Presentation on theme: "Approach to Adrenal Incidentalomas"— Presentation transcript:
1Approach to Adrenal Incidentalomas Moayad AssiriUrology R4KAUH
2Definition.Prevalence.Causes led to it discovery.DDx.Diagnostic approach-Hormonally.-Imaging.-? FNA.Management approach.F\U.Summary.References.
3(Clinically inapparent adrenal masses). Definition(Clinically inapparent adrenal masses).adrenal tumor not suspected prior to radiological studies led to it discovery.A disease of modern technology.J Endocrinal Metab Clin North Am 1997Except:-Pt w known non adrenal malignant tumor.-pt known HTN.
4Incidence of adrenal masses is 9 - 12% in autopsies. Incidence of AI is 2- 5 %.>Rt > lt .Bil 2 – 10 %.NATIONAL INSTITUTES OF HEALTH Management of the Clinically Inapparent Adrenal Mass (Incidentaloma).Final Statement. July 16, 2002
5Adrenal Incidentalomas Study - Chi Mei Medical Center 1998 Jan – 2002 DecAbdominal CT scan 70,101 in 5 years127 cases of AI in 256 cases of adrenal tumorsIncidence of AI: 0.18%Hormonally active: 4%
6Mayo clinic61,054 CT scans performed .Adrenal mass in 2066 pts ( 3.4%).16.5% were present incidental ( <1 cm ).Overall, AI 259 pts ( 0.4% )50% metastatic ca.25% other known lesions.7.5% symptomatic tumors.
7Abecassis et al, Toronto, Canada Prevalence of Adrenal Incidentalomas on CT ImagingStudyYearNumber of ScansNumber with MassFrequency (%)Abecassis et al, Toronto, Canada19851,459191.3Belldegrun et al,Boston, MA198612,000880.7Caplan et al,LaCrosse, WI19941,779331.9Glazer et al,St. Louis, MO19822,20016Herrera et al,Rochester, MN199161,0542590.4Prinz et al,Chicago,IL1,42340.3TOTAL(average)79,915419(0.9)Cheng & Shen2003701011270.18
8Causes led to discover IA 342 cases, men and 206 womenReasons for CT scan: nonspecific abdominal pain, % known abdominal or thoracic disease, renal problems, musculoskeletal painActa Endocrine (copenh)1989
9Age-dependent occurrence of adrenal adenomas Increases with Age1% in age < 30 y.3 -7 % in age > 50 y.Compensatory growth in response to local ischemic damage of arteriosclerotic diseaseHigher number of diagnostic procedures performed in aged patientsN Engl J Med, 1990
10Age-dependent occurrence of adrenal cortical adenomas autopsy studies with total of 57,262 subjects Endocrine and Metabolism Clinics of North America2000; 29(1):
11Clinical characteristics Per definition ,NO clinical symptoms or signs of adrenal disease should be present at the time of Dx.More detailed Q and careful PE might reveal evidence of subtle hormonal excess;-recent w.t gain-skin atrophy.-episodic of headaches.
12Àdrenal incidentaloma Majority are neither function nor malignant70-90%.The malignant tumors may and may not secrete hormonal.The 3 mains hormone-producing tumors:Cortisone producing adenoma SCCS 11%.Pheochromocytoma 7%.Aldoestrone producing adenoma 2%.
13________________________________________ PREVALENCE OF ADRENAL INCIDENTALOMASIN DIFFERENT SERIES_______________________________Type of Tumor Mantero et al Al-SIE Othorst_______________________________________________Nonhypersecretory tumorsHypersecretory tumorsCortisol-secreting adenomasAldosteronomasPheochromocytomasAdrenal carcinomasMyelolipomasCystsGanglioneuromasMetastasesUnselected patientsOncological patients________________________________________AI-SIE: Adrenal Incidentaloma Study Group of the Italian Society of EndocrinologyPrevalence (%)Endocrine and Metabolism Clinicsof North America 2000; 29(1):
14Adrenal cancer Benign Adenoma 50% Cyst 10% Myelolipoma 10% Pheochromocytoma %Metastases %Adrenal Cancer %The incidental adrenal mass. Am J Med 1996
15Differential Diagnosis of Adreanl Incidentalomas Benign nonfunctioningAdenomaAdrenolipomaAmyloidosisCyst / Pseudocyst Ganglioneuroma GranulomaInfectionHamartoma Hemangioma LeiomyomaLipoma MyelolipomaMalignant nonfunctioningAngiosarcoma Ganglioneuroblastoma Leiomyosarcoma Malignant schwannoma Metastatic carcinoma Malignant melanomaMalignant lymphomaAdrenocortical carcinomaEndocrine and Metabolism Clinicsof North America 2000; 29(1):
17After incidental discovery of an adrenal mass, 2 questions should be addressed Functional statushormonally active even in the absence ofa classic clinical presentationMalignant potentialany chance that the mass is malignant
18Important consideration Trying not to miss important pathology.Trying no to subject the pt to unnecessary procedure or surgery.Cost effect.
191-Endocrinology investigation significant endocrine activity increase with increase tumor size
20Subclinical Cushing’s Syndrome Most frequent hormonal abnormality (5 – 20%)Autonomous cortisol secretion without stigmata of Cushing’s syndromeDiagnostic criteria not yet clearly defined10-20 mg/dayControlled Primarily By ACTHNegative and Positive Feedback Between Cortisol and ACTH at Pituitary and Hypothalamic Levels
21Dx Increased Urinary Free Cortisol (UFC) Unsuppressed Serum Cortisol Levels After 1-mg Overnight DexamethasoneLow ACTH LevelsNo Clinical Signs Of Cushing SyndromeMantero F, Masini AM, Opocher G, Giovagnetti M, Arnaldi G. Horm Res 47:284–289, 1997
22Dexamethasone Suppression Test Low-dose: 1mg dexamethasone at 2300, followed by assay of cortisol at 0800 the following dayCortisol > 3 mcg/dl suggests autonomous secretionHigh-dose: 8 mg dexamethasone at 2300 with assay of cortisol at 0800 the next dayCortisol > 1 mcg/dl indicates autonomous secretionReduces false positives“Intermediate-dose”: 2 – 3 mg dexamethasone at 2300, followed by cortisol at 0800Cortisol > 3 mcg/dl reportedly suggestive of autonomyEasier to perform overnight suppression rather than 2-day oral load
23Association with Metabolic Syndrome? May contribute to, and worsen, hypertension, obesity , diabetes, dyslipidemia and osteoporosis1990’s Italian multiinstitutional study collection 1004 patients with adrenal incidentaloma41% prevalence HTN10% prevalence DM28% prevalence obesity
24Pheochromocytoma Approximately 5-7 % of adrenal incidentalomas. 0.5% among screened hypertensive pt’sCan be clinically silent and not suggested by historyMixed recommendations on diagnostic testing
25Dx24-h Urinary fractionated catecholamine excretion or free metanephrines.24 hour urine fractionated metanephrines recommended by some as first diagnostic testEspecially in incidentalomas without radiographic features suggestive of pheochromocytomaSensitivity and specificity between 91 – 98%Increased even further when fractionated catecholamines added
26Plasma Free Metanephrines Used when imaging characteristics and other pre-test probability of pheochromocytoma are high, but 24 hr urine normalDue to high sensitivity (97 – 100%) but low specificity (85 – 89%, ) of testNegative result quite effective at ruling out
27Which Is Better?Catecholamine-Secreting Tumors Histologically Proven In 31 of 340 Patients:Sensitivity Of Plasma Free Metanephrine 97% Specificity 98%Sensitivity Of Urinary Total Metanephrine And Catecholamines 90%; Specificity 85%Sawka et al. JCEM 88(2):
28Aldosteronism (Conns Sx) Quite rare cause <1%Most have already been diagnosed before become large enough to be detected by CT/MRIShould be evaluated in all hypertensive patients with incidentalomaSerum potassium not sufficient, but should be includedCommon to have normokalemia with aldosterone producting adrenal tumor 7 – 38%.
29Signs and Symptoms in Primary Hyperaldosteronism HypertensionHeadacheWeakness And/Or FatigueParesthesiasMuscle CrampsPolyuria, Polydipsia, NocturiaArrhythmias
30Aldosterone Production ug/dayStimulated by the Renin-Angiotensin System Decreased Perfusion PressureHyperkalemia Stimulates and Hypokalemia Inhibits Aldosterone SecretionACTH Acutely May Stimulate Aldosterone Secretion
31DxPlasma aldosterone/plasma renin activity ratio greater than 30 highly suggestiveEspecially with plasma aldosterone >15 ng/dlConfirm with aldosterone suppression testIV 0.9 NS infusion – 2L over 2 hrs, with supine aldosterone >10 suggestiveCan also do 24 hour urinary aldosterone while patient orally ingests 5000 mg sodium/day x 3 daysUrinary aldosterone >14 mcg/24ºACE’s and ARB’s can also falsely elevated PRA and should typically be avoided during testing
32Appropriate screening tests should be performed if the patient has clinical features that are suggestive of increased adrenal functionDiagnosisSuggestive Clinical FeaturesLaboratory TestsPheochromocytomaHypertension, Paroxysmal Symptoms (eg, palpitation, diaphoresis, headache, pallor, tremor)24-hr urine:fractionated metanephrines fractionated catecholaminesBlood:fractionated metanephrinesSC Cushing's syndrome (SCCS)Central obesity, proximal muscle weakness, thin skin, supraclavicular fat pad, facial plethoraFor patients lacking symptoms of CS:1-mg overnight dexamethasone suppression test
33DiagnosisSuggestive Clinical FeaturesLaboratory TestsPrimary aldosteronismHypertension, hypokalemiaPlasma aldosterone concentrationPlasma renin activityAdrenocortical carcinomaMass effect symptoms, symptoms related to excess glucocorticoid, mineralocorticoid, androgen, or estrogen secretionSerum dehydroepiandrosterone sulfateMeasures of clinically indicated steroid
35Stepwise diagnostic approach Step I :1- 24-h Urinary catecholamine excretion or free metanephrines.2- Serum cortisol after dexamethasone suppression 1mg at 11 pm PO.3-HTN , Serum K and – PAC\PRA ratio.
36Stepwise diagnostic approach Step II : confirmatory test.1- MRI . CT scan or 123-I-MIBG scintigraphy or 131 I-MIBG.2- high-dose dexamethasone 8mg suppression test. If +ve.CRH test analysis of diurnal cortisol secretion, and 24-h urine free cortisol.3- confirm with aldosterone suppression test.And 24-h urine aldosterone .
37Stepwise diagnostic approach Step III. Revaluation-repeat screening tests after 2 years in patient with a tumor size of > 3 cm.
39Imaging Characteristics Hounsfield Units for Relative Densities of Various SubstancesSubstance Hounsfield units(H)-1,000Air-50FatWater+40Soft tissue (i.e., muscle)+100 to +400Calculus+ 1,000BoneHounsfield units = units of x-ray attenuation used in CT. each pixel is assigned a value on a scale from ,000 to +1,000.CT ScanHounsfield ScaleMeasures xray attenuationEach number represents a shade of grey, with air and boneWater as zeroAir = -1000Bone = +1000
40CT scan Attenuation On CT Scan Is Measured In Hounsfield Units (HU) Lipid-Rich Masses Are Usually BenignLipid-Rich Lesions Have Low AttenuationLow Attenuation Lesions Have Low HU Values
42Adrenocortical carcinoma Size large, typically > 4 cmShape irregular with unclear marginsTexture inhomogenous with mixed densitiescompared with liverLaterality usually solitary and unilateralCT > 10 HU without contrast and >30-40 HU 30 minafter contrast administrationMRI hyperintense to liver on T2-weighted imagePresence of necrosis, hemorrhage, or calcifications-- commonGrowth usually rapid
43Adrenal cancer CTContrast-enhanced CT scan through the abdomen of a 56-year-old man reveals a complex solid and cystic, calcified mass (arrow) in the right suprarenal fossa extending into the adjacent liver. The tumor proved at surgery to be a carcinoma of the adrenal cortex. .
44Malignant PotentialImaging phenotype and mass size are two major predictors of malignancyAdditional test that may be preformed to predict malignancy include image-guided needle biopsy and iodocholesterol scintigraphyHormonal evaluation is not predictive of malignancyApproximately 41% of 1,891 published cases of adrenocortical carcinoma, was not hormone-secreting
45sizeThe probability that an AI is ACC is increases with increasing size of the lesion.90% of all ACC is > 6 cm in size.The prevalence of ACC related to size of tumor2% in tumors < 4 cm.6% in tumors 4-6 cm.25% in tumor > 6 cm.Resection all tumor > 4 cm- 8 benign tumors removed for each cancer resected.
46Imaging Phenotypes of Adrenal Incidentalomas Adrenal cortical adenomas Size small, typically < 3 cmShape round to oval with smooth marginsTexture homogenous and low density compared with liverLaterality usually solitary and unilateralCT < 10 HU without contrast and <37 HU 30 min aftercontrast administrationMRI isointense to liver on T2-weighted imagePresence of necrosis, hemorrhage, or calcifications-- rareGrowth usually stable size over time or very slow growth
47Adrenal adenoma hypodense Abdominal CT showing a 1.5-cm round hypodense left adrenal cortical adenoma (arrow).
48Pheochromocytoma Size large, typically > 3 cm Shape round to oval with smooth marginsTexture inhomogenous with cystic textureLaterality usually solitary and unilateralCT >10 HU without contrast and >40 HU 30 min after contrast administration, usually vascular, marked enhancementMRI marked hyperintense compared with liver on T2-weighted imagePresence of necrosis, hemorrhage, or calcifications-- hemorrhage and cystic necrotic areas commonGrowth very slow
49Pheochromocytoma silent Abdominal CT showing an 8-cm left adrenal mass (arrow) discovered incidentally. Note the vascular and inhomogenous imaging characteristics of this mass. Biochemical evaluation was consistent with a clinically silent pheochromocytoma, which was confirmed at surgery..
50MRI of the abdomen shows a 4 MRI of the abdomen shows a 4.5-cm right adrenal pheochromocytoma (arrows). Upper panel: T1-weighted image. Lower panel: T2-weighted image shows increased signal intensity typical of a pheochromocytoma.
51Metastasis Size variable, frequently < 3 cm Shape round to irregular with unclear marginsTexture inhomogenousLaterality often bilateralCT > 10 HU without contrast and >40 HU 30 min after contrast administration, usually vascular, enhancement on tumor rimMRI hyperintense compared with liver on T2-weighted imagePresence of necrosis, hemorrhage, or calcifications-- hemorrhage and cystic necrotic areas commonGrowth usually slow
52Imaging Characteristics AdenomaAdrenocorticalCarcinomaPheochromocytomaMetastasisSize< 3 cm diameter>4 cm diameter>3 cm diameterUsually <3 cmShapeRound, smoothMarginsIrregular, no clear marginsRound/oval, clear marginsOval/irregular, unclear marginsTextureHomogenousHeterogenous, mixed densitiesHeterogenous, cysticLateralizeSolitary, unilateralSolitary, unilateralyBilateralCT Attenuation<10 HU>25 HUCT Washout at 10 minutes>50%<50%T2 MRI Appearance (compare to liver)=++++Necrosis, Ca, hemorrhageRareCommonOccasionalGrowth rateSlowRapidVariable
53Nuclear Imaging Radionuclide Scintigraphy PET – most useful in patients with oncologic history and incidentaloma100% sensitive determining both metastasis and benign adenomas based on adrenalectomy studies
55MIBG – used to confirm suspicion of pheochromocytoma, little utility in eval of incidentalomas in general
56NP-59 – radiolabeled cholesterol derivative, preferentially taken up by adrenal adenomas Unilateral uptake suggests functional adenomas, and may be useful in screening for subclinical cushing’s syndrome
573- Fine-needle aspiration biopsy (FNA) cannot distinguish a benign adrenal mass from the rare adrenal carcinoma.It can distinguish between an adrenal tumor and a metastatic tumor.FNA may be indicated :when there is a suspicion of cancer outside the adrenal gland,or in the patient undergoing a staging evaluation for a known cancer.? Infection.NATIONAL INSTITUTES OF HEALTH Management of the Clinically Inapparent Adrenal Mass (Incidentaloma).Final Statement. July 16, 2002
58FNA is not useful in the routine evaluation. Tumors that most commonly metastasize to adrenals are carcinomas of lung, breast, kidney and gastrointestinal tract, melanoma or lymphomaFNA is not free of S.E .FNA is not useful in the routine evaluation.Pheochromocytoma should always be excluded before attempting FNA biopsy of an adrenal massNATIONAL INSTITUTES OF HEALTH Management of the Clinically Inapparent Adrenal Mass (Incidentaloma).Final Statement. July 16, 2002
60Bilateral massesAnalyses from two large adrenal incidentaloma studies with 887 and 202 patients showed that bilateral masses were found in 10 to 15 percent of cases.Bilateral adrenal masses can be seen withmetastatic disease,congenital adrenal hyperplasia,cortical adenomas, lymphoma,infection (eg, tuberculosis, fungal),hemorrhage,ACTH-dependent Cushing's,pheochromocytoma,amyloidosis,infiltrative disease of the adrenal glands, andACTH-independent bilateral macronodular adrenal hyperplasia
61Adrenalectomy? Individualized approach The decision to operate on pt should be based on :Suspicious of the presence of malignancy.Evidence of function of the tumor.Pt age .Pt preference .
62Adrenalectomy? Recommended for: all patients with mass size > 6 cm, pheochromocytoma,aldosteronism,and Cushing’s syndromeAldosteronism and CS can be treated medically, but surgical approach favoredMedicalSpironolactoneInhibits sodium-postassium exchange in the distal tubule, normalizes serum K and may lower blood pressure.
634 – 6 cm massesEither surgical approach or close follow-up considered reasonable*Strongly consider adrenalectomy:if imaging phenotype suspicious,increase in size > 1 cm during f/u,or development of hormonal hyperfunction during f/u.
64No difference between open and laparoscopic approaches Considered in SCS, especially in pt’s < 40 or 50 y/o, and those with disorders attributable to hypercortisolism- Caution for postoperative adrenal insufficiency in SCS patients taken to adrenalectomy.No difference between open and laparoscopic approachesComplication rate of ~3%Special consideration :-Poor surgical patient – FU.-Not possible or difficult FU – Sx.Izaki H et al. Indications for laparoscopic adrenalectomy for non-functional adrenal tumor with hypertension: usefulness of adrenocortical scintigraphy. Int J Urol 2006:13(6):
6552 patients underwent adrenalectomy 5 patients had malignancy: 342 pts AI.52 patients underwent adrenalectomy5 patients had malignancy:4 adrenocortical carcinomas and one metastasis1.2% of 342 had cancerNo malignancy < 5 cm in diameter287 of 342 had follow-up; 90% at one yearNone had extension of tumor or hormonal excessHerrera et al, Surgery
66(1) Hormonal screening on patients with an AI > 1 cm, Conclusions:(1) Hormonal screening on patients with an AI > 1 cm,(2) any patient with a hyper-secretory state should undergo adrenalectomy,(3) advise adrenalectomy on AIs > 4 cm and(4) comparison CT scans at 3 month intervals for those choosing observation only of their AI < 4 cmHerrera et al, Surgery
67National survey on AIPurpose: To evaluate AI based on imaging size aloneStrict exclusion criteria1004 enrolled; 584 women and 420 menAll patients underwent CT scan or MRIMontero, JCEM
6885% underwent hormonal evaluation Results: 9.2% had SCS, 1.6% had an aldosteronoma and 4.2% had pheochromocytomasAll these patients underwent adrenalectomyA total of 380 patients underwent adrenalectomy.Montero, JCEM
69Table 4 Histological picture in relation with gender, age, and mass size (CT measurement). Mantero, JCEM
70(1) An AI > 4 cm is 93% sensitive for detecting all malignancies Conclusions:(1) An AI > 4 cm is 93% sensitive for detecting all malignanciesand (2) Pain at presentation may be associated with a malignant outcomeMantero, JCEM
71The Mayo Clinic Study432 Patients With Adrenal Incidentaloma Retrospectively EvaluatedTumor Diameter Averaged 2.5 cm.Most Malignant Tumors Measured > 5 cm.Removing All Tumors > 4 cm Would Have Removed Eight Benign Tumors For Every CarcinomaIncidentally discovered adrenal tumors: an institutional perspective. Herrera MF; Grant CS; van Heerden JA; Sheedy PF; Ilstrup DM. Surgery 1991 Dec;110(6):
72Incidentaloma Follow-Up No single approach is proof yet.1st Follow up m with another FU at 12 m.Repeat hormone screening after 12m.Then annually y
73IA Mass Risk of progression Adrenal Hyperfunction:Unlikely If Lesion < 3 cmCortisol Hypersecretion Most Likely Disorder4% After 1 Year9.5% Within 3 Years None ThereafterMass Enlargement:8% After 1 Year18% After 5 YearsMost Enlargement Occurred Within 3 YearsBarzon et al J Clin Endocrinol Metab 1999
74Summary Relatively common – prevalence ~ 2 – 5 %. Increases with age, so expected to increase further in future.1 in every million adrenal tumors are malignantUp to 20% are hyperfunction.All patients with incidentaloma need hormonal eval-24º urinary metanephrines-Midnight dexamethasone suppression test-PAC\PRA ratio in pt’s with underlying HTN or hpokalemia.No optimal radiologic test to distinguish between benign and malignant tumors
75Summary FNA of little value. Sx indicated for hyperfunction masses , size >6cm and possibility of malignancy .Malignant tumors more likely to be > 4 cmNearly all masses <4 cm are benignNo consensus on follow-up
76ReferencesNATIONAL INSTITUTES OF HEALTH Management of the Clinically Inapparent Adrenal Mass(Incidentaloma).Final Statement. July 16, 2002Endocrine and Metabolism Clinics of North America 1997Endocrine and Metabolism Clinics of North America 2000; 29(1):AI-SIE: Adrenal Incidentaloma Study Group of the Italian Society of EndocrinologyBarzon et al J Clin Endocrinol Metab 1999Acta Endocrine (copenh)1989N Engl J Med, 1990
77ReferencesEndocrine and Metabolism Clinics of North America 2000; 29(1):Mantero F, Masini AM, Opocher G, Giovagnetti M, Arnaldi G. Horm Res 47:284–289, 1997Sawka et al. JCEM 88(2):Izaki H et al. Indications for laparoscopic adrenalectomy for non-functional adrenal tumor with hypertension: usefulness of adrenocortical scintigraphy Int J Urol 2006:13(6):Incidentally discovered adrenal tumors: an institutional perspective. Herrera MF; Grant CS; van Heerden JA; Sheedy PF; Ilstrup DM. Surgery 1991 Dec;110(6):