patients with severe hemophilia, only 90% have evidence of
HEMOPHILIA
Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX
deficiency) are the most common and serious congenital
coagulation factor deficiencies. Clinical findings are virtually identical.
Hemophilia C: Factor XI. AD. Frequent in Ashkenazi Jews,
Replacement therapy should be considered and given
preoperatively, depending on the nature of the surgical procedure.
Fresh-frozen plasma (FFP) is used. Patients undergoing dental
extractions can be monitored closely and may benefit from treatment
with fibrinolytic inhibitors like aminocaproic acid, with plasma
replacement therapy used only if hemorrhage occurs. PTT is often
longer than it is in patients with either severe factor VIII or factor IX
deficiency. This may also be confirmed by specific assays. Half-life of
factor XI: 48 hr, maintaining adequate levels of factor XI commonly is
not difficult.
Factors VIII and IX participate in a complex required for the activation
of factor X. Together with phospholipid and calcium, they form the
tenase, or factor X activating, complex. In vivo, the complex of
factor VIIa and tissue factor activates factor IX to initiate clotting.
In the laboratory, prothrombin time (PT) measures the activation of
factor X by factor VII and is therefore normal in patients with factor VIII
or factor IX deficiency.
After injury, the initial hemostatic event is formation of the platelet
plug, together with the generation of the fibrin clot that prevents
further hemorrhage.
In hemophilia A or B, clot formation is delayed and is not robust.
Inadequate thrombin generation leads to failure to form a tightly
cross linked fibrin clot to support the platelet plug. Patients with
hemophilia slowly form a soft, friable clot. When untreated bleeding
occurs in a closed space, such as a joint, cessation of bleeding may
be the result of tamponade.
With open wounds, in which tamponade cannot occur, profuse
bleeding may result in significant blood loss.
The clot that is formed may be friable, and rebleeding occurs during
the physiologic lysis of clots or with minimal new trauma.
Neither factor VIII nor factor IX crosses the placenta; bleeding
symptoms may be present from birth or may occur in the fetus.
Only 2% of neonates with hemophilia sustain intracranial
hemorrhages, and 30% of male infants with hemophilia bleed with
circumcision.
Obvious symptoms such as easy bruising, intramuscular hematomas,
and hemarthroses begin when the child begins to cruise. Even in
CPC CRAM LIKE HELL NOTES
increased bleeding by 1 yr. of age.
The hallmark of hemophilic bleeding is hemarthrosis. Bleeding into the
joints may be induced by minor trauma; many hemarthroses are
spontaneous. Earliest joint hemorrhages appear most commonly in
the ankle.
They complain of a warm, tingling sensation in the joint as the first sign
of an early joint hemorrhage. Bleeding into the iliopsoas muscle
requires specific mention. A patient may lose large volumes of blood
into the iliopsoas muscle, verging on hypovolemic shock, with only a
vague area of referred pain in the groin. The hip is held in a flexed,
internally rotated position owing to irritation of the iliopsoas. The
diagnosis is made clinically from the inability to extend the hip but
must be confirmed with ultrasonography or CT.
Treat first, image second!
Life-threatening hemorrhages require replacement therapy to
achieve a level equal to that of normal plasma (100 IU/dL, or 100%).
Patients with mild hemophilia who have factor VIII or factor IX levels >5
IU/dL usually do not have spontaneous hemorrhages. These
individuals may experience prolonged bleeding after dental work,
surgery, or injuries from moderate trauma and may not be diagnosed
until they are older.
The laboratory screening test that is affected is PTT. In severe
hemophilia, the PTT value is usually 2-3 times the upper limit of normal.
Results of the other screening tests of the hemostatic mechanism
(platelet count, bleeding time, prothrombin time, and thrombin time)
are normal.
Specific assay for factors VIII and IX will confirm the diagnosis of
hemophilia. If correction does not occur on mixing, an inhibitor may
be present.
Severe hemophilia is characterized as having <1% activity of the
specific clotting factor, and bleeding is often spontaneous.
Moderate hemophilia has factor levels of 1-5% and usually require
mild trauma to induce bleeding.
Mild hemophilia has levels >5%, may go many years before the
condition is diagnosed, and frequently require significant trauma to
cause bleeding.
The genes for factors VIII and IX are carried near the terminus of the
long arm of the X chromosome and are therefore X linked traits.
African-Americans often have a different factor VIII haplotype, and
this difference may be the reason that African-Americans have higher
inhibitor formation.
Prophylaxis is the standard of care for most children with severe
hemophilia to prevent spontaneous bleeding and early joint
deformities.
Page 1
 With mild factor VIII hemophilia, the patients endogenously
produced factor VIII can be released by the administration of
desmopressin acetate.
Desmopressin is ineffective in moderate or severe factor VIII
deficiency.
For mild hemophilia A, intranasal form of desmopressin acetate can
also be used. The dose is 150 g (1 puff ) for children weighing <50 kg
and 300 g (2 puffs) for children and young adults weighing >50 kg.
Desmopressin is not effective in the treatment of factor IXdeficient
hemophilia.
Anticipatory guidance, including the use of car seats, seatbelts, and
bike helmets.
Avoid high-risk behaviors. Older boys should be counseled to avoid
violent contact sports
Avoid aspirin and other nonsteroidal anti-inflammatory drugs.
Give appropriate vaccinations against hepatitis B.
Patients exposed to plasma-derived products should be screened
periodically for hepatitis B and C, HIV, and abnormalities in liver
function.
APLASTIC ANEMIA
Failure of all 3 cell lines produced in the bone marrow resulting in
anemia, leukopenia, and thrombocytopenia (pancytopenia).
Decrease in white, red and platelet.
The marrow is essentially empty with the absence of precursor cells.
Caused by radiation, toxins such as benzenes, NSAIDS,
chloramphenicol, alcohol and chemotherapeutic alkalytic agents.
Infections such as tuberculosis, fungus and bacterial, hepatitis, HIV,
CMV, EBV, Parvovirus B19 in immunocompromised patient, congenital
aplastic anemia (fanconi Anemia), paroxysmal nocturnal
hemoglobinuria, folate deficiency and drugs..
Pts commonly present with bleeding from pancytopenia. Fatigue from
anemia and infections from neutropenia.
The absence of classical association such as benzene, radiation, or
chloramphenicol would not exclude a diagnosis of aplastic anemia.
In aplastic anemia it is as if the bodys own T cells are rejecting it as
foreign. That is why drugs that prevent organ transplantation are
effective.
Most common etiology is idiopathic.
Pancytopenia on CBC is the first test.
Bone marrow biopsy confirms the diagnosis when alternative
etiologies for pancytopenia are not present.
CPC CRAM LIKE HELL NOTES
The marrow is empty of almost all precursor cells and cell as evidence
of primary of metastatic cancer, infection or fibrosis.
Ct of the chest to check for thymoma causing aplastic anemia.
The marrow is hypoplastic and fat filled with no abnormal cells seen.
Best initial management: correct underlying cause of pancytopenia.
Bone marrow transplantation for young and healthy patients.
Allogenic transplant can cure up to 80-90% of patients under 50.
If bone marrow transplant is not possible, immunosuppressive therapy
should be applied.
Combination of Antithymocyte globulin, cyclosporine and
prednisone.
These agents can lead to remission in 60-70%.
It is believed that T lymphocytes are primarily causal into the bone
marrow failure so drugs are used to degrease the T cell response.
BMT is always ALLOGENIC; you cannot do an autologous transplant
from someone with no bone marrow.
PERIPHERAL ARTERY DISEASE
A disorder in which blood supply tor extremities is obstructed.
A condition where there is stenosis or occlusion in the aorta or the
arteries of the limbs.
Atherosclerosis: most common cause.
Other causes: thrombosis, embolism, vasculitis, fibromuscular dysplasia
or entrapment.
Highest in the 6th and 7th decade of life.
Men>women.
Increased risk in smokers, DM, hypercholesterolemia, hypertension
and renal insufficiency.
Usually in the medium and large sized vessels.
Primary sites of involvement: femoral and poptiliteal (80-90%), tibial
and peroneal (40-50%), iliac arteries (30-40%) and abdominal aorta.
Distal vessels are commonly affected in the elderly.
Most common symptom: Intermitted claudication. (pain in walking,
relieved by rest)
Occurs at night when legs are horizontal and improves when legs are
in a DEPENDENT POSITION.
Peripheral arterial disease predisposes to loss of skin appendages such
as hair follicles and sweat glands. Pulses are lost in very late disease,
therefore you should check for loss of hair and sweat gland sin legs.
Decreased or absent pulses distal to the obstruction, presence of
bruits over the narrowed artery and muscle atrophy.
Page 2
 Elevation of the legs and repeated flexing of the cough muscles
produces PALLOR ON SOLES.
When in dependent position, rubor may occur.
Record arterial blood pressure nonivasely by placement of BP cuffs at
the ankles and use of Doppler device to auscultate or record blood
flow from the dorsalis pedis and posterior tibial arteries.
Systolic BP of the legs is decreased.
BP is greater in the legs than the arms when standing because of the
effect of gravity. The difference is based on a patients height, but it
would be expected to be at least 60 to 80 mm Hg greater in the lower
extremities. When lying flat, BP should be equal in the arms and legs.
If, when lying flat, BP is more than 10% less in the legs than in the arms
(ABI 0.9), obstruction to flow is present. Severe PAD is an ABI 0.6.
Ankle rachial index is the clear first choice in the evaluation of PAD. It
serves to establish a diagnosis, although it does not determine the
precise location of the lesion. An ABI 0.9 indicates vascular disease.
N: 1-1.50; borderline: 0.91-0.90; Abnormal :< .90.
It is premature to go straight to angiography. Angiography is the most
accurate test, but it is not the one to establish an initial diagnosis of
PAD. It can reveal the anatomic location to determine the site of
repair.
Doppler ultrasounds are not needed if you can feel a pulse. They are
also not as important as determining the difference in BP between
upper and lower extremities. You should not refer to vascular surgery
for a simple diagnostic procedure such as ABI, which you can do.
Duplex Ultrasonography or angiogram is used to detect lesions in the
native arteries and bypass grafts. It also provides a direct and
noninvasive means of assessing both anatomic characteristics or
peripheral arteries and the fictional significance of stenosis.
Prognosis: 15-30% 5 yr. mortality rate.
25-30% will have knee amputation within 1 year.
Worse prognosis in those who continue to smoke and with
uncontrolled DM.
Best initial therapy:
o Smoking cessation. Most effective drug to help stop smoking:
BUPROPION. Nicotine patches and gums are more effective
than education alone, but bupropion or varenicline is more
effective than nicotine replacement.
o Platelet inhibitors: Aspirin/Clopidogrel. Warfarin is not
indicated due to major bleeding.
o Blood pressure control: ACE inhibitors, Beta adrenergic
blockers. Intensive antiHPN therapy goal: <120mmHg SBP and
<140mmHg standard. Best medication for BP control in PAD is
ACE inhibitors. ACE inhibitors have some impact in modifying
the progression of disease in PAD. CCBs are not particularly
effective in PAD. The benefit of a CCB, alpha-antagonist, and
CPC CRAM LIKE HELL NOTES
diuretic are not more than the benefit of simply controlling BP.
There is no disease-modifying effect of the medications listed
above on PAD.
o Statins to keep LDL <100mg/dl PAD is equivalent to coronary
disease, so it is important to lower the LDL to 100 mg/dL, in
patients with PAD. With an LDL of 142 mg/dL, diet, exercise,
and weight loss are insufficient to control the level. Statins are
therapeutically equivalent for use on Step 3. Niacin is not as
effective as a statin. Niacin is relatively contraindicated in
diabetes because it can cause glucose elevation. Ezetimibe
lowers LDL, but has no proven mortality benefit or proof that it
alters the natural history of any form of vascular disease. BP
goal with PAD is >130/80mmHg.
o Physical activity: supervised exercise programs 30-45 minutes
per session three to five times a week for at least 12 weeks,
prolong walking distance.
The single most effective therapy is CILOSTAZOL, which is both
antiplatelet and antispasmodic. It is a phosphodiesterase inhibitor with
vasodilator and antiplatelet properties; it increases claudication
distance by 40-60-% and improves the measures and quality of life.
The most frequently used procedure is the aortobifemoral bypass
using knitted Dacron grafts with 99% immediate graft patency.
Operative mortality rate is 1-3% mostly due to ischemic heart disease.
OSTEOARTHRITIS
Is the most common joint disease in humans.
The target tissue in OA is articular cartilage.
There is destruction of cartilage along with secondary remodeling and
hypertrophy of the bone.
It rarely involves the wrist, elbows, shoulders or ankles.
Unlike RA this is not an inflammatory disease.
Knee OA is the leading cause of chronic disability in the elderly.
Marjor risk factors include age, female sex, genetic factors, major joint
trauma, repetitive stress and obesity.
Obesity is one of the major risk factors involved.
The most common joint affected is the knee; the second most
common joint affected is the base of the thumb.
PAIN in the joint, develops after inactivity, worsens with prolonged use,
and relieved with rest. Lasts for 20-30 minutes. Lasts for less than
30minutes in the morning. Typically affects those over 50 years old.
The major joints are involved in OA are the weight bearing joints (hip
and knee) and the small joints of the fingers (PIPs and DIPs), these
joints are affected in an oligoarticular-asymmetric or monoarticular
Page 3
 pattern. The joint involvement is very slow, progressive and irreversible.
Because the cartilage fails and there is increased pressure on articular
bone, joint pain increases with exercise and is relieved by rest.
Morning stiffness is always <20-30min. crepitation may be noted with
movement of the joint, there are no systemic manifestations in OA.
Laboratory tests are always normal especially indices of inflammation.
This ESR and C reactive protein are always normal in OA. Leukocytes
<2,000 leukocytes on joint aspiration.
X-ray findings include osteophytes and unequal joint space. Joint
space narrowing with dense subchondral bone.
Osteophytes (spurs) are the reparative efforts by the bone.
Bouchards nodes: PIP
Heberdens nodes: DIP.
Diagnosis made clinically and on x-ray findings.
Treatment is aimed at reducing pain and maintains mobility, since
there is no cure for OA.
Nonpharmacological measures: reduction of joint loading by
correction of poor posture and weight loss. Physical therapy and
exercise programs should be designed to maintain range of motion,
strengthen periarticular muscles and improve physical fitness.
The first drug of choice is Acetaminophen, it is reasonable to add on
analgesic doses of NSAIDs if there is no relief.
CoX 2 inhibitors: Celecoxib remains on the market from this class of
medications. These medications have a decreased incidence of GI
hemorrhage because they do not inhibit the enzyme that generates
prostaglandins that produce the mucous barrier in the stomach.
There is an increased risk of CVD with the use of COX 2.
Cautious dosing should be prescribed in elderly patients because
they are at highest risk for the side effects associated with NSAIDs,
especially GI (ulcers hemorrhage, etc.). COX 2 inhibitors may be used
in patients who are at high risk for GI complications.
Another modality is with the use of capsaicin cream which depletes
local sensory nerve endings of substance P.
Orthopedic surgery and joint arthroplasty are reserved for cases in
which aggressive medical treatment has been unsatisfactory.
Intraarticular injection of hyaluronic acid has been approved for
treatment of knee OA that hasnt responded to pharmacologic
treatment.
CPC CRAM LIKE HELL NOTES
AMYOTROPHIC LATERAL SCLEROSIS
Is an idiopathic disorder of both upper and lower motor neurons.
ALS has a unique presentation of muscle weakness combined with
signs of upper motor neuron loss, cranial nerve palsies, respiratory
involvement and lower motor neuron destruction, while at the same
time preserving bowel, bladder sensory, cognitive and sexual
function.
The cranial nerve or bulbar, palsies result in dysphagia, difficulty
chewing, decreased gag reflex, dysarthria (difficulty in articulating
words), and difficulty in handling saliva.
Since there is often respiratory muscle involvement recurrent
aspiration pneumonia is the most common cause of death.
A weak cough is also characteristic and this inly worsens the
respiratory problem.
Sensory, sexual, autonomic and cognitive functions are normal in ALS.
There is no pain from abnormal sensory neuropathy because this is
entirely a motor neuron disease.
On the upper hand the upper motor neuron involvement gives
significant spasticity that can lead to pain. Mentation, bowel, bladder
and sexual function remain intact for the same reason.
In other words, a fully mentally alert patient loses nearly all motor
control while still being able to think and perceive. The patient
becomes fully aware of being trapped in a body that does not
function.
Head ptosis occurs because the extensor muscles of the neck to
become too weak to keep the head up.
Upper motor neuron manifestations are weakness with spasticity and
hyperreflexia.
Lower motor neuron manifestations are weakness with muscle
wasting, atrophy, and fasciculation, this includes tongue atrophy.
The combination of upper and lower motor neuron weakness is the
unique presentation of ALS.
The most accurate confirmatory test is the electromyogram, which will
show diffuse axonal disease.
CPK levels are sometimes mildly elevated, and the CSF and MRI scans
are normal.
The only treatment that may slow down the progression of the disease
is RILOZOLE, which is thought to work by inhibiting glutamate release.
Death typically in 3-5 years, secondary to respiratory failure.
Spasticity is treated with BACLOFEN and TIZANIDINE.
Page 4
 o Central precocious puberty/ Gonadotropin-dependent:
PRECOCIOUS PUBERTY this occurs because of increased secretion of estrogen
that is dependent on premature release of
gonadotropins from the hypothalamus and pituitary.
True precocious puberty is defined as activation of the hypothalamic- Idiopathic: the most common explanation is
pituitary axis with sexual maturation before the age 8 in females and 9 constitutional without a pathologic process
in males. It is usually idiopathic but can be caused by central nervous present, accounting for 80% precocious puberty.
system lesions. The age of the patient is usually 6 or 7 years old.
In pseudoprecocious puberty, secondary sex characteristics develop The diagnosis is usually one of exclusion after CNS
prematurely because of high circulating levels of androgen or imaging is shown to be normal. Management is
estrogen. GnRH agonist suppression (LEUPROLIDE or
It is more common in girls than boys. LUPRON) of gonadotropins until appropriate
Complete puberty is characterized by the occurrence of all pubertal maturity and height can be reached.
changes. CNS pathology: rare cause of precocious
o The most common initial change is thelarche (breast puberty.
development at age 9-10). o Peripheral precocious puberty/Gonadotropin-
o This is followed by anarche (pubic and axillary hair at age independent: this occurs when estrogen production is
10-11). independent of gonadotropin secretion from the
o Maximal growth rate occurs at age 11 and 12. hypothalamus and pituitary.
o Finally, the last change is menarche (onset of menses at McCune Albright syndrome: also known as
age 12-13). polyostotic dysplasia, this disorder is
Idiopathic or Constitutional characterized by autonomous stimulation of
o Precocious complete isosexual puberty aromatase enzyme production of estrogen by
o 6 year old girl the ovaries. The syndrome includes multiple cystic
o Normal head MRI bone lesions and Caf Au Lait skin spots. This
CNS lesions accounts for 5% of precocious puberty.
o Precocious complete isosexual puberty Management is by administration of aromatase
o 4 year old girl enzyme inhibitor.
o Abnormal head MRI Granulosa cell tumor: rare cause of precocious
McCune Albright syndrome puberty is a gonadal stromal cell ovarian tumor
o Precocious complete isosexual puberty that autonomously produces estrogen. A pelvic
o 6 year old girl mass can be identifies on examination.
o Caf-au-lait skin lesions Management involves the removal of the tumor.
Granulosa cell ovarian tumor Patients with idiopathic precocious puberty should be maintained
o Precocious complete isosexual puberty with inhibition of the hypothalamic-pituitary-ovarian axis until the
o 6 year old girl chronologic age catches up with the bone age.
o Pelvic mass Signs of estrogen excess (breast development and possibly vaginal
Incomplete isosexual precocious puberty: involves only one change, bleeding): suggest ovarian cysts or tumors.
thelarche, adrenarche, or menarche. This condition is a result of either Signs of androgen excess (pubic and or axillary hair, enlarged clitoris,
transient hormone elevation or unusual end-organ sensitivity. and or acne). Suggest adrenal tumors or CAH.
Management is conservative. Treatment:
Complete isosexual precocious puberty: all changes of puberty are o Central precocious puberty: Leuprolide is first line
seen including breast development, growth spirt, and menstrual therapy; physical changes regress or cease to progress.
bleeding. The primary concern is premature closure of the distal o Peripheral precocious puberty: treat the cause.
epiphyses of the long bones, resulting in short stature. Fertility and Ovarian cysts: will usually regress spontaneously.
sexual response are not impaired.

CPC CRAM LIKE HELL NOTES

Page 5
 CAH: treat with glucocorticoids. Surgery is not
required for the treatment of ambiguous
genitalia.
Adrenal or ovarian tumors: require surgical
resection.
McCune Albright syndrome: Antiestrogens
(Tamoxifen) or estrogen synthesis blockers
(Ketoconazole or Testolactone) may be
effective.
Idiopathic: GnRH agonist.
CNS lesions: Medical or surgical treatment
Ovarian tumor: Surgical excision
McCune-Albright: Aromatase inhibitors
OVARIAN CANCER
Most ovarian tumors are benign, but malignant tumors are the
leading cause of death from reproductive tract cancer.
Risk factors: age, low parity, decreased fertility, or delayed
childbearing, family history.
Frequency of female genital tract cancer:
endometrial>ovarian>cervical.
Number of deaths: ovarian>endometrial>cervical.
The BRCA1 mutation carries a 45% lifetime risk of ovarian cancer. The
BRCA 2 mutation is associated with a 25% lifetime risk.
Lynch II syndrome or hereditary nonpolyposis colorectal cancer
(HNPCC) is associated with an increased risk of colon, ovarian,
endometrial and breast cancer. OCPS taken for 5 years or more
decreases risk by 29%.
Both benign and malignant ovarian neoplasms are generally
asymptomatic.
Epithelial: most common type, elderly.
Germ cell, second most common type, younger age group.
Stromal: least common and occurs in all age group.
Mild, nonspecific GI symptoms or pelvic pressure/pain may be seen.
Early disease is typically not detected on routine pelvic exam.
Some 75% present with advanced malignant disease, as evidenced
by abdominal pain and bloating, a palpable abdominal mass and
ascites.
Increased CA 125 in 80% of cases in epithelial tumors.
Usually asymptomatic or minimally symptomatic until late in disease
course.
Abdominal pain, fatigue, weight loss, changes in bowel habits,
menstrual irregularity, ascites and mass.
CPC CRAM LIKE HELL NOTES
Tumor markers: increased CA 125 is associated with epithelial cell
cancer (90% of ovarian cancers) but is used only as a marker for
progression and recurrence.
o Premenopausal women: increased CA 125 may point to
benign disease such as endometriosis.
o Postmenopausal women: increased CA 125 (>35 units)
indicates an increased likelihood that the ovarian tumor is
malignant.
Transvaginal ultrasound: used to screen high-risk women and as the
first step in the workup of symptomatic women. (e.g., pelvic fullness,
pelvic pain).
Malignant mass: fixed, solid or firm, bilateral in location with nodular
cul-de-sac, >8cm, solid or cystic solid, multilocular septations, bilateral
in location and has ascites.
Benign mass: mobile, cyst inconsistency, unilateral in location with
smooth cul-de-sac. <8cm, cystic consistency, unilocular septations,
unilateral location and with calcifications.
Tumor marker:
o Epithelial: CA 125, most common type. Older women.
o Germ cell: LDH, hCG and alpha fetoprotein.
o Stromal tumors: estrogen and testosterone.
o Endodermal sinus: AFP
o Sertoli-Leydig tumor: postmenopausal, masculinization, and
increased testosterone level.
o Embryonal carcinoma: AFP and h CG
o Choriocarcinoma: hCG, pelvic mass and postmenopausal
women.
o Dysgerminoma: LDH
o Granulosa cell: inhibin
o Serous Carcinoma: postmenopausal woman, pelvic mass or
increase in CEA or CA 125 level.
Premenarchal women: masses >2cm require close clinical follow-up
and often surgical removal.
Premenopausal women:
o Observation is appropriate for asymptomatic, mobile,
unilateral, simple cyst masses <8-10cm in diameter. Most
resolve spontaneously.
o Surgically evaluate masses >8-10cm in diameter, and those
that are complex or unchanged on repeat pelvic
examination and ultrasound.
o Single oophorectomy for tumors detected in those who still
wishes to maintain fertility.
Postmenopausal women:
o Closely follow with ultrasound asymptomatic, unilateral simple
cysts <5cm in diameter with a normal CA 125.
o Surgically evaluate palpable masses.
Page 6
 Surgery: surgical staging: TAHBSO with omentectomy and pelvic and
parotic lymphadenectomy.
Benign neoplasms warrant tumor removal or unilateral
oophorectomy.
Postoperative chemotherapy: routine except for women with early
stage or low grade ovarian cancer.
Radiation therapy: effective dysgerminomas.
Women with BRCA 1 gene mutation should be screened annually with
ultrasound and CA 125 testing. Prophylactic oophorectomy is
recommended by age 35 or whenever childbearing is completed.
OCP use decreases the risk of ovarian cancer.
5 year survival improves with early detection, but because tumor is
frequently in advanced stages by time of detection, prognosis is often
poor.
Staging
o Stage 1: limited to the ovaries.
o Stage 2: extend to the pelvis.
o Stage 3: peritoneal metastases or positive nodes. Most
common stage at diagnosis.
o Stage 4: distant metastasis.
PRIMARY BILIARY CIRRHOSIS
Is an idiopathic autoimmune disorder that occurs more often in
middle aged women.
Autoimmune disease with intrahepatic bile duct destruction leading
to accumulation of cholesterol, bile acids and bilirubin.
Bilirubin levels do not elevate until the disease is extremely far
advanced, which is usually after 5-10 years.
It has as strong association with other autoimmune diseases such as
Sjogren syndrome, RA and scleroderma.
The most common symptoms are fatigue and pruritus.
Some asymptomatic patients have elevated alkaline phosphatase
level when measured for other reasons. Osteoporosis and
hypothyroidism are found in 20-30% of patients.
Transaminases are often normal. The most common abnormality
Jaundice, xanthomas, skin hyperpigmentation, hepatosplenomegaly
is elevation of alkaline phosphatase and gamma glutamyl
transpeptidase (GGTP). Total IgM levels are also elevated.
The most specific blood test is the antimitochondrial antibody.
Biopsy is always the best way to diagnose liver disease. It is the only
test more specific than antimitochondrial antibodies.
Other labs: increased alkaline phosphatase, increased GGt, normal
AST and ALT, increased cholesterol, increased bilirubin (total and
direct) later in disease course; positive antinuclear antibody (ANA).
CPC CRAM LIKE HELL NOTES
There is no specific therapy for primary biliary cirrhosis. Steroids will not
help.
Bile acid medication such as URSODEOXYCHOLIC ACID and
CHOLESTYRAMINE are used with variable success. Ultraviolet light is
recommended to treat the pruritus.
URSODEOXYCOLIC ACID improves liver function and reduces
symptoms.
COLCHICINES or METHOTREXATE can be added in severe cases.
Liver transplant for late stage PBC may be considered.
PRIMARY SCLEROSING CHOLANGITIS
Progressive destruction of intrahepatic and extrahepatic bile ducts
leading to fibrosis and cirrhosis.
This is an idiopathic disorder of the biliary system most commonly
associated with inflammatory bowel disease.
Although it is more often found with ulcerative colitis, it can also occur
with Chrons disease. Cancer of the biliary system can develop in 15%
of patients from the chronic inflammation.
Risk factors include ulcerative colitis, male>female.
Possibly asymptomatic, fatigue, pruritus, RUQ pain, fever, night sweats,
jaundice, xanthomas.
Labs include increased alkaline phosphatase, increased FFT, normal
AST and ALT, increased cholesterol, increased bilirubin (total and
direct), possible positive perinuclear antineurophil, increased bilirubin
(total and direct), possible positive perinuclear antineurtophil
cytoplasmic antibodies (pANCA); biopsy appears similar to that for
PBC.
The presentation and general laboratory tests are generally the same
as those for primary biliary cirrhosis, except that the antimitochondrial
antibody test will be negative.
The most specific test for primary sclerosis cholangitis is and ERCP or
transhepatic cholangiogram.
This is the only chronic liver disease in which a liver biopsy is not the
most accurate test.
ERCP shows structuring and irregularity of extrahepatic and
intrahepatic bile ducts. Example beads on string.
Treatment includes endoscopic stenting of strictures; surgical
resection of affected ducts and liver transplant may be required in
progressive cases.
Treatment is the same as for primary biliary cirrhosis with
URSODEOXYCHOLIC ACID.
Also liver transplant may be considered.
Page 7

GRAVES DISEASE/ THYROTOXICOSIS
Graves disease is an automimmune disorder, and the most common
caused of hyperthyroidism.
It causes the production of antibodies (thyroid stimulating
immunoglobulin or TSI), which in turn stimulate the thyroid to secrete t4
and t3.
Intrinsic thyroid autonomy can also result from a hyperfunctioning
adenoma (toxic adenoma) or it can be caused by toxic multinodular
goiter (Plummer disease), a non-autoimmune disease of the elderly
associated commonly with arrhythmia and CHF and sometimes the
consequence of simple goiter.
Transient hyperthyroidism results from subacute thyroiditis (painful) or
lymphocytic thyroiditis (painless, postpartum). For treatment purposes,
it is important to distinguish primary hyperthyroidism (Graves disease
or toxic adenoma) from thyroiditis.
Drugs such as amiodarone, alpha interferon, and lithium can induce
thyrotoxicosis. Excess iodine, as may occur in people taking certain
expectorants, or iodine-containing contrast agents for imaging studies
may cause hyperthyroidism. Extrathyroid source of hormones include
thyrotoxicosis factitia and ectopic thyroid tissue (struma ovarii,
functioning follicular carcinoma). Rarely, hyperthyroidism can result
from excess production of TSH (secondary hyperthyroidism).
Painless and diffuse enlargement: graves
Painless and nodules: plummer
Painful and diffuse: subacute thyroiditis
No thyroid enlargement or thyroid not palpated: factitious.
Graves disease (toxic diffuse goiter = hyperthyroidism + diffuse goiter
+ exophthalmos + dermopathy) deserves a special mention. In
Graves there is formation of autoantibodies which bind to the TSH
receptor in thyroid cell membranes and stimulate the gland to
hyperfunction (TSI).
o Commonly affects patients age <50
o Women > men
o Significant genetic component, i.e., a person is more likely to
be affected if they have family member with the disease
o Commonly triggered by stress, infection, and pregnancy
o Patients with another autoimmune disease such as type 1
diabetes or pernicious anemia are more likely to be affected
o Smoking causes increased risk of disease and may make the
exopthalmos worse
Clinical Findings. Graves is associated clinically with diffuse painless
enlargement of the thyroid. Nervous symptoms predominate in
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younger patients, whereas cardiovascular and myopathic symptoms
are more common in older patients. Atrial fibrillation can also be seen.
Other clinical findings include emotional lability, inability to sleep,
tremors, frequent bowel movements, excessive sweating, and heat
intolerance. Weight loss (despite increased appetite) and loss of
strength also are seen. Proximal muscle weakness may be a
prominent symptom in many cases and can be the primary reason
why the patient sees a physician. Dyspnea, palpitations, angina, or
cardiac failure may occur. The skin is warm and moist, and palmar
erythema is present along with fine and silky hair in hyperthyroidism.
Ocular signs include staring, infrequent blinking, and lid lag. Menstrual
irregularity such as oligomenorrhea occurs. Osteoporosis and
hypercalcemia can occur from increases in osteoclast activity.
Diagnosis. The diagnosis of Graves is made on history and physical
examination. Lab studies include suppressed TSH and high serum free
T4 and T3 (Note, in secondary hyperthyroidism, TSH is elevated). The
RAIU is increased (Note, in subacute thyroiditis and factitious
hyperthyroidism, RAIU is decreased). TSI, antithyroglobulin and
antimicrosomal antibodies are elevated.
Treatment. Treatment involves relief of symptoms and correction of
the thyrotoxic state.
Adrenergic hyperfunction is treated with beta-adrenergic blockade
(propranolol). Correcting the high thyroid hormone levels can be
achieved with an anti-thyroid medication (methimazole or
propylthiouracil) which blocks the synthesis of thyroid hormones
and/or by treatment with radioactive iodine. Methimazole is
preferred, as it has a longer half-life, reverses hyperthyroidism more
quickly, and has fewer side effects than propylthiouracil.
Methimazole requires an average of 6 weeks to lower T4 levels to
normal and is often given before radioactive iodine treatment; it can
be taken 1x/ day.
Because of its potential for liver damage, propylthiouracil is used only
when methimazole is not appropriate; it must be taken 23x/ day.
Antithyroid drugs during pregnancy. Propylthiouracil was the
traditional drug of choice during pregnancy because it is associated
with less severe birth defects than methimazole. But experts now
recommend that propylthiouracil be given during the first trimester
only. This is because there have been rare cases of liver damage in
people taking propylthiouracil. After the first trimester, women should
switch to methimazole for the rest of the pregnancy. For women who
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 are nursing, methimazole is probably a better choice than
propylthiouracil (to avoid liver side effects). Both drugs can cause
agranulocytosis.
The most commonly used permanent therapy for Graves disease is
radioactive iodine.
Indications for its use (overusing antithyroid agents alone) include:
o Large thyroid gland
o Multiple symptoms of thyrotoxicosis
o High levels of thyroxin
o High titers of TSI
Because of the high relapse rate (>50%) associated with antithyroid
therapy, many physicians in the United States prefer to use
radioactive iodine as first-line therapy. Patients currently taking
antithyroid drugs must discontinue the medication at least 2 days prior
to taking the radiopharmaceutical since pretreatment with
antithyroid drugs reduces the cure rate of radioiodine therapy in
hyperthyroid diseases. With radioactive iodine, the desired result is
hypothyroidism due to destruction of the gland, which usually occurs
2-3 months postadministration, after which hormone replacement
treatment is indicated.

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