Transcript Cushing`s disease - Texas Tech University Health Sciences Center

Board Pearls
in Endocrinology
Part 1
Rey Vivo, MD
Assistant Professor of Medicine
Texas Tech University Health Sciences Center
Objectives
• Discuss frequently tested Endocrine cases in the
IM Boards
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Pituitary
Cushing’s, Adrenal Incidentaloma
Amenorrhea, Hirsutism, Anorexia vs. Bulimia
Parathyroid, Calcium homeostasis, Bone disorders
Hemochromatosis, Wilson’s disease
Diabetes insipidus
• Examine practice questions from MKSAP 14 and
other sources
Pituitary
Pituitary tumors
FUNCTIONAL
Prolactinoma
GH-secreting adenoma
Acromegaly
ACTH-producing adenoma
Cushing’s disease
NON-FUNCTIONAL
Chromophobe adenoma
Prolactinoma
• PEARLS:
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S/Sx: galactorrhea, infertility, amenorrhea
Prolactin >200 ug/L
Check TSH: need to R/O hypothyroid always
Drugs: Reglan, H-blockers, estrogens
Treatment indicated only if fertility desired or very
symptomatic
• Medical tx: bromocriptine or cabergoline
• Surgical tx: if drug-resistant or intolerant
Board Q
• A post-menopausal 57F presents to the clinic with galactorrhea.
She denies taking any medications. Prolactin level is normal. What
is the most appropriate next step in evaluating this patient?
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A. Cranial MRI
B. Measure TSH
C. Start cabergoline
D. Recheck prolactin in 1 year
E. Refer to surgery
Board Q
• A 42F presents with galactorrhea. She has no significant medical
history and is not taking any medications. She qualified that her
symptom occurs on manipulation of nipples only. Her TSH and
prolactin levels are WNL. Pregnancy test is negative. MRI of the
brain is unremarkable. Next best step?
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A. Remeasure prolactin in 6 months
B. Start bromocriptine
C. Refer for radiation therapy
D. Avoid manipulation of nipples
MKSAP Q #52
• A 38M is evaluated for fatigue, decreased libido, and worsening
headaches of 2 years. PE bitemporal hemianopsia. The testes are
<10 mL and soft. Labs: testosterone level of 165 ng/dL (low), LH
level of 0.5 mU/mL (low) and a prolactin level of 2520 ng/mL (high).
Levels of IGF-1, TSH, free thyroxine, and cortisol are normal. MRI of
the head shows a 2.7-cm pituitary mass arising from the sella and
elevating the optic chiasm. What is the most appropriate
management?
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A. Remeasure prolactin level in 3 months
B. Start testosterone therapy
C. Start dopamine agonist therapy
D. Refer for transsphenoidal surgery
E. Refer for radiation therapy
Acromegaly
• PEARLS:
– S/Sx: bitemporal hemianopsia, macroglossia,
acanthosis nigricans (IR), increased sweating, heat
intolerance
– Screen: age- and gender-matched IGF-1 levels
(increased)
– Confirm: OGTT – GH not suppressed to <2 ug/L after
2 hours; then MRI
– Tx: TSS, then irradiation
Acromegaly
MKSAP Q #6
• A 58F has a remote history of a pituitary macroadenoma treated with
surgery and radiation. Recently, she noted fatigue and weight gain
of 7 kg, particularly in the abdomen, and daily headaches. She is 8
years postmenopausal. Meds: MV, a calcium supplement and
acetaminophen for headaches. She also has cold intolerance,
constipation and nausea. On PE, BP is 124/80, pulse 90/min. She
is pale and has mild periorbital edema, dry skin, and thin, brittle hair.
DTRs are mildly delayed. Labs: hematocrit 32%, electrolytes WNL,
morning cortisol low normal, estradiol undetectable, FSH normal, LH
normal, prolactin 8 ng/mL, TSH 0.2 µU/mL, free T4 0.5 ng/dL, GH
undetectable, IGF-1 low. Pituitary MRI shows postoperative changes
but no clear evidence for residual tumor. Which of the following is
the most likely cause of these findings?
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A. Primary hypothyroidism and menopause
B. Central adrenal insufficiency
C. Growth hormone deficiency
D. Panhypopituitarism
E. Pituitary apoplexy
Cushing’s syndrome
Cushing’s syndrome
ACTH
Cortisol
DHEA
Mechanism
Cushing’s
disease
(Pit. lesion)
High
High
High
All zones produce
hormones
Adrenal
adenoma/
hyperplasia
Low
High
Low
Does not involve
DHEA-producing cells
Adrenal
carcinoma
Low
High
High
Increased DHEA levels
Cushing’s
• PEARLS
– S/Sx: buffalo hump, purple striae, proximal
weakness, hyperglycemia, hypertension,
hypokalemia, osteoporosis, hirsutism*
– Screen: 24 hr. urine free cortisol (>50ug/day),
overnight dexamethasone suppression test (plasma
cortisol > 5 ug/dL)
• Dexa 1 mg at 2300,
check cortisol at 0800 the next morning
MKSAP Q #5
• A 38F is evaluated for a 13.2-lb weight gain over 2 years. She was
recently found to have a fasting blood glucose of 130 mg/dL and 136
mg/dL on two separate visits. She is taking no medications other
than a multivitamin and has taken no prescribed medications in the
past 5 years. On physical examination, the patient's BMI is 32 and
blood pressure 160/94 mm Hg. The patient has scant terminal hairs
over her chin, mild acne over her face, and violaceous striae,
bilaterally over her lateral abdomen. Her face is full, abdomen
prominent, and her arms and legs seem disproportionately thin.
Which of the following is the most appropriate next step?
• A. Serum cortisol, 1600 hrs
• B. 24-hour urine collection for cortisol
• C. Serum cortisol, 0800 hrs, following dexamethasone 8 mg the
prior evening
• D. Serum ACTH, 0800 hrs
• E. MRI of the head
Board Q
• 35F with obesity, purple abdominal striae and hyperglycemia is
evaluated for possible cortisol excess. She receives a 1 mg of
dexamethasone at midnight and plasma cortisol level drawn at 8AM
is 15 ug/dL (N <5 ug/dL). What is the next most appropriate test?
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A.
B.
C.
D.
CT of the brain
CT of the abdomen
2-day low dose dexamethasone suppression
2-day high dose dexamethasone suppression
Cushing’s
• PEARL:
– Definitive diagnosis:
2-day low-dose dexamethasone
suppression test
• Give dexa 0.5 mg Q6, check plasma
cortisol on 2nd day
• (+) test: failure of plasma cortisol to fall to
<5 ug/dL
Adrenal Incidentaloma
Incidentaloma
• Pheochromocytoma
– S/Sx: episodic HA,
sweating, palpitations,
HTN, postural hypotension
– Dx: urine/plasma
metanephrines
– Localize: CT or MRI; MIBG
scan for extra-adrenal
lesions
– Pre-op Tx:
Phenoxybenzamine
• Conn’s syndrome
– S/Sx: diastolic HTN,
hypokalemia, polyuria,
polydipsia
– Dx: plasma renin low,
aldosterone high
– Tx: Spironolactone,
surgery
Adrenal Incidentaloma
• PEARLS:
– 1st step: hormonal assessment (urine free cortisol,
urine/plasma metanephrines, paired plasma renin and
aldosterone)
– CT features of carcinoma:
• >3 cm. in size
• Irregular border, heterogenous consistency
• Attenuation value >10 Housfield units
– Follow up: Repeat CT 3-6 months
– Surgical Tx: If functional or >6cm or enlarging on
serial CT
Board Q
• Abdominal CT scan of an otherwise healthy 51M displays an
incidental 3 cm left adrenal mass. He is referred to your outpatient
clinic for further evaluation. He reports family history of “abdominal
tumor”. BP is 140/100. What is the next step?
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A.
B.
C.
D.
Repeat CT in 6 months
Refer for surgical excision
Refer to Endocrinologist
Check serum catecholamines, renin, aldosterone and
urine cortisol
• E. Start HCTZ and follow up in 1 year
MKSAP Q #39
• A 56M is evaluated for anorexia and a 5-kg unintentional weight
loss. He has vague abdominal discomfort and occasional flank pain.
He does not have polyuria, polydipsia or increased pigmentation. On
PE, BMI is 27 and BP is 108/72. Aside from mild tenderness to deep
palpation over the left upper abdominal quadrant, the examination is
unremarkable. CT abdomen shows a 6-cm left adrenal mass.
Attenuation value of the mass is 32 Hounsfield units. The margins of
the lesion are irregular and the consistency is heterogeneous. Xray
of the lungs and kidneys were unremarkable. Plasma fractionated
metanephrines are normal. Plasma aldosterone/plasma renin
activity (ARR) is 6 (normal <12). Serum cortisol at 0800 hrs after
dexamethasone 1 mg the preceding evening is 1.4 µg/dL. Next best
step?
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A. Selective adrenal venous sampling
B. Repeat biochemical evaluation and CT in 6 months
C. Iodocholesterol imaging of the adrenals
D. Referral for surgical resection of mass
MKSAP Q #80
• A 36M is evaluated in the ED for headache and palpitations. He is
anxious, tremulous, and diaphoretic. The blood pressure is 198/106
mm Hg, and the pulse rate is 110/min. He has been hypertensive for
the past 2 years, but has been suboptimally controlled with a
combination of hydrochlorothiazide, diltiazem, and lisinopril. He
frequently experiences episodic headache and diaphoresis, during
which his blood pressure is alarmingly high. These episodes had
been attributed to migraine headaches, but addition of propranolol
for prophylaxis worsened their frequency and severity. What is the
most appropriate next step?
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A. Serum catecholamines
B. Serum potassium
C. Insulin-like growth factor 1
D. Fractionated plasma metanephrines
E. 24-hour urine collection for cortisol
MKSAP Q #91
• A 43M has persistent hypertension. At 29, he was found to have BP
of 160/100 and was initially treated with a β-blocker. Since then, his
BP has remained high despite weight loss, compliance with therapy,
and abstinence from alcohol. His current meds consist of maximal
doses of HCTZ, atenolol, lisinopril, and amlodipine. On PE, his BMI
is 26 and BP is 156/98. He has no striae, normal facies and no
abdominal bruits. The fasting glucose is 98 mg/dL, potassium is 3.3
meq/L, and creatinine is 1.3 mg/dL. What are the most appropriate
tests?
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A. Serum insulin-like growth factor 1
B. 24-hour urine for free cortisol
C. Plasma fractionated metanephrines
D. Plasma aldosterone/plasma renin activity ratio
E. Magnetic resonance angiography of the renal arteries
Amenorrhea
Amenorrhea
Anatomic
1.
2.
3.
Congenital defects
of vagina, hymen
Mullerian agenesis
Asherman
syndrome
Ovarian failure
1.
2.
3.
4.
5.
Turner syndrome
Premature
menopause
21 hydroxylase
deficiency
17 alpha
hydroxylase def.
Polyglandular
ovarian failure
Chronic
anovulation
Estrogen present
(bleeds after Prog.)
1. Functional
hypothalamic
amenorrhea
2. PCO
Estrogen absent
1. Hypogonadotropic
hypogonadism
Amenorrhea
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5 Most common “P”s:
1. Pregnancy
2. Prolactinoma
3. Premature menopause
4. PCO syndrome
5. Pituitary failure
– Excessive stress/exercise
Check FSH
Progesterone
challenge
PCO syndrome
• PEARLS:
– aka Stein Leventhal syndrome
– Major associations: insulin resistance, virilization,
acanthosis nigricans
– Excess fat…high estrogen (aromatization of excess
androgen)…low FSH and high LH (positive
feedback)…LH/FSH ratio >2…bleeding after
progesterone because estrogen is present
– Tx: weight reduction, OCP, clomiphene (increases
FSH secretion)
Board Q
• 22F is training for the marathon and is running 50 miles/week. She
has also recently started a post-graduate course. She consults for
amenorrhea in the last 10 months and is becoming concerned. BMI
is 18. Pregnancy test is negative. Prolactin level is normal. LH and
FSH are equally low. What is the most appropriate next step in
management?
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A. Psychiatry consult
B. MRI of the brain
C. No further tests. Advise to cut down on exercise program.
D. No further tests. Return in 1 year; if symptoms persist, refer to
gynecology.
Board Q
• 38F is evaluated for amenorrhea. She reports cessation of menses
since 6 months ago. She denies any excessive stress or exercise.
She denies any medications. Pregnancy test in negative. Prolactin
and TSH levels are normal. Serum LH and FSH are both elevated
and serum estradiol is low. What is the most likely diagnosis?
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A. Panhypopituitarism
B. PCO syndrome
C. Hypogonadotropic hypogonadism
D. Premature menopause
Amenorrhea
• PEARL: FSH level
Premature menopause
Hypogonadotropic
hypogonadism
MKSAP Question 57
• A 26F is evaluated for amenorrhea. Her last menstrual period was 3
months ago, and three home pregnancy tests have been negative.
She states that she has no other symptoms and takes no
medications. Menarche occurred at age 12 years, and her menstrual
cycle has been regular until 3 months ago. Upon further questioning,
she recounts weekly headaches and occasional galactorrhea on
breast palpation. PE is normal. Deep tendon reflexes are normal.
Serum prolactin level is 1665 ng/mL. What is the most likely cause
of her hyperprolactinemia?
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A. Pregnancy
B. Cirrhosis
C. Primary hypothyroidism
D. Prolactin-producing pituitary tumor
Hirsutism
Hirsutism
• PEARLS:
– Drugs: phenytoin, anabolic steroids, minoxidil,
cyclosporine
– 4 tests to consider:
Testosterone
High in ovarian CA (older age)
DHEA
High in Cushing’s disease, Adrenal CA
LH, FSH
Ratio >2 in PCO syndrome
ACTH
High: Cushing’s disease; Low: Adrenal
CA; Normal: PCO syndrome
Board Q
• 19F presents to the outpatient clinic for hirsutism. In the last year,
she has observed noticeable hair growth involving her upper lip and
sideburns. She is not on any medications. She has normal periods
are regular intervals and has no signs of virilization. BMI is 20. All
endocrine work-up is within normal limits. She mentions that her
aunt had similar facial hair pattern. What is the next best step?
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A. Cosmetic measures, i.e. bleaching/removal of hair
B. Empiric trial of OCP
C. 24 hour urine free cortisol
D. CT abdomen to look for any masses
MKSAP Q #18
• A 68F is evaluated for facial hair, voice deepening, and increased
muscle mass over the past 6 months. She has not changed
medications recently. She also notes that she is more aggressive
and irritable recently. PE reveals a full beard and terminal hairs on
the chest and abdomen. The clitoris is 3 cm long, 2 cm across, and
firm. Laboratory results include a serum total testosterone of 350
ng/dL (high). What is the best next step?
• A. Measure serum prolactin, DHEA-sulfate, and 17hydroxyprogesterone
• B. Start spironolactone therapy
• C. Measure serum free and bioavailable testosterone
• D. Perform 4-day dexamethasone suppression test for cortisol and
DHEA-sulfate
• E. CT scan of abdomen and pelvis
Board Q
• 24F is very concerned about excessive facial hair growth. On
examination, she looks very thin and she admits having lost 35 lbs in
“a short period of time”. She has also experienced absence of
menses and severely dry skin. Pulse rate is 48/min. Serum
potassium is very low. Which of the following findings is most likely
part of this disease?
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A. Antisocial behavior
B. Binge eating
C. Hypothermia
D. Dental caries
Anorexia vs Bulimia
Anorexia nervosa
Bulimia
Intake restriction
Vomiting
Common
Rare
100%
50%
Brady, hypotension
Common
Rare
Hirsutism
Common
Rare
Hypothermia
Common
Rare
Antisocial behavior
Rare
Common
Binge eating
Rare
Common
Body weight
Markedly low
Near normal
Complications
Hypokalemia,
arrhythmias
+ Aspiration,
esoph/gastric rupture
Weight control
Ritualized exercise
Amenorrhea
Board Q
• 21F is brought to the office by her mother to the office for facial
swelling. She admits to episodes of recurrent vomiting. BMI is
normal. She is afebrile. She has dental caries and bilateral parotid
gland enlargement. There are excoriations on her knuckles. Blood
work reveals hypokalemic alkalosis. What is the most likely
diagnosis?
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A. Anorexia nervosa
B. Bulimia
C. Parotitis
D. Sjogren’s syndrome
Thank you
Part 2
27 May 2008