Presentation on theme: "Approach to Adrenal Incidentalomas Moayad Assiri Urology R4 KAUH."— Presentation transcript:
Approach to Adrenal Incidentalomas Moayad Assiri Urology R4 KAUH
Definition. Prevalence. Causes led to it discovery. DDx. Diagnostic approach -Hormonally. -Imaging. -? FNA. Management approach. F\U. Summary. References.
(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 1997 Except: -Pt w known non adrenal malignant tumor. -pt known HTN. Definition
Incidence 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
Adrenal Incidentalomas Study - Chi Mei Medical Center 1998 Jan – 2002 Dec Abdominal CT scan 70,101 in 5 years 127 cases of AI in 256 cases of adrenal tumors Incidence of AI: 0.18% Hormonally active: 4%
Mayo clinic 1985-1990 61,054 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.
Prevalence of Adrenal Incidentalomas on CT Imaging StudyYearNumber of ScansNumber with MassFrequency (%) Abecassis et al, Toronto, Canada 19851,459191.3 Belldegrun et al, Boston, MA 198612,000880.7 Caplan et al, LaCrosse, WI 19941,779331.9 Glazer et al, St. Louis, MO 19822,200160.7 Herrera et al, Rochester, MN 199161,0542590.4 Prinz et al, Chicago,IL 19821,42340.3 TOTAL(average)79,915419(0.9) Cheng & Shen2003701011270.18
Causes led to discover IA 342 cases, 136 men and 206 women Reasons for CT scan: Reasons for CT scan: nonspecific abdominal pain, 60% known abdominal or thoracic disease, renal problems, musculoskeletal pain Acta Endocrine (copenh)1989
Age-dependent occurrence of adrenal adenomas 1% in age < 30 y. 3 -7 % in age > 50 y. Compensatory growth in response to local ischemic damage of arteriosclerotic disease Higher number of diagnostic procedures performed in aged patients N Engl J Med, 1990 Increases with Age
Age-dependent occurrence of adrenal cortical adenomas autopsy studies with total of 57,262 subjects Endocrine and Metabolism Clinics of North America 2000; 29(1):159-185
Clinical 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.
Àdrenal incidentaloma Majority are neither function nor malignant 70-90%. The malignant tumors may and may not secrete hormonal. The 3 mains hormone-producing tumors: 1. Cortisone producing adenoma SCCS 11%. 2. Pheochromocytoma 7%. 3. Aldoestrone producing adenoma 2%.
PREVALENCE OF ADRENAL INCIDENTALOMAS IN DIFFERENT SERIES _______________________________ Type of Tumor Mantero et al Al-SIE Othorst _______________________________________________ Nonhypersecretory tumors 76.0 74.0 70-94 Hypersecretory tumors Cortisol-secreting adenomas 14.0 9.2 0-14 Aldosteronomas 1.0 1.4 0-7 Pheochromocytomas 3.4 4.2 0-11 Adrenal carcinomas 1.0 4.0 0-25 Myelolipomas 2.0 3.0 7-15 Cysts 1.0 1.9 4-22 Ganglioneuromas 1.0 1.5 0-6 Metastases Unselected patients 1.0 0.7 0-21 Oncological patients 32-73 ________________________________________ AI-SIE: Adrenal Incidentaloma Study Group of the Italian Society of Endocrinology Prevalence (%) Endocrine and Metabolism Clinics of North America 2000; 29(1):107-126
Adrenal cancer Benign Adenoma 50% Cyst 10% Myelolipoma 10% Pheochromocytoma 10% Metastases 6-30% Adrenal Cancer 0.01% The incidental adrenal mass. Am J Med 1996
Benign nonfunctioning Adenoma Adrenolipoma Amyloidosis Cyst / Pseudocyst Ganglioneuroma Granuloma Infection Hamartoma Hemangioma Leiomyoma Lipoma Myelolipoma Malignant nonfunctioning Angiosarcoma Ganglioneuroblastoma Leiomyosarcoma Malignant schwannoma Metastatic carcinoma Malignant melanoma Malignant lymphoma Adrenocortical carcinoma Endocrine and Metabolism Clinics of North America 2000; 29(1):159-185 Differential Diagnosis of Adreanl Incidentalomas
Hyperfunctioning mass - Pheochromocytoma - Preclinical Cushings syndrome - Primary aldosteronism - Nodular hyperplasia - Congenital adrenal hyperplasia - Masculinizing or feminizing tumor - Primary malignancy (Adrenocortical carcinoma) Pseudoadrenal mass - Mistaken vasculature - Liver - Lymph nodes - Pancreatic mass - Spleen - Renal mass - Stomach mass - Technical artifact Differential Diagnosis of Adreanl Incidentalomas Endocrine and Metabolism Clinics of North America 2000; 29(1):159-185
After incidental discovery of an adrenal mass, 2 questions should be addressed Functional status hormonally active even in the absence of a classic clinical presentation Malignant potential any chance that the mass is malignant
Important consideration Trying not to miss important pathology. Trying no to subject the pt to unnecessary procedure or surgery. Cost effect.
Subclinical Cushings Syndrome Most frequent hormonal abnormality (5 – 20%) Autonomous cortisol secretion without stigmata of Cushing s syndrome Diagnostic criteria not yet clearly defined 10-20 mg/day Controlled Primarily By ACTH Negative and Positive Feedback Between Cortisol and ACTH at Pituitary and Hypothalamic Levels
Dx Increased Urinary Free Cortisol (UFC) Unsuppressed Serum Cortisol Levels After 1-mg Overnight Dexamethasone Low ACTH Levels No Clinical Signs Of Cushing Syndrome Mantero F, Masini AM, Opocher G, Giovagnetti M, Arnaldi G. Horm Res 47:284–289, 1997
Dexamethasone Suppression Test Low-dose: 1mg dexamethasone at 2300, followed by assay of cortisol at 0800 the following day – Cortisol > 3 mcg/dl suggests autonomous secretion High-dose: 8 mg dexamethasone at 2300 with assay of cortisol at 0800 the next day – Cortisol > 1 mcg/dl indicates autonomous secretion – Reduces false positives Intermediate-dose : 2 – 3 mg dexamethasone at 2300, followed by cortisol at 0800 – Cortisol > 3 mcg/dl reportedly suggestive of autonomy Easier to perform overnight suppression rather than 2-day oral load
Association with Metabolic Syndrome? 1990s Italian multiinstitutional study collection 1004 patients with adrenal incidentaloma – 41% prevalence HTN – 10% prevalence DM – 28% prevalence obesity May contribute to, and worsen, hypertension, obesity, diabetes, dyslipidemia and osteoporosis
Pheochromocytoma Approximately 5-7 % of adrenal incidentalomas. 0.5% among screened hypertensive pts Can be clinically silent and not suggested by history Mixed recommendations on diagnostic testing
Dx 24-h Urinary fractionated catecholamine excretion or free metanephrines. 24 hour urine fractionated metanephrines recommended by some as first diagnostic test Especially in incidentalomas without radiographic features suggestive of pheochromocytoma Sensitivity and specificity between 91 – 98% Increased even further when fractionated catecholamines added
Plasma Free Metanephrines Plasma free metanephrines – Used when imaging characteristics and other pre-test probability of pheochromocytoma are high, but 24 hr urine normal – Due to high sensitivity (97 – 100%) but low specificity (85 – 89%, ) of test – Negative result quite effective at ruling out
Which 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): 553-558. 2003.
Aldosteronism (Conns Sx) Quite rare cause <1% – Most have already been diagnosed before become large enough to be detected by CT/MRI Should be evaluated in all hypertensive patients with incidentaloma Serum potassium not sufficient, but should be included – Common to have normokalemia with aldosterone producting adrenal tumor 7 – 38%.
Hypertension Headache Weakness And/Or Fatigue Paresthesias Muscle Cramps Polyuria, Polydipsia, Nocturia Arrhythmias Signs and Symptoms in Primary Hyperaldosteronism
Aldosterone Production 100-150 ug/day Stimulated by the Renin-Angiotensin System Decreased Perfusion Pressure Hyperkalemia Stimulates and Hypokalemia Inhibits Aldosterone Secretion ACTH Acutely May Stimulate Aldosterone Secretion
Dx Plasma aldosterone/plasma renin activity ratio greater than 30 highly suggestive – Especially with plasma aldosterone >15 ng/dl Confirm with aldosterone suppression test – IV 0.9 NS infusion – 2L over 2 hrs, with supine aldosterone >10 suggestive – Can also do 24 hour urinary aldosterone while patient orally ingests 5000 mg sodium/day x 3 days Urinary aldosterone >14 mcg/24 º
Appropriate screening tests should be performed if the patient has clinical features that are suggestive of increased adrenal function DiagnosisSuggestive Clinical FeaturesLaboratory Tests PheochromocytomaHypertension, Paroxysmal Symptoms (eg, palpitation, diaphoresis, headache, pallor, tremor) 24-hr urine: fractionated metanephrines fractionated catecholamines Blood: fractionated metanephrines SC Cushing's syndrome (SCCS) Central obesity, proximal muscle weakness, thin skin, supraclavicular fat pad, facial plethora For patients lacking symptoms of CS: 1-mg overnight dexamethasone suppression test
DiagnosisSuggestive Clinical Features Laboratory Tests Primary aldosteronism Hypertension, hypokalemiaPlasma aldosterone concentration Plasma renin activity Adrenocortical carcinoma Mass effect symptoms, symptoms related to excess glucocorticoid, mineralocorticoid, androgen, or estrogen secretion Serum dehydroepiandrosterone sulfate Measures of clinically indicated steroid
Stepwise 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.
Stepwise 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.
Step III. Revaluation -repeat screening tests after 2 years in patient with a tumor size of > 3 cm. Stepwise diagnostic approach
Imaging Characteristics CT Scan – Hounsfield Scale Measures xray attenuation Each number represents a shade of grey, with air and bone Water as zero Air = -1000 Bone = +1000 Hounsfield Units for Relative Densities of Various Substances Substance Hounsfield units(H) -1,000Air -50Fat 0Water +40Soft tissue (i.e., muscle) +100 to +400Calculus + 1,000Bone Hounsfield units = units of x-ray attenuation used in CT. each pixel is assigned a value on a scale from -1,000 to +1,000.
CT scan Attenuation On CT Scan Is Measured In Hounsfield Units (HU) Lipid-Rich Masses Are Usually Benign Lipid-Rich Lesions Have Low Attenuation Low Attenuation Lesions Have Low HU Values
Computed Tomographic Scans Unenhanced CT: Adenomas: < 10 HU Malignancies: > 18 HU Sensitivity: 73% Specificity: 96% Delayed Enhanced CT: Adenomas: < 30 HU Malignancies: > 30 HU Sensitivity 95% And Specificity: 100%
Adrenocortical carcinoma Size large, typically > 4 cm Shape irregular with unclear margins Texture inhomogenous with mixed densities compared with liver Laterality usually solitary and unilateral CT > 10 HU without contrast and >30-40 HU 30 min after contrast administration MRI hyperintense to liver on T2-weighted image Presence of necrosis, hemorrhage, or calcifications-- common Growth usually rapid
Adrenal cancer CT Contrast-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..
Malignant Potential Imaging phenotype and mass size are two major predictors of malignancy Additional test that may be preformed to predict malignancy include image-guided needle biopsy and iodocholesterol scintigraphy Hormonal evaluation is not predictive of malignancy Approximately 41% of 1,891 published cases of adrenocortical carcinoma, was not hormone-secreting
size The 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 tumor 2% 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.
Imaging Phenotypes of Adrenal Incidentalomas Adrenal cortical adenomas Size small, typically < 3 cm Shape round to oval with smooth margins Texture homogenous and low density compared with liver Laterality usually solitary and unilateral CT < 10 HU without contrast and <37 HU 30 min after contrast administration MRI isointense to liver on T2-weighted image Presence of necrosis, hemorrhage, or calcifications-- rare Growth usually stable size over time or very slow growth
Adrenal adenoma hypodense Abdominal CT showing a 1.5-cm round hypodense left adrenal cortical adenoma (arrow).
Pheochromocytoma Size large, typically > 3 cm Shape round to oval with smooth margins Texture inhomogenous with cystic texture Laterality usually solitary and unilateral CT >10 HU without contrast and >40 HU 30 min after contrast administration, usually vascular, marked enhancement MRI marked hyperintense compared with liver on T2-weighted image Presence of necrosis, hemorrhage, or calcifications-- hemorrhage and cystic necrotic areas common Growth very slow
Pheochromocytoma 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..
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.
Metastasis Size variable, frequently < 3 cm Shape round to irregular with unclear margins Texture inhomogenous Laterality often bilateral CT > 10 HU without contrast and >40 HU 30 min after contrast administration, usually vascular, enhancement on tumor rim MRI hyperintense compared with liver on T2-weighted image Presence of necrosis, hemorrhage, or calcifications-- hemorrhage and cystic necrotic areas common Growth usually slow
Imaging Characteristics AdenomaAdrenocortical Carcinoma Pheochromocytom a Metastasis Size< 3 cm diameter>4 cm diameter>3 cm diameterUsually <3 cm ShapeRound, smooth Margins Irregular, no clear margins Round/oval, clear margins Oval/irregular, unclear margins TextureHomogenousHeterogenous, mixed densities Heterogenous, cystic Heterogenou s, mixed densities LateralizeSolitary, unilateral Solitary, unilateralyBilateral CT Attenuation <10 HU>25 HU CT Washout at 10 minutes >50%<50% T2 MRI Appearance (compare to liver) =+++++ Necrosis, Ca, hemorrhage RareCommon Occasional Growth rateSlowRapidSlowVariable
Nuclear Imaging PET – most useful in patients with oncologic history and incidentaloma – 100% sensitive determining both metastasis and benign adenomas based on adrenalectomy studies Radionuclide Scintigraphy Radionuclide Scintigraphy
MIBG – used to confirm suspicion of pheochromocytoma, little utility in eval of incidentalomas in general
NP-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
3- 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
Tumors that most commonly metastasize to adrenals are carcinomas of lung, breast, kidney and gastrointestinal tract, melanoma or lymphoma FNA 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 mass NATIONAL INSTITUTES OF HEALTH Management of the Clinically Inapparent Adrenal Mass (Incidentaloma). Final Statement. July 16, 2002
Bilateral masses Analyses 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 with – metastatic disease, – congenital adrenal hyperplasia, – cortical adenomas, lymphoma, – infection (eg, tuberculosis, fungal), – hemorrhage, – ACTH-dependent Cushing's, – pheochromocytoma, – amyloidosis, – infiltrative disease of the adrenal glands, and – ACTH-independent bilateral macronodular adrenal hyperplasia
Adrenalectomy? 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.
Adrenalectomy? Recommended for: all patients with mass size > 6 cm, pheochromocytoma, aldosteronism, and Cushing s syndrome Aldosteronism and CS can be treated medically, but surgical approach favored Medical Spironolactone Inhibits sodium-postassium exchange in the distal tubule, normalizes serum K and may lower blood pressure.
4 – 6 cm masses – Either 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.
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 approaches Complication 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):677-81.
342 pts AI. 52 patients underwent adrenalectomy 5 patients had malignancy: 4 adrenocortical carcinomas and one metastasis 1.2% of 342 had cancer No malignancy < 5 cm in diameter 287 of 342 had follow-up; 90% at one year None had extension of tumor or hormonal excess Herrera et al, Surgery
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 cm Herrera et al, Surgery
National survey on AI Purpose: To evaluate AI based on imaging size alone Strict exclusion criteria 1004 enrolled; 584 women and 420 men All patients underwent CT scan or MRI Montero, JCEM
85% underwent hormonal evaluation Results: 9.2% had SCS, 1.6% had an aldosteronoma and 4.2% had pheochromocytomas All these patients underwent adrenalectomy A total of 380 patients underwent adrenalectomy. Montero, JCEM
Table 4 Histological picture in relation with gender, age, and mass size (CT measurement). Mantero, JCEM
Conclusions: (1) An AI > 4 cm is 93% sensitive for detecting all malignancies and (2) Pain at presentation may be associated with a malignant outcome Mantero, JCEM
The Mayo Clinic Study 432 Patients With Adrenal Incidentaloma Retrospectively Evaluated Tumor Diameter Averaged 2.5 cm. Most Malignant Tumors Measured > 5 cm. Removing All Tumors > 4 cm Would Have Removed Eight Benign Tumors For Every Carcinoma Incidentally discovered adrenal tumors: an institutional perspective. Herrera MF; Grant CS; van Heerden JA; Sheedy PF; Ilstrup DM. Surgery 1991 Dec;110(6):1014-21
Incidentaloma Follow-Up No single approach is proof yet. 1 st Follow up 3 - 6 m with another FU at 12 m. Repeat hormone screening after 12m. Then annually. 2 -3 y
IA Mass Risk of progression Adrenal Hyperfunction: Unlikely If Lesion < 3 cm Cortisol Hypersecretion Most Likely Disorder 4% After 1 Year 9.5% Within 3 Years None Thereafter Mass Enlargement: 8% After 1 Year 18% After 5 Years Most Enlargement Occurred Within 3 Years Barzon et al J Clin Endocrinol Metab 1999
Summary Relatively common – prevalence ~ 2 – 5 %. – Increases with age, so expected to increase further in future. 1 in every 4000-1.6 million adrenal tumors are malignant Up to 20% are hyperfunction. All patients with incidentaloma need hormonal eval -24º urinary metanephrines -Midnight dexamethasone suppression test -PAC\PRA ratio in pts with underlying HTN or hpokalemia. No optimal radiologic test to distinguish between benign and malignant tumors
Summary FNA of little value. Sx indicated for hyperfunction masses, size >6cm and possibility of malignancy. Malignant tumors more likely to be > 4 cm Nearly all masses <4 cm are benign No consensus on follow-up
References AI-SIE: Adrenal Incidentaloma Study Group of the Italian Society of Endocrinology Acta Endocrine (copenh)1989 N Engl J Med, 1990 Endocrine and Metabolism Clinics of North America 2000; 29(1):159-185 NATIONAL INSTITUTES OF HEALTH Management of the Clinically Inapparent Adrenal Mass (Incidentaloma).Final Statement. July 16, 2002 Endocrine and Metabolism Clinics of North America 1997 Barzon et al J Clin Endocrinol Metab 1999
References Endocrine and Metabolism Clinics of North America 2000; 29(1):107- 126 Mantero F, Masini AM, Opocher G, Giovagnetti M, Arnaldi G. Horm Res 47:284–289, 1997 Sawka et al. JCEM 88(2): 553-558. 2003. 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):677-81. Incidentally discovered adrenal tumors: an institutional perspective. Herrera MF; Grant CS; van Heerden JA; Sheedy PF; Ilstrup DM. Surgery 1991 Dec;110(6):1014-21