Tumor adrenaldr Putra Hendra SpPDUNIBA

Adrenal Histology

Regulation of adrenal gland secretionACTHCortisolCortisol

Overview of the interactions of hormones in response to stress

Adrenal Gland Role in GAS

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Approach to the Adrenal MassFunctional versus Non-functional?

Malignant versus Benign?

DiagnosisPreviously, histopathology was gold standard

Currently, various imaging techniques are regarded as ideal, due to ease:CT with or without contrast (83% accurate in diagnosing malignancy)MRI (94% accurate) Scintigraphy (92% accurate)

Unilateral adrenal massesFunctional leisonsAdrenal adenoma Adrenal cortical carcinoma.Pheochromocytoma

Non Functional leisonsAdrenal adenoma Adrenal cortical carcinoma.GanglioneuromaMyelolipomaHemorrhage in adrenal gland.Metastases to the adrenal gland.

Bilateral adrenal massesFunctional leisonsACTH dependant cushing syndromeCongenital adrenal hyperplasia.pheochromocytoma

Non Functional leisonsInfection(T.B,Fungus).Infiltrative (amyloidosis ,leukemia,lymphoma)Hemorrhage.

DiagnosisNo. (%) of LesionsAdenoma788 (75)Myelolipoma68 (6)Hematoma47 (4)Cyst13 (1)Pheochromocytoma3 (0.3)Macronodular Hyperplasia1 (0.1)Adrenal Cortical Neoplasm of unknown malignant potential1 (0.1)Presumed benign by imaging/clinical stability128 (12)Total1049 (100)

Functional tumors:Adrenal Medullary Tumors:PheochromocytomaChildhood tumors: ganglioneuromas, neuroblastomasAdrenal Cortical Tumors: Cortisol-secreting adenomaAldosteronomaCarcinoma

ADRENAL GLAND DYSFUNCTIONHypercortisolism= Cushings SyndromeHypocortisolism= Addisons DiseaseConn syndromePheochromocytoma

Hypo- & Hyper- Function of the Adrenal Cortex

PheochromocytomaCatecholamine Physiology/PathophysiologyClinical PresentationEpidemiologySigns & SymptomsDiagnosisBiochemicalLocalizationManagementPreoperativeOperativePostoperativePregnancy

Pheochromocytoma0.01-0.1% of HTN populationFound in 0.5% of those screenedM = F3rd to 5th decades of lifeRare, investigate only if clinically suspicion:Signs or SymptomsSevere HTN, HTN crisisRefractory HTN (> 3 drugs)HTN present @ age < 20 or > 50 ?Adrenal lesion found on imaging (ex. Incidentaloma)

FREQUENCY OF VARIOUS DIAGNOSES IN HYPERTENSIVE PATIENTS 1980s

PRIMARY CAREREFERRAL Essential 92-95% 89% Chronic kidney dis 3-6% 5% Renovascular dis 0.2-1.0% 4% Pheochromocytoma 0.1-0.2% 0.2% Aldosteronism 0.1-0.3% 0.5% Cushings syndrome 0.1-0.2% 0.2% Coarctation 0.1-0.2% 1% Oral contraceptives 0.2-1.0%

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Catecholamine Producing TumorsNeural CrestSympathoadrenal Progenitor Cell(Neuroblasts)Sympathetic Ganglion CellIntra-adrenal Extra-adrenalPheochromocytomaGanglioneuromaNeuroblastoma

TyrosineL-DopaDopamineNorepinephrineEpinephrineCatecholaminesNormetanephrineMetaneprinePNMTDBHCOMTCOMTMetabolitesHomovanillic acid(HVA)MAO, COMTMAOMAOTumor Secretion: Large Pheo: more metabolites

(metabolized within tumor before release) Small Pheo: more catecholamines Sporadic Pheo: Norepi > Epi Familial Pheo: Epi > Norepi Paraganglioma: Norepi Cheodectoma, glomus jugulare: Norepi Gangioneuroma: Norepi Malignant Pheo: Dopamine, HVA Neuroblastoma: Dopamine, HVA

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Clinical manifestationsIntermittent hypertension or even hypotension headache 71%, palpitations 65%, sweating 65% and dizziness 15%, sense of doomVomiting 28%, weakness 17%, nervousness 10%, pallor 16%, dyspnea 19%, substernal pain 12%, and abdominal pain 12%Glycosurianeutrophelia

Pheo: Signs & SymptomsThe five Ps: (5P)Pressure (HTN)90%Pain (Headache)80%Perspiration71%Palpitation64%Pallor42%Paroxysms (the sixth P!)The Classical Triad: (3P)Pain (Headache), Perspiration, PalpitationsLack of all 3 virtually excluded diagnosis of pheo in a series of > 21,0000 patients

Pheo: Paroxysms, Spells10-60 min durationFrequency: daily to monthlySpontaneousPrecipitated:Diagnostic procedures, I.A. Contrast (I.V. is OK)Drugs (opiods, unopposed -blockade, anesthesia induction, histamine, ACTH, glucagon, metoclopramide)Strenuous exercise, movement that increases intra-abdo pressure (lifting, straining)Micturition (bladder paraganlgioma)

Pheo: Signs & SymptomsN/V, abdo pain, severe constipation (megacolon)Chest-painsAnxietyAngina/MI with normal coronaries:Catecholamine induced: myocardial oxygen consumption or coronary vasospasmCHFHTN hypertrophic cardiomyopathy diastolic dysfn.Catechols induce dilated cardiomyopathy systolic dysfn.Cardiac dysrhythmia & conduction defects

Pheo: Signs (metabolic)HypercalcemiaMild glucose intoleranceLipolysisWeight-lossKetosis > VLDL synthesis (TG)

Pheo: Rule of 1010% extra-adrenal (closer to 15%)10% occur in children10% familial (closer to 20%)10% bilateral or multiple (more if familial)10% recur (more if extra-adrenal)10% malignant10% discovered incidentally

DiagnosisPlasma free metanephrines most sensitive testseen 99% of patients24 urinary catecholamines (2x normal is diagnostic)VMAClonidine suppression test

24h Urine Collection24h urine collection:Creatinine, catecholamines, metanephrines, vanillymandelic acid (VMA), +/-dopamineHPLC with electrochemical detection or mass spectPositive results (> 2-3 fold elevation):24h Ucatechols > 2-fold elevationULN for total catechols 591-890 nmol/d 24h Utotal metanephrines > 1.2 ug/d (6.5 umol/d)24h UVMA > 3-fold elevationULN 35 umol/d for most assays

Suppression/Stimulation TestingClonidine suppressionMay precipitate hypotensive shock!Unlike normals, pheo patients wont suppress their plasma norepi with clonidineGlucagon stimulationMay precipitate hypertensive crisis!Pheo patients, but not normals, will have a > 3x increase in plasma norepi with glucagon

Localization: ImagingCT abdomenAdrenal pheo SEN 93-100%Extra-adrenal pheo SEN 90%MRI> SEN than CT for extra-adrenal pheo

MIBG Scan123I or 131I labelled metaiodobenzylguanidineMIBG catecholamine precurosr taken up by the tumorInject MIBG, scan @ 24h, 48h, 72hLugols 1 gtt tid x 9d (from 2d prior until 7d after MIBG injection to protect thyroid)False negative scan:Drugs: Labetalol, reserpine, TCAs, phenothiazinesMust hold these medications for 4-6 wk prior to scan

Pheo ManagementPrior to 1951, reported mortality for excision of pheochromoyctoma 24 - 50 %HTN crisis, arrhythmia, MI, strokeHypotensive shockCurrently, mortality: 0 - 2.7 %Preoperative preperation, -blockade?New anesthetic techniques?Anesthetic agentsIntraoperative monitoring: arterial line, EKG monitor, CVP line, Swan-GanzExperienced & Coordinated team:Endocrinologist, Anesthesiologist and Surgeon

Pheo: Unresectable, Malignant-blockadeSelective 1-blockers (Prazosin, Terazosin, Doxazosin) 1st line as less side-effectsPhenoxybenzamine: more complete -blockade-blockerCCB, ACE-I, etc.Nuclear Medicine Rx:Hi dose 131I-MIBG or 111indium-octreotide depending on MIBG scan or octreoscan pick-upSensitize tumor with Carboplatin + 5-FU

Cortisol-secreting Adenoma:the sweet partEpi: F > M; ages 30-50sSigns/Symptoms:May lead to clinical or sub-clinical Cushings syndromeMost commonly: obesity, HTN, glucose intolerance or DMII, hypercholesterolemiaLabwork demonstrates:Low DHEA-sulfate (increased cortisol suppresses pituitary-adrenal axis)Elevated 24 hour urinary cortisol

Adrenal Cortical Carcinoma:the sex hormonesEpi: Rare: 0.02% of cancers, 0.3 cases/million worldwideF > M; two age peaks:

Aldosteronomas:the salty partEpi: M, age 30-40Signs/Symptoms: Screen all HTN pts with incidental massLabwork reveals:Increased serum aldosteroneDecreased plasma renin activity

Primary Hyperaldosteronism (Conn's Disease)Solitary adrenal adenomas (80-90%)Bilateral adrenal hyperplasia (10-20%)Idiopathic HyperaldosteronismAccounts for 50% of cases at some referral centersAdrenal Carcinoma (rare)Unilateral Adrenal Hyperplasia (very rare)

TherapyIf tumor with lateralization, laparascopic adrenalectomyIf tumor without lateralization (incidentaloma), or hyperplasia, then aldosterone blockadeSpironolactoneEplerinone

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Medical Therapy of PA eplerenone 50-200 mg/day (give BID) spironolactone 25 - 100 mg / day

( amiloride allows for lower spironolactone)

FH-1: dexamethasone 0.25-1.0 mg/day

Eplerenone

affinity 20 X > spironolactonePotency of effect 75% of spironolactoneBinding affinity for androgen and progesterone receptors 1000-fold lower than spironolactone

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