures [jamanetwork.com]

  Osteoporosis CAIS women appear to have a higher than average risk of thinning of the bones (osteoporosis) but possibly not with an associated tendency to increased fracture. [bionity.com]

• Suggestibility

  These findings provide evidence for X-linkage of this disorder, and suggest that the mutations that give rise to this phenotype are probably allelic to the mutations of the androgen receptor that cause testicular feminization. [ncbi.nlm.nih.gov]

  Two types have been suggested: Type I refers to the familial incomplete male pseudohermaphrodism and Type II is the autosomal recessive. Undetermined; however, it is certainly common because of its often mild and variable features. [accessanesthesiology.mhmedical.com]

• Confusion

  At birth, the baby may have ambiguous genitals, which leads to confusion over the baby's sex. The syndrome is passed down through families (inherited). Women are not affected but may carry the gene. [ufhealthjax.org]

  At birth, the infant may have ambiguous genitalia, leading to confusion of the baby’s sex. [luriechildrens.org]

  People with confusing sexual organs have normally been subjected to surgery during infancy. Surgery on the sexual parts is necessary only when it is essential for the health of the child. [syndromespedia.com]

  At birth, the baby may have ambiguous genitals, which leads to confusion over the baby’s sex. The syndrome is passed down through families (inherited). Women are not affected but may carry the gene. [coordinatedhealth.com]

  At birth, the baby may have ambiguous genitals, which leads to confusion over the baby's sex. The syndrome is passed down through families (inherited). [account.allinahealth.org]

• Stroke

  Use cautiously with asthma or a history of ulcers or stroke. Avoid if pregnant. Children should not take doses larger than what is commonly found in foods. [naturallivingcenter.net]

• Microphallus

  The phenotype in 11 affected family members ranged from a minimal defect in virilization in two (microphallus and bifid scrotum), to a more severe abnormality in eight (perineoscrotal hypospadias) and to almost complete male pseudohermaphroditism in one [nejm.org]

  In its most severe form, the male pseudohermaphrodite may have hypospadias, cryptorchism, bifid scrotum, microphallus, atrophic ectopic testes, pseudovagina, gynecomastia, and absent vas deferens. [accessanesthesiology.mhmedical.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 [4].

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 [5] [6] [7]. 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 [8] [9] [10] [11]. 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.

• Testosterone Increased

  If the gonads are testes, there will be an increase in the level of serum testosterone in response to the hCG, regardless of testicular descent.[1] The magnitude of the testosterone increase can help differentiate between androgen resistance and gonadal [en.wikipedia.org]

• Hyperglycemia

  Perioperative control of blood glucose levels to prevent hypoglycemia or severe hyperglycemia. Difficult intubation if cervical spine mobility is limited. [accessanesthesiology.mhmedical.com]

• Erythrocytosis

  […] has not received adequate evaluation.63,64 Weight gain may occur during testosterone replacement therapy, due to the accumulation of lean body mass and fluid.64 Mild acne may also occur.64 Sleep apnea may occasionally develop in older men and cause erythrocytosis [jamanetwork.com]

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]

There are two main types of clinical studies: Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. [rarediseases.info.nih.gov]

Treatment guidelines are still evolving. Possible treatments for PAIS include: Surgery may be done to reduce breasts, repair undescended testicles, or reshape the penis to provide a more male appearance. [limamemorial.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]

Home Patient Information Overview Historical Perspective Classification Pathophysiology Causes Differentiating Androgen insensitivity syndrome from other Diseases Epidemiology and Demographics Risk Factors Screening Natural History, Complications and Prognosis [wikidoc.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. [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]

Treatment and prognosis These patients have an increased incidence of malignancy in the undescended testes: seminoma gonadoblastoma Mayer-Rokitansky-Küster-Hauser syndrome has female karyotype with normal female genitalia, and ovaries, but the uterus [radiopaedia.org]

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 minimal impairment, partial response or complete lack of androgen response (androgene resistance). [urology-textbook.com]

Disorders of sexual development: etiology, evaluation, and medical management. In: Partin AW, Dmochowski RR, Kavoussi LR, Peters CA, eds. Campbell-Walsh-Wein Urology. 12th ed. Philadelphia, PA: Elsevier; 2021:chap 48. Reviewed By: Anna C. [ufhealth.org]

Sasco AJLowenfels ABPasker-De Jong Not Available Epidemiology of male breast cancer: a meta-analysis of published case-controlled studies and discussion of selected etiological factors. Int J Cancer. 1993;53538- 549Google ScholarCrossref 41. [jamanetwork.com]

Endocrine epidemiology of male breast cancer. Anticancer Res. 8, 845–850 (1988). CAS PubMed Google Scholar Thomas, D.B. et al. Breast cancer in men: risk factors with hormonal implications. Am. J. Epidemiol. 135, 734–748 (1992). [nature.com]

Jump to navigation Jump to search Androgen insensitivity syndrome Microchapters Home Patient Information Overview Historical Perspective Classification Pathophysiology Causes Differentiating Androgen insensitivity syndrome from other Diseases Epidemiology [wikidoc.org]

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]

Molecular and Systemic Pathophysiology Androgens play a crucial role in various stages of male development (masculinization and virilization). [link.springer.com]

Jump to navigation Jump to search Androgen insensitivity syndrome Microchapters Home Patient Information Overview Historical Perspective Classification Pathophysiology Causes Differentiating Androgen insensitivity syndrome from other Diseases Epidemiology [wikidoc.org]

Pathophysiology Underlying defect is the partial deficiency of androgen receptors (AR), causing partial androgen resistance, and not because of a lack of androgen synthesis. [accessanesthesiology.mhmedical.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. [9] Pathophysiology [emedicine.medscape.com]

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]

In addition, the defective androgen receptor might have prevented suppressive effects of androgens on the Leydig cells. [ncbi.nlm.nih.gov]

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]

Secondary Prevention Cost-Effectiveness of Therapy Future or Investigational Therapies Case Studies Case #1 Androgen insensitivity syndrome On the Web Most recent articles Most cited articles Review articles CME Programs Powerpoint slides Images American [wikidoc.org]

1. Hannema SE, Scott IS, Rajpert-De Meyts E, Skakkebaek NE, Coleman N, Hughes IA. Testicular development in the complete androgen insensitivity syndrome. J Pathol. 2006;208:518–27.
2. Gottlieb B, Pinsky L, Beitel LK, Trifiro M. Androgen insensitivity. Am J Med Genet. 1999;89:210-7.
3. Van Batavia JP, Kolon TF. Fertility in disorders of sex development: A review.J Pediatr Urol. 2016 Nov 3. [Epub ahead of print] Review
4. Sinnecker GH, Hiort O, Nitsche EM, Holterhus PM, Kruse K. Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group. Eur J Pediatr. 1997;156:7–14.
5. Galani, A, Kitsiou-Tzeli S, Sofokleous C, Kanavakis E, Kalpini-Mavrou A. Androgen insensitivity syndrome: clinical features and molecular defects. Hormones (Athens). 2008; 7:217-29.
6. Quigley CA, Bellis AD, Marschke KB, el-Awady MK, Wilson EM, French FS. Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev.1995;16:271-321.
7. Turan V, Yeniel O, Ergenoğlu M, Terek C, Ulukuş M. Incomplete androgen insensitivity (Reifenstein syndrome) - a case report.J Turk Ger Gynecol Assoc. 2010;11:110-2.
8. Griffin JE. Androgen resistance--the clinical and molecular spectrum.N Engl J Med. 1992;326:611.
9. Chen MJ, Vu BM, Axelrad M, et al. Androgen Insensitivity Syndrome: Management Considerations from Infancy to Adulthood. Pediatr Endocrinol Rev. 2015;12:373-87.
10. Gottlieb B, Pinsky L, Beitel LK, Trifiro M. Androgen insensitivity. Am J Med Genet. 1999;89:210-7.
11. Hiort O. Clinical and molecular aspects of androgen insensitivity. Endocr Dev. 2013;24:33-40.