A challenging diagnosis of complete androgen insensitivity syndrome in a young Eritrean woman: a case report

doi:10.21203/rs.3.rs-4936279/v1

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Case Report

A challenging diagnosis of complete androgen insensitivity syndrome in a young Eritrean woman: a case report

https://doi.org/10.21203/rs.3.rs-4936279/v1

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Background:Androgen insensitivity syndrome is a rare X-linked disorder in which a 46xy individual fails to virilize normally owing to varying degrees of impairment in androgen receptor function. Androgen insensitivity syndrome manifests in a spectrum of phenotypes.

Case presentation: A 27-year-old Eritrean who identified as a female presented with a history of primary amenorrhea and dyspareunia. Physical examination revealed the absence of pubic and axillary hair. The patient was tall, measuring 1.84 cm, and had a 4 cm long blind-ended vaginal pouch. Ultrasonography revealed an absent uterus and fallopian tubes. Hormone analysis and Barr body test were performed. The patient underwent orchidectomy.

Conclusion: Androgen insensitivity syndrome presents a broad spectrum of phenotypes. Therefore, a high index of suspicion is crucial among healthcare professionals to enable prompt diagnosis prior to the assignment of gender.

Obstetrics & Gynecology

Androgen insensitivity syndrome

amenorrhea

dyspareunia

case report

inguinal hernia

Androgen insensitivity syndrome (AIS), formerly known as testicular feminization syndrome, is a fascinating and complex condition that affects 1 in 20,400 live births [1]. It is caused by varying degrees of impairment in androgen receptors, which are encoded by a gene located in the X chromosome. This impairment results in the failure of genetically male, 46xy individuals to virilize normally. AIS manifests with a wide range of clinical presentations. This variability is directly related to the degree of dysfunction in androgen receptors, which can range from complete receptor absence to a spectrum of residual functionality [2]. Complete androgen insensitivity syndrome, (CAIS) the focus of this case report, is more common than its partial counterpart. Most patients with CAIS identify as females, a fact that is influenced by their upbringings and societal norms. Despite their female phenotype, individuals with CAIS have 46xy karyotype and bilateral testes with serum testosterone concentrations typical of adult males. The SRY gene, located on the short arm of the Y chromosome, is responsible for encoding the testis-determining factor, which in turn affects male sex development and helps in the regression of female characteristics. Although the sex of an embryo is genetically predetermined at the time of fertilization, gonads go through a period of indifference where no morphological characteristics of either sex can be identified. Around the eighth week of gestation, gonads start to differentiate into male testes under the influence of the SRY gene of the Y chromosome. Moreover, the Sertoli cells of the male testes produce Mullerian inhibitory factor, which suppresses the development of the paramesonephric system that gives rise to the uterus, uterine tubes, and upper 1/3 of the vagina.

The diagnosis of CAIS is made clinically with some biochemical support. Confirmation lies in genetic sequencing of the coding region of the responsible gene. The growth pattern and body habitus of CAIS are that of an average female with normal breast development and a blind vaginal pouch. Individuals lack pubic and axillary hair. Interestingly, they typically achieve a final height comparable to that of average male, suggesting that androgen insensitivity does not impact linear growth [3].

This publication aims to underscore the need for increased awareness and understanding of AIS. Given the relative infrequency of AIS, further research is essential to enhance healthcare professionals' knowledge and readiness to manage patients with this condition. Individuals with AIS need a well-integrated and organized form of management, which can be provided only in facilities equipped with healthcare workers trained in handling intersex.

A 27-year-old Eritrean woman presenting with the chief complaint of primary amenorrhea, dyspareunia and infertility sought care at our Gynecology outpatient department in December 2020. Physical examinations revealed tall stature, underdeveloped breasts with a pale areola and a blind vaginal pouch. Notably, she lacked pubic and axillary hair. Bilateral and mobile groin masses measuring 3x2 cm indicative of undescended testis were palpable in the inguinal canal. The patient had well-developed labia with a short blind loop vagina measuring 4 cm. A small fistulous tract is identified at the tip of the vagina. During the speculum examination, the cervix could not be visualized. The patient was tall, with a height of 1.84 meters, consistent with the average male height range.

There was no similar history in the family. Pelvic ultrasonography and per rectal examination revealed the absence of a uterus and fallopian tubes. The hormonal analysis revealed follicle-stimulating hormone (4.03 IU/L), luteinizing hormone (25.7I U/L), estradiol (less than 5 pg/L), and testosterone (2.50 ng/mL). Unfortunately, the limited resources at our facility precluded us from performing karyotyping, the definitive diagnostic test for AIS. However, a Barr body test conducted on a buccal smear provided suggestive evidence of a 46, XY karyotype.

Counseling a patient with AIS requires a sensitive and culturally appropriate approach. We conducted multiple sessions over several weeks. Explaining the diagnosis and addressing her concerns about infertility were crucial aspects of the counseling process. She had been married for seven years and longed to have children. Her upbringing, cultural practices, and faith were taken into consideration while counseling. Throughout the counseling sessions, the patient's emotional journey and the societal pressures she faced became evident. She requested the presence of her father and wished for her diagnosis to remain confidential, highlighting the stigma and fear associated with her condition. Her main concern in learning the diagnosis is whether she will ever be able to conceive, a deeply personal and culturally significant issue. The patient, originating from a social environment where childbearing holds significant weight for women, exhibited emotional distress. Notably, she informed her husband of the potential infertility diagnosis and offered him the option of remarrying another woman. This decision reflects the complex dynamics of her personal relationships and cultural context.

Following discussion of the risks and benefits of orchidectomy, including the potential for malignant transformation of the testes, the patient elected to proceed with the surgery. After two weeks’ sessions of counseling and education, the patient underwent bilateral orchidectomy.

The histopathology report revealed findings consistent with seminiferous tubules with a collapsed ductal system and few spermatogonia in the peripheral area. No sign of malignancy was noted.

Following surgery, the importance of estrogen replacement therapy (ERT) is discussed in detail, emphasizing its role in maintaining bone health and secondary sexual characteristics. While financial limitations presented a challenge, the patient clearly understood the benefits of ERT and expressed a strong desire to pursue this treatment option.

Given the constraints imposed by our limited resources, we were unable to provide the patient with comprehensive care, including further psychological counseling and potential surgical interventions such as vaginal reconstructive surgery. Unfortunately, resource limitations also hinder the patient's ability to achieve her deeply cherished desire for childbearing and motherhood. Despite these challenges, the patient expressed relief at finally understanding her diagnosis and a newfound hope to navigate her future.

CAIS requires a multidisciplinary approach to care, with psychological support playing a central role. Once the diagnosis of AIS is established, there should be gradual but complete disclosure to patients about their condition. Age-appropriate counseling and education are recommended. There is also a general need to raise awareness among affected individuals, families, and the health care system in general, as patients with AIS often tend to suffer from psychological trauma and identity issues [4–8].

Support groups and counseling sessions should be offered to all patients with AIS.

Education among family members will not only help raise awareness but other potential carriers in the family can also be identified, as AIS has a broad spectrum of phenotypes with a relatively high rate of recurrence in subsequent pregnancies.

Other components of management can be broadly classified into medical and surgical care. The ultimate surgical care for patients with AIS is orchidectomy [9]. This is done to prevent malignant transformation of the testicles; however, the exact timing of orchidectomy is highly debated. Delaying orchidectomy until the postpubertal period is believed to help in the spontaneous production of estrogen from the peripheral aromatization of testosterone, hence allowing the development of secondary sexual characteristics. [10, 11]

Pre-pubertal malignancy in patients with CAIS is extremely rare. Surgical management of AIS may also encompass a staged approach. Dilator therapy can be employed as an initial intervention, followed by potential vaginal reconstructive surgery to address the blind vaginal pouch. This two-step approach aims to optimize the sexual function of patients. [12, 13]

Medical care for AIS involves the use of hormone replacement therapy with estrogen. This, in the long run, prevents osteoporotic bone degeneration. The absence of a uterus also validates the sole use of estrogen, as there is no fear of endometrial hyperplasia. Although the use of progesterone is still debated, its addition is theoretically believed to counteract the action of estrogen in breast tissues, and is believed to offer some degree of protection against some forms of breast cancer.

AIS individuals who wish to conceive a child can do so with the help of a surrogate mother and donor eggs fertilized with the partner's sperm or donor sperm.

AIS individuals require a coordinated and multidisciplinary approach to health care, with psychological input as the most crucial aspect of management. Individuals with AIS are often misgendered as male due to the presence of a Y chromosome. However, this may not always be true, as gender is the way an individual self-identifies and one’s concept of sexuality.

In conclusion, we emphasize the importance of ongoing healthcare professional education regarding AIS to enhance recognition of the diverse phenotypic presentations. This improved awareness will ensure patients with AIS receive appropriate diagnoses delivered with sensitivity and emotional support. Furthermore, we advocate for the establishment of a comprehensive referral network for individuals with AIS, connecting them with healthcare systems equipped for thorough diagnosis using all necessary facilities and offering a full spectrum of potential treatment options.

AIS

Androgen insensitivity syndrome

CAIS

Complete androgen insensitivity syndrome

ERT

Estrogen replacement therapy

Ethical approval and consent to participate

Written informed consent was acquired from the patient to publish this case report and any accompanying images. The confidentiality and rights of the patient were maintained at all times.

Consent for publication

Written informed consent was obtained from the patient for publication of the case report and the accompanying Images

Competing Interests

The authors declare that they have no competing interests.

Funding

This case review did not receive any grants.

Authors' contribution

SM drafted the manuscript, while MB and ST provided critical review. All authors were directly involved in the patient's care and counseling. All authors read and approved the final manuscript.

Acknowledgment

Not applicable

Availability of data and materials

The authors declare that the data supporting the findings of this case report are available within the article.

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Kathrins M, Kolon TF Malignancy in disorder of sex development. Transl Androl Urol 2016 Oct. 5(5): 794–798
Purves JT, Miles-Thomas J, Migeon C, Gearhart JP (2008) Complete androgen insensitivity: the role of the surgeon. J urol 180:1496
Ismail-Pratt IS, Bikoo M, Liao LM et al (2007) normalization of the vagina by dilator treatment alone in complete androgen insensitivity syndrome and Mayer-Rolitansky-Kuster-Hauser syndrome. Hum Repord. ; 22:2020

The authors declare no competing interests.

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A challenging diagnosis of complete androgen insensitivity syndrome in a young Eritrean woman: a case report

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