1. John
Martinelli
Ob/Gyn
Case:
Uterine
Fibroids/Anemia
11/17/13
Identifying
Data:
B.C.
is
a
pleasant
36-­‐year-­‐old
African-­‐American
woman,
G0,
who
was
admitted
to
NBIMC
per
the
ED
on
October
25,
2013.
Chief
Complaint:
Approximately
3
hours
prior
to
her
hospital
visit,
she
reported
“I
felt
dizzy
and
faint…I
thought
I
was
passing
out”.
History
of
Present
Illness:
B.C.
presented
to
the
NBIMC
ED
on
the
afternoon
of
October
25,
2013
after
experiencing
severe
syncope-­‐like
symptoms
while
working
alone
in
her
kitchen
at
home.
Her
sister
accompanied
her
and
was
responsible
for
driving
her
directly
to
the
ED
after
they
spoke
by
phone.
B.C.
stated
she
has
noticed
similar
symptoms
increasing
in
severity
over
a
period
of
approximately
5
years;
however,
she
never
pursued
medical
care
or
treatment.
She
felt
this
particular
episode
was
the
most
dramatic
which
prompted
her
to
seek
emergency
care.
Specifically,
the
presenting
event
lasted
approximately
2
–
3
minutes
and
was
consistent
with
possible
transient
bilateral
amaurosis
fugax,
lower
extremity
weakness,
as
well
as
vertigo.
She
did
not
believe
she
lost
consciousness
and
did
not
fall.
She
revealed
she
was
currently
having
her
menses
with
particularly
heavy
flow.
Past
Medical
History:
B.C.
admitted
she
has
not
seen
a
physician
in
approximately
8
years,
however,
she
did
recall
being
previously
diagnosed
with
anemia.
She
does
not
remember
being
given
a
reason
for
anemia.
At
that
time
she
was
advised
to
take
iron
supplements
and
a
daily
vitamin,
however,
she
has
not
been
compliant
due
to
lack
of
affordability.
Her
systemic
history
is
otherwise
unremarkable
and
she
denies
diabetes,
hypertension,
asthma,
thyroid
dysfunction,
SLE,
or
renal
disease.
Obstetrical
History:
None.
G0.
Gynecologic
History:
Upon
questioning,
was
significant
for
an
approximate
5-­‐year
history
of
menorrhagia
and
menometrorrhagia
with
irregular
prolonged
heavy
menses
occurring
every
28
–
45
days
lasting
7
–
10
days
and
random
spotting.
Her
menses
is
often
associated
with
intermittent
abdominal
and
pelvic
pain
along
with
transient
vertigo,
which
seems
to
be
increasing
in
frequency
and
duration.
1

2. Medications:
None.
Allergies:
NKA/NKDA.
Surgical
History:
None.
Social
History:
B.C.
is
a
housewife
living
in
a
rented
apartment
with
her
husband
who
works
as
a
laborer.
They
have
no
children.
She
believes
her
environment
is
safe
and
states
she
is
happily
married.
She
and
her
husband
do
their
best
to
maintain
a
healthy
and
balanced
diet.
There
is
no
evidence
of
abuse
and
she
denies
cigarettes,
alcohol,
or
illicit
drug
use.
Family
History:
Mother
–
Hypertension,
controlled
with
medication.
Father
–
Unknown/Deceased.
Siblings
–
None.
Review
of
Systems:
General:
(?)
Vertigo
(prior
to
ED
visit).
No
Fever/Chills.
Skin:
(-­‐)
Rash.
Head:
(-­‐)
Headache.
Eyes:
(?)
Transient
Bilateral
Amaurosis
Fugax
(prior
to
ED
visit).
Ears:
(-­‐)
Hearing
loss.
Neck:
(-­‐)
Neck
pain/Stiffness.
Cardio:
(-­‐)
Chest
pain/Palpitations.
Pulm:
(-­‐)
Respiratory
Distress.
Gastro:
(-­‐)
Nausea/Vomiting/Diarrhea.
GU:
(-­‐)
Vaginal
Discharge/Urethral
Discharge/Dysuria/Hematuria.
Neuro:
(?)
Transient
Lower
Extremity
Weakness
(prior
to
ED
visit).
Musc:
(?)
Transient
Lower
Extremity
Weakness
(prior
to
ED
visit).
Psych:
(-­‐)
Depression,
Anxiety,
AAO
x
3.
Physical
Exam:
Vitals:
T:
98.6
PP:
71
RR:
20
BP:
166/97
SpO2:
100%
(RA)
H:
5ft
6in
W:
206lbs
BMI:
33.13
2

3. Skin:
No
Bruising,
Lesions,
or
Rash.
Head:
Normocephalic/Atraumatic.
Eyes:
PERRLA(-­‐)APD,
EOM’s:
Full
(-­‐)Diplopia,
CVF:
Full
360degs
OU,
ONH:
0.2/0.2
(-­‐)Disc
Edema
OU,
Retina:
(-­‐)Heme/Exudate
to
mid-­‐
periphery
OU,
Macula:
Healthy
OU,
Ant
Segment:
WNL/Anicteric
OU,
(-­‐)Subconjunctival
or
Petechial
Hemes,
VA:
20/20
OU.
Ears:
No
Hearing
Loss.
Otoscopic
Exam
N/A
(deferred).
Neck:
Supple,
No
JVP,
No
Thyromegaly,
No
Lymphadenopathy.
Cardio:
RRR,
S1,
S2,
No
Murmur/Gallop.
Pulm:
Clear
to
Auscultation
b/l.
Gastro:
Lower
Abdomen
with
Firm
Mass
palpated,
(-­‐)Tenderness.
Pelvic:
Menses
(deferred).
Neuro:
AAO
x
3,
DTR
3+
b/l,
Normal
Gait.
Musc:
Normal
Tone/Strength
at
UE/LE
Psych:
AAO
x
3.
Appropriate
Affect.
Imaging:
Pelvic
ultrasound
revealed
a
14-­‐week
size
uterus
with
multiple
fibroids
evident.
Labs:
WBC:
7.7
Hgb/Hct:
9.4/30.4
Plt:
504
Na:
140
Cl:
111
BUN:
11
K:
4.6
HCO3:
26
Cr:
0.62
Glu:
68
PT:
9.9
PTT/INR:
32/0.9
Assessment
and
Plan:
B.C.’s
5-­‐year
history
of
menorrhagia
and
menometrorrhagia
coincides
with
her
increasing
symptomatology
and
frequency
of
episodic
vertigo.
This
appears
to
have
culminated
in
a
near
syncope
event
with
lower
extremity
weakness
along
with
transient
bilateral
amaurosis
fugax.
The
significance
of
the
pelvic
ultrasound
findings
revealing
an
enlarged
uterus
secondary
to
multiple
fibroid
proliferation
sets
the
stage
for
her
diagnosis
and
treatment
plan.
Understanding
the
pathophysiology
of
uterine
fibroid
proliferation,
its
potential
consequences,
diminished
hemoglobin
and
hematocrit,
combined
with
B.C.’s
symptomatology,
leads
to
a
classic
top
differential.
However,
perhaps
exacerbating
her
clinical
presentation,
is
a
relatively
low
random
blood
glucose.
In
addition,
her
blood
pressure
was
found
to
be
significantly
elevated
which
may
be
a
contributing
factor
as
well.
3

4. Differential
Diagnosis:
1. Multiple
uterine
leiomyoma’s
(fibroids)
leading
to
dysfunctional
uterine
bleeding
(menorrhagia/menometrorrhagia)
creating
hemorrhagic
iron
deficiency
anemia
with
secondary
transient
neurologic
sequelae
of
vertigo,
lower
extremity
weakness,
and
bilateral
amaurosis
fugax.
2. Hypertension
with
possible
peripheral
vascular
disease
and
associated
ischemia/hypoxia
contributing
to
the
syncope-­‐like
episode(s).
3. Hypoglycemia
as
a
contributor
to
the
syncope-­‐like
episode(s).
Plan:
1. Open
abdominal
myomectomy
(patient
refuses
hysterectomy
to
preserve
fertility).
Scheduled
11/8/13.
2. Monitor,
will
schedule
PCP
evaluation
post-­‐myomectomy.
3. Monitor,
will
schedule
PCP
evaluation
post-­‐myomectomy.
Operative
Course:
B.C.
underwent
an
open
abdominal
myomectomy
under
general
anesthesia
on
her
scheduled
date.
26
fibroid
masses
of
various
sizes,
most
of
which
were
submucosal,
were
excised
and
subsequently
sent
to
pathology.
Pathology
confirmed
the
diagnosis
of
multiple
uterine
leiomyoma.
B.C.
tolerated
the
procedure
well
with
minimal
blood
loss
and
without
complication.
Her
immediate
post-­‐operative
course
was
uneventful.
Discussion:
Uterine
leiomyoma’s
or
fibroids
are
the
most
common
neoplasia
found
in
the
female
reproductive
system
occurring
in
20-­‐25%
of
all
women.
They
are
found
even
more
frequently
in
approximately
40%
of
menstruating
women
over
the
age
of
50
and
occur
twice
as
frequently
in
black
women
in
comparison
to
the
Caucasian
or
Asian
population.
Uterine
leiomyoma’s
can
occur
at
any
time
between
menarche
and
menopause
with
their
highest
prevalence
in
women
35-­‐49
years
of
age.
Fibroids
represent
dysregulated
production
of
myometrial
extracellular
matrix
with
multiple
etiologic
theories.
If
myomectomy
is
required,
fibroids
have
been
shown
to
recur
after
surgery
in
anywhere
from
10-­‐50%
of
cases.
This
is
largely
dependent
on
the
initial
size
and
number
of
fibroids
prior
to
myomectomy.
However,
they
tend
to
eventually
resolve
with
decreased
hormonal
stimulation
characteristic
of
menopause.
4

5. There
are
three
major
classifications
of
uterine
fibroids
based
on
their
anatomic
location
or
extension:
1. Submucosal
–
least
frequent.
Because
of
the
close
association
with
endometrial
tissue,
submucosal
fibroids
are
particularly
associated
with
heavy
and
prolonged
menses
(menorrhagia)
as
well
as
an
increased
incidence
of
pregnancy
loss.
They
may
extend
and
become
pedunculated
into
the
uterine
cavity
or
even
prolapse
into
the
vagina.
2. Intramural
–
within
the
uterine
wall.
Increased
proliferation
and
growth
is
linked
primarily
to
mass-­‐effect.
This
can
include
abdominal
pain
and
distention
due
to
gastrointestinal
compression
with
potential
obstruction.
Urinary
urgency
and
frequency
can
also
ensue
secondary
to
bladder
compression.
3. Subserosal
–
with
peripheral
uterine
extension.
As
with
submucosal
fibroids,
these
can
also
become
pedunculated
with
extension
into
the
abdomen
and
peritoneum.
The
uterine
ligaments,
ureters,
bladder,
sidewall,
as
well
as
any
abdominal
structure
can
potentially
become
involved
depending
on
the
anatomical
location,
duration,
and
rate
of
extension.
It
should
be
understood
that
most
women
who
are
found
to
have
fibroids
are
often
without
symptoms.
Routine
gynecologic
examinations
normally
lead
to
the
diagnosis,
with
observation
the
only
treatment
indicated.
However,
in
those
women
who
present
with
complications
from
fibroid
proliferation,
management
is
structured
based
on
any
variety
of
findings.
Initial
signs
and
symptoms
can
be
mild
to
severe,
and
again,
are
dependent
on
the
degree
of
neoplastic
proliferation
and
involved
structures.
This
may
include
dysfunctional
uterine
bleeding,
iron
deficiency
anemia,
fibroid
torsion,
pelvic
pain
and/or
pressure,
abdominal
pain
and/or
distention,
constipation,
bowel
obstruction,
genitourinary
complications,
dysuria,
urinary
frequency/urgency,
ureteral
compression
with
secondary
hydronephrosis,
renal
failure,
peripheral
edema,
premature
uterine
contractions,
recurrent
pregnancy
loss,
infertility,
and
others.
Pathophysiology:
With
respect
to
pathophysiology,
a
uterine
fibroid
is
known
to
be
a
leiomyoma.
In
general,
leiomyoma’s
are
monoclonal
tumors
of
smooth
muscle,
which
may
occur
anywhere
in
the
body
that
contains
smooth
muscle.
The
trigger
for
this
neoplastic
proliferation
is
not
well
understood,
however,
studies
involving
genotypic
patterns,
prenatal
and
lifetime
hormonal
exposure,
race,
nulliparity
(increased
estradiol
exposure),
obesity
(increased
aromatization),
polycystic
ovarian
syndrome
(increased
estrone
exposure),
diabetes,
as
well
as
hypertension
have
revealed
certain
clues.
5

6. Neoplastic
proliferation
is
strongly
associated
with
levels
of
both
estrogen
and
progesterone.
However,
even
this
correlation
is
not
completely
understood
in
that
estrogen
and
progesterone
have
lead
to
growth
restriction
in
certain
circumstances.
In
addition,
it
is
known
that
fibroids
during
pregnancy
remain
relatively
stable,
implying
that
extremely
high
steroid-­‐based
hormone
levels
during
pregnancy
may
actually
be
protective.
It
has
been
postulated
that
a
possible
interaction
occurs
between
estrogen
receptors
and
oxytocin
receptors
suppressing
the
usual
proliferative
effect
of
these
hormones.
The
exact
downstream
proliferative
effect
of
estrogen
and
progesterone
is
quite
complex
and
is
believed
to
involve
a
multitude
of
interactions.
Estrogen
has
been
found
to
up-­‐regulate
IGF-­‐1,
EGFR,
TGF-­‐beta1,
TGF-­‐beta3,
and
PDGF.
The
perpetual
survival
of
leiomyoma
cells
is
permitted
by
down-­‐regulation
of
the
tumor
suppressor
gene
p53,
increased
expression
of
the
anti-­‐apoptotic
factor
PCP4,
and
increased
antagonizing
PPAR-­‐gamma
signaling.
Prolactin
is
believed
to
also
play
a
role
in
this
cascade
of
events.
In
addition,
progesterone
is
thought
to
promote
and
sustain
leiomyoma
proliferation
through
the
up-­‐regulation
of
EGF,
TGF-­‐beta1,
as
well
as
TGF-­‐beta3,
and
permitting
survival
via
the
up-­‐regulation
of
another
anti-­‐
apoptotic
protein
Bcl-­‐2
in
conjunction
with
the
down-­‐regulation
TNF-­‐alpha.
In
the
pre-­‐menopausal
period,
uterine
fibroids
have
been
associated
with
an
overexpression
of
both
estrogen
and
progesterone
receptors.
Regarding
the
black
population
and
an
increased
prevalence
and
incidence
of
uterine
fibroids,
a
unique
estrogen
receptor
genotype
of
ER-­‐alpha
has
been
found
to
be
present
to
a
greater
extent.
Therefore,
the
greater
frequency
of
this
genotype
in
black
women
may
also
explain
the
high
prevalence
and
incidence
of
fibroids
in
this
group.
The
robust
nature
of
leiomyoma’s
and
uterine
fibroids
is
exemplified
in
their
inherent
ability
to
promote
their
own
growth.
This
is
achieved
via
the
aberrant
expression
of
both
aromatase
and
17-­‐beta-­‐hydroxysteroid
dehydrogenase.
It
is
through
these
enzymes
that
circulating
androstenedione
is
aromatized
creating
even
greater
levels
of
estradiol.
The
disease
process
has
the
ability
to
essentially
feed
itself.
Therefore,
aromatase
inhibitors
are
currently
being
considered
for
treatment.
Furthermore,
aromatase
overexpression
is
known
to
be
particularly
pronounced
in
black
women.
Genetic
studies
and
karyotyping
have
shown
that
approximately
40-­‐50%
of
leiomyoma’s
demonstrate
a
detectable
chromosomal
abnormality.
Interestingly,
multiple
fibroids
obtained
from
the
same
individual
will
oftentimes
have
unrelated
genetic
irregularities.
However,
it
has
been
discovered
that
specific
mutations
of
a
protein
known
as
MED12
have
been
present
in
70%
of
leiomyoma’s.
Epidemiologic
studies
concentrating
on
patterns
of
inheritance
have
revealed
first-­‐degree
relatives
having
a
2
½
fold
risk
with
a
6-­‐fold
risk
for
early
onset
cases.
In
addition,
monozygotic
twins
have
a
double
concordance
rate
for
hysterectomy
due
to
fibroid
complications
versus
dizygotic
twins.
6

7. It
is
interesting
to
note
that
leiomyoma’s
including
uterine
fibroids
have
reduced
vascularity.
This
is
in
contrast
to
most
neoproliferative
disease,
which
requires
significant
neovascularization
in
order
to
maintain
and
sustain
tissue
growth.
Cyr61
is
a
gene
found
in
leiomyoma’s
(and
other
tumors),
which
in
addition
to
being
involved
in
tumor
suppression,
is
also
known
for
its
role
in
promoting
vasoproliferation.
It
is
paradoxically
down
regulated
in
this
particular
disease
process
resulting
in
the
decreased
vascularity
characteristic
of
fibroids.
With
respect
to
hypertension
and
its
association
with
fibroids,
the
mechanism
leading
to
neoplastic
proliferation
is
thought
to
be
two-­‐fold.
It
has
been
hypothesized
that
hypertensive
uterine
artery
atherosclerosis
with
subsequent
tissue
inflammation
may
contribute
to
the
disease
process.
In
addition,
angiotensin
II
and
its
receptor
activity
in
the
hypertensive
state
have
been
implicated
as
well.
Overall
Impression:
B.C.
is
a
36-­‐year-­‐old
African-­‐American
lady
who
presented
with
classic
signs
and
symptoms
of
uterine
fibroids
including
abdominal
pain,
palpable
abdominal
mass,
and
dysfunctional
uterine
bleeding
including
menorrhagia
and
menometrorrhagia.
She
reported
increasing
frequency
and
severity
of
her
symptomatology
over
a
period
of
approximately
5
years,
for
which
she
also
began
to
experience
episodes
of
vertigo.
This
culminated
in
near-­‐syncope
with
vertigo,
amaurosis,
and
lower
extremity
weakness,
which
prompted
her
to
seek
immediate
emergency
medical
attention.
The
implication
of
progressive
hemorrhagic
iron
deficiency
anemia
and
associated
transient
neurologic
sequelae
can
be
characteristic
of
chronic
uterine
fibroids.
Her
presenting
findings
including
African-­‐American
ethnicity,
nulliparity,
obesity,
pre-­‐
menopausal
state,
hypertension,
diminished
hemoglobin/hematocrit,
physical
exam,
as
well
as
pelvic
ultrasound
results
support
active
fibroid
formation
and
proliferation.
Subsequent
abdominal
myomectomy
and
pathology
confirmed
the
diagnosis
of
multiple
uterine
fibroids.
With
an
intact
uterus
void
of
fibroid
proliferation,
the
prognosis
for
B.C.
is
good
with
respect
to
persistent
iron
deficiency
anemia
and
associated
symptoms.
However,
her
existing
factors
of
hypoglycemia
as
well
as
hypertension
can
potentially
produce
similar
symptomatology,
albeit
via
different
mechanisms
involving
glucose
load
and
peripheral
vascular
disease.
She
was
therefore
referred
to
a
new
primary
care
physician
for
appropriate
follow-­‐up
care.
Finally,
regarding
B.C.’s
desire
to
possibly
have
children
in
the
future,
her
chances
to
have
a
successful
pregnancy
are
improved.
It
has
been
shown
that
myomectomy
for
submucosal
fibroids
will
indeed
improve
fertility,
however,
myomectomy
for
other
fibroid
types
have
not
been
shown
to
be
of
benefit
in
this
regard.
In
addition,
a
cesarean
section
may
be
indicated
related
to
the
extensive
nature
of
her
surgery
–
7

8. due
to
increased
potential
for
placenta
previa,
accreta,
abruption,
or
possible
uterine
rupture.
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DG,
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Engl
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8