Reproductive endocrinology

Question 1

What is congenital adrenal hyperplasia

Answer 1

Autosomal recessive inheritance
Most common cause of ambiguous genitalia

Females: 46XX, clitoral enlargement, labial fusion, urogenital sinus

Usually due to 21-hydroxylase deficiency, obstructs cortisol production and thus there is no negative feedback to switch off ACTH

Dx: 17-hydroxyprogesterone, salt wasting in infants

Question 2

Adolescent development

Answer 2

Growth spurt (Gr)
Breast (B)
Pubarche (P)
Adrenarche (A)
Menarche (M)

GraB PAM

Question 3

When do you evaluate amenorrhea

Answer 3

Amenorrhea and

• No menses within 3 ears of thelarche
• No secondary sexual characteristics
• Age 14 with history or exam suggestive of eating disorder
• 14 with hirsutism
• Age 15 regardless of development
• > 90 days without menses in menstruating adolescent

Question 4

What is precocious puberty

Answer 4

Age 7 in white American girls and 6 in black American girls

2.5 standard deviations earlier than mean age

Question 5

Delayed puberty

Answer 5

No breasts by 12-13 yo

Question 6

What is the differential dx for hirsutism

Answer 6

Familial
PCOS
CAH
Tumor (ovary or adrenal)
Drugs (androgens, danazol)
Hypothyroidism, severely elevated prolactin
Cushing’s disease

Question 7

What labs would you do for hirsutism

Answer 7

Total testosterone (r/o abnormal ovarian or adrenal fx)
DHEAS (r/o anormal Andreal function)
17-OH progesterone (r/o CAH)

Question 8

What is the tx for hirsutism

Answer 8

1. OCP– decreased androgen production and increases SHBG levels causing increased binding and less free androgen)
2. Spironolactone (blocks androgen receptor and inhibits 5alpha reductase)
3. Finasteride (5alpha reductase inhibitor, inhibits testosterone–> DHT)
4. Flutamide (blocks androgen receptor)
5. Vaniqua (eflornithine)– blocks ornithine decarboxylase
6. Cosmetic
7. Weight loss– increases SHBG, decreases free testosterone

Question 9

Primary amenorrhea

Answer 9

No menses by 13yo in absence of secondary sexual characteristics

No menses by 15yo with secondary sexual characteristics

No menses before 15yo with secondary sexual characteristics and who have cyclic pain

Question 10

Work up for primary amenorrhea

Answer 10

Divided into presence or absence of breast development (marker of estrogen action and ovarian function) and the Presence or absence of uterus

hCH
FSH
TSH
Prolactin
Consider E2 and FT4
Pelvic US
MRI in complex cases

Question 11

Amenorrhea, uterus, breast devo

Answer 11

Estrogen present–> secondary amenorrhea

1. Hypothalamic causes
2. Pituitary causes
3. Ovarian causes
4. Uterine causes (outflow tract)

Question 12

Amenorrhea, absent brest devo

Answer 12

Estrogen absent

1. Gonadal failure
   a. 45X ( Turner’s)
   b. 46X (arm deletion)
   c. Mosaicism (X/XX, X/XXX)
   d. Pure XX or YX gonadal dysgenesis
   e. 17 Alpha hydroxylase deficiency
2. CNS hypothalamic-pituitary-hypogonadotropic hypogonadism
   - CNS lesion (pituitary adenoma, craniopharyngiomas)
   - Hypothalamic failure 2/2 inadequate GnRH (Kallman’s anosmia)
   - Isolated gonadotropin deficiency
   - Constitutional delay

Question 13

Amenorrhea, absent uterus, breast devo

Answer 13

1. Uterovaginal agenesis (Rokitansy-Huster-Kuster-Hauser Syndrome)
   - normal pubic hair
2. Androgen insensitivity (T-fem, YX)
   - Remove internal gonads after puberty, increased risk of tumors
   - short or absent vagina with sparse pubic hair

Question 14

Amenorrhea, absent uterus, absent breast devo

Answer 14

1. XY, elevated gonadotropins, T normal or less
2. 17, 20-Desmolase def
3. Agonadism
4. 17-alpha hydroxylase de (46XY)

Question 15

Secondary amenorrhea

Answer 15

No menses for >3mo in females with normal menstrual cycles, or >6mo in females with irregular cycles

Question 16

How do you evaluate primary amenorrhea

Answer 16

1. Exclude pregnancy
2. History: stress, nutritional factors, weight change
   medications, ad symptoms of hypoE
3. Physical: Mullerian structures present?
   – short blind ending vagina– Mullerian agenesis or androgen insensitivity–> total T and karyotype
   – vaginal agenesis or atresia or transverse vag septum
   – Cervical atresia (pain/hematometra)
4. If vagina is normal and cervix present do labs
   - TSH/prolactin
   - FSH and estradiol
   - Progesterone withdrawal challenge
   – If bleeding, normal labs = anovulation
   – If not bleeding, normal labs = E + P challenge
   – E+P challenge (Congugated estradiol 1.25mg x14 days, then CEE + MPA x10 days)
   – If bleeding, not making adequate Estrogen
   – If no bleeding, abnormal outflow tract (Asherman’s, anomaly_
5. FSH/LH levels
   - Normal

Question 17

Primary insufficiency dx criteria

Answer 17

Need two random tests at least 1 month apart

• Elevated FHS/LH
• Neg pregnancy test
• Normal PRL, TSH