Complete Androgen Insensitivity Syndrome

• Genetically female.
• Presents with primary amenorrhoea like CAIS and also normal external female genitalia.
• Normal secondary sexual characteristics.
• Genetic condition which causes the agenesis of the mullerian ducts.

• Most commonly caused by 21-hydroxylase deficiency.
• Milder cases may present later in life with primary amenorrhoea.
• Unlikely due to presence of other hormonal imbalances that would be noticeable.

References

6. Michala L, Goswami D, Creighton SM, Conway GS. Swyer syndrome: presentation and outcomes. BJOG : an international journal of obstetrics and gynaecology. 2008;115(6):737-41. Epub 2008/04/16.

7. Morcel K, Camborieux L, Guerrier D. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Orphanet journal of rare diseases. 2007;2:13. Epub 2007/03/16.

8. Mustafa R, Hashmi HA, Baqai Z. Complete androgen insensitivity syndrome in an X Y female. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2006;16(8):563. Epub 2006/08/11.

9. Okada T, Sasaki S, Honda S, Miyagi H, Minato M, Todo S. Irreducible indirect inguinal hernia containing uterus, ovaries, and Fallopian tubes. Hernia : the journal of hernias and abdominal wall surgery. 2011. Epub 2011/01/08.

1. Gottlieb B, Beitel LK, Trifiro MA. Androgen Insensitivity Syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. GeneReviews. Seattle (WA)1993.

2. Holmes-Walker DJ, Conway GS, Honour JW, Rumsby G, Jacobs HS. Menstrual disturbance and hypersecretion of progesterone in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clinical endocrinology. 1995;43(3):291-6. Epub 1995/09/01.

3. Hughes IA, Deeb A. Androgen resistance. Best practice & research Clinical endocrinology & metabolism. 2006;20(4):577-98. Epub 2006/12/13.

4. Kumar P, Clarks M. Kumar & Clark’s Clinical Medicine. Seventh ed. Edinburgh: Elsevier; 2009. p 1360. pg. 1014

5. Mallin SR. Congenital adrenal hyperplasia secondary to 17-hydroxylase deficiency. Two sisters with amenorrhea, hypokalemia, hypertension, and cystic ovaries. Annals of internal medicine. 1969;70(1):69-75. Epub 1969/01/01.

Introduction

Complete Androgen

Insensitivity in Males

• Scale of disease from mild to complete.
• Is present in males with 46 XY genotype.
• Is difficult to diagnose because of the lack of symptoms.

By Stuart Taylor and Sean McKeon

In the

Clinic

• Occurs in genetic males.
• Other name for condition is 'Pure gonadal dysgenesis'.
• Patients typically have normal external genitalia and Mullerian ducts.
• Gonads are defective and cannot produce oestrogens which is only detected at puberty.

Mullerian Agenesis-MRKH

Swyer Syndrome

Congenital Adrenal Hyperplasia

Signs

Symptoms

Treatment /Management

Amenorrhoea and

delayed puberty

Branches

Symptom

Surgery

Amenorrhoea + delayed puberty

(cc) photo by theaucitron on Flickr

Abnormal

Swelling

Psychological

• Primary amenorrhoea as patient has never menstruated.

• Differentials of amenorrhoea may be:
• Primary ovarian failure
• Decrease in gonadotrophin levels

Scanty pubic hair

Striking, tall and lean

Structural

defects

Lack of Axillary hair?

HRT

• Abnormal swelling of the labia in the female.

• Differentials:
• Testicular herniation
• Inguinal bowel herniation
• Irritation or infection

Differential Diagnosis Tree

• Absence of female internal duct system which includes the uterus, ovaries and fallopian tube.
• 'Short' vagina 2" in depth compared to 3 to 4" and is blind ended.
• Presence of testes located in the abdomen.

• May be more likely a sign than a symptom.

• Women unlikely to complain that they haven't got hairy armpits.

Sometimes abnormal characteristics due to hormonal genetic differences.

How is the condition diagnosed?

Types of Androgen Insensitivity Syndrome- and why there are different types

• Fig. 1. Schematic representation of a grading scheme for clinical classification of AIS. Grades are numbered I through 7 in order of increasing severity (more defective masculinization). Grade 1: normal masculinization in utero; grade 2: male phenotype with mild defect in masculinization (e.g., isolated hypospadias); grade 3: male phenotype with severe defect in masculinization—small penis, perineoscrotal hypospadias, bifid scrotum or cryptorchidism; grade 4: severe genital ambiguity— clitoral-like phallus, labioscrotal folds, single perineal orifice; grade 5: female phenotype with posterior labial fusion and clitoromegaly; grade 6/7: female phenotype (grade 6 if pubic hair present in adulthood, grade 7 if no pubic hair in adulthood). (Adapted from Quigley CA, DeBellis A, Marschke KB, El-Awady MK, Wilson EM, French FS. Androgen receptor defects: historical, clinical, and molecular perspectives. Endocrine Rev 1995; 1 6(3):282; with permission.)

• Complete androgen insensitivity syndrome (CAIS): typical female external genitalia present
• Partial androgen insensitivity syndrome (PAIS): predominantly female, predominantly male or ambiguous external genitalia
• Mild androgen insensitivity syndrome (MAIS): typical male external genitalia

• Analysis of the following may occur:
• Karyotype test or fluorescent in situ hybridization

• Levels of testosterone and

dihydrotestosterone (DHT)

• Mutation analysis of the

androgen receptor gene

What happens after diagnosis-Treatment options

• Surgery- usually gonadectomy/orchidectomy (uncertainty over best timing), vaginal lengthening procedures, cosmetic genital reconstructive surgery.

• HRT- hormone replacement therapy: CAIS= oestrogen replacement, initial low dose, progesterone if appropriate, PAIS= same treatment if female identity, if male DHT may be administered.

• Psychological support- most important aspect from patient’s perspective. Parental support and genetic counselling can also be given. Primary care practitioner or pediatric endocrinologist can coordinate care as part of multi-disciplinary team.