Absite Review Series: Adrenal Gland Disorders

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Absite Review Series:
Adrenal Gland
Disorders
Sean Rim
7/11/2008
www.downstatesurgery.org
Questions
Which of the following are effective initial
treatments of acute adrenal insufficiency?
A. Normal
A
N
l saline
li bolus
b l
B. Potassium
C IV glucocorticoids
C.
D. IV mineralocorticoids
E. A and C
F. All of the above
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Questions
The most common cause of congenital
adrenal hyperplasia is related to which
enzyme deficiency?
A. 11-hydroxylase
B. 17-hydroxylase
y
y y g
C. 3-hydroxyhydrogenase
D. 21-hydroxylase
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Questions
Which of the following is the most
common cause of endogenous
Cushing’s syndrome/disease?
A. Adrenal adenoma
B. Adrenal carcinoma
C. Pituitaryy adenoma
D. Ectopic ACTH
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Questions
A CT scan demonstrates an 8 cm right
adrenal mass extending into liver and
kidney Which of the following are
kidney.
appropriate?
A. En bloc resection
B. Radiation followed by en bloc resection
C. Mitotane followed by en bloc resection
D. Chemoradiation followed by en bloc
resection
www.downstatesurgery.org
Questions
Which of the following are
contraindications to laparoscopic
adrenalectomy?
A. Pheochromocytoma
B. Adrenocortical cancer
C. Bilateral adrenal lesions
D. Prior abdominal surgery
E. A and B
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Adrenal Glands
|Paired
glands with two distinct functional organs
|Third most highly perfused organ behind kidney and
thyroid, 2000mL/kg/min
z
Cortex
• Mesodermal
z
Medulla
• Ectodermal
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Adrenal Glands
|Paired
glands with two distinct functional organs
|Third most highly perfused organ behind kidney and
thyroid, 2000mL/kg/min
z
Cortex
• Mesodermal
• 4th to
t 5th week
k
z
Medulla
• Ectodermal
• 5th to
t 6th week
k
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Adrenal Glands
|Paired
glands with two distinct functional organs
|Third most highly perfused organ behind kidney and
thyroid, 2000mL/kg/min
z
Cortex
• Mesodermal
• 4th to
t 5th weekk
• Glucocorticoids,
mineralocorticoids,
sex steroids
z
Medulla
• Ectodermal
• 5th to
t 6th weekk
• Catecholamines
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Adrenal Glands
|Paired
glands with two distinct functional organs
|Third most highly perfused organ behind kidney and
thyroid, 2000mL/kg/min
z
Cortex
• Mesodermal
• 4th to
t 5th weekk
• Glucocorticoids,
mineralocorticoids, sex
steroids
• Hyperaldosteronism,
Cushing’s,
virilization
z
Medulla
•
•
•
•
Ectodermal
5th to
t 6th weekk
Catecholamines
Pheochromocytoma
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Anatomy
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Anatomy
|
Arterial supply is diffuse
Inferior phrenic artery
z Juxtaceliac aorta
z Renal artery
y
z
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Anatomy
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Anatomy
|
Venous drainage is solitary
Left vein ~2 cm into renal
z Right ~0.5 cm into IVC
z 20% variable
z
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Anatomy
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Histology
Cortex is 2 mm
| >80% mass
| Medulla
M d ll h
has
extensive autonomic
fibers and ganglion
cells
|
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Series of oxidative
reactions via
cytochrome P-450
membrane
associate
enzymes
Reticularis
Fasiculata
Glomerulosa
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Steroid hormones
|
|
|
|
|
Low molecular weight, lipophilic signaling
molecules
E t cells
Enter
ll and
d bi
bind
d tto iintracellular
t
ll l
receptors
Slower response than membrane binding
peptides
Levels altered by
yp
pregnancy,
g
y, nephrotic
p
syndrome, cirrhosis
Metabolized in liver and excreted via kidney
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Mineralocorticoids
Aldosterone regulates circulating fluid
volume and electrolyte balance
| Promotes Na and Cl retention in distal
tubule
| K and H secreted
| Will see expansion
p
of BP and
intracellular volume with aldosterone
|
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Mineralocorticoids
|
|
Renin-angiotensin-aldosterone axis is
responsive to delivery of sodium to the DCT
Low sodium delivery triggers release of
renin from JGA
z
z
z
|
|
Shock
Renal artery vasoconstriction
Hyponatremia
Renin cleaves angiotensinogen (liver) to
angiotensin-1
ACE ((lungs)
g ) cleaves to angiotensin-2
g
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Glucocorticoids
Generate a catabolic state in
response to stress
| Alters
Alt
carbohydrate,
b h d t protein,
t i and
d lilipid
id
metabolism to increase blood glucose
| Increase gluconeogensis
| Decrease peripheral glucose uptake
| Sensitizes
S
iti
arterial
t i l smooth
th muscle
l to
t
beta-adrenergic stimulation
|
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Glucocorticoids
Potent anti-inflammatory and
immunosuppressive agents
| Reduce
R d
circulating
i l ti llymphocyte
h
t and
d
eosinophils and increase neutrophils
| Decrease cytokine and Ig production
| Suppress histamine release
| Inhibit
I hibit phospholipase
h
h li
A2 tto reduce
d
prostaglandins
|
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Glucocorticoids
Hypothalamus release CRF into
pituitary
| Results in ACTH secretion
| ACTH bind G p
protein coupled
p
receptors on adrenocortical cell
surface
| Steroidogenesis is upregulated
|
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Glucocorticoids
ACTH is released in a pulsatile
fashion, circadian rhythm
| Peak in AM
| Negative
g
feedback occurs at both
hypothalamic and pituitary levels
|
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Rate limiting
step
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Exclusive to
chromaffin cells
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Stable
metabolites
used for
markers
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Catecholamines
Alpha-1: Vasoconstriction of skin and
GI tract
| Alpha-2: Attenuate sympathetic
outflow in preynapse
| Beta-1: Increase HR and contractility
| Beta-2: Smooth muscle relaxation in
unterus, bronchi, skeletal muscle
arterioles
|
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Congenital Adrenal Hyperplasia
Six enzyme defects have been
identified
| 90% caused by CYP21A2 deficiency
(21-hydroxylase)
| Usually manifests as salt-wasting form
|
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Congenital Adrenal Hyperplasia
|
|
|
|
|
|
Decreased negative feedback
Hypovolemia, hyperkalemia,
h
hyperreninemia
i
i
Shunts towards adrenal androgens
A bi
Ambiguous
genitalia
it li iin ffemales
l
Dx via elevated 17-hydroxyprogesterone
Tx via glucocorticoid and mineralocorticoid
replacement
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Questions
The most common cause of congenital
adrenal hyperplasia is related to which
enzyme deficiency?
A. 11-hydroxylase
B. 17-hydroxylase
y
y y g
C. 3-hydroxyhydrogenase
D. 21-hydroxylase
www.downstatesurgery.org
Questions
The most common cause of congenital
adrenal hyperplasia is related to which
enzyme deficiency?
A. 11-hydroxylase
B. 17-hydroxylase
y
y y g
C. 3-hydroxyhydrogenase
D. 21-hydroxylase
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Primary Adrenal Insufficiency
|
Addison’s disease
z
z
z
z
z
z
z
z
Weakness
F i
Fatigue
Anorexia
Nausea
Weight loss
Hyperpigmentation
Hypotension
Electrolyte disturbance
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Primary Adrenal Insufficiency
Congenital adrenal dysgenesis
| Defective steroidogenesis
| Adrenal destruction
|
Autoimmune
z Infectious (TB, fungal, viral)
z Metastases
z Adrenal hemorrhage (WaterhouseFriderichsen syndrome)
z
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Secondary Adrenal Insufficiency
Steroid withdrawal
| Surgical
g
cure of Cushing’s
g
| Panhypopituitarism
|
Neoplasm
z Granulomatous disease
z Sheehan
Sheehan’s
s sydrome
z
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Adrenal Crisis
Life-threatening
| Occurs in p
patients with marginal
g
function subjected to significant
physiologic stress
| Initial treatment is volume and
glucocorticoids
| Mineralocorticoid effects take several
days
y
|
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Questions
Which of the following are effective initial
treatments of acute adrenal insufficiency?
A. Normal
A
N
l saline
li bolus
b l
B. Potassium
C IV glucocorticoids
C.
D. IV mineralocorticoids
E. A and C
F. All of the above
www.downstatesurgery.org
Questions
Which of the following are effective initial
treatments of acute adrenal insufficiency?
A. Normal
A
N
l saline
li bolus
b l
B. Potassium
C IV glucocorticoids
C.
D. IV mineralocorticoids
E. A and C
F. All of the above
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Adrenal Insufficiency in Sepsis
Acute reversible dysfunction of HPA
axis
| >30% in critically ill patients
|
Adrenal ACTH resistance
z Decreased sensitivity of target tissues
z
|
Vasopressor dependent septic shock
may benefit from 5 to 7 day course of
physiologic
p
y
g dose steroids
|Minneci
PC, Deans KJ, Banks SM, et al: Meta-analysis: The effect of steroids on survival and
shock during sepsis depends on the dose. Ann InternMed 2004; 141:47-56.
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Meta-analysis: The effect of steroids on survival and shock
during sepsis depends on the dose
|Minneci
PC, Deans KJ, Banks SM, et al: Meta-analysis: The effect of
steroids on survival and shock during sepsis depends on the dose. Ann
InternMed 2004; 141:47-56.
www.downstatesurgery.org
Meta-analysis: The effect of steroids on survival and shock
during sepsis depends on the dose
|Minneci
PC, Deans KJ, Banks SM, et al: Meta-analysis: The effect of
steroids on survival and shock during sepsis depends on the dose. Ann
InternMed 2004; 141:47-56.
www.downstatesurgery.org
Bonus Question
|
A patient has abdominal pain, T 102, systolic
BP 60, HR 120, labored breathing.
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Bonus Question
|
A patient has abdominal pain, T 102, systolic
BP 60, HR 120, labored breathing. Dr. Kurtz
asks you what the cortisol level
level. Your response
is
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Bonus Question
|
A patient has abdominal pain, T 102, systolic
BP 60, HR 120, labored breathing. Dr. Kurtz
asks you what the cortisol level
level. Your response
is
z A. The sepsis protocol is stupid
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Bonus Question
|
A patient has abdominal pain, T 102, systolic
BP 60, HR 120, labored breathing. Dr. Kurtz
asks you what the cortisol level
level. Your response
is
z A. The sepsis protocol is stupid
z B. The ER never sent it
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Bonus Question
|
A patient has abdominal pain, T 102, systolic
BP 60, HR 120, labored breathing. Dr. Kurtz
asks you what the cortisol level. Your response
is
z A. The sepsis protocol is stupid
z B.
B The ER never sent it
z C. It’s pending but the patient was already
started on steroids (physiologic dose)
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Primary Hyperaldosteronism
Resistant hypertension and
hypokalemia
| 1% of patients with hypertension
| Mean age
g at diagnosis
g
~50
| Slight male predilection
| Symptoms usually related to
hypokalemia
|
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Primary Hyperaldosteronism
Potentially curable cause of significant
cardiovascular disease
| Higher
Hi h risk
i k ffor stroke,
t k MI,
MI a-fib,
fib LV
hypertrophy compared to age and
systolic BP matched controls
| Risks decrease with successful
removal of aldosteronoma
| Responsiveness to spironolactone is
good p
prognostic
g
sign
g
ag
|
Milliez P, Girerd X, Plouin PF, et al: Evidence for an increased rate of cardiovascular events in
patients with primary al-dosteronism. J Am Coll Cardiol 2005; 45:1243-1248.
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Evidence for an increased rate of cardiovascular events in
patients with primary aldosteronism
124 patients with primary
hyperaldosteronism over a three year
period
| 465 age and BP matched controls
|
Stroke
z MI
z Atrial fib
z
12.9%
4%
7.3%
vs
vs
vs
3.4%
0.6%
0.6%
Milliez P, Girerd X, Plouin PF, et al: Evidence for an increased rate of cardiovascular events
in patients with primary al-dosteronism. J Am Coll Cardiol 2005; 45:1243-1248.
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Primary Hyperaldosteronism
Aldosteronoma (unilateral) and
idiopathic (bilateral) account for >90%
| Goal is to identify and lateralize
|
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Primary Hyperaldosteronism
Laparoscopic adrenalectomy is the
preferred method
| Cure in 75% to 95%
|
Normalize BP
z Normalize plasma and urine
aldosterone
z Resolve hypokalemia
z
|
24 hours to weeks
Lal G, Duh QY: Laparoscopic adrenalectomy—indications and
technique. Surg Oncol 2003; 12:105-123.
www.downstatesurgery.org
Cushing’s
Cushing
s Syndrome
Obesity
| Hirsuitism
| Amenorrhea
| Easy bruising
| Extreme muscle weakness
|
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Cushing’s
Cushing
s Syndrome
Most common cause is exogenous
| Endogenous is rare
|
5 to 10 per million
z 75% have Cushing’s disease
z
• ACTH-secreting
C
pituitary adenoma
15% Primary adrenal
z 10% Ectopic ACTH
z
• Neurodendocrine tumors
• Bronchogenic malignancies
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Cushing’s
Cushing
s Syndrome
|
5x increase in mortality
Hypertension
z Diabetes
z Truncal obesity
y
z
Lindholm J, Juul S,
S Jorgensen JO,
O et al: Incidence and late prognosis
of Cushing's syndrome: A population-based study. J Clin Endocrinol
Metab 2001; 86:117-123.
www.downstatesurgery.org
Questions
Which of the following is the most
common cause of endogenous
Cushing’s syndrome/disease?
A. Adrenal adenoma
B. Adrenal carcinoma
C. Pituitaryy adenoma
D. Ectopic ACTH
www.downstatesurgery.org
Questions
Which of the following is the most
common cause of endogenous
Cushing’s syndrome/disease?
A. Adrenal adenoma
B. Adrenal carcinoma
y adenoma
C. Pituitary
D. Ectopic ACTH
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High does
dexamethasone
will not
suppress
ectopic ACTH
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Cushing’s
Cushing
s Syndrome
|
|
|
|
|
|
Laparoscopic adrenalectomy
90% successful
Perioperative stress dose
Hydrocortisone 100 mg IV every 8H for 3
doses
Tapered to physiologic replacement doses
over weeks to years
Failure may be due to local or distant
recurrence
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Adrenocortical Carcinoma
One per million
| Nearly
y all occur at 40 to 50 yyears
| Mean size at discovery 9-12 cm
| 5 year survival 15% to 20%
| >50% functional
|
Cushing s
Cushing’s
z Virilization
z
Icard P, Goudet
G
P, Charpenay
C
C
C, et al: Adrenocortical
carcinomas: Surgical trends and results of a 253-patient series
from the French Association of Endocrine Surgeons study
group. World J Surg 2001; 25:891-897.
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Adrenocortical Carcinoma
Radical OPEN surgery
| En bloc resection of adjacent
j
organs
g
and regional lymphadenectomy
| Right
g sided tumors >9 cm have high
g
chance of invading into IVC and right
heart
| May need cardiopulmonary bypass
|
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Adrenocortical Carcinoma
|
Incomplete resection
z
|
<1 year survival
Mitotane
Derivative of DDT
z Direct adrenocortical toxin
z Adjuvant and primary therapy
z GI and neurologic toxicity
z
Dackiw AP, Lee JE, Gagel
G
RF, et al: Adrenal cortical
carcinoma. World J Surg 2001; 25:914-926.
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Questions
A CT scan demonstrates an 8 cm right
adrenal mass extending into liver and
kidney Which of the following are
kidney.
appropriate?
A. En bloc resection
B. Radiation followed by en bloc resection
C. Mitotane followed by en bloc resection
D. Chemoradiation followed by en bloc
resection
www.downstatesurgery.org
Questions
A CT scan demonstrates an 8 cm right
adrenal mass extending into liver and
kidney Which of the following are
kidney.
appropriate?
A. En bloc resection
B. Radiation followed by en bloc resection
C. Mitotane followed by en bloc resection
D. Chemoradiation followed by en bloc
resection
www.downstatesurgery.org
Incidentaloma
|
|
2.1% of autopsies
1% to 4% of abdominal imaging studies
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Incidentaloma
|
Size and risk of carcinoma
<4 cm = 2%
z 4 cm to 6 cm = 6%
z >6 cm = 25%
z
Sturgeon C, Kebebew E: Laparoscopic adrenalectomy for
malignancy. Surg Clin North Am 2004; 84:755-774.
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Metastases To Adrenals
|
|
|
|
Autopsy studies reveal 25% of adrenal
involvement in patients with carcinoma
50% are bilateral
Lung, GI, breast, kidney, pancreas, skin
Resection of isolated mets increases
survival
z
z
z
20 to 30 months median survival for
complete resection
12 months for incomplete resection
6 months for no resection
Sebag F, Calzolari F, Harding J, et al: Isolated adrenal
metastasis: The role of laparoscopic surgery. World J
Surg 2006; 30:888-892.
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Positioning
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Port Placement
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Right Adrenalectomy
1. Division of
triangular
ligament
2. Divide plane
between adrenal
and IVC
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Right Adrenalectomy
1. Identify and
ligate adrenal
vein and
arteries
2. Dissect off
diaphragm
superiorly,
kidney
inferiorly
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Left Adrenalectomy
1. Mobilize
spleen and
splenic
flexure
2 Leave
2.
kidney in
place
3. Mobilize
tail of the
pancreas
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Left Adrenalectomy
1. Ligate
vessels
essels
2. Dissect off
kidney and
diaphragm
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Open adrenalectomy
1.
Used for cancer
operation
2.
En Bloc removal
may include
stomach, spleen,
pancreas
3.
Take periadrenal
fat and lymphatic
tissue
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Questions
Which of the following are
contraindications to laparoscopic
adrenalectomy?
A. Pheochromocytoma
B. Adrenocortical cancer
C. Bilateral adrenal lesions
D. Prior abdominal surgery
E. A and B
www.downstatesurgery.org
Questions
Which of the following are
contraindications to laparoscopic
adrenalectomy?
A. Pheochromocytoma
B. Adrenocortical cancer
C. Bilateral adrenal lesions
D. Prior abdominal surgery
E. A and B
www.downstatesurgery.org
References
|
|
|
|
|
|
|
|
Minneci PC, Deans KJ, Banks SM, et al: Meta-analysis: The effect of steroids on survival and
shock during sepsis depends on the dose. Ann InternMed 2004; 141:47-56.
Milliez P, Girerd X, Plouin PF, et al: Evidence for an increased rate of cardiovascular events in
patients with primary al-dosteronism. J Am Coll Cardiol 2005; 45:1243-1248.
Lal G, Duh QY: Laparoscopic adrenalectomy—indications and technique. Surg
Oncol 2003; 12:105-123.
Lindholm J, Juul S, Jorgensen JO, et al: Incidence and late prognosis of Cushing's syndrome: A
population-based study. J Clin Endocrinol Metab 2001; 86:117-123.
Icard P, Goudet P, Charpenay C, et al: Adrenocortical carcinomas: Surgical trends and results
of a 253-patient series from the French Association of Endocrine Surgeons study group. World
J Surg 2001; 25:891-897.
Dackiw AP, Lee JE, Gagel RF, et al: Adrenal cortical carcinoma. World J Surg 2001; 25:914926.
Sturgeon C, Kebebew E: Laparoscopic adrenalectomy for malignancy. Surg Clin North
Am 2004; 84:755-774.
Sebag F, Calzolari F, Harding J, et al: Isolated adrenal metastasis: The role of laparoscopic
surgery. World J Surg 2006; 30:888-892.
www.downstatesurgery.org
Questions
1.
Which of the following are effective initial treatments of acute adrenal insufficiency?
A. Normal saline bolus
B. Potassium
C. IV glucocorticoids
D. IV mineralocorticoids
E. A and C
F. All of the above
2.
The most common cause of congenital adrenal hyperplasia is related to which enzyme deficiency?
A. 11-hydroxylase
B. 17-hydroxylase
C. 3-hydroxyhydrogenase
D. 21-hydroxylase
3.
Which of the following
g is the most common cause of endogenous
g
Cushing’s
g syndrome/disease?
y
A. Adrenal adenoma
B. Adrenal carcinoma
C. Pituitary adenoma
D. Ectopic ACTH
|
A CT scan demonstrates an 8 cm right adrenal mass extending into liver and kidney. Which of the following are
appropriate?
A. En bloc resection
B. Radiation followed by en bloc resection
C. Mitotane followed by en bloc resection
D. Chemoradiation followed by en bloc resection
|
Which of the following are contraindications to laparoscopic adrenalectomy?
A. Pheochromocytoma
B. Adrenocortical cancer
C. Bilateral adrenal lesions
D. Prior abdominal surgery
E. A and B