Absite Review Series: Adrenal Gland · PDF fileAbsite Review Series: Adrenal Gland Disorders Sean Rim 7/11/2008

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


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


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


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


QuestionsQuestions

Which of the following are contraindications to laparoscopic adrenalectomy?

A. PheochromocytomaB. Adrenocortical cancerC. Bilateral adrenal lesionsD. Prior abdominal surgeryE. A and B


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






4th t 5th k


5th t 6th k• 4th to 5th week • 5th to 6th week






4th t 5th k


5th t 6th k• 4th to 5th week• Glucocorticoids,

mineralocorticoids, sex steroids

• 5th to 6th week• Catecholamines

sex steroids






4th t 5th k


5th t 6th k• 4th to 5th week• Glucocorticoids,

mineralocorticoids, sex steroids

• 5th to 6th week• Catecholamines• Pheochromocytoma

steroids• Hyperaldosteronism,

Cushing’s, virilization


AnatomyAnatomywww.downstatesurgery.org

AnatomyAnatomy

Arterial supply is diffuseInferior phrenic arteryJuxtaceliac aortaRenal arteryy



AnatomyAnatomy

Venous drainage is solitaryLeft vein ~2 cm into renal Right ~0.5 cm into IVC20% variable





HistologyHistology

Cortex is 2 mm>80% massM d ll hMedulla has

extensive autonomicfibers and ganglionfibers and ganglioncells



Series of oxidative reactions via

Reticularisreactions via cytochrome P-450 membrane associate enzymes

Fasiculata

Glomerulosa


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


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


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


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



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



Hypothalamus release CRF into pituitaryResults in ACTH secretionACTH bind G protein coupled p preceptors on adrenocortical cell surfaceSteroidogenesis is upregulated



ACTH is released in a pulsatile fashion, circadian rhythmPeak in AMNegative feedback occurs at both ghypothalamic and pituitary levels



Rate limiting stepstep


Exclusive to chromaffin cellschromaffin cells


Stable metabolites used for markers


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


Congenital Adrenal HyperplasiaCongenital Adrenal Hyperplasia

Six enzyme defects have been identified90% caused by CYP21A2 deficiency (21-hydroxylase)Usually manifests as salt-wasting form




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


QuestionsQuestions




QuestionsQuestions




Primary Adrenal InsufficiencyPrimary Adrenal Insufficiency

Addison’s diseaseWeaknessF iFatigueAnorexiaNauseaNauseaWeight lossHyperpigmentationHyperpigmentationHypotensionElectrolyte disturbance


Primary Adrenal InsufficiencyPrimary Adrenal Insufficiency

Congenital adrenal dysgenesisDefective steroidogenesisAdrenal destruction

AutoimmuneInfectious (TB, fungal, viral)MetastasesAdrenal hemorrhage (Waterhouse-Friderichsen syndrome)


Secondary Adrenal InsufficiencySecondary Adrenal Insufficiency

Steroid withdrawalSurgical cure of Cushing’sg gPanhypopituitarism

NeoplasmNeoplasmGranulomatous diseaseSheehan’s sydromeSheehan s sydrome


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


QuestionsQuestions




QuestionsQuestions




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.


Meta-analysis: The effect of steroids on survival and shock during sepsis depends on the dose



Meta-analysis: The effect of steroids on survival and shock during sepsis depends on the dose



Bonus QuestionBonus Question

A patient has abdominal pain, T 102, systolic BP 60, HR 120, labored breathing.



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




A. The sepsis protocol is stupidB. The ER never sent it



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)




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



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.


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.



Aldosteronoma (unilateral) and idiopathic (bilateral) account for >90%Goal is to identify and lateralize





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.


Cushing’s SyndromeCushing s Syndrome

ObesityHirsuitismAmenorrheaEasy bruisingEasy bruisingExtreme muscle weakness






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



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.


QuestionsQuestions




QuestionsQuestions





High does dexamethasone will not suppress ectopic ACTH



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


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.




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



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.


QuestionsQuestions




QuestionsQuestions




IncidentalomaIncidentaloma

2.1% of autopsies1% to 4% of abdominal imaging studies


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.



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.


PositioningPositioningwww.downstatesurgery.org

Port PlacementPort Placementwww.downstatesurgery.org

Right AdrenalectomyRight Adrenalectomy

1. Division of triangulartriangular ligament

2. Divide plane between adrenalbetween adrenal and IVC


Right AdrenalectomyRight Adrenalectomy

1. Identify and ligate adrenal vein and arteries

2. Dissect off diaphragm superiorly, kidneykidney inferiorly


Left AdrenalectomyLeft Adrenalectomy

1. Mobilize spleen andspleen and splenic flexure

2 Leave2. Leave kidney in place

3. Mobilize3. Mobilize tail of the pancreas


Left AdrenalectomyLeft Adrenalectomy

1. Ligate esselsvessels

2. Dissect off kidney and diaphragmdiaphragm


Open adrenalectomyOpen adrenalectomy

1. Used for cancer operation

2. En Bloc removal may include stomach, spleen, pancreas

3. Take periadrenal fat and lymphatic tissue


QuestionsQuestions




QuestionsQuestions




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.


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?


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


Absite Review Series: Adrenal Gland · PDF fileAbsite Review Series: Adrenal Gland Disorders Sean Rim 7/11/2008

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