What is the diagnostic approach for a 12-year-old girl with Tanner stage 3 (Tanner scale of pubertal development) breast development, scant pubic and axillary hair, and primary amenorrhea, presenting with a blind vaginal pouch?

From the Guidelines

A comprehensive evaluation for a 12-year-old girl with Tanner stage 3 development, scant pubic and axillary hair, developed breasts, blind pouch vagina, and primary amenorrhea should begin with a detailed history and physical examination, including inspection of the external genitalia and assessment of the hymen for patency and configuration, as outlined in the American Academy of Pediatrics clinical report 1. The initial assessment should focus on determining the underlying cause of the patient's presentation, which may include Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome) or complete androgen insensitivity syndrome. Key components of the diagnostic approach include:

• Karyotype analysis to determine genetic sex
• Laboratory tests, such as FSH, LH, estradiol, testosterone, DHEAS, 17-hydroxyprogesterone, and thyroid function tests, to assess hormonal status
• Pelvic ultrasound to evaluate internal reproductive organs and determine the presence or absence of a uterus and ovaries
• MRI of the pelvis to provide more detailed anatomical information about the reproductive tract
• Renal ultrasound to check for associated urinary tract anomalies, which are common in Müllerian agenesis
• Bone age assessment to determine developmental status The goal of this systematic approach is to establish an accurate diagnosis, which is essential for guiding appropriate management, including potential hormonal therapy, psychological support, and future discussions about fertility options and vaginal creation procedures when the patient is ready, as emphasized in the American Academy of Pediatrics clinical report 1.

From the Research

Diagnostic Approach

The diagnostic approach for a 12-year-old girl with Tanner stage 3 breast development, scant pubic and axillary hair, and primary amenorrhea, presenting with a blind vaginal pouch, involves several steps:

• Physical examination to assess pubertal development, including Tanner staging of breast and pubic hair development 2
• Hormonal tests to evaluate estrogen and testosterone levels, as well as gonadotropin levels 3, 4, 5
• Imaging studies, such as pelvic ultrasound and magnetic resonance imaging (MRI), to evaluate the presence and development of internal genitalia, including the uterus and ovaries 3, 4, 6
• Karyotype analysis to determine the presence of any chromosomal abnormalities, such as a 46,XY karyotype, which is characteristic of Complete Androgen Insensitivity Syndrome (CAIS) and Swyer syndrome 3, 4, 5
• Consideration of disorders of sex development (DSD), such as CAIS, Swyer syndrome, and Mayer-Rokitansky-Küster-Hauser syndrome (MRHKS), which can present with similar clinical features 3, 4, 5

Differential Diagnosis

The differential diagnosis for this patient includes:

• Complete Androgen Insensitivity Syndrome (CAIS), characterized by a 46,XY karyotype, normal female external genitalia, and absence of Mullerian structures 3
• Swyer syndrome, characterized by a 46,XY karyotype, normal female external genitalia, and gonadal dysgenesis 4, 5
• Mayer-Rokitansky-Küster-Hauser syndrome (MRHKS), characterized by vaginal and uterine agenesis, but normal ovarian function and a 46,XX karyotype 3
• Isochromosome mosaic Turner syndrome, characterized by a 46,X,i(X)(q10) karyotype, short stature, and gonadal dysgenesis 6

Diagnostic Tests

Diagnostic tests that may be useful in evaluating this patient include:

• Hormonal tests, such as estrogen and testosterone levels, as well as gonadotropin levels 3, 4, 5
• Imaging studies, such as pelvic ultrasound and MRI, to evaluate internal genitalia 3, 4, 6
• Karyotype analysis to determine the presence of any chromosomal abnormalities 3, 4, 5
• Biopsy or excision of gonadal tissue to evaluate for the presence of gonadoblastoma or other tumors 3, 4, 5