2 - pediatric genital abnormalities Flashcards
1
Q
source of problem if appropriate gonadotropins but low testosterone in neonatal period
A
gonadal
2
Q
source of problem if low gonadotropinsat expected surge in neonatal period
A
central
3
Q
most common cause of 46 xx DSD
A
CAH
4
Q
non-CAH cause of 46xx DSD
A
maternal virilizing condiitons
5
Q
2 examples of maternal virilizing conditions causing 46xx DSD
A
p450 aromatase deficiency with no T to E, or elevated maternal androgens
6
Q
46 xx dsd - CAH effect on males and females
A
males already virilized, females virilize
7
Q
46 xx dsd - CAH missing hormone
A
cortisol insufficiency +/- aldosterone- shunt of steroid toward sex steroi
8
Q
enzyme deficiencies for 3 types of CAH involved in virilization
A
21-hydroxylase
11b- hydroxylase
3-b hydroxysteroid dehydrogenase
9
Q
physical location of these enzyme deficiencies
A
adrenal cortex
10
Q
most common enzyme CAH
A
21-oh - 90%
11
Q
CAH inheritance
A
autosomal recessive
12
Q
what precourser is elevated in 21-OH deficiency - 2
A
elev 17-oh progesterone and androstenedione
13
Q
2 genes responsible for 21-OH deficiency
A
CYP21A and B
14
Q
location of CYP21A/B genes for 21-OH deficiency
A
chr 6
15
Q
symptoms of 21-OH deficiency
A
classic - simple virilization, salt wasting 75%
16
Q
medication for 21-OH deficiency
A
fludrocortisone
17
Q
2nd most comm CAH
A
11 b-hydroxylase
18
Q
symptoms of 11b-OH deficincy - 2
A
virilization, HTN
19
Q
what precourser is elevated in 11b-OH deficiency
A
deoxy corticosterone (DOC) and elevated 17-oh progesterone
20
Q
steroids for 11-b OH deficiency?
A
no fludrocortisone
21
Q
symptoms of 3b-hydroxysteroid dehydrogenase deficiency
A
salt wasting, male ambiguous gniralia
22
Q
what is elevated in 3b-hydroxysteroid dehydrogenase deficiency
A
pregnenalone (DHEA)
23
Q
workup for suspected CAH
A
karyotype, pelvic us, genitogram, hormone assays
24
Q
who gets prenatal treatment for possible CAH
A
when family hx CAH
25
what is prenatal tx for CAH
dexamethasone given by 9th wk to prevent virilization
26
caveat with prenatal tx for CAH
7/8 tx'd unnecessarily because inheritance is AR
27
implication of nonclassic CAH
infertility may be only implication
28
treatment of nonclassic CAH
dexamethasone
29
what does STAR stand for (star mutation)
steroidogenic acute regulatory protein
30
what is STAR mutation
proximal steroid synthesis disorder
31
presentation of STAR mutation
severe glucocorticoid and mineralocorticoid production deficiency at 1 mo, severe secondary hyperpigmentation
32
what is implication of STAR mutation
female phenotype in XX/XY, no androgen production or potential
33
what does TART stand for
testicular adrenal rest tumors
34
who gets TART
poorly controlled 46 XY CAH w increased ACTH
35
puberty and nodules in TART
puberty contributes to increased size of lesions due to LH receptors on nodules
36
where are TART nodules found
nodular growth in rete testis
37
TART histology
similar to leydig cells but no reinke crystals
38
TART outcome
often result in primary gonadal failure
39
how does TART result in primary gonadal failure
obstructive azoospermia, peritubular fibrosis
40
how to treat TART
maximize compliance w steroid therapy. Remove only in pain
41
what is swyler syndrome
pure gonadal dysgenesis - 46XY with no testosterone or MIS
42
swyler syndrome phenotype
normal F internal and external genitalia (but 46 xy), normal height, primary amenorrhea, delayed puberty
43
swyler and SRY mutation
found in 20%
44
initial mgmt of swyler syndrome
gonadectomy due to risk of malignancy
45
partial gonadal dysgenesis definition
mix of mullerian and wolfian structures
46
partial gonadal dysgenesis phenotype
depends on amount of testosterone child exposed to
47
partial gonadal dysgenesis- gonads
gonads - poorly differentiated testicular tubules and ovarian like stroma
48
genotype for mixed gonadal dysgenesis
45 XO, 46 XY
49
significance of mixed gonadal dysgenisis found on amniocentesis
95% boys have nl phenotype --> expression of mosiacism varies
50
phenotype for mixed gonadal dysgenisis
wide range - turner stigmata - female external and internal genitalia to nl male w subfertility
51
turner syndrome genotype
45 XO
52
turner syndrome - phenotype
Female but no pubic hair, breast, or menses. and short stature
53
turner gonads
streak
54
turner mosaic genotype
45XO, 46 XX
55
turner mosiac presentation - 2
pubertal development uncommon, secondary amenorrhea (similar to regular turners)
56
turner stigmata - 7
```
short stature
coarctation of aorta
horseshoe kidney
broad chest
webbed neck, low hairline, low ears
```
57
what is 46 XY DSD
UNDERvirilization +/- DSD
58
potential causes of 46 xy DSD - 3
androgen synthesis, conversion, insensitivity
59
androgen syn defect outcome
micropenis +/- hypospadius, mullerian tissue absent b/c testicular tissue present
60
structure of penis in micropenis
urethra/prepuce small but formed
61
main cause of micropenis
failed stimulation after 14 wks due to primary hypogonadism, hypogonadotrophic hypogonadism
62
micropenis tx
early testosterone tx
63
inheritance of androgen conversion defect
AR
64
phenotype of androgen conversion defect
pseudovaginal perineoscrotal hypospadius -no tubularization of urethra or elongation of phallus. no mullerian structures present b/c nl sertoli function and nl T
65
what enzyme is involved in androgen conversion defect
5alphareductase-type 2 defic
66
enzyme missing in androgen conversion defect
low DHT
67
outcome of androgen converson defect
masculinize with puberty
68
androgen insensitivity - pathophys
wide number of mutations - some bind DHT but not T
69
androgen insensitivity inheritance
x-linked recessive
70
complete androgen insensitivity - phenotype
internal female genital tract abscent but distal vag and hymen present - from UG sinus.
rudimentary wolfian structures present because no response to T. often hernia
71
how does complete androgen insensitivity present
primary amenorrhea
72
mgmt of complete androgen insensitivity
do karyotype
73
what is ovotesticular DSD
both ovarian and teticular tissue on gonadal biopsy
74
ovotesticular DSD - karyotype
most 46 XX some 46 XY, some mosaic
75
ovotesticular DSD - gonad phenotype
unilat or bilat ovary, testis, or ovotstis.
76
ovotesticular DSD mgmt
removal of discordant genital organs with assigned sex. ex - if ovarian protion remains in male, may get breast development.
77
what is ovotesticular DSD
true hermaphrodite
78
what is MRKH
mullerian agenesis
79
MRKH - whats missing - 2
absence of uterus, upper vagina, renal agenesis/anomaly common
80
MRKH whats present
distal 1/3 vag- from ug sinus, ovaries present and have nl pubertal development
81
MRKH - how do they present
primary amenorrhea
82
tumors in DSD - 3
GCT, gonadoblastoma, itgcn
83
what tumor presents in turner syndroe and why
gonadoblastoma b/c have streak gonad
84
tumors in turner synd - gonad mgmt
Gonadectomy in childhood if 45 XO/46XY mosaic
85
mixed gonadal dysgenisis - gonadal mgmt - streak vs descended gonad
in streak gonad, early gonadectomy due to presence of Y
| if descended nl testis, do bx @ 10 yo to r/o itgcn and consider XRT
86
relative risk of testicular tumor - H/I/L
```
hi - XY gonadal dysgenesis
int - XO/XY
low - CAIS - 5-10% postpubertal
ovotesticular DSD - cryptorchid risk
other XY DSD - no inc risk other than cryptorchid
```
87
descent of urorectal septum - destination and function
destination of septum is mature colacal membrane and splits cloaca into ug sinus membrane and anal menbrane
88
when is urorectal septum descended
complete by 7 wks
89
urorectal septum descent is temporally related to what?
mullerian fusion
90
classic vs cloacal exstrophy and relation to urorectal septum
classic - after complete descent
| cloacal - before complete descent
91
exstrophy epispadius complex - 5
```
exstrophic bladder (halves)
abd wal efect
pubic diastasis
penile/clitoral malformations
vaginal duplication
```
92
persistent cloaca
extreme anorectal malformation in females
highly variable anatomy
rectal atresia
single vs duplicate vag /atresia
93
classic bladder exstrophy assd w/?
nothing
94
cloacal exstrophy assd w/?
```
midline defects (omphalocele, cardiac, spinal dysraphism (905)
GI - duplications
renal abn
cryptorchidism
lower ext malformations
```
95
persistent exstrophy assd w/?
obstructive uropathy (w/ hydrocolpos)
cardiac
renal abn
sacral abd/ tethered cord
96
what % teticles are not descended by 1 yr
1%
97
when do most testicles descend by
6 mo
98
what initiates masculinization in fetus
SRY gene
99
primary amenorrhea DDX
MRKH, complete androgen insensitivity
100
at how many wks are genital organs first seen
5 wks
101
what genital organs are seen at 5 wks - 3
indifferent gonad, mesonephric duct, and mullerian ducts
102
gene determining sexual differentiation
sex determining region y (SRY)
103
what is the gene product of SRY
high mobility group box sequence
104
function of high mobility group box
DNA binding motief that kinks DNA altering gene expression and leading to formatin of testis and male phenotype.
105
what if SRY is absent in XY
phenotypic females
106
how does rete testis develop
once induced to form testis, gonad develops clustered cords of germ cells that converge to form rete testis
107
source of germ cells for spermatogenisist?
cells converging to form rete testis serve as renewing source of germ cells for spermatogenisis
108
testosterone produciton in first 12 wks
testosterone made by differentiating leydig cells at 8 wks, then declines by 12 wks
109
testosterone and mesonephric duct
testosterone stimulates mesonephric duct to form ureter in both sexes
110
mesonephric duct develops into what 4 structures
vas deferens, epididumis, ejaculatory duct, and SV
111
WT1 and early secual development
helps genital ridge become bipotential gonad
112
2 genes involved in differentiation of indifferent gonad from urogenital ridge
WT1 (may explain association with genital abn in denys drach and WAGR), SF1 (steroidogenic factor 1)
113
2 genes involved in formation of testis
SRY and SOX 9
114
2 genes involved in formation of ovary
Wnt4, and DAX1 (doseage sensitive sex reversal region of x chromosome)
115
3 structures that come from mullerian duct
fallopian tubes, uterus, and upper vagina
116
2 vestigial structures of mullerian duct in male
appendix testis and prostatic utricle
117
persistent mullerian duct syndrome inheritance
x linked or autosomal dominant
118
persistent mullerian duct syndrome -what is it?
male with nl phenotype but also fully developed uterus and fallopian tube due to incomplete involution of mullerian derivatives
119
what is persistent mullerian duct syndrome
mullerian inhibitory substance not secreted
120
what is hernia uteri unguinalis
hernia containing uterus and fallopian tubes in persistent MDS
121
what secretes insulin-like 3
leydig cells
122
what does insulin like 3 do?
promotes transabdominal testis migration that begins testis descent into scrotum
123
how does testis descent begin
result of differential growth of gubernaculum tesis
124
how long after birth can it take for descent to occur
upto 1 yr
125
role of DHT
masculinizes genital ridge to form external genitalia, including penis, scrotum, and prostate
126
MIS deficiency - what is it
problem with production of MIS by sertoli cells or its action on target receptors
127
MIS deficiency AKA
heria uteri inguinale
128
MIS defciency presentation
encountering fallopian tubes and uterus during hernia surgery or exploration for undescended testis
129
MIS deficiency undescended testicle problem
both testicles can be on one side with vas running within the wall of the uterus
130
mis deficiency found at orchiopexy mgmt
proceed with orchiopexy, split uterus sagitally if the vas is tethered
131
hypospadius - when does androgen stimulation play its role
9-12 wks of delopment
132
androgen effect on urethral development
genital tubercle to elongate and UG folds to migrate toward midline and fuse, enclosing urethral groove
133
root cause of hypospadius
arrested penile development
134
associated gu abnormalities with hypospadius
none
135
when to do hypospadius surgery
> 3 mo and < 18 mo (genital awareness)
136
when does normal testicular descent happen
28th wk
137
timing of correction for cryptorchidism
wait until atleast 4 months - most undescended will come down by then with neonatal T surge. best to do by 1 yr old to maximize fertility
138
why do orchidopexy by 1 yr ideally
fertility - germ cell counts decrease after 1 yo. initially normal
139
treatment for testicle found in groin on us
surg not indicated for us findings for undescended testis.
140
tests to order if bilateral nonpalpable testis
FSH, LH, and testosterone
141
what lab result indicates anorchia
FSH > 3x nl
142
if FSH/LH < 3x nl and bilateral udt - what next
give HCG stim to detect any rise in testosterone
143
bilateral nonpalpable testis and any phallic development - significance
considered female with CAH regardless of phallic development
144
hematologic problem mimmicing torsion
henoch-schonlein purpura
145
small or large communicating hydrocele in infants
usually resolve within 1-2 yrs of life
146
varicocele management in adolescents - 3 mgmt steps
1. initial observation, catchup growth happens often, 2. varicocele ligation if ipsilateral volume loss > 20%, 3. abnormal semen analysis in tanner 5 teenager
147
bilateral testicles found at hernia repair in female - meediate mgmt?
finish hernia repair. che has complete androgen insensitivity
148
mgmt of testicles in complete androgen insensitiviy
will eventually need to be removed, can remain during childhood
