Absite Review Series: Adrenal Gland · PDF fileAbsite Review Series: Adrenal Gland Disorders...
Transcript of Absite Review Series: Adrenal Gland · PDF fileAbsite Review Series: Adrenal Gland Disorders...
Absite Review Series:Adrenal Gland DisordersDisorders
Sean Rim7/11/2008
www.downstatesurgery.org
QuestionsQuestions
Which of the following are effective initial treatments of acute adrenal insufficiency?
A N l li b lA. Normal saline bolusB. PotassiumC IV glucocorticoidsC. IV glucocorticoidsD. IV mineralocorticoidsE. A and CF. All of the above
www.downstatesurgery.org
QuestionsQuestions
The most common cause of congenital adrenal hyperplasia is related to which enzyme deficiency?
A. 11-hydroxylaseB. 17-hydroxylaseC. 3-hydroxyhydrogenasey y y gD. 21-hydroxylase
www.downstatesurgery.org
QuestionsQuestions
Which of the following is the most common cause of endogenous Cushing’s syndrome/disease?
A. Adrenal adenomaB. Adrenal carcinomaC. Pituitary adenomayD. Ectopic ACTH
www.downstatesurgery.org
QuestionsQuestions
A CT scan demonstrates an 8 cm right adrenal mass extending into liver and kidney Which of the following arekidney. Which of the following are appropriate?
A. En bloc resectionB. Radiation followed by en bloc resectionC. Mitotane followed by en bloc resectionD. Chemoradiation followed by en bloc resection
www.downstatesurgery.org
QuestionsQuestions
Which of the following are contraindications to laparoscopic adrenalectomy?
A. PheochromocytomaB. Adrenocortical cancerC. Bilateral adrenal lesionsD. Prior abdominal surgeryE. A and B
www.downstatesurgery.org
Adrenal GlandsAdrenal Glands
Paired glands with two distinct functional organsThird most highly perfused organ behind kidney and
thyroid, 2000mL/kg/min
Cortex• Mesodermal
Medulla• Ectodermal
www.downstatesurgery.org
Adrenal GlandsAdrenal Glands
Paired glands with two distinct functional organsThird most highly perfused organ behind kidney and
thyroid, 2000mL/kg/min
Cortex• Mesodermal
4th t 5th k
Medulla• Ectodermal
5th t 6th k• 4th to 5th week • 5th to 6th week
www.downstatesurgery.org
Adrenal GlandsAdrenal Glands
Paired glands with two distinct functional organsThird most highly perfused organ behind kidney and
thyroid, 2000mL/kg/min
Cortex• Mesodermal
4th t 5th k
Medulla• Ectodermal
5th t 6th k• 4th to 5th week• Glucocorticoids,
mineralocorticoids, sex steroids
• 5th to 6th week• Catecholamines
sex steroids
www.downstatesurgery.org
Adrenal GlandsAdrenal Glands
Paired glands with two distinct functional organsThird most highly perfused organ behind kidney and
thyroid, 2000mL/kg/min
Cortex• Mesodermal
4th t 5th k
Medulla• Ectodermal
5th t 6th k• 4th to 5th week• Glucocorticoids,
mineralocorticoids, sex steroids
• 5th to 6th week• Catecholamines• Pheochromocytoma
steroids• Hyperaldosteronism,
Cushing’s, virilization
www.downstatesurgery.org
AnatomyAnatomywww.downstatesurgery.org
AnatomyAnatomy
Arterial supply is diffuseInferior phrenic arteryJuxtaceliac aortaRenal arteryy
www.downstatesurgery.org
AnatomyAnatomywww.downstatesurgery.org
AnatomyAnatomy
Venous drainage is solitaryLeft vein ~2 cm into renal Right ~0.5 cm into IVC20% variable
www.downstatesurgery.org
AnatomyAnatomywww.downstatesurgery.org
www.downstatesurgery.org
www.downstatesurgery.org
HistologyHistology
Cortex is 2 mm>80% massM d ll hMedulla has
extensive autonomicfibers and ganglionfibers and ganglioncells
www.downstatesurgery.org
www.downstatesurgery.org
Series of oxidative reactions via
Reticularisreactions via cytochrome P-450 membrane associate enzymes
Fasiculata
Glomerulosa
www.downstatesurgery.org
Steroid hormonesSteroid hormones
Low molecular weight, lipophilic signaling moleculesE t ll d bi d t i t ll lEnter cells and bind to intracellular receptorsSlower response than membrane bindingSlower response than membrane binding peptidesLevels altered by pregnancy, nephrotic y p g y, psyndrome, cirrhosisMetabolized in liver and excreted via kidney
www.downstatesurgery.org
MineralocorticoidsMineralocorticoids
Aldosterone regulates circulating fluid volume and electrolyte balancePromotes Na and Cl retention in distal tubuleK and H secretedWill see expansion of BP and pintracellular volume with aldosterone
www.downstatesurgery.org
MineralocorticoidsMineralocorticoids
Renin-angiotensin-aldosterone axis is responsive to delivery of sodium to the DCTLow sodium delivery triggers release ofLow sodium delivery triggers release of renin from JGA
ShockRenal artery vasoconstrictionHyponatremia
Renin cleaves angiotensinogen (liver) toRenin cleaves angiotensinogen (liver) to angiotensin-1ACE (lungs) cleaves to angiotensin-2( g ) g
www.downstatesurgery.org
GlucocorticoidsGlucocorticoids
Generate a catabolic state in response to stressAlt b h d t t i d li idAlters carbohydrate, protein, and lipid metabolism to increase blood glucoseIncrease gluconeogensisIncrease gluconeogensisDecrease peripheral glucose uptakeS iti t i l th l tSensitizes arterial smooth muscle to beta-adrenergic stimulation
www.downstatesurgery.org
GlucocorticoidsGlucocorticoids
Potent anti-inflammatory and immunosuppressive agentsR d i l ti l h t dReduce circulating lymphocyte and eosinophils and increase neutrophilsDecrease cytokine and Ig productionDecrease cytokine and Ig productionSuppress histamine releaseI hibit h h li A2 t dInhibit phospholipase A2 to reduce prostaglandins
www.downstatesurgery.org
GlucocorticoidsGlucocorticoids
Hypothalamus release CRF into pituitaryResults in ACTH secretionACTH bind G protein coupled p preceptors on adrenocortical cell surfaceSteroidogenesis is upregulated
www.downstatesurgery.org
GlucocorticoidsGlucocorticoids
ACTH is released in a pulsatile fashion, circadian rhythmPeak in AMNegative feedback occurs at both ghypothalamic and pituitary levels
www.downstatesurgery.org
www.downstatesurgery.org
Rate limiting stepstep
www.downstatesurgery.org
Exclusive to chromaffin cellschromaffin cells
www.downstatesurgery.org
Stable metabolites used for markers
www.downstatesurgery.org
CatecholaminesCatecholamines
Alpha-1: Vasoconstriction of skin and GI tractAlpha-2: Attenuate sympathetic outflow in preynapseBeta-1: Increase HR and contractilityBeta-2: Smooth muscle relaxation in unterus, bronchi, skeletal muscle arterioles
www.downstatesurgery.org
Congenital Adrenal HyperplasiaCongenital Adrenal Hyperplasia
Six enzyme defects have been identified90% caused by CYP21A2 deficiency (21-hydroxylase)Usually manifests as salt-wasting form
www.downstatesurgery.org
www.downstatesurgery.org
www.downstatesurgery.org
Congenital Adrenal HyperplasiaCongenital Adrenal Hyperplasia
Decreased negative feedbackHypovolemia, hyperkalemia, h i ihyperreninemiaShunts towards adrenal androgensA bi it li i f lAmbiguous genitalia in femalesDx via elevated 17-hydroxyprogesteroneTx via glucocorticoid and mineralocorticoidTx via glucocorticoid and mineralocorticoid replacement
www.downstatesurgery.org
QuestionsQuestions
The most common cause of congenital adrenal hyperplasia is related to which enzyme deficiency?
A. 11-hydroxylaseB. 17-hydroxylaseC. 3-hydroxyhydrogenasey y y gD. 21-hydroxylase
www.downstatesurgery.org
QuestionsQuestions
The most common cause of congenital adrenal hyperplasia is related to which enzyme deficiency?
A. 11-hydroxylaseB. 17-hydroxylaseC. 3-hydroxyhydrogenasey y y gD. 21-hydroxylase
www.downstatesurgery.org
Primary Adrenal InsufficiencyPrimary Adrenal Insufficiency
Addison’s diseaseWeaknessF iFatigueAnorexiaNauseaNauseaWeight lossHyperpigmentationHyperpigmentationHypotensionElectrolyte disturbance
www.downstatesurgery.org
Primary Adrenal InsufficiencyPrimary Adrenal Insufficiency
Congenital adrenal dysgenesisDefective steroidogenesisAdrenal destruction
AutoimmuneInfectious (TB, fungal, viral)MetastasesAdrenal hemorrhage (Waterhouse-Friderichsen syndrome)
www.downstatesurgery.org
Secondary Adrenal InsufficiencySecondary Adrenal Insufficiency
Steroid withdrawalSurgical cure of Cushing’sg gPanhypopituitarism
NeoplasmNeoplasmGranulomatous diseaseSheehan’s sydromeSheehan s sydrome
www.downstatesurgery.org
Adrenal CrisisAdrenal Crisis
Life-threateningOccurs in patients with marginal p gfunction subjected to significant physiologic stressInitial treatment is volume and glucocorticoidsMineralocorticoid effects take several daysy
www.downstatesurgery.org
QuestionsQuestions
Which of the following are effective initial treatments of acute adrenal insufficiency?
A N l li b lA. Normal saline bolusB. PotassiumC IV glucocorticoidsC. IV glucocorticoidsD. IV mineralocorticoidsE. A and CF. All of the above
www.downstatesurgery.org
QuestionsQuestions
Which of the following are effective initial treatments of acute adrenal insufficiency?
A N l li b lA. Normal saline bolusB. PotassiumC IV glucocorticoidsC. IV glucocorticoidsD. IV mineralocorticoidsE. A and CF. All of the above
www.downstatesurgery.org
Adrenal Insufficiency in SepsisAdrenal Insufficiency in Sepsis
Acute reversible dysfunction of HPA axis>30% in critically ill patients
Adrenal ACTH resistanceDecreased sensitivity of target tissues
Vasopressor dependent septic shockVasopressor dependent septic shock may benefit from 5 to 7 day course of physiologic dose steroidsp y g
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
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 QuestionBonus Question
A patient has abdominal pain, T 102, systolic BP 60, HR 120, labored breathing.
www.downstatesurgery.org
Bonus QuestionBonus Question
A patient has abdominal pain, T 102, systolic BP 60, HR 120, labored breathing. Dr. Kurtz asks you what the cortisol level Your responseasks you what the cortisol level. Your response is
www.downstatesurgery.org
Bonus QuestionBonus Question
A patient has abdominal pain, T 102, systolic BP 60, HR 120, labored breathing. Dr. Kurtz asks you what the cortisol level Your responseasks you what the cortisol level. Your response is
A. The sepsis protocol is stupid
www.downstatesurgery.org
Bonus QuestionBonus Question
A patient has abdominal pain, T 102, systolic BP 60, HR 120, labored breathing. Dr. Kurtz asks you what the cortisol level Your responseasks you what the cortisol level. Your response is
A. The sepsis protocol is stupidB. The ER never sent it
www.downstatesurgery.org
Bonus QuestionBonus 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
A. The sepsis protocol is stupidB The ER never sent itB. The ER never sent itC. It’s pending but the patient was already started on steroids (physiologic dose)
www.downstatesurgery.org
www.downstatesurgery.org
www.downstatesurgery.org
Primary HyperaldosteronismPrimary Hyperaldosteronism
Resistant hypertension and hypokalemia1% of patients with hypertensionMean age at diagnosis ~50g gSlight male predilectionSymptoms usually related toSymptoms usually related to hypokalemia
www.downstatesurgery.org
Primary HyperaldosteronismPrimary Hyperaldosteronism
Potentially curable cause of significant cardiovascular diseaseHi h i k f t k MI fib LVHigher risk for stroke, MI, a-fib, LV hypertrophy compared to age and systolic BP matched controlssystolic BP matched controlsRisks decrease with successful removal of aldosteronomaremoval of aldosteronomaResponsiveness to spironolactone is a good prognostic signg p g g
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.
www.downstatesurgery.org
Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism
124 patients with primary hyperaldosteronism over a three year period465 age and BP matched controls
Stroke 12.9% vs 3.4%MI 4% vs 0.6%Atrial fib 7.3% vs 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.
www.downstatesurgery.org
Primary HyperaldosteronismPrimary Hyperaldosteronism
Aldosteronoma (unilateral) and idiopathic (bilateral) account for >90%Goal is to identify and lateralize
www.downstatesurgery.org
www.downstatesurgery.org
www.downstatesurgery.org
Primary HyperaldosteronismPrimary Hyperaldosteronism
Laparoscopic adrenalectomy is the preferred methodCure in 75% to 95%
Normalize BPNormalize plasma and urine aldosteroneResolve hypokalemia
24 hours to weeksLal G, Duh QY: Laparoscopic adrenalectomy—indications and technique. Surg Oncol 2003; 12:105-123.
www.downstatesurgery.org
Cushing’s SyndromeCushing s Syndrome
ObesityHirsuitismAmenorrheaEasy bruisingEasy bruisingExtreme muscle weakness
www.downstatesurgery.org
www.downstatesurgery.org
www.downstatesurgery.org
www.downstatesurgery.org
Cushing’s SyndromeCushing s Syndrome
Most common cause is exogenousEndogenous is rare
5 to 10 per million75% have Cushing’s disease
C• ACTH-secreting pituitary adenoma15% Primary adrenal10% Ectopic ACTH10% Ectopic ACTH
• Neurodendocrine tumors• Bronchogenic malignanciesBronchogenic malignancies
www.downstatesurgery.org
Cushing’s SyndromeCushing s Syndrome
5x increase in mortalityHypertensionDiabetesTruncal obesityy
S OLindholm 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.
www.downstatesurgery.org
QuestionsQuestions
Which of the following is the most common cause of endogenous Cushing’s syndrome/disease?
A. Adrenal adenomaB. Adrenal carcinomaC. Pituitary adenomayD. Ectopic ACTH
www.downstatesurgery.org
QuestionsQuestions
Which of the following is the most common cause of endogenous Cushing’s syndrome/disease?
A. Adrenal adenomaB. Adrenal carcinomaC. Pituitary adenomayD. Ectopic ACTH
www.downstatesurgery.org
www.downstatesurgery.org
High does dexamethasone will not suppress ectopic ACTH
www.downstatesurgery.org
Cushing’s SyndromeCushing s Syndrome
Laparoscopic adrenalectomy90% successfulPerioperative stress doseHydrocortisone 100 mg IV every 8H for 3 ddosesTapered to physiologic replacement doses over weeks to yearsover weeks to yearsFailure may be due to local or distant recurrence
www.downstatesurgery.org
Adrenocortical CarcinomaAdrenocortical Carcinoma
One per millionNearly all occur at 40 to 50 yearsy yMean size at discovery 9-12 cm5 year survival 15% to 20%5 year survival 15% to 20%>50% functional
Cushing’sCushing sVirilization
G C CIcard 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.
www.downstatesurgery.org
www.downstatesurgery.org
Adrenocortical CarcinomaAdrenocortical Carcinoma
Radical OPEN surgeryEn bloc resection of adjacent organs j gand regional lymphadenectomyRight sided tumors >9 cm have high g gchance of invading into IVC and right heartMay need cardiopulmonary bypass
www.downstatesurgery.org
Adrenocortical CarcinomaAdrenocortical Carcinoma
Incomplete resection<1 year survival
MitotaneDerivative of DDT Direct adrenocortical toxinAdjuvant and primary therapyAdjuvant and primary therapyGI and neurologic toxicity
GDackiw AP, Lee JE, Gagel RF, et al: Adrenal cortical carcinoma. World J Surg 2001; 25:914-926.
www.downstatesurgery.org
QuestionsQuestions
A CT scan demonstrates an 8 cm right adrenal mass extending into liver and kidney Which of the following arekidney. Which of the following are appropriate?
A. En bloc resectionB. Radiation followed by en bloc resectionC. Mitotane followed by en bloc resectionD. Chemoradiation followed by en bloc resection
www.downstatesurgery.org
QuestionsQuestions
A CT scan demonstrates an 8 cm right adrenal mass extending into liver and kidney Which of the following arekidney. Which of the following are appropriate?
A. En bloc resectionB. Radiation followed by en bloc resectionC. Mitotane followed by en bloc resectionD. Chemoradiation followed by en bloc resection
www.downstatesurgery.org
IncidentalomaIncidentaloma
2.1% of autopsies1% to 4% of abdominal imaging studies
www.downstatesurgery.org
IncidentalomaIncidentaloma
Size and risk of carcinoma<4 cm = 2%4 cm to 6 cm = 6%>6 cm = 25%
Sturgeon C, Kebebew E: Laparoscopic adrenalectomy for malignancy. Surg Clin North Am 2004; 84:755-774.
www.downstatesurgery.org
www.downstatesurgery.org
Metastases To AdrenalsMetastases To Adrenals
Autopsy studies reveal 25% of adrenal involvement in patients with carcinoma50% are bilateral50% are bilateralLung, GI, breast, kidney, pancreas, skinResection of isolated mets increases survival
20 to 30 months median survival for complete resectioncomplete resection12 months for incomplete resection6 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.
www.downstatesurgery.org
PositioningPositioningwww.downstatesurgery.org
Port PlacementPort Placementwww.downstatesurgery.org
Right AdrenalectomyRight Adrenalectomy
1. Division of triangulartriangular ligament
2. Divide plane between adrenalbetween adrenal and IVC
www.downstatesurgery.org
Right AdrenalectomyRight Adrenalectomy
1. Identify and ligate adrenal vein and arteries
2. Dissect off diaphragm superiorly, kidneykidney inferiorly
www.downstatesurgery.org
Left AdrenalectomyLeft Adrenalectomy
1. Mobilize spleen andspleen and splenic flexure
2 Leave2. Leave kidney in place
3. Mobilize3. Mobilize tail of the pancreas
www.downstatesurgery.org
Left AdrenalectomyLeft Adrenalectomy
1. Ligate esselsvessels
2. Dissect off kidney and diaphragmdiaphragm
www.downstatesurgery.org
Open adrenalectomyOpen adrenalectomy
1. Used for cancer operation
2. En Bloc removal may include stomach, spleen, pancreas
3. Take periadrenal fat and lymphatic tissue
www.downstatesurgery.org
QuestionsQuestions
Which of the following are contraindications to laparoscopic adrenalectomy?
A. PheochromocytomaB. Adrenocortical cancerC. Bilateral adrenal lesionsD. Prior abdominal surgeryE. A and B
www.downstatesurgery.org
QuestionsQuestions
Which of the following are contraindications to laparoscopic adrenalectomy?
A. PheochromocytomaB. Adrenocortical cancerC. Bilateral adrenal lesionsD. Prior abdominal surgeryE. A and B
www.downstatesurgery.org
ReferencesReferences
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; 25:914-926. 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
QuestionsQuestions
1. Which of the following are effective initial treatments of acute adrenal insufficiency?A. Normal saline bolusB. PotassiumC. IV glucocorticoidsD. IV mineralocorticoidsE. A and CF. All of the above
2. The most common cause of congenital adrenal hyperplasia is related to which enzyme deficiency?A. 11-hydroxylaseB. 17-hydroxylaseC. 3-hydroxyhydrogenaseD. 21-hydroxylase
3. Which of the following is the most common cause of endogenous Cushing’s syndrome/disease?g g g yA. Adrenal adenomaB. Adrenal carcinomaC. Pituitary adenomaD. 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 resectionB. Radiation followed by en bloc resectionC. Mitotane followed by en bloc resectionD. Chemoradiation followed by en bloc resection
Which of the following are contraindications to laparoscopic adrenalectomy?A. PheochromocytomaB. Adrenocortical cancerC. Bilateral adrenal lesionsC. Bilateral adrenal lesionsD. Prior abdominal surgeryE. A and B
www.downstatesurgery.org