Update on the Pathophysiology and Risk Factors for the Development of Malignant Testicular Germ Cell Tumors in Complete Androgen Insensitivity Syndrome

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.

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“…Annual US follow-up of labioscrotal and/or inguinal gonads is recommended. For abdominal gonads monitoring MRI is more helpful (50).…”

Section: Gonadal Tumor Risk In Aismentioning

confidence: 99%

Androgen insensitivity syndrome: a review

Batista¹,

Costa²,

Rodrigues³

et al. 2018

Archives of Endocrinology and Metabolism

129

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“…An overview of reported cases in children and adults since 2000 is presented in Table 1; before that time, a molecular genetic diagnosis was most often not available and published series mostly reported on a mix of clinical diagnoses, including also many cases with gonadal dysgenesis, who are known to have a much higher risk [12]. Whereas the risk for GGCC has been estimated at less than 1% in childhood, uncertainty prevails concerning this risk in retained gonads after adolescence [13]. Therefore, it has been recommended to perform gonadectomy towards the end of puberty, allowing for spontaneous pubertal (breast) development, through the peripheral conversion of excess testosterone into oestradiol [1, 14, 15].…”

Section: Introductionmentioning

confidence: 99%

Management of Gonads in Adults with Androgen Insensitivity: An International Survey

et al. 2018

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Background: Complete and partial androgen insensitivity syndrome (CAIS, PAIS) are associated with an increased risk of gonadal germ cell cancer (GGCC). Recent guidelines recommend gonadectomy in women with CAIS in late adolescence. Nevertheless, many adult women prefer to retain their gonads. Aims: This study aims to explore attitudes towards gonadectomy in AIS in centres around the world, estimate the proportion of adults with retained gonads and/or who developed GGCC, and explore reasons for declining gonadectomy. Methods: A survey was performed among health care professionals who use the International DSD Registry (I-DSD). Results: Data were provided from 22 centres in 16 countries on 166 women (CAIS) and 26 men (PAIS). In CAIS, gonadectomy was recommended in early adulthood in 67% of centres; 19/166 (11.4%) women refused gonadectomy. Among 142 women who had gonadectomy, evidence of germ cell neoplasm in situ (GCNIS), the precursor of GGCC, was reported in 2 (1.4%) out of 8 from whom pathology results were formally provided. Nine out of 26 men with PAIS (34.6%) had retained gonads; 11% of centres recommended routine gonadectomy in PAIS. Conclusion: Although development of GGCC seems rare, gonadectomy after puberty is broadly recommended in CAIS; in PAIS this is more variable. Overall, our data reflect the need for evidence-based guidelines regarding prophylactic gonadectomy in AIS.

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“…MRI has been shown to be superior but it is not cost-effective for surveillance [11]. Also, classical tumor markers of testicular germ cell tumors, aFP and BHCG are of limited use due to their rare expression in seminomas that encounter the main portion of germ cell tumors in androgen insensitivity syndromes [12].…”

Section: Discussionmentioning

confidence: 99%

Partial androgen insensitivity syndrome in a 68-year-old patient

Sezgin¹,

Dönmez²,

Dirican

et al. 2019

Endocr J

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Partial androgen insensitivity syndrome (PAIS) is a form of disorders of sexual development. Besides the issues of gender assignment, the fate of gonads in these patients poses a challenging problem. Debate still remains on the need and/or timing of gonadectomy in either complete or partial androgen insensitivity syndromes. In this case report, we present a 68year-old patient who was raised as a woman, stayed married for 45 years and admitted to our endocrinology department with complaint of male type hair distribution after initial examination following move to a nursing home. Physical examination revealed no breast development, a phallus of 6 cm, labia majoras that include testes and a blind ending vagina. Chromosomal analysis confirmed 46,XY with intact SRY and AZF regions. Pelvic ultrasonography and magnetic resonance imaging results indicated testicular tissue in labia majoras in addition to a rudimentary prostate. Gonadectomy was not offered to the patient due to lacking evidence of benefit in this age group and considering possible hormonal side effects. Our patient might be the oldest patient to be diagnosed with PAIS. Treatment and follow-up protocols for adults with PAIS are not standardized and therefore these patients should be individually evaluated and treated. Risks and benefits of surgery should be kept in mind when suggesting gonadectomy.

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Update on the Pathophysiology and Risk Factors for the Development of Malignant Testicular Germ Cell Tumors in Complete Androgen Insensitivity Syndrome

Cited by 61 publications

References 51 publications

Androgen insensitivity syndrome: a review

Androgen insensitivity syndrome: a review

Management of Gonads in Adults with Androgen Insensitivity: An International Survey

Partial androgen insensitivity syndrome in a 68-year-old patient

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