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

Approach to the Adrenal MassFunctional atau Non-functional?

Malignant atau Benign?

DiagnosisDahulu: histopathology was gold standard

Sekarang: 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 Adrenal adenoma Adrenal cortical carcinoma.Pheochromocytoma

Non Functional

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

Bilateral adrenal massesFunctional

ACTH dependant cushing syndromeCongenital adrenal hyperplasia.pheochromocytoma

Non Functional

Infection(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

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 1980sPRIMARY 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%

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, HVATH

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

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

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: 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

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

Adrenal cortex Primary Hyperaldosteronism Primary hyperaldosteronism excess aldosterone secretion which is independent of the renin-angiotensin system (Conns syndrome)Causes:Aldosterone secreting adenomaBilateral hyperplasia of the cortexRarely carcinomaClinical features:Hypertension, hypokalemia, sodium retention, muscle weakness, paraesthesia, ECG changes, cardiac decompensationHyperadrenalisms

Aldosterone is primarily involved with fluid and electrolyte balance.

Aldosterone secretion causes sodium reabsorption in the distal renal tubule in exchange for potassium and hydrogen ions.

The net effects are, fluid retention, decrease in plasma potassium and metabolic alkalosis.

ENaCNCCTNKCC2NHEsN Engl J MedAldosterone

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

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

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

**12/01/10*renin-angiotensin system: renin, secreted by the juxtaglomerular apparatus, activates the precursor angiotensinogen. This liberates angiotensin I, then angiotensin II, a vasoconstrictor and stimulant to the secretion of aldosterone.***Figure 1. Sites of Diuretic Action in the Nephron.The percentage of sodium reabsorbed in a given region is indicated in parentheses.K+-sparing agents collectively refers to the epithelial sodiumchannelinhibitors (e.g., amiloride and triamterene) and mineralocorticoidreceptorantagonists (e.g., spironolactone and eplerenone). Sodium isreabsorbed in the distal tubule and collecting ducts through an aldosterone-sensitive sodium channel and by activation of an ATP-dependent sodiumpotassium pump. Through both mechanisms, potassium is secretedinto the lumen to preserve electroneutrality. Sodium-channel inhibitorspreserve potassium by interfering with the sodiumpotassium pump,whereas mineralocorticoid-receptor antagonists spare potassium throughtheir inhibitory effect on aldosterone. NaHCO3 denotes sodium bicarbonate.*