adrenal disease—selected topics · a 50‐year‐old woman has a 3‐cm right adrenal mass...
TRANSCRIPT
Adrenal Disease—Selected Topics
Kaushik Mukherjee MD
Faculty Advisor: James Broome MD
•
A 50‐year‐old woman has a 3‐cm right adrenal mass discovered incidentally during an
abdominal CT scan for epigastric pain. She has been healthy since undergoing
lumpectomy for stage I breast cancer 7 years previously.
The next step should be…
Mea
sure
men
t of..
. M
easu
rem
ent o
f...
CT‐gu
ided
FNA
Det
erm
inat
ion .
.. O
pera
tive e
xci...
20% 20% 20%20%20%
1.
Measurement of urinary free cortisol
2.
Measurement of 24‐ hour urinary
metanephrines
3.
CT‐guided FNA
4.
Determination of plasma aldosterone
concentration to plasma renin activity
ratio
5.
Operative excision
Adrenal Incidentaloma
•
1‐5% of patients undergoing CT for other reasons
•
Most are asymptomatic
Adrenal IncidentalomaBilateral or
Unilateral?
BilateralUnilat
eral
Functional?Yes
No
Adenoma
(cortisol)
Pheo
Aldosterone(Conn’s)
Cortical Adenoma (60%)Adrenocortical carcinoma
MetastasesCysts
Lipomas
Adrenal cortical
hyperplasia
Bilateral Pheo
(10% of all pheo)
Metastatic
lesions
Lymphoma
Myelolipoma
TB
Management of Incidentalomas
Incidentaloma
discovered Lab studies
Imaging
Review
How big?How bright?How uniform?
MRI??
PlasmaOR
Urine metanephrines
Dexamethasone
suppression test
Plasma aldosterone and
rennin
FunctionalFour‐Five cmIrregular
None of those
Re‐image at 4 and 12
months
Repeat labs at 12
months
Taking new patients…
Imaging CharacteristicsHou
nsfeld units
Cortical adenomas < 10(high lipid content)
ACCA > 18(more water content)
CTMRI + Gadolinium
Adenomas dim on T2W imaging;Pheos and mets are bright
Chemical‐shift imaging‐Adenomas lose intensity on opposed‐phase images
‐Pheo or carcinoma do NOT show loss of intensity
H2O Lipid
In phase
H2O Lipid
Out of phase
•
Characteristics of adrenocortical carcinoma include all of the following EXCEPT
All of the following EXCEPT
Size
> 6 c
m in
... Es
troge
n pr
odu.
.. Ir
regu
lar sh
ap...
Bioc
hem
ically
...
Rare
ly bi
later
...
20% 20% 20%20%20%1.
Size > 6 cm in diameter
2.
Estrogen production in
30% cases
3.
Irregular shape/margin on
CT
4.
Biochemically active in 2/3
of cases
5.
Rarely bilateral
Adrenocortical carcinoma
•
Rare: incidence of 0.5‐
2/million adults•
Bimodal age distribution–
1st
5 years–
4th‐5th
decades•
Present late (12‐15 cm)–
Abdominal/back pain–
60% hyperfunctioning•
30% cortisol•
20% androgen•
Estrogen/aldosterone rare
•
Labs–
Test for hypercortisolism–
Test for adrenal androgens
(DHEA, testosterone)
•
Management–
Resection only chance for
cure
–
No laparoscopic surgery–
Mitotane chemotherapy•
Toxic to adrenal cortex•
Other drugs being studied–
Radiation usually not
effective, only palliative
–
Can consider RFA
Adrenocortical Carcinoma Staging
Stage Description
I T1 (≤
5 cm) N0 M0
II T2 (>5cm) N0 M0
III T3 (locally invasive) N0 M0T1‐T2 N1 M0
IV T4 (invades adjacent organs) N0‐1 M0Any T, Any N, M1
5‐year survival 32‐48% with complete resection.CT/MRI/PET needed to identify or rule out
distant mets.
Genetic Signature for ACCA
Survival Curves for ACCA
Cushing’s Syndrome
Symptoms Signs
Weight gain Obesity (central)
Florid complexion Moon facies
Menstrual
abnormalities,
decreased libido
Abnormal fat
distribution
Spontaneous
bruising
TelangiectasiasSkin striae
Muscle
weakness/fatigue
Osteopenia/Osteoporosis
Mood swingsDepressionInsomnia
Hirsutism
Workup of Cushing’s Syndrome24 hr urinary free cortisol
Overnight dexamethasone
suppression test
1‐3mg dex given PO at 2300,
measure plasma cortisol at 0800
Normal < 1.8 ug/dLCushing > 10 ugdL
N
o
r
m
a
l
No Cushing’s
Syndrome
Abnormal Plasma ACTH
Low (<5 pg/m
L)
CT Abdomen
(look for
adrenal mass)
High or upper‐
normal ACTH
Look for
pituitary Cushing syndrome
ectopic ACTH‐secreting tumor
High/Upper Normal ACTH on High Dose Dexamethasone Suppression Test
High‐dose dexamethasone
suppression test
2x6mg or 1x8mg dose,
measure cortisol before,
during, and after
Cushing’s
disease
(pituitary mass)
Suppressed
plasma/urinary
cortisol (<50%
basal level)
Ectopic ACTH‐producing
tumor
Small cell lung CA 50%Thymic tumors
CarcinoidMTC
Cortisol levels unchanged
70‐80% diagnostic accuracyCan correlate with CRH stimulation test
Alternatives:Pituitary MRI, petrosal sinus sampling
•
Which of the following statements about the surgical management of primary sporadic
pheochromocytoma is TRUE?
Which is TRUE?
Preo
pera
tive p
... Pr
eope
rativ
e M...
Preo
pera
tive M
... La
paro
scop
ic o..
. M
ost p
atien
ts ...
20% 20% 20%20%20%1.
Preoperative
phenoxybenzamine is not
needed
2.
Preoperative MIBG scan often
identifies extra‐adrenal disease
3.
Preoperative MIBG scan reduces
postop complications
4.
Laparoscopic operation is
associated with more
intraoperative hypotension
5.
Most patients require beta
blockade, followed by alpha
blockade
Pheochromocytoma
•
Arise from chromafin tissue
•
85‐90% in adrenal gland
–
Extra‐adrenal pheos
cannot secrete
epinephrine
•
Peak incidence 4th‐5th
decades
of life
•
“10% rule”
–
10% bilateral
–
10% extra‐adrenal
–
10% malignant
•
Paroxysmal hypertension–
Chest pounding–
tachycardia –
Headache–
Anxiety–
Fever–
Flushing–
Sweating–
Impending sense of doom•
Hypertensive Crises–
Severe headaches–
Diaphoresis–
Visual changes–
MI/CHF–
Stroke
DO NOT BIOPSY AN ADRENAL MASS WITHOUT SENDING PLASMA OR URINE METANEPHRINES
Workup for Pheo
•
Labs–
Plasma•
Fractionated metanephrines•
Very sensitive (but will have
some false +)
–
Urine•
VMA test least specific,
affected by Starbucks, no one
really uses it…
•
Urine metanephrine analysis
has fewer false positives
•
Imaging (If biochemically
positive)
–
CT–
Bright on T2W MRI
–
MIBG•
Used for–
Metastatic disease–
Extra‐adrenal tumors–
Other imaging inconclusive•
Sens: 77‐87%•
Spec: 96‐100%•
Good for following patients
with malignant pheos
Pheo Syndromes
MEN 2A
Pheo (30‐50%)Medullary thyroid
carcinoma
Parathyroid tumors
MEN 2B
Pheo (30‐50%)Medullary thyroid
carcinoma
Mucosal neuromas
Ret(en) oncogene (Chr 10)
VHL (3 letters, chromosome 3)
Pheo (14%)*Bilateral renal tumors/cysts
Cerebellar/spinal hemangioblastomasRetinal angiomas
Pancreatic cysts/tumorsEpididymal cystadenomasInner ear canal tumors
Others
Neurofibromatosis (Chr 17, same as # of
letters in the word)
Familial paraganglioma and extra‐
adrenal pheochromocytoma
(Succinate Dehydrogenase gene)
*NEJM 1993(329):1531‐1538.
•
A 37 year old hypertensive man has a left‐ sided 3.4 cm adrenal mass. Initial studies including a 24 hour urine collection for free
catecholamine and catecholamine metabolites, an overnight 1 mg
dexamethasone suppression test, serum electrolytes, BUN, and creatinine have all been within normal limits.
The next diagnostic study should be
High
‐dos
e dex
a...
Plas
ma c
atec
ho...
Plas
ma a
ldoste
...
PET
MRI
20% 20% 20%20%20%1.
High‐dose dexamethasone
suppression test
2.
Plasma catecholamine determination
3.
Plasma aldosterone concentration to
plasma renin activity ratio
4.
PET
5.
MRI
Primary hyperaldosteronism (Conn’s Syndrome)
•
8‐12% of hypertensive patients•
Consider in–
Early onset
–
Refractory–
Hypertension with hypokalemia (60% normokalemic)
•
Pathophysiology–
Increased aldosterone secretion from adrenals
–
Increased Na retention, expanded intravascular volume–
Suppression of renin secretion
–
Na+/K+ exchange in distal tubule K+ depletion, alkalosis–
Countermovement of H+ ions makes alkalosis worse
–
Significant K+ depletion can also present with mild glucose
intolerance
Pathophysiology of Conn’s Syndrome
Na+/K+ ATPase
Urine stream
Na+H+ K+
Breakdown
•
30‐50% Aldosteronoma
•
Remainder with bilateral adrenal hyperplasia (MEDICAL THERAPY)
–
Dietary Na+ restriction
–
K+ supplementation
–
Spironolactone
–
Eplerenone (less androgen binding)
•
Familial subtypes also present but rare
Workup for Primary Hyperaldosteronism
PAC/PRA ratio >25‐30PAC > 15 ng/dL
PRA < 0.2‐0.5 ng/mL/hr
Salt loading(high‐salt diet 3 days,
correct K+, collect 24
hour urine on day 3)
>12 ug/24 hr
OR
IV salt loadingPAC > 10 ng/dL
MicroadenomaNormal adrenals
>40‐50
Adrenal vein
samplingLook for
cortisol > 4x
on one side
<40‐50
with >
1cm ade
noma
Summary
•
Understanding pathophysiology will help with understanding the diagnostic pathway
•
Understanding the diagnostic pathway will help you understand the workup
•
Dr. Broome likes to do laparoscopic adrenalectomies