A 16-year-old girl comes to the office due to not having started her menstrual period. The patient says that all her friends have started their periods and she is concerned that she is "behind." She has had no nipple discharge or change in vision or weight. The patient has no chronic medical conditions and takes no daily medications. She recently became sexually active and uses condoms for contraception. Height is at the 70th percentile and weight is at the 40th percentile for age. Vital signs are normal. On physical examination, there is sexual maturity rating (Tanner) stage 4 breast development with minimal axillary and pubic hair. The external genitalia are normal and the vagina is 3 cm in length; the cervix is not visible. No uterus, cervix, or ovaries are palpated on bimanual examination. Laboratory studies include a negative pregnancy test and a testosterone level of 400 ng/dL (normal: 15-75 [female]; 300-1,000 [male]). Which of the following is the most likely diagnosis in this patient?

Question

A 16-year-old girl comes to the office due to not having started her menstrual period.  The patient says that all her friends have started their periods and she is concerned that she is "behind."  She has had no nipple discharge or change in vision or weight.  The patient has no chronic medical conditions and takes no daily medications.  She recently became sexually active and uses condoms for contraception.  Height is at the 70th percentile and weight is at the 40th percentile for age.  Vital signs are normal.  On physical examination, there is sexual maturity rating (Tanner) stage 4 breast development with minimal axillary and pubic hair.  The external genitalia are normal and the vagina is 3 cm in length; the cervix is not visible.  No uterus, cervix, or ovaries are palpated on bimanual examination.  Laboratory studies include a negative pregnancy test and a testosterone level of 400 ng/dL (normal: 15-75 [female]; 300-1,000 [male]).  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

11ec25c8_d9a5_040c_bc81_b1fd615e935a_MD0003_00 This patient with primary amenorrhea (absent menarche by age ≥15 with secondary sexual characteristics) and male-range testosterone levels most likely has androgen insensitivity syndrome (AIS). Patients with AIS are genotypically male (46,XY) but phenotypically female due to a nonfunctioning androgen receptor. AIS During fetal development, males with AIS have functioning cryptorchid testes that produce anti-Müllerian hormone (AMH) and testosterone. AMH causes regression of the Müllerian structures (eg, uterus, cervix, upper third of the vagina); therefore, female internal genitalia do not develop. Although testosterone is produced, the nonfunctioning androgen receptor on male reproductive structures (eg, Wolffian ducts, urogenital sinus) prevents male external genitalia (eg, penis, prostate) development and patients default to female external genitalia (eg, shortened lower two-thirds of the vagina). At puberty, testosterone increases to the pubertal male range and is aromatized into estrogen, resulting in breast development and tall stature. Minimal to no axillary or pubic hair development occurs due to peripheral androgen resistance. Diagnosis is with karyotype analysis, and management includes a prophylactic gonadectomy due to the increased risk of testicular cancer associated with cryptorchidism. (Choice A) Genotypically male (46,XY) patients with 5-alpha-reductase deficiency cannot convert testosterone to dihydrotestosterone and appear phenotypically female at birth. In contrast to AIS, patients with 5-alpha-reductase deficiency develop virilization at puberty (eg, clitoromegaly) and have no breast development. (Choice C) Patients with Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome) have primary amenorrhea due to the lack of female internal genitalia. These patients have otherwise normal female development (eg, pubic and axillary hair) and female-range testosterone levels, making this diagnosis unlikely. (Choice D) Sertoli-Leydig cell tumors are a type of sex cord-stromal ovarian tumor that produces high testosterone levels. Patients can have amenorrhea; however, they typically have concomitant virilization (eg, clitoromegaly) and a large adnexal mass. (Choice E) A transverse vaginal septum can cause amenorrhea, but such patients have female internal genitalia (ie, uterus) and female-range testosterone levels. (Choice F) Patients with Turner syndrome (45,X) have primary amenorrhea due to nonfunctioning streak ovaries. These patients have short stature, a uterus, and no breast development, making this diagnosis unlikely in this patient. Educational objective: Androgen insensitivity syndrome is due to a nonfunctioning androgen receptor that results in genotypically male (46,XY) patients appearing phenotypically female. Patients have primary amenorrhea (due to lack of female internal genitalia), normal breast and female external genitalia development, and minimal or no axillary and pubic hair. References: Androgen insensitivity syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/22698698) Androgen insensitivity syndrome: a review. (http://www.ncbi.nlm.nih.gov/pubmed/29768628)

A 16-Year-Old Girl Comes to the Office Due to Not