Disorders of Sexual Development + Hypogonadism B&B Flashcards
what are the following sex chromosome disorders?
a. 45 X
b. 47 XXY
c. XYY
a. 45 X: Turner syndrome
b. 47 XXY: Klinefelter syndrome
c. XYY: Double Y male (tall + learning disability/autism)
how does ovotesticular DSD (disorder of sexual development) present?
ovaries AND testes are present, genitalia are abnormal
most cases are XX and infertile
How does gestational hyperandrogenism present?
maternal source of androgens in pregnancy leads to hirsutism and virilization of BOTH the mother and the fetus
May be caused by luteoma (rare ovarian mass secreting testosterone/DHT) or aromatase deficiency or exogenous progestin/androgen administration
Swyer Syndrome
XY gonadal dysgenesis - female external genitalia with XY and no ovaries + streak gonads (mainly fibrous, risk of malignancy)
Müllerian ducts intact (no MIH from Sertoli cells) - uterus, cervix, upper vagina develop
no puberty/menstruation (no ovaries to produce estrogen) - given estrogen supplementation
Pt is a 15yo F presenting to the pediatrician due to lack of puberty or menarche. Imaging reveals an intact uterus, cervix, and vagina; however, “streak gonads” are present. What is the diagnosis and what supplement is advised?
Swyer syndrome: XY gonadal dysgenesis - female external genitalia with XY and no ovaries + streak gonads (mainly fibrous, risk of malignancy)
Müllerian ducts intact (no MIH from Sertoli cells) - uterus, cervix, upper vagina develop
no puberty/menstruation (no ovaries to produce estrogen) - given estrogen supplementation
how does 5-alpha reductase deficiency present? what inheritance pattern is it?
5-alpha reductase required for conversion of testosterone to DHT, which is required for male external genitalia
AR disorder - 46,XY male with normal internal genitalia but absent external male genitalia (may be ambiguous, predominately female)
masculinization can occur at puberty due to increased testosterone
Pt is a 12yo F presenting to their pediatrician with concerns of masculinization. PE reveals female external genitalia; however, the child is karyotyped and found to be 46, XY. Subsequent imagine reveals cryptorchidism (undescended testes), as well as male internal genitalia ending in an blind vagina. A uterus is not present. What is the diagnosis?
5-alpha reductase deficiency: required for conversion of testosterone to DHT, which is required for male external genitalia
AR disorder - 46,XY male with normal internal genitalia but absent external male genitalia (may be ambiguous, predominately female)
masculinization can occur at puberty due to increased testosterone
how does complete androgen insensitivity syndrome present (CAIS)?
mutation of androgen receptor in XY males – no internal or external male general development
However, testes form in utero due to SRY gene – Sertoli cells secrete MIH, so there is degeneration of mullerian structures (no internal female genitalia either)
phenotypically female with abdominal testes, amenorrhea at puberty (no uterus), no armpit/pubic hair (depends on androgens)
however, breasts develop because testosterone is converted to estrogen
Pt is a 15yo F presenting to her pediatrician with concern of primary amenorrhea. PE reveals female external genitalia and breast development. Further, no pubic or armpit hair is present. However, imaging is done which reveals abdominal testes and a total lack of internal genitalia. What is the diagnosis?
complete androgen insensitivity syndrome present (CAIS): mutation of androgen receptor in XY males – no internal or external male general development
However, testes form in utero due to SRY gene – Sertoli cells secrete MIH, so there is degeneration of mullerian structures (no internal female genitalia either)
phenotypically female with abdominal testes, amenorrhea at puberty (no uterus), no armpit/pubic hair (depends on androgens)
however, breasts develop because testosterone is converted to estrogen
what is the cause of Kallmann Syndrome?
GnRH deficiency due to impaired migration of these neurons to the hypothalamus (XLR KAL1 mutation) —> hypogonadotropic hypogonadism + anosmia (lack of smell)
often discovered a puberty, affects males more often:
females - underdeveloped breasts, no axillary hair, primary amenorrhea
males - no facial/body hair, no increase in muscle mass, failure of voice to deepen (may be micropenis/cryptorchidism at birth)
Pt is a 15yo M presenting to their pediatrician with concerns of a lack of puberty. PE reveals a skinny patient with no body or facial hair, and a high voice. During the interview, the patient reveals they lack a sense of smell. What is the most likely diagnosis?
Kallmann Syndrome: GnRH deficiency due to impaired migration of these neurons to the hypothalamus (XLR KAL1 mutation) —> hypogonadotropic hypogonadism + anosmia (lack of smell)
often discovered a puberty, affects males more often:
females - underdeveloped breasts, no axillary hair, primary amenorrhea
males - no facial/body hair, no increase in muscle mass, failure of voice to deepen (may be micropenis/cryptorchidism at birth)
Which of the following will present with HIGH LH levels?
a. gonadal failure
b. testosterone tumor
c. exogenous testosterone
d. pituitary failure
e. CAIS (complete androgen insensitivity syndrome)
recall LH stimulates production of testosterone
gonadal failure and CAIS will present with HIGH LH, all others will present with low LH
What is the most common cause of primary amenorrhea?
Turner syndrome
how does Mullerian agenesis present?
congenital absence of vagina, no cervix or uterus —> primary amenorrhea
normal secondary characteristics (breast, pubic hair) because ovaries and hypothalamus/pituitary are normal
[note 50% will have renal or skeletal abnormality - missing 1 kidney, duplicated collecting system, etc]
how do the following cause secondary amenorrhea?
a. corticosteroids/Cushing syndrome
b. cirrhosis
c. spironolactone
a. corticosteroids/Cushing syndrome: cortisol suppresses GnRH
b. cirrhosis: disrupts hormone metabolism
c. spironolactone: anti-androgen (disrupts estrogen/ androgen balance), may stimulate progesterone receptors
