LC Exam 1 Week 1

Question 1

SRY gene location, function, and action

Answer 1

Short arm on Y chromosome
Sex determining region
Differentiation into testes at 7 wks

Question 2

Important ovarian differentiation genes

Answer 2

RSPO1 and WNT4 lead to ß-catenin (inhibit testes promote ovary)
FOXL2
DAXI

Question 3

Important genes for genital ridge formation

Answer 3

WT-1 (Wilms tumor)
WT-1 deletions lead to dysgenesis and Wilms tumor
NR5A1 aka SF-1
SF-1 deletions lead to gonad dysgenesis, adrenal failure, and persistent mullerian structures

Question 4

Important testicular differentiation genes

Answer 4

SRY

SOX-9 (target of SRY)

Question 5

Mesonephric and paramesonephric counterparts

Answer 5

Meso = Wolffian ducts (Epi, VD, SV)
Para = Mullerian ducts (FT, uterus, upper vagina)

Question 6

Male testicular sections in early development and cell that produces

Answer 6

Testosterone (Leydig)
Antimullerian hormone (Sertoli)

Question 7

External structure embryology male and female:
Genital tubercle
Urethreal folds
Labial/scrotal folds

Answer 7

GT: glands penis, clitoris
UF: penile urethra, labia minora
L/SF: scrotum, labia majora

Question 8

Hymen

Answer 8

connection between genitourinary and Mullerian/vagina

Question 9

Male development with testosterone

Answer 9

1st trimester: HCG stimulates Leydig cells
After: HPG axis required (hormone production starts around 10 wks)
External completed by 13 wks

Question 10

4 steps in mullerian development

Answer 10

1. Elongation
2. Fusion
3. Canalization
4. Septal reabsorption

Question 11

3 vaginal obstructions

Answer 11

1. imperforate hymen (caudal end of sinovaginal bulb)
2. transverse vaginal sinus (failed at vaginal plate)
3. vaginal atresia (failed at UG sinus, below vaginal plate)

Question 12

Class I mullerian defects: agenesis
4 types
Failure

Answer 12

Mullerian agenesis or hypoplasia
Vaginal, fundal, cervical, or tubal
Failed elongation

Question 13

Class II mullerian defects: unicornuate
4 types
Failure

Answer 13

Unicornuate
Failure of one duct to reach UG sinus with contralateral duct
Communicating, non-communicating, no cavity, no horn
Failed elongation

Question 14

Class III mullerian defects: didelphys
Pathophys
Failure

Answer 14

Uterine didelphys
Failure to fuse in the midline (failed fusion)
2 distinct cavities with longitudinal septum and two endometrial cavities and cervices
Longitudinal septum in vagina also common

Question 15

Consequence of class III defect: didelphys

Answer 15

Obstructed hemivagina
Ipislateral renal anomaly
Progressive pain due to enlarging endo

Question 16

Class IV mullerian defect: bicornate
2 types
Timing
Failure

Answer 16

Bicornate
Complete (extends to os) or partial (confined to fundus)
Occurs at 9th week gestation
Failure of fusion

Question 17

Class V mullerian defect: septate
2 types
Failure

Answer 17

Septate
Complete (extends to os) or partial (confined to fundus)
Failed septal reabsorption
Most common abnormality, may be Asx.

Question 18

Class VI and VII mullerian defects

Answer 18

VI: arcuate - no consequences
VII: DES exposure

Question 19

Obstructive vs. non-obstructive congenital vaginal/uterine defects

Answer 19

Obstructive: cyclic pain

Non-obstructive: usually no pain

Question 20

Treatment for failed vaginal canilization

Answer 20

DON’T ASPIRATE

Remove surgically

Question 21

Neo vaginal options

Answer 21

1. Vaginal dilators

2. Surgical plasty

Question 22

Sertoli cell functions

Answer 22

Respond to FSH (GPCR)
Secrete AMH (degenerate mullerian)
Form blood sperm barrier
Secrete androgen binding protein (ABP): maintain high local T concentration for spermatogenesis
Convert androgen to estrogen via aromatase (also happens in adipose tissue)
Secrete inhibin (growth factor for Leydig, neg on FSH)

Question 23

Leydig cell functions

Answer 23

Respond to LH (GPCR)
Secrete testosterone (responsible for Wolffian)
Secrete StAR and sterol carrier protein (steroidogenesis)

Question 24

Male HPG feedback

Answer 24

Androgens: neg on GnRH and LH/FSH
Estrogens: neg on LH/FSH
Inhibin: neg on FSH
IGF-1: stimulates GnRH
T/E2: stimulate GH secretion

Question 25

Actions of androgens in males

Answer 25

Differentiation of internal and external genitals Initiation and maintenance of spermatogenesis Development of 2ndary sex characteristics Anabolic

Question 26

Prepubertal vs. post pubertal FSH and LH levels in the male

Answer 26

Prepuberty: FSH>LH Postpuberty: LH>FSH, due to preferential LH stimulation by GnRH and potentially inhibin release

Question 27

Estrogen effects on bone growth

Answer 27

Stimulates bone growth Accelerates maturation Epi closure (narrows growth window)

Question 28

Does Molly really smell like burritos?

Answer 28

Yes, but it's kind of sexy

Question 29

Venous drainage

Answer 29

Left ovary/testis: left gonadal vein, left renal vein, IVC | Right ovary/testis: right gonadal vein, IVC

Question 30

Klinefelter syndrome: chr, pathophys, sx

Answer 30

47XXY Dysgenesis of seminiferous tubules: low inhibin, high FSH Abnormal Leydig: low T, high LH, high E2 conversion Eunuchoid body, tall, gynecomastia, barr body, hypogonadism

Question 31

Turner syndrome: chr, pathophys, sx

Answer 31

45XO Menopause before menarche Decreased E2 leads to increased FSH/LH 1˚ amenorrhea, preductal coarctation, cystic hygroma

Question 32

``` Testosterone/LH levels in (and ex of): Defective androgen receptor Testosterone-secreting tumor, exo steroids 1˚ hypogonadism Hypogonadotropic hypogonadism ```

Answer 32

1. AIS: increased T and LH 2. Tumor/steroid: increased T and decreased LH 3. Gonadal dysgenesis/failure: decreased T and increased LH 4. Hypothalamus/pit dysfxn: decreased T and LH

Question 33

46XX DSD: characteristics, example, hormone levels

Answer 33

Ovaries present, extgen is virilized or ambiguous CAH, SRY translocation, ovotesticular Exo androgens during pregnancy

Question 34

46XY DSD: characteristics, example, hormone levels

Answer 34

Testes present, extgen is female/ambiguous AIS (no sexual hair -vs mull agenesis-, increased T, E2, LH) Androgen production problems: 5alpha reductase def CAH/decreased sex hormones production: StAR or 17 anything

Question 35

CAH: common types

Answer 35

1. 21-hydroxylase 2. 11-ß hydroxylase 3. StAR (chole filled adrenal glands) 4. 3ß-hydroxysteroid DH 5. 17alpha hydroxlyase or 17,20 lyase

Question 36

17 CAH and StAR with regards to DSD | Potassium status?

Answer 36

46XX DSD: Normal at birth, failure to develop 2ndary sex characteristic during puberty 46XY DSD: Undervirilized at birth Hypokalemia in both

Question 37

One CAH that produces undervirilized in males and virilized in females

Answer 37

3ß-hydroxysteroid DH | High block

Question 38

Female puberty onset: Breast tanner II Menarche Bone age

Answer 38

Breasts: 10.5 (earlier in Black/Hispanic) Menarche: 12 Bone age: 10.5-11

Question 39

``` Male puberty onset: Testes Pubic hair Penile enlargement Height velocity Bone age ```

Answer 39

``` Testes: 12 (9-14) Hair: 12 Enlargement: 13 Height velocity: 14 Bone age: 11.5-12 ```

Question 40

Congenital hypogonadatropic hypogonadism

Answer 40

Prader Willi Kallman Septo-optic-dysplasia Idiopathic

Question 41

Acquired hypogonadatropic hypogonadism

Answer 41

Pituitary/hypothalmic tumor Cranial irradiation CNS infection AI hypophysitis

Question 42

Hypergonadotropic hypogonadism

Answer 42

Primary ovarian and testicular failure Klinefelters, Turners Galactosemia Cryptorchidism

Question 43

Central precocious puberty

Answer 43

``` 5% of girls = CNS abnormality 50% of boys = CNS abnormality Mass effect tumor Hydrocephalus Trauma Irradiation ```

Question 44

Peripherial precocious puberty in females

Answer 44

``` Ovarian cyst Granulosa cell tumor Exogenous estrogens Lavendar products Severe primary hypothyroidism (TSH = FSH) - delayed bone growth ```

Question 45

Peripherial precocious puberty in males

Answer 45

Adrenal tumor Leydig cell tumor Testotoxicosis: LH receptor mutation/activation hCG secreting tumor McCune Albright Syndrome Late onset CAH Severe primary hypothyroidism (TSH = FSH) - delayed bone growth

Question 46

Evaluation of precocious puberty: LH and GnRH stim

Answer 46

Random LH: post-pubertal = central Random LH: pre-pubertal = GnRH stim Stim = pre-pubertal = peripheral Stim = post-pubertal = central

Question 47

Treatment of: Central precocious puberty Peripheral: ovarian cyst, McCune-Albright, testotoxicosis, CAH

Answer 47

``` Central: GnRH analogue Ovarian cyst: watchful wait/fu McCune: Aromatase inhibitor Testotoxicosis: Aromatase inhibitor + androgen blocker OR ketoconazole CAH: GC's ```

Question 48

Lymph drainage

Answer 48

ovaries/testes: para-aortic lymph nodes vagina/vulva/scrotum/anus: superficial inguinal prostate/cervix/proximal vagina: deep inguinal