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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 11  |  Issue : 4  |  Page : 232-235

Complete androgen insensitivity syndrome: A rare case report


1 Professor, Department of Pathology, Dr D.Y Patil Medical College, Hospital and Research Centre, Dr. D.Y Patil Vidyapeeth, Pune, Maharashtra, India
2 Resident, Department of Pathology, Dr D.Y Patil Medical College, Hospital and Research Centre, Dr. D.Y Patil Vidyapeeth, Pune, Maharashtra, India
3 Associate Professor, Department of Pathology, Dr D Y Patil Medical College, Hospital and Dr D Y Patil Vidyapeeth, Pune, Maharashtra, India
4 Professor and HOD, Department of Pathology, Dr D Y Patil Medical College, Hospital and Dr D Y Patil Vidyapeeth, Pune, Maharashtra, India

Date of Submission22-Aug-2022
Date of Decision21-Sep-2022
Date of Acceptance23-Sep-2022
Date of Web Publication29-Oct-2022

Correspondence Address:
Yaminy Pradeep Ingale
I-302, Dwarka Suncrest Phase 3, Near Kapse Lawns, Rahatani, Pune - 411 017, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/NJCA.NJCA_144_22

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  Abstract 


Androgen receptor gene mutations on Xq12, which also have a 46XY karyotype abnormality, are the root cause of the X-linked uncommon recessive disorder of sex development known as androgen insensitivity syndrome (AIS). Complete AIS existed as a female, with normal breast, no uterus, ovaries, and fallopian tube with a blind-ending vagina but the presence of bilateral undescended testis either in the inguinal canal, abdomen, or labioscrotal junction and elevated testosterone levels. This was a rare case of a 22-year-old female patient who presented with primary amenorrhea. Ultrasonography showed gonads in the mid parts of inguinal canals on both sides, reaching up to the superficial ring. On investigation, increased in level of serum testosterone, follicle-stimulating hormone along with the luteinizing hormone was seen. AIS is actually very disturbing to individuals and families, so close collaboration between radiologist, pathologist, treating consultants, and psychiatrists are required for the proper management.

Keywords: Complete androgen insensitivity syndrome, gonads, puberty


How to cite this article:
Kambale T, Patel P, Ingale YP, Gore C. Complete androgen insensitivity syndrome: A rare case report. Natl J Clin Anat 2022;11:232-5

How to cite this URL:
Kambale T, Patel P, Ingale YP, Gore C. Complete androgen insensitivity syndrome: A rare case report. Natl J Clin Anat [serial online] 2022 [cited 2023 Feb 6];11:232-5. Available from: http://www.njca.info/text.asp?2022/11/4/232/359874




  Introduction Top


The androgen receptor gene on Xq12, which also possesses a 46XY karyotype abnormality, is the uncommon recessive sex development disorder known as androgen insensitivity syndrome (AIS).[1] According to the degree of genetic masculinization, it is divided into complete, mild, or partial AIS. Complete AIS is presented as that of a typical female, with normal breast appearance, no uterus, no ovaries, and fallopian tube with the blind-ending vagina, but the presence of bilateral undescended testis either in the inguinal canal, abdomen, or labioscrotal junction and elevated testosterone levels. Complete AIS, a rare condition that affects 2 to 5 cases out of every 100,000 genetically male people, and partial AIS, which affect 5 to 6 cases out of every 100,000 genetically male people.[2] This was a rare and interesting case of complete androgen sensitivity syndrome.


  Case Report Top


A 22-year-old patient phenotypically presented as female came with complaints of primary amenorrhea to the outpatient department of Dr. D. Y. Patil Medical College, Pimpri, Pune. There was no history of the consanguineous marriage of parents or any similar type of presentation in the family or in first-degree relatives. Clinical examination revealed normal intellectual function with a height of 168 cm and weight of 58 kg with no hoarseness of voice. By Tanners Stage II (breast bud palpable under the areola) and Tanners Stage III (genital and axillary hair growth), the patient exhibited underdeveloped secondary sexual features (sparse axillary and pubic hairs).

On per vaginal findings, there was a short blind-ending vagina (3 cm), a cervix that could not be visualized per speculum examination, a small clitoris, and well-developed labia. Bilateral solitary swelling of size 2 cm × 3 cm on the right inguinal canal and 2 cm × 2 cm on the left inguinal canal were palpated, which were soft, freely mobile, not tender on palpation, and non reducible. The cough impulse test, which was done, is negative.

Routine tests were within the normal limits, and serological special tests showed serum testosterone 162.22 ng/dL, follicle-stimulating hormone (FSH) 38.55 mUI/mL, luteinizing hormone (LH) 40.04 mUI/mL, and anti-Mullerian hormone 6.47 μg/L.

Ultrasonography examination showed gonads in the mid parts of inguinal canals on both sides, reaching up to the superficial ring. Both the gonads carry the testicular signature and are accompanied by epididymis and cord-like structures at the cranial end of the respective testis. Testis showed somewhat homogeneous echogenicity and a few 2 mm diameter tiny cystic areas with no mass lesion or calcification [Figure 1].
Figure 1: Ultrasonography showing both the gonads in mid parts of the inguinal canal on both sides reaching up to the superficial ring and both the gonads carrying testicular signature (Blue arrow: right testis, Yellow arrow: left testis)

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The karyotype was done, confirming the 46 XY pattern [Figure 2].
Figure 2: Karyotyping mapping showing 46 XY Karyotype (Blue arrow: X chromosome, Black arrow: Y Chromosome)

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In order to reduce the chance of cancer, the patient had bilateral orchidectomy, which involved the removal of both undescended testicles. This was done after the patient, and her parents received counseling. The bilateral orchidectomy specimen was sent in 10% formalin to the department of pathology for histopathological examination. Grossly, the specimen showed the right testis measuring 3 cm × 3 cm and the left testis measuring 2.5 cm × 2 cm with bilateral attached epididymis and spermatic cord [Figure 3].
Figure 3: Grossly bilateral testis measuring 2 cm × 3 cm right testis and 2 cm × 2 cm left testis with attached are epididymis and spermatic cord

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Histopathological examination from both the testes showed seminiferous tubules atrophy and peritubular fibrosis. The interstitial areas showed Leydig cell hyperplasia. A small nodule of Sertoli cell hyperplasia was also noted. The surrounding tissue showed dilated vascular spaces and congested blood vessels with few areas of fibrosis. Spermatogenesis was absent in both testes [Figure 4]. Based on history, clinicoradiological features, and histopathology report, the AIS was confirmed.
Figure 4: Photomicrograph showing sertoli cell nodule (Long arrow) with atrophy of seminiferous tubules with no spermatogenesis (short arrow) (H and E × 100)

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The patient and her extended family were advised genetic sequencing test as the condition is an autosomal recessive disorder. After surgery, the patient was advised to undergo hormone replacement treatment and psychological counseling.

Informed consent has been taken from the patient for research purposes and publication (Letter no. I. E. S. C./114/2022 dated September 01, 2022).


  Discussion Top


Complete AIS occurs because the cells are totally unable to respond to the androgens; it is clinically important when it occurs in persons who have been exposed to a remarkable amount of testosterone at an indefinite time in their lives. It inhibits the masculinization of the male genitalia, along with the development of secondary sexual characteristics throughout puberty due to androgenic hormones and the cells' insensitivity in the developing fetus. However without any remarkable disfigurement does allow the sexual development of the female genitalia.[3]

The male Wolffian duct system and the female Mullerian duct system both develop at the beginning of the embryonic stage in all human fetuses (female). The presence of androgens generated by the gonads causes the Wolffian duct system to develop, while the Mullerian duct system is inhibited within the bodies of the unaffected karyotype 46XY at the 7th week of gestation. Despite having a Y chromosome, those who have CAIS will have a typical outward female habitus but lack a uterus and have a blind end vaginal canal. The Y chromosome causes gonads to develop into testis rather than ovaries earlier in a distinct process, and they remain undescended at the position of the ovaries. This makes those people more vulnerable to gonadal cancer and also makes them infertile.[4],[5]

AIS is classified into three categories as complete AIS when the external genitalia develops into a female. The second category is mild AIS when it develops into the male gender and the third category is partial AIS, when genitalia is partly but not completely masculinized.[6]

The Mullerian structures such as the uterus, cervix, ovaries, both the fallopian tube, short blind-ended vagina, and bilateral undescended testis are absent, There is absent or scant pubic and axillary hairs, along with normal to the underdeveloped breast are seen in patients with complete AIS.[6],[7]

Primary amenorrhea in puberty is a typical presentation of AIS, occasionally during the premenarche period when a patient presents with bilateral inguinal swelling, and in rare cases, later in life when a patient having infertility issues. If the genetic sex confirmed on the karyotype differs from the karyotype mapped from the amniotic fluid, it can be identified before birth. Although there are no diagnostic criteria for AIS, raised testosterone hormone levels, normal or raised serum FSH, LH, and estradiol levels, karyotype mapping, radiological findings, and mutation in the AR gene on molecular genetic testing can aid in the diagnosis.[8]

The majority of treatment is symptomatic. The AR gene mutation currently has no particular therapy. Following the evaluation, the patient and parents should be informed, and a decision should be made. To lower the risk of cancer in undescended testis, an orchiectomy should also be done. About 3.6% of people are 25 years old, while 33% are 50 years old, according to numerous researches. Although it is uncommon, some females choose vaginoplasty to create a functional vagina. Surgery to change a person's sex may be advantageous for those who desire to identify as males. Frequent DEXA scans to check for bone density along with hormonal replacement therapy, calcium and Vitamin D supplementation are advised to the patient.[6],[9]

We reported a complete androgen insensitivity case because of its rarity and its multidisciplinary management.


  Conclusion Top


AIS is very rare and disturbing to individual and family, so close collaboration between radiologist, pathologist, treating consultants, and psychiatrists are required for appropriate management. A multidisciplinary approach that includes bilateral gonadectomy, thorough and repetitive psychological counseling, and estrogen replacement, will be beneficial to the patient. If a woman diagnosed with androgen insensitivity syndrome receives appropriate support and counseling, her medical and psychological prognosis is excellent.

Declaration of patient consent

The authors certify that they have obtained patient consent. The patient has given her consent for his images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published, and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Chang C, Yeh S, Lee SO, Chang TM. Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: Lessons learned from mice lacking AR in specific cells. Nucl Recept Signal 2013;11:e001.  Back to cited text no. 1
    
2.
Oakes MB, Eyvazzadeh AD, Quint E, Smith YR. Complete androgen insensitivity syndrome – A review. J Pediatr Adolesc Gynecol 2008;21:305-10.  Back to cited text no. 2
    
3.
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.  Back to cited text no. 3
    
4.
Morris JM. The syndrome of testicular feminization in male pseudohermaphrodites. Am J Obstet Gynecol 1953;65;6:1192-211.  Back to cited text no. 4
    
5.
Batista RL, Costa EM, Rodrigues AS, Gomes NL, Faria JA Jr., Nishi MY, et al. Androgen insensitivity syndrome: A review. Arch Endocrinol Metab 2018;62:227-35.  Back to cited text no. 5
    
6.
Fulare S, Deshmukh S, Gupta J. Androgen insensitivity syndrome: A rare genetic disorder. Int J Surg Case Rep 2020;71:371-3.  Back to cited text no. 6
    
7.
Malipatil V, Malipatil P, Chaitanya VM. Androgen insensitivity syndrome, a case report and literature review. Int J Res Med Sci 2016;4:1830-3.  Back to cited text no. 7
    
8.
Brown CJ, Goss SJ, Lubahn DB, Joseph DR, Wilson EM, French FS, et al. Androgen receptor locus on the human X chromosome: Regional localization to Xq11-12 and description of a DNA polymorphism. Am J Hum Genet 1989;44:264-9.  Back to cited text no. 8
    
9.
Hines M, Ahmed SF, Hughes IA. Psychological outcomes and gender-related development in complete androgen insensitivity syndrome. Arch Sex Behav 2003;32:93-101.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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