Unit 1 Flashcards
1
Q
Peds Os Coxa (Innominate) - what features ensure us that the os coxa is pediatric and when does it fuse
A
Triradiate cartilage
fuse by 25 yo
2
Q
what makes up SI joint
A
auricular surface of os coxa articulates with sacrum
3
Q
pubic symphysis: Why is it this kind of joint?
A
only want movement during child birth (flex and expand)
4
Q
sacrospinous lig
A
ischial spin to sacral spine
5
Q
between sacrotuberous lig and sacrospinous exiting greater sciatic foramen
A
pudendal n and int. pudendal art. and vein
6
Q
through gap in obturator membrane
A
obturator n, a, v (L2-L4) -> med compartment of thigh
7
Q
what forms Pudendal n.
A
S2-S4
8
Q
weak spot of pelvis and what does it effect?
A
pubic rami
will effect pelvic stability
could have laceration or rupture of internal organs (bladder)
9
Q
Through pelvic inlet:
S1 of sacrum to sup pubic symphysis anteriorly
A
true pelvis
reproductive organ
10
Q
sup. to pelvic inlet is:
A
false pelvis: inf. abdominal viscera
11
Q
most post. muscle
A
coccygeus and overlying sacrospinous lig
12
Q
levator ani fxn
A
supports and elevates ligament, fecal continence
tonically contracted
all posterior to rectum
13
Q
innervation for levator ani
A
pudendal n.
14
Q
other attachment of levator ani
A
attachment to tendinous arch (central thickening of fascia of internal obturator)
15
Q
what grades are stretching and tearing of pelvic floor during pregnancy?
A
skin, fascia (grade 1)
levator ani components (grade 2)
16
Q
consequences of tearing levator ani?
A
incontinence
urinary stress incontinence (sneeze, cough, sudden laugh/intra-abd pressure)
17
Q
rectovesical pouch - clinical relevance?
A
collects fluid if standing up - most inf point of abd cavity (blood internal hemorrhage, pus from infxn, ascites)
18
Q
what is migration of testes?
A
start sup. lumbar region and migrate down, and is guided by gubernaculum (fibrous tract) and connected to deep inguinal ring
19
Q
diverticulum of peritoneum/porcessus vaginalis and fxns to:
A
push it’s way through abd layers and forming inguinal canal and pulls along abd wall to cover spermatic cord and scrotum
creates serous potential space that covers testes and forms tunica vaginalis - covers testes
20
Q
Crytorchidsm
A
when testes don’t descend - usu along their natural migration
21
Q
dartos fascia fxn and make up:
A
dartos muscle is within = smooth muscle
will crincle up skin of testes to elevate if temp cools
22
Q
epididymis parts and fxn:
A
head = receives form
body
tail = convuluted and straightens and becomes continuous with ductus/vas deferens
23
Q
ductus deferens what’s inside?
A
spermatic cord testicular artery (from abd aorta because testes move down) pampiniform venous plexus cremateric fascia and musc. internal and external spermatic fascia
24
Q
drainage of testicular v
A
L testicular v = renal
R testicular v = IVC
25
testicular torsion causes and progression
usu. congenital abnl of processus vaginalis
twisting of spermatic cord
occlude pampiniform venous plexus -> back up of venous blood -> edema and swelling -> compress testicular artery
no anastomoses -> ischemia
26
variococele
more often on left side -> more acute angle, and more pressure -> valves may be more dysfxn
if pain -> could be cancer, tumor
27
ductus deferens, what does it join?
joins seminal gland/vesicles and secretes seminal fluid -> forms
28
trigone in bladder -> demarcated by?
openings of ureters and inf opening of urethra
29
male urethra - different parts?
intramural in neck of bladder
prostatic -> goes through prostate where it first receives semen, combines with seminal and prostatic fluid
short intermediate or membranous
penile or spongy urethra
30
prostatic urethra contains:
prostatic ducts + opening of ejaculatory duct
31
which ducts pass through perineal membrane?
bulbourethral glands
32
BPH (benign prostate hypertrophy)
central/middle part and impinges on prostatic urethra and can push up on neck of bladder and bladder
33
complications of BPH
dysuria
| urgency
34
post and sup to bladder
uterus
| anteverted (anteplex orientation) = most common
35
Female pouch/continuation of abd cavity
```
vesicouterine pouch (ant and smaller)
rectouterine pouch (pouch of Douglas) -> lowest point
```
36
permetrium joins with
perineum
37
myometrium fxn:
contracts during childbirth
dilation of cervix
generate force to expel fetus
38
endometrium fxn:
grow new BV and where implantation occurs, and is shed during monthly cycle if no fetus
39
narrowing of uterus
isthmus
40
opening of uterus
internal os
41
what part of uterus atrophies post menopause
body of uterus
42
fxn of fimbrae
projects into ovary, guide egg as ovulated from ovary
43
fertilation usu in?
ampulla
44
where can ectopic pregnancy occur?
peritoneum cavity, uterine tube
45
Broad ligament
covering and surround uterine tube = mesosalpinx
mesentary = mesovarium
mesometrium = remaining
46
insertion of round ligament
labia majora (analagous to spermatic cord, remnant of gubernaculum also ligamen of ovary is remnant)
47
ligament of ovary fxn
tethers ovary
48
suspensory ligament
covers ovarian vessels (arteries and veins)
49
ovarian a. comes from?
abd aorta
50
ligaments
thickening of endopelvic fascia
tranverse cervical
uterosacral
51
primary support of uterus?
bladder
52
uterine artery relationship and where does it come from?
ant and sup to ureter
and from int iliac
so don't clamp/cut ureter with historectomy
53
Uterine artery anastomoses
with ovarian
54
Vaginal artery anastomoses
with internal pudendal
55
Ischial tuberosity and pubic symphysis comprise what?
urogenital triangle
56
Ischial tuberosity and coccyx comprise what?
anal triangle (at an angle to urogeneital triangle, not flat)
57
contents of deep perineal pouch in females
urethra passes through
1. urethral sphincter
2. (transverse over sup. perineal memb) deep trans. perineal m.
58
Contents of Deep Perineal pouch in males
1. bulbourethral gland
59
sup. pouch in females (DOUBLE CHEC?)
1. bulbs of vestibule
2. crus -> angle body and glans of clitoris
3. ischiocavernosus
3. bubospongiosus
60
sup. pouch in males
1. crus of penis
2. bulb of penis
3. ischiocavernosus around the crus
4. bulbospongiosus musc. around bulb of penis
5. sup transverse per.
61
corpus spongiosum expands to form
glans penis
62
deep dorsal vein relationship
post to fascia and imp for erection
63
nerve blocks in female perineum
ilioinguinal n. block if still feeling pain
| pudendal n. (esp. for tearing during childbirth -do near ischial spine for most prox)
64
what is Prader classification?
degrees of virilization where stage 0 is nl female and 5 is nl male
65
testing of virulization
FISH for Y (probes for SRY) and can get back within 48 hrs
karyotype and microarray takes a couple days
further work-up if SRY is present
imaging = US for presence of uterus
laparoscopy = best way to eval
66
46, XX DSD DDx?
95% CAH
46, XX sex reversal (SRY translocation onto X)
Ovotesticular DSD (both ovarian and testicular tissue) -> most have xx karyotype, mom exposed or has high androgens
67
what makes SRY so easy to translocate
proximal pseudoautosomal region of Y
68
46, XY DSD pure gonadal dysgenesis
present with lack of puberty - no breast development or menstrual cycle because internal and external is female but no ovaries
69
mixed gonadal dysgenesis (45x/46,xy)
mosaic -> different karyotype in different cells
usu testes on one side and streak gonad on other side
testes is usu abnl
70
testicular regression
usu within first year
| present with cryptorchidism
71
46, xy WT-1 mutation
present with bilateral wilm's tumor before they did lots of genetic testing
androgen insensitivity was initial dx
72
46, xy, der(9)t(2;9)(p22.2;p24.3) underexpression of DMRT2
gonadal dysgenesis
female genetalia
mental delays
orig. dx of androgen insensitivity
73
46, xy DSD
any of these, not enough testosterone
under virulized xy
- 5alpha reductase
74
5 alpha reductase deficiency
undervirulized but degree varies
testes usu in inguinal canal or labial-scrotal folds (should be able to palpate gonads)
wollfian ducts differentiated
make AMA so don't have mullerian structures
at puberty, spontaneous virilization occurs (at puberty type 1 is expressed and test. can be converted to DHT
Type 2 in newborn is deficient
75
Androgen insensitivity syndrome
mut in androgen receptor gene
| complete -> picked up in childhood (hernia) or puberty with primary menorrhea
76
CAIS
XY - testes develop, can't respond to testosterone though they are making, wollfian ducts mostly regress, testes make normal AMA so mullerian structures go away -> no internal duct system
External - very female, no clitoral megaly, nl labia, separate urethra/vagina openings
vagina ends into a wall -> no cervix or uterus
77
CAIS
gonads intra-abdominal or inguinal canal because testost. needed for descent
bilateral inguinal hernias common
at puberty, spontaneous breast development because such high testosterone from testes that is converted to estrogen
little or no pubic/axillary hair
female gender identity
78
what is management of CAIS?
avoid gender assignment before expert evaluation (esp at birth or before thorough eval)
center with experienced interdisciplinary team -> endo, urologist, gyn, psych, geneticist
communicate with pt/families, respect concerns and address in confidence
79
DSD Outcomes
gender dysphoria underestimated in past and gender counseling as well as sexual counseling should be part of multi-disciplinary service available to pt with DSD
try not to encourage surgery
80
what is precursor to all steroid hormones?
cholesterol
81
3 B HSD converts what to what?
pregnenolone to progesterone
17OHpreg -> 17OHprogesterone
dehydroepiandrosterone -> androstenedione
82
what happens when cortisol goes down
increased CRH and ACTH
83
CAH pathophys?
one of many enzyme def that leads to decreased cortisol, and increased CRH/ACTH
drives adrenal gland to make more hormones in pathways that aren't affected by def.
84
CAH enzyme def
```
21-hydroxylase = 95%
11B-hydroxylase = ~5%
```
85
21 hydroxylase def hormone pattern?
decreased cort and aldo
increased androgens
most prominent feature = virilization
86
Clinical features of 21 OHase def?
```
female = virilization of external genitalia - clit megaly, GU sinus aka one opening (mullerian develops fine and no wollfian ducts develop)
males = nl external genitalia
```
hyperpigmentation
- MSH and ACTH from POMC (more MSH and ACTH can bind to MSH receptor)
hypoNA, hyperK due to aldo def.
mild forms - present later with early pubic hair, axillary hair, penile/cliterol enlargement
87
KNOW THIS: Dx of 21 OHase def?
dx suspected in virilized XX infant or XY with hypoNA and hyperK and vomiting
measure 17OH progesterone -> now on newborn screen
88
KNOW THIS: Tx of 21 OHase def?
surgery in females
replace def hormones and suppress ACTH overproduction
Glucocort (hydrocortisone and increased for illness/stress), mineralcort (florinef and salt supplements) , acute adrenal insufficiency - IM/IV solu-cortef
89
11BOHas def
virilization similar to 21-OHase def
no salt wasting
HTN frequent finding
more of late dx
90
StAR protein clinical features
rare
91
3B HDD
virilization in girls = similar to 21 OHase def
| undervirilization in boys = difference between 21 OHase def
92
17alpha OHase, 17,20 Lyase Def
decr. androgens
but no def. of aldo
HTN secondary to incr 11-deoxycorticosterone
hypoK
female failure to develop 2ry sex characteristics at puberty
male = undervirilized
93
Which def are salt wasting and which one arent?
```
Salt Wasting
- 3B HDD
- StAR protein Def
No Salt Wasting
11B-OHase Def
```
94
Pathophys of StAR protein Def
Cholesterol stays in cholesterol ester -> fatty adrenal gland = lipoid in adrenocortical tissue
StAR involved in transfer of cholesterol from outer to inner mito membrane
95
KNOW THIS: Monitoring Tx of 21-OHase Def?
Lab: 17OHP, androstenedione, testosterone
Growth
Skeletal Maturation
96
what gives rise embryologically to all GU system?
intermediate mesoderm
97
what are cardinal steps in mullerian dev?
```
elongation
fusion
canalization
septal resorption
+ union of mullerian (cephalad) with GU sinus (caudad)
```
98
cloaca divides into
anal and GU
99
sinovaginal bulbs
develop vagina from that
| where mullerian system connects
100
upper vagina develops from?
paramesonephric duct (mullerian)
101
lower vagina develops from?
GU sinus (not skin) and migrates out
102
uterine tube migration
comes together to form fundus of uterus at top and bottom (septal/walls of tube) part has to resorb to form uterus
103
Obstructive lesions - sx depends on level of obstruction
| Vagina obstruction
- imperforate Hymen - failure of caudal end of sino-vagninal bulbs to canalize
- transverse vaginal septum - Failed Canalization of the Vaginal Plate. this is where the Mullerian ducts meet Urogenital Sinus
- Vaginal atresia
Failure of Canalization of Urogenital Sinus Below Vaginal Plate
104
when is intervention probably not necessary?
If it doesn't obstruct menstrual flow, affect fertility, or affect sexual function.
105
Imperforate Hymen Tx:
blue discoloration behind hymen - blood building up
| - tx: surgery, very easily
106
transverse vaginal septum Tx:
more superior and thicker than hymen
excise
area is demuted and have to stitch close
107
Vaginal atresia Tx:
no vagina or uterus
incision posteriorly and skin graft is made and placed
bed rest so skin is re-vascularized
108
Failed cardinal steps of dev: elongation
mullerian agenesis
| Unicornuate Uterus
109
Failed cardinal steps of dev: Fusion
```
uterine didelphys
(2 cervix)
```
110
Failed cardinal steps of dev: septal reabsorption
septate uterus
| 2 uterus, 1 cervix, 1 vagina
111
Which chromosome is androgen receptor gene on?
x chromosome
112
what is default pathway for genitalia dev?
female
wollfian ducts will involute and die
without AMH -> mullerian ducts differentiate
dev of female ducts and external genetale is indep of gonadal hormones
If no gonads, female format
results
113
Leydig cells fxn
make testosterone (95%) which move into sertoli cells
- spermatogenesis
make StAR and SCP (sterol-carrier protein)
- Transport cholesterol to mitochondrial side chain
cleavage enzyme
- Stimulate steroidogenesis
Respond to LH through a G-protein coupled
receptor (GPCR)
114
sertoli cells fxn
FSH - stim aromatase to make estrogen
form blood testes barrier
- AI response to own sperm (don't want) and want to protect from pathogens/toxins
nurture developing sperm
APB - conc. locally so right level for spermatogenesis
secrete inhibin and other growth factors - in response to FSH
respond to FSH through GPCR
115
Cross-talk between Leydig and Sertoli cells via FSH
- FSH also induces release of other Leydig cell growth factors from
Sertoli cells (TGFa, TGFB, IGF-1, FGF-2)
- FSH (acting on Sertoli cells) regulates proliferation and
development of Leydig cells to provide adequate Testosterone for spermatogenesis
- Testosterone from Leydig Cells synergizes with FSH to increase
Androgen binding protein (ABP) production in Sertoli cells to
maintain high local T concentrations
116
Hypothal-Pit-Testicular Axis
GnRH stimulates production of
FSH and LH from pituitary
LH acts on Leydig cells
Increased Testosterone
Increased StAR and SCP
```
FSH acts on Sertoli Cells
Increased Androgen binding
protein (ABP)
Increased Aromatase
Increased growth factors
Increased spermatogenesis
Increased inhibin
```
117
H-P-T Axis: Neg. Feedback
- Androgens (Testosterone) inhibit release of GnRH from
hypothalamus
- Androgens (and Estrogen) inhibit LH and FSH release from pituitary
- Inhibin suppresses FSH production from pituitary gonadotrophs
118
hCG: role in doping in sports?
LH substitute -> stim testosterone release
- would have to be pulsatile because these hormones are
- stimulates fetal tissue to produce testosterone
- hCG can be produced from some cancers
119
what happens with aging in males with FSH/LH if gonadal fxn is compromised?
in males pituitary fxn starts to decline -> produce less LH/FSH even with loss of neg feedback with steroid hormones
decr spermatogenesis => decr. inhibin -> elevated FSH
FSH is sensitive marker of fertility in males
120
Actions of Androgens?
Differentiation and development of male internal and external
genitalia-T, DHT
Initiation and maintenance of Spermatogenesis-T,DHT, E
Development and maintenance of 2nd sex characteristics
Anabolic
121
Actions of Androgens specifically with dev. and maintenance 2ry sex characteristics?
Growth of external genitalia-T, DHT
Male pattern of hair growth-DHT (baldness) also beard growth
Sebaceous gland secretions-DHT
Inhibition of breast growth (mammillary gland) -T
Behavioral responses, Libido-T, E, DHT
Negative feedback at hypothalamus, pituitary-E, T
Stimulation of Androgen binding protein synthesis-T
122
Androgens action on Liver?
incr VLDL, LDL and decr HDL
123
Anabolic androgen action?
Muscle growth, strength
beer belly
bone growth - T -> E via aromatase
124
before puberty levels of LH/FSH?
FSH> LH
125
after puberty levels of LH/FSH?
LH> FSH
126
Male Pubertal Growth hormones?
Increased Growth Hormone
| Increased Testosterone
127
growth spurt in females?
higher estrogen dampens growth and counters growth hormone
128
Male growth spurt?
Pubertal growth spurt
Average 28cm (11”)
Accounts for 10cm (4”) height disparity in males vs females
129
Post pubertal males comparison to females?
150% of female muscle mass
150% of female skeletal and lean body mass
200% of female muscle cell number
50% of female body fat
130
Effects of androgens mediated by?
ONE ANDROGEN Receptor
Hormone Dependent TF
- specific to organs or tissues though
-Effects mediated by same receptors and molecular
mechanisms
Interactions with Insulin-like growth factor (IGF-1)/
Growth Hormone (GH) axis
131
Androgens and Growth Androgenic Effects
Growth and development of male reproductive tract
Secondary sexual characteristics
Behavioural responses
132
Androgens and Growth
| Anabolic Effects
Growth of somatic tissue
Linear body growth (long bones)
Nitrogen retention, protein synthesis
Muscle development
133
What happens with too much testosterone?
- converted to estrogen
| - so want to prevent, Aromatase inhibitors etc.
134
Interaction of the GH/IGF-1 and HPT axes
```
GH/IGF-1 stimulate
gonadal functional
IGF-1 stimulates
GnRH secretion
Testosterone and
Estrogen stimulate GH
secretion and growth
```
135
GH effect on long bone growth?
```
GH causes balanced growth and
ossification; bones continue to
lengthen through childhood and
pubertal ages under its influence in the
absence of sex steroids.
```
136
sex steroids effect on long bone growth?
```
promote ossification
epiphyses narrows and eventually closes
• Stimulates bone growth
• Accelerates bone maturation
• Promotes epiphyseal closure
• Dominant effect is to narrow growth window limiting
long-bone growth
• Growth ’levels off’ after puberty ( under control of
GH/IGF-1 axis)
```
137
how does pre-pubertal abuse of steroids look?
grow faster then end up shorter
rapid rate of growth but end up shorter
(could be using because congenital anomaly causes need for steroids)
138
Consequences of Steroid Abuse? GU
Infertility-decreased sperm production
Gynecomastia- breast development
Testicular atrophy
Fluid retention, Kidney failure
139
Consequences of Steroid Abuse? CV
Increase LDL decreased HDL-atherosclerosis
High blood pressure
Heart attack and stroke
Enlargement of left ventricle
140
Consequences of Steroid Abuse? Psych and Drugs
Psychiatric disturbances- mania, delusions, rage & irritability -> anecdotal in humans and seen in animal models, insomnia
Gateway drug b/c injectable -> Increased risk of HIV or hepatitis and other infections
141
Consequences of Steroid Abuse? Hair/Bones/Liver/Skin
Baldness and excessive body hair
Short stature
Tendon rupture - disproportionate musc. dev.
Liver cancer, pelios hepatis (blood filled cysts)
Severe acne, cysts, oily scalp
142
hypogonadotropic hypogonadism
testes nl, baby is making plenty of testosterone in first trimester, penis is nl,
2nd phase of testicular dissent (b/c decr testosterone in 2nd and 3rd trimester)
- lack of puberty due to absence of GnRH and/or gonadotropin secretion from brain
- characterized by low gonadotropins
- complete or partial, temp. or permanent
143
puberty in fetus/infancy?
not de novo event (reactivation because active from 2nd trimester on)
- active in fetal development
- continues to fxn in infancy "mini-puberty" (boys only until 6 mo, 18 mo in girls -> gives idea of what is developing)
- after infancy, axis enters quiescent state, referred to as juvenile pause
144
In juvenile pause what NT is higher?
Gabba, more inhib
| keeps pre-pubertal
145
indicator of puberty?
LH > FSH pulses at night
146
HPG axis during puberty?
process is gradual
| GnRH increasing first at night and increased LH
147
pre-puberty hormones?
FSH> LH
148
Lab evidence of Puberty?
Leuprolide = analoge of GnRH
look at response of LH
pubertal respons is > 5.6mlU/ml
if give and LH peaks at 2 or 3 -> pre-pubertal
149
physical changes of Gonadarche (girls) -> due to estrogen
```
breast dev.
genital growth (labia minora)
maturation of vaginal mucosa
uterine/endometrial growth
body comp changes (female fat distribution - hips)
menarche (estrogen and progesterone)
```
150
Only change early on in boys for gonadarche?
enlargement of testes (mediated by FSH and LH) - @ 4-5 ml of testes -> can happen 6mo to yr before pubic hair
151
physical changes of Gonadarche (boys) -> due to testosterone from testes or adrenals
```
scrotal changes (thins)
sexual hair (upper lip, chin, sideburns, axilla, pubic area)
penile growth
prostatic/seminal vesicle growth
deepening of voice (late)
incr muscle mass (late)
```
152
physical changes of Gonadarche (boys and girls)
linear growth acceleration
bone age advancement - mediate by estrogen in both boys and girls and testosterone is converted by aromatase enzyme in boys
153
Aromatase inhibitor to pubertal boy?
slows skeletal maturation
| testosterone goes through the roof
154
Adrenarche what is it and what does it cause?
increased adrenal androgens (DHEA-S, androstenedione) which cause pubarche
girls - pubic hair, axillary hair, body odor, and acne -> because ovaries aren't making
in boys - androgen is androgen
-> causes same changes but not specifically from adrenals
155
Timing of Puberty Tanner 2 Breast development - Girls
early age, mean
white - 8 yrs, 10.4 years
black - 6.6, 9.5
Hispanic - 6.8, 9.8
156
Menarche for caucasians?
between tanner 3 and 4 generally
157
menarche for girls?
early age, mean
white - 10.65 yrs, 12.55 years
black - 9.7, 12.06
Hispanic - 10.05, 12.25
158
Tanner stages- Breast
```
1 = pre-pubertal
2 = breast bud, just under or extended from areola
```
159
Tanner stages- Pubic
Stage 1: Prepubertal (can see velus hair similar to abdominal wall)
Stage 2: Sparse growth of long, slightly pigmented hair, straight or curled, at base of penis or along labia
Stage 3: Darker, coarser and more curled hair, spreading sparsely over junction of pubes
Stage 4: Hair adult in type, but covering smaller area than in adult; no spread to medial surface of thighs
Stage 5: Adult in type and quantity, with horizontal distribution ("feminine")
160
Timing of Puberty - boys
testes > 3 ml = 11.8 yo (9-14)
pubic hair = 12 y0
penile enlargement = 13 yo
peak height velocity = 14 yo (mid to late puberty = fast growth) w/ more musc mass and deepening of voice
161
Tanner Stages boys
pubic hair and testicular volumes stages
genital stages- professor disregards
```
4 = triangular
5 = diamond shape
```
162
delayed puberty criteria for dx?
no pubertal signs by 13 yrs in girls and 14 yrs in boys
or lack of progression
- no menarche by 4 yrs after onset of breast development (puberty starts)
- no completion of genital growth in boys after 5 years
163
bone age and puberty?
onset of puberty is commensurate with child's biologic age (bone age)
- girls start at bone age of 10.5 - 11
boys = 11.5-12
164
delayed puberty and hormones
- low gonadotropins = hypogonadotropic (or central hypogonadism)
- elevated gonadotropins = hypergonadotropic (or primary) hypogonadism
165
constitutional growth delay
- onset and progression of puberty corresponds with bone age
- growth continues later in life but reaches height potential
- FH of "late bloomers"
- decelaration of linear growth w/i first 2 yrs of life
- normal linear growth after this with delayed bone age
166
Tx of constitutional delay
reassurance
- for boys sometimes short course testosterone, for girls, short course of estrogen
- re-eval in 4-6 mo
167
difference between constitutional delay and hypogonadotropic hypogonadism
bone age (if older and no puberty might be hormones)
- presence/absence of adrenarche
- HGHG = boys and girls -> gonadarche and adrenarche is delayed
- adrenarche will start when it should
168
unicoid body habitus
arms and legs are longer than should
not going through puberty at right time
low upper to lower ratio
arm span bigger than hight
169
Congenital causes of HGHG
part of multiple hormone deficiencies - septo-optic dysplasia -> mult pit def from abnl brain development
- genetic syndromes = prader-willi syndrome (most common)
- hypotonia, wants to eat a lot
170
IHH = idiopathic hypogonadotropic hypogonadism
absence of any structural abnormalities of hypothalamus or pituitary
isolated defect in GnRH or gonadotropins
171
Kallman syndrome ?
IHH plus anosmia/hyposmia
- agenesis of hypoplasia of olfactory sulci and/or lobes
- association between from defect in shared developmental origins of GnRH and olfactory neurons -> migration of neurons
- genes assoc with IHH = Kal-1, FGFR1 ... -> only accounts for 30% of cases
172
Fxn'l or revesible causes of HGHG
chronic illness, malnutrition
stress, excessive exercise (even in absence of low body wt)
anorexia, hyperprolactinemia(oma), hypothyroidism
173
Acquired Causes of HGHG?
pituitary or hypothalamic tumor, cranial irradiation, CNS infection, infiltrative diseases (histiocytosis, granulomatous disease, hemachromatosis), AI hypophysitis
174
HGHG
primary gonadal failure leads to decr. neg feedback
| high LH and FSH - most common in girls = Turner Syndrome
175
Primary Ovarian Failure
- Turner Syndrome
- XX or XY complete gonadal dysgenesis (XY = SRY, no testes - not picked up until puberty because don't start, will have adrenarche, nl internal and external genitalia, usu tall)
- galactosemia
- radiation
- chemotherapy (alkylating agents)
- AI
176
Turner Syndrome
- Frequent
- 45, X karyotype in 50% with the rest being moasaics or structural abnormalities of X chromosome
- may have no phenotypic characteristics except for short stature
177
Turner Syndrome phenotype percentages
100% short stature
94% ovarian failure
CV, thyroiditis, hx of otitis, dysmorphic facies = common
178
Primary Testicular Failure
- Klinefelter's Syndrome
- cryptorchidism
- testicular regression syndrome
- radiation (usu ok testosterone but lower sperm)
- chemotherapy
179
Klinefelter's Syndrome
most common, typically present with gynecomastia, smaller testes than expected for degree of virilization - tanner 4, usu don't present with delayed puberty, miss because don't check testes size
- 1/1000
47, xxy (or can have 3 or 4 x -> more X, more dev probs and behavioral probs)
- hyalinization and fibrosis of seminiferous tubules
180
phenotype Klinefelter's Syndrome?
microphallus, infertil, small testes, learning disabilities, eunochoid, delayed or arrested puberty, gynecomastia, infertility
181
Eval of Delayed Puberty
bone age (growth delay, hypothyroid... why?
- if bone age is older -> check labs
- Labs: gonadotropins, test in boys and estradiol in girls, may consider TSH, T4, Prolactin, CBC, ESR, BMP
- karyotype if elevated gonadotropins
182
Tx of hypogonadism
- Boys
testosterone Q3-4 wks initially low dose to gradually incr (gels are annoying)
- Girls
estrogen alone followed by cyclic therapy with estrogen and progesterone (add if have uterus like in Turner)
183
Complete Precocious Puberty Signs
```
onset and progression of changes
- accel linear growth
- advancement of skeletal age
Can be:
- Central (GnRH dependent)
OR
- Peripheral (GnRH independent)
```
184
Incomplete Precocious Puberty
```
benign thelarche
benign adrenarche
Defn:
boys - dev prior to 9 yrs of age
girls - dev prior to 8 yr in caucasian, 6.5-7 in AA and hispanic
```
185
Central Precocious Puberty
same physical ∆ and lab testing are consistent with progressive ∆ of HPG axis activation
- 5% in girls = CNS abnormality
- 50% of time in boys is caused by CNS abnormality - lower threshold to image boys because more common
186
Central Precocious Puberty Causes
- Hypothalamic Hamartoma (present in first 2-3 yrs of life)
- treat medically
anything that disrupts inhibition of HPG axis
- suprasellar tumor
- hydrocephalus
- previous CNS infection
- major head trauma
- cranial irradiation
187
Causes of Peripheral Puberty
| Girls: Estrogen mediated
Ovarian cysts
granulosa cell tumor
exogenous estrogens
lavender or tea tree oil products
188
Ovarian cysts
ovarian follicles form cysts (prepubertal FSH stimulation, can secrete estrogen for breast development but usu present with vaginal bleeding)
- areola gets dark as estrogen increases but as estrogen goes down - causes bleeding
- trans-abdominal US to assess and do it at that time
- assoc with McCune- Albright Syndrome
189
McCune-Albright Syndrome
lethal if mutation in all cells
- constituative activation in alpha subunit of stim G-protein
- triad of precocious puberty, cafe-au-lait spots (doesn't cross midline usu or follows dermatome), polyostotic fibrous dysplasia (MOST COMMON)
- can also have GH excess, hyperthyroidism, Cushing's syndrome
190
Peripheral Precocious Puberty Boys
Adrenal tumor
Leydig cell tumor
hCG secreting tumor (LH like, stims Leydig cells to make testosterone)
McCune-Albright Syndrome (rare)
Late-onset congenital adrenal hyperplasia
191
presentation of adrenal tumor and late-onset congenital adrenal hyperplasia
```
pubic hair
maybe axillary hair
maybe some growth acceleration
testes = small (no LH/FSH)
bone age advancement
```
LABS differentiate between the two
192
hCG secreting tumor
- testes a little bit enlarged but not as large as central precocious puberty
- more virilization compared to how big testes are
193
Familial testotoxicosis
Periph precocious puberty in boys
- testes somewhat enlarged from leydig hyperplasia
- high testost from early on
- sign. penile growth
- mutation of LH receptor - activated
- AD with only male penetrance
- Autonomous Leydig cell activity
- more virilization compared to how big testes are
194
severe primary hypothyroidism
TSH > 500 and close to 1000
- both sexes
- mechanism may be hormonal overlap - TSH is like FSH
- girls can present with ovarian cysts, high estrogen, vaginal bleeding
- boys - stim of sertoli cells, no testosterone so no leg hair etc. don't have stim of leydig cell = macro-orchidism
- delayed bone age and poor linear growth
195
Eval of precocious puberty
hx
- growth pattern (nl or accel)
- BONE AGE
- tanner staging, size and symmetry of testes, cafe au lait, neuro findings
- GnRH stim test or random gonadotropins
196
NL ranges for LH for Tanner stages and labs values to test for puberty
tanner 1 = .02-.18
tanner 2 = .02-4.7
so if do random LH and is above .18 then it is dx of precocious puberty but if below then have to do GnRH stim and if LH is above 5 then diagnostic
197
eval of precocious puberty in girls
estradiol and pelvic US
198
eval of precocious puberty in boys
testosterone, androstenedione, DHEA-S, 17-OH progesterone, hCG
- adrenal/testicular US based on lab results -> not first line
199
ovarian cyst eval
high estradiol but GnRH stim test is pre-pubertal -> do US
200
Tx of precocious puberty Central
```
GnRH analogue (Lupron/Supprelin) - down regulates pit GnRH receptors
supprelin suppresses better and just have implant so easier
decr gonadotropin secretion
```
201
Peripheral Precocious Puberty TX?
Cyst = watchful waiting
- If large enough, ovaries can have torsion around cyst -> monitor for pain
McCune - Aromatase inhibitor (letrozole)
Familial Testotoxicosis: aromatse inhibito to block bone age but then testoterone gets high -> androgen blocker OR ketoconazole (SE)
CAH - Glucocorticoids
202
Incomplete Pubertal Development causes?
Premature Thelarche
203
Premature Thelarche defn:
- onset of breast development w/o other assoc pubertal ∆
- no growth acceleration or bone age advancement
- breast development progresses very slowly or waxes and wanes in size
204
GnRH
```
Continuous = suppression
Pulsatile = increased
```
205
Exogenous Testosterone effects (Pharm)
```
Positive peripheral aspects but shuts down axis
testicular atrophy (give hCG) and decr. spermatogenesis
```
206
Testosterone most important androgen in?
muscle and liver
207
what actions in males mediated by estrogen receptors?
Bone
| - closure of epiphyseal plate, if doesn't then long bone growth continues -> osteoporotic
208
HRT used in aging men?
testosterone levels below normal (below 200-300) and with symptoms
- low libido - decreased morning erections - small testes
- low bone mineral density
- gynecomastia
FSH or gonadotropins for spermatogenesis
ONLY for testosterone def.
- inc inappropriate use b/c ads for non specific sx encouraging men
209
Symptoms related specifically to androgen def in aging males
LOW LIBIDO and Low Bone mineral density
210
Testosterone abuse in sports
all anabolic hormones (testost. analogs) also have androgenic SE
- block of LH-FSH release
- promotion of prostate growth
- trying cycling and stacking to reduce androgenic SE
211
Testosterone administration and most stable chemical form?
infrequent administration and most stable
make it ester and inject IM
half life clock doesn't start until in plasma
so this formulation extends half life
212
Oral testosterone = methyltestosterone pharmacokinetics and ADR:
alkylated to reduce first pass metabolism but has Hepatic side effects
213
Transdermal ADR and reasons for:
severe skin rash
sustained delivery over 24 hr pd (normalizes T levels)
- has a peak
214
Transdermal gel pros and cons:
$$, best at maintaining stable levels
215
ADR of Testosterone
```
AVOID androgens in infants and young
- decr spermatogeneis (androgenic)
reversible cholestatic jaundice (hepatotoxicity)
- incr PLT aggregation, arterial thrombosis
- roid rage
- concerns of stroke, MI, mortality
- no info on PSA, prostate enlargement
- gynecomastia
```
216
USE of testosterone where benefits outweigh risks:
HYPOGONADAL MEN (not just low T men)
217
pulsatile agonist
increases LH and FSH
218
Continuous agonist
blocks release - prior to desensitization -> LH/FSH will transiently rise and exacerbate
219
Finasteride = efficacy in prevention of male pattern baldness by virtue of its ability to:
reduce production of DHT
| 5 alpha reductase inhibitor
220
anti androgens flare sx?
no flare symptoms with antagonists
221
clinical uses of anti-androgens
BPH, Androgenetic alopecia (male pattern baldness), precocious puberty in boys, Hirsutism (PCOS)
222
first choice in hirsutism
estrogen-progestin contraceptive
| synth of androgens is not controlled -> increase binding globulin so free levels go down
223
ADR of anti androgens
```
leuprolide = hypogonadism
finasteride = decr libido
```
224
what size of testes will you know the male has gone through puberty?
>10-12 mls
225
low testosterone with hypogonadism
if at hypothalamus LH and FSH = nl or low
| if at testes LH and FSH is high and testosterone is low
226
Acquired central hypogonadism
GnRH pulse generator defect
Narcotics
Glucocorticoids - usu steroid injections
Supplements
227
what can cause GnRH pulse generators defects?
stress, severe illness, abnormal wt loss, low body fat
228
what other meds besides narcotics can cause hypogonadism?
opioids, other pain meds, synthetic marijauna
229
What supplements can cause central hypogonadism and what should you do about it?
prohormones, anabolic steroids - major cuase if undetectable LH, FSH
Take them all out since not FDA approved and then add them back one at a time
230
what do you do to recover from exogenous androgen supppression of hpt
time, data is weak to show any faster recover with clomiphene, hCG
231
how do we measure testosterone?
testosterone bound to protein, assays aren't good for free testosterone
232
why could total testosterone be incorrect?
because testosterone binding protein can change with age and reflect a false low
233
cause of borderline low testosterone in colorado?
obstructive sleep apnea
- cortisol and catecholamines from hypoxia
- decreased NO in cavernosal musc, decrease in cGMP
slight impairment of GnRH pulse generator
tx sleep apnea
234
low LH and FSH, low T, what is DDX? (pituitary hypogonadism)
prolactinoma, craniopharyngioma, rathke's cleft cyst, pituitary tumor (GH, ACTH, some gonadotrope), metastasis, hemachromatosis, inflammatory: lymphocytic hypophysitis
headache and blurred vision might be clues
235
hypogonadism (8ml bilateral), nl testosterone, high FSH and nl LH, no sperm
something went wrong with puberty (small testes)
LH and FSH shoul be equal and should be about 10-12
FSH higher than LH -> loss of inhibin which inhibits FSH
probably congenital due to no sperm and small testes -> hypergonadotropic hypogonadism (high FSHH +/- LH, low T)
236
congenital causes of hypergonadotropic hypogonadism
congenital anorchia
| klinefelter's
237
klinefelter's syndrome
delayed puberty, low inhibin, azospermis, eventual need for T replacement, mammogram, progressive tubular fibrosis, gynecomastia, if prime testes with hCG and sometimes harvest sperm, don't know if risk for DVT/PE
238
acquired causes of hypergonadotropic hypogonadism:
trauma/torsion
mumps orchitis
etoh: direct testicular toxin
dm
radiation/chemo
AI testicular failure: check for others (TSH, glucose, B12, vit D)
pituitary tumor gonadotrope (secreting FSH, nl LH and nl T)
239
late onset hypogonadism
Rare only 3-5% of men
seen with comorbidities (dz), incr wt, increase with age
and T levels increase with wt loss
240
tx of late onset hypogonadism
diet, lifestyle, wt loss
| - improve CV health, OSA, metabolic fitness, testosterone levels, sometimes improves ED
241
CAD events with Testosterone?
risk of event correlated with higher testosterone levels
242
potential mechanisms for cardiac risk?
induction or worsening of polycythemia
Worsening obstructive sleep apnea
Stimulation of platelet aggregation via Thromboxane A2 receptor density
Decrease in HDL levels
Salt and water retention
? Dose, type of T administration - high testosterones correlated with IM testosterone but too low is bad too
243
potential risks of testosterone tx? everything but CV
CHECK PSA, if rises more than 1.5 in 1 yr -> work up
Stimulation of prostate growth in previously undiagnosed prostate cancer (PSA rise 1.5/12mo w/u)
Risk of bladder outlet symptoms due to increase in prostate volume
Gynecomastia
Precipitation or worsening of sleep apnea
244
potential risks of testosterone tx? CV
Erythrocytosis, Edema in patients with pre-existing cardiac, renal, or hepatic disease, Increased cardiovascular events
245
Real hypogonadism with low LH, FSH, testosterone
Low LH, FSH, testosterone
- Genetic rare
- Acquired: narcotics, glucocorticoids, hemochromatosis, tumor, XRT, stress, illness
246
Not Real hypogonadism
OSA, T assay (effects of SHBG)
247
Real hypogonadism with High FSH, LH, low testosterone
Primary testicular failure (XXY, trauma, other)
| Gonadotrope pituitary tumor
248
tx testosterone indicated for what?
chronic narcotics -> testosterone
pituitary tumors and radiation -> hypopit
GnRH def
Klinefelter's
if want to try and figure it out but know at incr risk for CV
good at physiological levels but pharmacological levels is less good.
249
as testes distends they:
pulls peritoneum with it -> peritoneal pouch goes into scrotum -> can become traumatized/infxn
250
histology of testes: leydig cells, tunica albuguinea etc.
tunica albuguinea = white coat around outside - protect from abrasion
leydig cells -> testosterone -> driving force for spermatogenesis
blue elastic fibers of BM -> hold spermatogoonia
251
development of sperm
spermatogonium -> primary spermatocyte -> secondary -> spermatids -> spermiogenesis -> late spermatids
252
without BTB
made by: tight jxn between sertoli cells -> AI towards self (granulomatous inflam) -> can cause infertility
253
Congenital abnormalities of testis
maldescent, absence, fusion, cysts
254
maldescent of testis
cryptorchidism -> not found it's way properly into scrotum
can be found: abdominal, superficial or deep inguinal canal, opposite thigh, perineum, root of penis
Most in superficial inguinal canal
255
testes maldescent, reason why:
lots of ligamentous attachments (the one the doesn't degrade becomes high that pulls testes along)
256
cryptorchidism complications and facts:
easily traumatized
unilateral (75%) and mostly idiopathic
atrophy as early as 2 yo
contralateral testis may also regress
2 degrees cooler than body for optimal sperm development
5x increased risk of malignancy (in cryptorchid testis and contralateral testis)
257
when you tx cryptorchidism
the earlier the better
| reduce risk of malignancy and atrophy of contralateral testis
258
cryptorchidism histology at 2 yrs
∆ within tubules themselves
| leydig cells almost vanished
259
cryptorchidism histology at puberty
disorganized
260
cryptorchidism histology at adulthood
atrophy
| anaplasia and dysplasia
261
testicular atrophy
```
cryptorchidism
athersclerosis and DM - affect blood stream (big role in US)
worldwide = inflam and malnutrition
hypopit
hormone tx (prostate cancer)
klinefelter's syndrome
```
262
histology of testicular atrophy
layers of spermatocytes etc = thinner
can completely lose all germ cells - just sertoli cells are left (usu hard to see)
interstitium devoid of leydig
263
klinfelter's sclerosing tubular degeneration
tubular sclerosis
leydig cell hyperplasia (hormones) b/c elevated FSH/LH
decreased testosterone (no feedback on FSH/LH)
no elastic fibers
264
atrophy loss of hypertrophy of leydig
depends on etiology
265
varicocele anatomy and common causes
def abnormal dilatation of tortuosity of veins in pampiniform plexus
- venous valve insufficiency
- LS more common only 10% bilateral
266
varicocele assoc with infertility when:
bilateral,
possible thermal effect
Maturation arrest, hypospermatogenesis, abnormal sperm morphology
Possible epiphenomenon
267
twisting/ torsion -> infertility
| how does this cause?
block venous first- engorges with blood
- > hemorrhagic infarction because arterial pressure -> congestion of interstitium
- > pressure necrosis of testes parenchyma
- > PAINFUL (dramatic)
268
infertility with sperm specifically
dynein arms needed
| if missing -> infertility
269
inflam dz of testis and epididymis
```
Nonspecific epididymitis & orchitis
Mumps orchitis
Tuberculous orchitis
Syphilis
Granulomatous (autoimmune) orchitis
```
270
Nonspecific Epididymitis/Orchitis - causes in children through elderly?
children - rare but use assoc with UT malformation (Gm neg rods)
Sexually active adults – C. trachomatis, N. gonorrhoeae
Elderly - Enterobacteria
Direct extension from urinary tract
271
histology and pathogenesis of nonspecific epididymitis/orchitis
see pus
| infxn in this area -> acts like abscess -> necrosis quickly because disturb vascular flow
272
mumps orchitis
usu parotid infxn
1 - 2 wks after parotid involvement = mumps orchitis
painful/pressure
infertility uncommon because mumps is usu unilateral 70% of time
- shrunken and white scarring
273
what two disease of testes mimic eachother
TB and syphilis
274
TB orchitis
Epididymis → Testis
Usually part of systemic disease
Caseating granulomas- giant cells (look just like lung)
275
syphilius orchitis
```
gumma = coag necrosis that extend along blind ended arteries
Testis → Epididymis
Congenital or acquired
Plasma cells, lymphs
Obliterative endarteritis
```
276
Testicular Tumors
Germ cell tumors (95%)
- Seminoma
- Spermatocytic seminoma
- Embryonal
- Yolk sac
- Choriocarcinoma
- Teratoma
- Mixed
277
Germ cell tumors
- most are pure or mixed
- metastases can vary from primary
- tend to occur in young men (15-30)
Painless testicular enlargement
Predisposing factors: cryptochidism (5X), genetic factors (family history-5X), dysgenesis (50X)
Environmental factors?
Chromosomal changes: +12p
278
GERM CELL NEOPLASMS flow chart KNOW!
totipotential germ cell -> seminoma or can go to embryonal carcinoma
279
totipotential germ cell -> most primitive form
seminoma
280
embryonal carcinoma can go on to make what?
```
extra embryonic (Yolk sac, choriocarcinoma)
or embryonic (teratoma)
```
281
Testis seminoma
```
Most common (50%)
Fourth decade
Radiosensitive and chemosensitive
Good prognosis
Serum markers often negative - so primitive don't really have
- late stage = efface the testis
fish flesh tumor
```
282
histology of seminoma
- biphasic appearance = fried eggs
| - benign lymphocytes that go along with BV
283
Spermatocytic Seminoma
1-2% of GCT’s
Older age (>50 yrs)
Good prognosis - no report of metastasis
Serum markers negative
284
Spermatocytic Seminoma histology
biphasic appearance
all different sized nuclei
some stuck in spermatid (phenotypically)
mixoid, gelatinous structure
285
Embryonal Carcinoma
Pure – rare (3%)
Mixed – common (85%)
Third decade
Chemosensitive
Higher likelihood of extratesticular spread
Recurrences common
Markers variable: PLAP (placental alkaline phosphatase), placental lactogen, hCG
286
Embryonal Carcinoma histology (immature phase carcinoma)
```
destructive
lots of areas of necrosis, hemorrhage
cells = more anaplastic
big dark nuclei
more atypia
mitotic figures
some structure - primitive tubular arrangements
```
287
Teratoma
40% of testis tumors in infants
2-3% pure in adults
Mixed ~45%
Mature vs. Immature
Malignant transformation -> every part that is mature can undergo this
Chemoresistent – slow to progress but may undergo “malignant” change - surgically remove the rest
288
Malignant transformation of teratoma
if mature sq cell can get squamous cell carcinoma
| has seen pancreatic carcinoma from it
289
histology of teratoma
cysts - lined by mature tissues
Elements -> can have cartilage, epithelial lined surface, can be epidermis, respiratory epithelium, colon epithelium, pancreas with acinar, skeletal muscle, nervous tissue
the more immature, the more likely to progrees to metastasis
290
Yolk Sac Tumor
Pure common in children (80% of testicular tumors)
Part of mixed tumor in adults (40-50%)
Prognosis relatively good
Produces alpha-fetoprotein (AFP)
291
histology of yolk sac tumor
AFP globules
| AFP on IHC
292
Choriocarcinoma
```
Pure (0.3% of GCT’s)
Mixed (10%)
Aggressive – often metastasizes - often dx metastasis before finding primary tumor
Chemosensitive, but worse prognosis
Produces hCG
functional- functions like placenta
```
293
histology of choriocarcinoma
hemorrhagic
destructive
sinsitial trophoblast and cytotrophoblasts
294
most common cancer in testes in adults?
mixed tumor
295
Testis Cancer Staging
I - confined to testis
II - retroperitoneal nodes or below diaphragm
III - outside retroperitoneal nodes or above diaphragm
296
Testis Cancer Serum Markers
AFP
hCG
Placental-like Alkaline Phosphatase (PLAP)
Human placental lactogen
297
Testicular Tumors (5% that aren't germ cell)
```
Sex-cord/stromal tumors
Leydig cell
Sertoli cell
Granulosa cell
Mixed
Lymphoma
```
298
Leydig Cell Tumors
2% of all testicular neoplasms
90% benign
10% malignant
Often masculinizing, some feminizing (because produce testosterone and sometimes can be converted via aromatase)
299
sertoli cell tumor
more rare, more serious
very malignant
metastasize early
seminiferous tubules gone bad -> more sertoli, more invasive -> go into blood stream
300
most common testicular tumor in men over age of 60
remember not GERM CELL
| Lymphoma is answer!
301
Penile Lesions
```
Condyloma Acuminatum
Verrucous carcinoma
Carcinoma in situ
- Bowen’s disease
- Erythroplasia of Queyrat
Squamous cell carcinoma
Other malignancies
```
302
Genital warts
```
HPV- papillary outgrowths
atypia in squamous cells
koilocytosis = big hollow cells (clear cytopasm) with wrinkled raison like nucleus
virus filled cells
16,18, 30-33 -> high risk
```
303
limited lesions of penis
Verrucous carcinoma (wart like, large wart, keritinizing, local destruction without metastasizing)
Carcinoma in situ
- Bowen’s disease
- Erythroplasia of Queyrat (mucosa of uncircumsized male)
304
Carcinoma in situ
full thickness dysplasia of squamous epithelium
305
Penile malignancies epithelial
```
Epithelial (95%)
Squamous cell carcinoma (95%)
Melanoma (1%)
Basal cell carcinoma (1%)
Urethral TCC (2%)
```
306
Penile malignancies mesenchymal
```
Mesenchymal (5%)
Leimyosarcoma
Fibrosarcoma
Rhabdomyosarcoma
Kaposi’s sarcoma
Angiosarcoma
Hemangioendothelioma
```
307
Penile Squamous Carcinoma
0.3-0.6% of male cancers
0.5-1.0 per 100,000
60-80 years of age
African American:Caucasian 2:1
“Chimney sweeps disease”
Precursor lesion: carcinoma in situ
308
Penile Squamous Carcinoma gross findings and histology
ulcerative lesions, destructive
pointlike downward lesions of skin -> then become glandlike
- invasion doesn't have to be too far to get to blood -> dissemination
309
most cancers effect what of prostate?
peripheral zone
310
BPH effects what of prostate?
transitional zone
311
cell layers of tubular alveolar gland
2 cell layers tall columnar = secretory
Basal or stem cell
Malignancies lose 2 cell morphology
312
Prostatic Diseases
Inflammation
Hyperplasia
Neoplasia
313
Prostatic dz: sx?
Can be asymptomatic until advanced
| Symptoms, when present, are usually those of urethral obstruction or irritation while urinating
314
inflammation of prostate
```
Acute Prostatitis
Chronic Prostatitis
- Bacterial = rare
- “abacterial” = more common
- granulomatous
```
315
Acute Prostatitis
Focal or diffuse polymorphonuclear inflammation
Enterobacter (E. coli), S. aureus most common, also think about STI bugs
Direct extension from urinary tract
Can be iatrogenic
316
iatrogenic causes?
prostatitis
| miss 45 degree angle and damage prostate
317
Chronic Prostatitis
Mononuclear cell inflammation
Often associated with atrophy
Unclear etiology - ? Response to occult infection, dietary
Histologic chronic inflammation much more common than clinical prostatitis
Granulomatous form
318
Granulomatous form of chronic prostatitis
Granulomatous form
Eroded corpora amylacea
Tuberculosis
319
Chronic Prostatitis on histology
inflam infiltrate
around and into epithelium
atrophic changes
columnar cells have regressed
320
BPH
Benign nodular enlargement of prostate
Most common proliferative disease of prostate
Blacks>Whites>Asians -> reflects same trend as cancer
Histologic BPH: Rule of “10’s”
Clinical BPH age 60
Lower urinary tract symptoms (LUTS)
NOT PREMALIGNANT
321
LUTS voiding
voiding symptoms - hesitancy, poor urine flow, dribbling, incomplete bladder emptying
322
LUTS storage
increased frequency >7x/day
nocturia
urgency
urge incontinence
323
histology of BPH
transitional zone near urethra
| large nodules confined to transitional zone
324
classification of BPH nodules
3 major components that can be in any combo
| epithelium, fibroblasts/stroma, smooth muscle
325
BPH nodules - more stroma
worse it is symptomatically and more refractory to tx
326
BPH natural hx complications:
```
LUTS most common – quality of life impact
Complications:
Acute urinary retention
Recurrent UTI/ pyelonephritis
Renal failure
Incontinence
```
327
BPH natural hx management
Management:
Medical - recently is main tx
Minimally invasive therapy (ex. Microwave thermotherapy)
Surgery (TURP) - lot of morbidity (incontinence)
328
Prostatic Carcinoma
Most common non-skin cancer of adult males (~20% of all male cancers)
~200,000 new cases per year
Second leading cause of male cancer deaths (~27,000 per year)
More men die with PCa than of it
- US sees most because if you screen for it you'll find it
- Asians = low risk
329
Prostatic Cancer Risk Factors
Age - older, more likely
Race - AA more likely
Genetics - father had it, 4x more likely
Diet - thought to because asians living in Japan who move here adopt our risk of prostate cancer
DM - might effect mortality of prostate cancer
330
Prostatic Carcinoma screening problems:
Effects peripheral zone > transition zone
Screening:
Serum prostate specific antigen (PSA) - not prostate or cancer specific
Digital rectal exam - only see posterior part of prostate 10% sensitive
Blind “random” biopsies still gold standard for diagnosis
- Only ~ 50% sensitive
- Many cancers detected will never be life threatening-
331
grade progression of prostate carcinoma
thought prostate goes from low grade to high grade
can start as high grade -> this progression doesn't always occur
- multifocal disease
multiple grades
2 tumors within prostate = different grades
332
Relationship of PIN and PCa
Believed to represent noninvasive precursor to some prostate cancers
Genetic and molecular changes similar to PCa
Increases with age, peak prevalence 5-10 yrs before PCa [Sakr 1993]
30-50% of prostates with PIN harbor prostate cancer
333
Prostatic adeno dx criteria
```
Uniform round glands
Infiltrative pattern
Single cell layer (loss of basal cells)
Nuclear enlargement -prominent nucleoli
Perineural invasion
```
334
Prognostic factors of prostate cancer
Grade most important
Stage
Tumor volume (PSA) - monitoring tool, larger = more likely to metastasize
Molecular markers – research in progress
335
gleason grading of prostate
degree of invasiveness is in architecture = GLEASON SCORE
= ragged sheets vs. morphologic resemblance to nl prostate
Score = most + 2nd most
most informative about eventual mortality
336
high grade malignancy in gleason score
lack of glandular formation
337
metastasis of prostate cancer
lymph or hematologic spread of prostate cancer
| can get into spain -> pathologic fracture and pain
338
survival of prostate cancer
```
Pelvic lymph nodes 95%
Seminal vesicles 85%
Established capsular penetration 48%
Focal capsular penetration 33%
Organ confined 10%
organ confined doesn't mean you're out of woods
```
339
random biopsy of prostate
might miss cancer or a high grade tumor because of multiple focality
combining epigenetic and genetic might be more
340
genomics of prostate cancer
genes tell us more than grade - could determine prognosis by genes (deletions, amplifications)
341
Prostate CancerTreatment Options
```
Surgery – radical prostatectomy
External beam radiation
Brachytherapy (radioactive “seeds”)
Cryotherapy
Hormone ablation – mainline therapy for advanced metastatic PCa - eventually fails
Chemotherapy
```
342
new concept TX of prostate cancer
New concepts:
Expectant management
Targeted focal therapy
343
BOTTOM LINE OF PROSTATE CANCER
~200,000 new cases expected
3/4 receive localized treatment (~150,000)
40% will experience PSA recurrence (60,000/yr)
~27,000 deaths expected
Autopsy: 30% of men > 50 years have PCa
SOOOOOO MANY MEN ARENT DYING OF PROSTATE CANCER THAT ARE BEING TREATED BUT WE'RE NOT CATCHING THE ONES THAT NEED TO BE TREATED
344
new theories on how to tx/cure prostate cancer
need improved imaging and biomarkers to better assess tumor burden and aggressiveness
want to treat the people that will die of prostate cancer but not find and treat the ones that will die of other causes (not their prostate cancer)
haven't done a good job of separating sleeping giants and mean mice
