A 14-year-old girl is brought to the office for a routine physical examination. The patient is starting high school and is going to be on the school's cross-country team. She has no concerns today. She is healthy and takes no daily medications. Family history is significant for hypertension in her mother. The patient has not undergone menarche and is not sexually active. Height and weight are at the 25th percentile for age. Physical examination shows sexual maturity rating (Tanner) stage 1 breast development. The abdomen is soft, nontender, and nondistended. A small, nonreducible mass is palpated in the left inguinal area. On pelvic examination, the external genitalia appear normal, and there is no pubic hair. The vagina ends in a blind pouch. Sonogram confirms the absence of a uterus, cervix, and ovaries. Karyotype is 46,XY. Which of the following is the best next step in management of this patient?
Androgen insensitivity syndrome | |
Pathophysiology |
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Clinical features |
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Management |
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This patient appears as a genotypical male (46,XY) but phenotypical female, indicating androgen insensitivity syndrome (AIS), a condition in which nonfunctioning androgen receptors result in peripheral androgen resistance. These patients typically have primary amenorrhea (no menarche in girls age ≥13 without secondary sexual characteristics) due to the lack of female internal genitalia (eg, uterus).
The testes of patients with AIS are functionally normal but are typically cryptorchid/undescended (as testicular descent is an androgen-dependent process) and may be found in the abdomen, inguinal canal (eg, nonreducible mass in this patient), or labia majora. Patients with cryptorchid testes are at increased risk of testicular cancer (eg, dysgerminoma, gonadoblastoma), due in part to an elevated intraabdominal temperature that causes abnormal spermatogenesis and aberrant germ cell differentiation. Therefore, management of these patients includes an elective gonadectomy; timing of the procedure is based on possible current malignancy, symptoms (eg, pain), and the potential benefits of androgen-stimulated puberty (eg, attainment of adult height).
(Choices B and C) Estrogen replacement and growth hormone therapy are used in the management of Turner syndrome (45,X). Patients with Turner syndrome often have amenorrhea but they typically have a normal uterus. Estrogen therapy is used in the development of secondary sexual characteristics and prevention of osteoporosis. Growth hormone therapy is used for the management of their associated short stature. Estrogen therapy may be used to maintain feminization in patients with AIS after a gonadectomy.
(Choice D) A hymenectomy is performed for an imperforate hymen, which often presents as a blue-hued vaginal mass bulging from the introitus, secondary to retained menses. Patients with an imperforate hymen have female internal genitalia (eg, uterus) and a 46,XX karyotype.
(Choice E) Low-dose corticosteroids are used in the treatment of nonclassical congenital adrenal hyperplasia (CAH). Girls with nonclassical CAH have a 46,XX karyotype and typically show signs of androgen excess (eg, premature pubarche, nodulocystic acne) rather than delayed puberty.
(Choice F) Reassurance is indicated for patients with constitutional delay of puberty as they have primary amenorrhea but a female karyotype.
Educational objective:
Patients with androgen insensitivity syndrome are genotypically male (46,XY) but appear phenotypically female. These patients are at increased risk of testicular cancer due to their bilateral cryptorchid testes; therefore, management includes an elective gonadectomy.