When does gonadal differentiation take place?

With what other type of anomalies do mullerian abnormalities are found? 

Renal anomalies (due to embryology)

Wolffian ducts

= Mesonephric ducts 

What do mesonephric ducts give rise to? 

vas deferens, seminal vesicles, epididymis 

Paramesonephric ducts

other name? 

Mullerian ducts 

What do paramesonephric ducts give rise to? 

fallopian tubes, uterus, and upper 1/3 vagina

Lateral fusion defects examples

Uterus didelphys w/ double vagina, uterus arcuatus, uterus bicornis w/ 1 vagina. 

male and female INTERNAL genitalia: same or different precursors?

DIFFERENT

*remember that in

Men: mesonephric=wolffian ducts--> vas deferens, seminal vesicles, epididymis

Women: paramesonephric=mullerian ducts--> fallopian tubes, uterus, and upper 1/3 vagian

Female and male EXTERNAL genitalia- same or different precursors?

SAME

*remember that big chart of analogous structures that we need to know for STEP; think penis (male) and clitoris (women) = EXTERNAL 

Streak ovaries, short stature, X0, wide-spaced nipples, meiotic non-disjunction 

Turner Syndrome

*this should be second nature by now! 

Abnormal androgen production, abnormal receptor status, inability to convert to testosterone to DHT, androgen insensitivity are examples of? 

Male pseudohermaphroditism

*these individuals are 46XY, and thus have male gonads but they are going to have failure of virilization --> phenotypically female

Ambiguous Genitalia 

According to Dr. Parker think Congenital Adrenal Hyperplasia 

21-alpha hydroxylase deficiency most common cause

growth, active phase of hair growth cycle

Anagen phase

how much free testosterone is in circulation

1%, the rest 99% is bound in SHBG (sex hormone binding globulin)

What levels of testosterone indicate a tumor? 

>200 ng/dl

*I don't know how important it is to remember this but I hope NOT that important

Where is DHEA-S produced

EXCLUSIVELY in the adrenal gland

>700 mcg/dl indicate an adrenal tumor

Testosterone to _____ via 5-alpha reductase enzyme

DHT (dihydrotestosterone)

*responsible for differentiation of external genitalia, male hair distribution, increase in size of epididymis, vas deferens, prostate, and seminal vesicles [check this w/ First Aid]

What is the treatment of Hirsutism? 

OCPs

MOA of OCPs

increase SHBG, Suppress LH production, Decrease Testosterone production, some inhibition of 5-alpha reductase, decrease DHEA-S production

Hormone values in PCOS 

increased LH, 

increased androgens and estrogen, 

decreased FSH 

Define Precocious Puberty 

Development of secondary sexual characteristics prior to age 8 in girls and 9.5 in boys 

What is delayed puberty? 

age 13 w/out secondary sexual characteristics or 15 w/ them 

GRaB PAM pnemonic

related to timing of puberty and sequence of events 

growth, breast, pubarchy, adrenarchy, menarche

*pubarche: appearance of pubic hair

*adrenarche: maturation of adrenal cortex w/ increased production of androgens

*menarche: first menstrual bleeding

Premature activation of HP axis, sequence of development typical but EARLIER, affects females > males; girls usually idiopathic & males: structural lesion-neuro

GnRH dependent 

Goal and tx for GnRH dependent precocious puberty 

Goal: prevent further progression until age appropriate & preserve adult height

Tx: GnRH agonist is treatment of choice 

Triad: +/- precocious puberty, café au lait spots, bony fibrous dysplasia 

McCune-Albright Syndrome 

Feminizing Disorders 

Estrogen-Secreting Tumors (granulosa, stromal, theca)

Peutz: Jeghers: Aut. Dominant, mucocutaneous pigment, GI polyps, & sex cord tumors; risk for colon, stomach, small intestine, breast & pancreatic cancer 

What are the basic signs of Delayed puberty in girls and boys?  

Girls: no thelarche by 13; no menarche by 15

Boys: no testicular volumetric increase by 14. 

Constitutional Delayed Puberty

FamilyHx positive, skeletal maturation delayed, peak height less than predicted but in genetic height range, no delayed beyond 16(girls) or 18(boys), endocrine parameters are sim to gonadotropin deficient, pubertal progression & linear growth eventually advance

*I think of these as late bloomers

Hypogonadotropic Hypogonadism

Ex: Kallmann's syndrome w/ lack of smell (anosmia)

absent or decreased fxn of male testes or female ovaries: lack of GnRH --> lack of FSH & LH -->abnl sexual develop in puberty 

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001427/

How do GnRH analogs manage central precocity? 

Analogs block the action of native GnRH at the gonadotrope (ant. pituitary) by down-regulating the GnRH receptors @ the surface of the cell, leading to suppression of LH & FSH secretion.

Characterized by sexual precocity, testicular enlargement, maturation of Leydig cells & seminiferous tubules despite absence of gonadotropin secretion. 

Familial testotoxicosis

Receptor mutation that leads to constitutive activation in the absence of ligand. 

Familial Testotoxicosis 

How can hypothyroidism cause sexual precocity? 

decr. T3/T4 --> incrsd. TSH, which cross reacts w/ FSH receptor or increased FSH release in response to hypothyroidism

short stature, webbing of the neck, amenorrhea, sexual infatilism, coarctation of the aorta, NORMAL intellectual development. 

45 XO, a.k.a Turner Syndrome

*I'm telling u this should be engraved in your brain by now. 

Some pts with mosaicism have a Y chromosome in their genetic make-up, what does this predispose them to?  

They may develop a gonadal malignancy

*she repeated this like 3x in her lecture

XXY, phenotypic males, small testes, gynecomastia, mental retardation, meiotic or mitotic non-disjunction, hyalinization of the seminiferous tubules & absent spermatogenesis. 

Kleinfelter's Syndrome

Male Pseudohermaphroditism

46 XY, gonads are testes, failed virilization of external genitalia

Androgen Insensitivity 

type of male pseudohermaphroditism

abnormal androgen receptor

46 XY, abdominal testes, phenotypically females

@ puberty--> abundant breast tissue

*think Jamie Lee Curtis!

Why do ppl w/ androgen insensitivity have breasts and absent internal female genitalia and vagina ends in blind pouch? 

They do have testes --> MIF and

increased LH d/t failed testosterone fdback inhibition (receptors aren't working) --> turn into estrogen via aromatase --> lots of estrogen --> breasts

46 XY, severe hypospadias, no mullerian structures, minimal virilization, pts undergo marked virilization at the time of puberty 

"Penis at 12"

5 alpha-reductase deficiency

*This enzyme converts testosterone to DHT.

Female Pseudohermaphroditism

46 XX, normal ovarian tissue, mullerian structures are normal (uterus/tubes/upper 1/3 vagina) but deficiency in steroid synthesis enzymes

increased DHEA, androstenedione & testosterone

virilization of female external genitalia

hyponatremia, hyperkalemia, dehydration

21-hydroxylase deficiency 

*if u see electrolyte abnormalities + ambiguous genitalia in the question stem think this

Increased 11-deoxycorticosterone (DOC) 

and HTN

11-Beta hydroxylase defficiency 

True Hermaphroditism

Coexistence of Ovarian & testicular tissue; external genitalia ambisexual; raised as males secondary to size of the phallus