Adrenal incidentaloma by Supphachoke Khemla MD. Supphawatana phaphun MD. 20 March 2552

Cross Sectional Anatomy Normal size (Lt or Rt adrenal) : 3 cm × 6 mm Retroperitoneum organ Gerota’s fascia : connect the gland to upper pole of the kidney

Introduction Mass lesion greater than 1 cm. Serendipitiously discovered by radiologic examinations Such as : - Computed tomography (CT) - Magnetic resonance imaging (MRI) Two questions - Is it malignancy ? - Is it functioning ?

Prevalence Autopsy : Total 739 cases (adrenal masses between 2 mm – 4 cm) - 9 % normotensive - 12 % hypertension The Mayo clinic - 61,054 abdominal CT scans - 1985 – 1990 - adrenal masses : 2,066 cases (3.4%)

Prevalence The Mayo clinic 2,066 cases : - 50% metastasis cancer - 25% other known lesions - 7.5% symptomatic tumors - 16.5% incidental (include nodules < 1cm) - Overall incidental adrenal tumor (> 1cm) = 0.4 %

Prevalence Recent study : high resolution scanner - report prevalence from CT abdomen = 4.4% Demonstration : enlarged & unusually shaped 1. one adrenal mass 2. bilateral adrenal masses

Bilateral masses Studies : 887 and 202 cases (with adrenal incidentaloma) - bilateral 10-15% - causes : - metastasis - pheochromocytoma - congenital adrenal hyperplasia - amyloidosis - cortical adenoma - infiltrative disease of adrenal gl. - lymphoma - Infections : TB, fungus - hemorrhage - ACTH-dependent Cushing’s - ACTH-independent bilateral macronodular adrenal hyperplasia

Bilateral masses One adrenal mass : non-functioning cortical adenoma Contralateral adrenal mass : hormone secreting +++ All patients with bilateral adrenal masses should be screened for adrenocortical hyper/hypo function +++

Evaluate for malignancy Primary adrenal carcinoma : quite rare Others : - metastasis (particularly lung cancers) Evaluate : size and imaging characteristics (imaging phenotype)

Size The maximum diameter is predictive of malignancy Important : if the smaller is at the time of diagnosis, the better overall prognosis Adenocortical carcinomas - significantly asso. with mass size - 90% > 4 cm

Size The National Italian Study Groups - 4 cm cutoff - sensitivity 93 % - specificity 76 %

Imaging phenotype MRI or CT 3-5 mm. cuts : predict histological type of adrenal tumor Characteristics of the mass example ; lipid-rich nature of cortical adenomas (benign tumor)

CT scan Density (black is less dense) Spectrum : Air -black, Bone-white Hounfield scale is a semiquantitative method of measuring x-ray attenuation Typical precontrast Hounsfield unit (HU) valves adipose tissue = -20 to – 150 HU kidney = 20 to – 150 HU if adrenal mass < 10 HU on unenhanced CT (ie, has density of fat) likelihood benign adenoma 100 %

CT scan contrast-enhanced CT - adenoma : rapid contrast medium washout - non-adenoma : delayed contrast medium washout 10 mins after administration pf contrast - adenoma : absolute contrast media washout > 50 % ( 100% sensitivity & specificity) if compared with carcinomas, metastasis or pheochromocytoma

CT scan Imaging phenotype does not predict hormone function, it can predict underlying pathology, and surgical resection

MRI Although CT : primary adrenal imaging MRI has advantages in certain clinical situations Several difference MRI 1. - conventional spin-echo MRI - was the first - T1 and T2 - distinguish benign adenomas from malignancy and pheochromocytoma

MRI 2- gadolinium-DPTA-enhanced MRI - adenoma : mild enhancement and rapid washout of contrast - malignancy : rapid and marked enhancement and a slower washout pattern

MRI 3 - Chemical shift imaging (CSI) - lipid sensitive imaging - principle : hydrogen protons in water, lipid molecules - chemical shift technique 1. in-phase : water & lipid are aligned : signal intensity high 2. out of phase : opposite from each other : signal intensity low

MRI Interpretation - benign adrenal cortical adenoma : lose signal on out-of-phase images, but appear relatively bright on in-phase images

Others PET (Positron emission tomography) - fluoro-2-deoxy-D-glucose (FDG) - high sensitivity for detect malignancy - however : 16% benign cortical lesions may have FDG-PET uptake - Metomidate (MTO) PET : lack of MTO – specific to non-adrenal cortical origin (metastasis & pheochromocytoma

Others PET (Positron emission tomography) - FDG-PET and MTO-PET are not recommend (cost and insufficiency data to support their routine use)

Imaging characteristics

Benign adenoma Benign cortical adenoma Round & homogenous density  < 4 cm, unilateral low unenhanced CT attenuate values (<10HU) Rapid contrast washout (10 min) Absolute contrast washout >50% Isointensity with liver on both T-1 & T-2 (MRI) Chemical shift : lipid on MRI

Pheochromocytoma Increase attenuate on nonenhanced CT (>20HU) Increase mass vascularity Delayed contrast washout (<10 cm) Absolute contrast washout <50 % High signal intensity on T-2 MRI Cystic and hemorrhage Variable size

Pheochromocytoma

Adrenocortical carcinoma Irregular shape Inhomogenous density (central necrosis) > 4 cm, unilateral, calcify High unenhanced CT (>20HU) Delayed contrast washout (10 min) Absolute contrast washout < 50 % Hypointensity compared with liver T-1 and high to intermidiateintensity T-2 MRI High standard uptake value (SUV) on FDG-PET-CT study Evidence of local invasion or metas.

Metastasis Irregular, inhomogenous Bilateral High enhanced CT (>20 HU) Enhancement with contrast Delayed contrast washout (10 min) Absolute contrast washout < 50% Isointensity or slightly less intense than liver T-1 , high to intermediate intensity T-2 MRI (represent water increase)

Others Adrenal cysts Adrenal hemorrhage myelolipoma

Fine-needle aspiration biopsy Cannot distinguish a benign adrenal mass from the rare adrenal carcinoma Thus; FNA biopsy - indicated a suspicion of cancer outside the adrenal gland - staging evaluation for a known cancer - not useful routine evaluation

IS IT FUNCTIONAL? 6% - 20% of adrenal incidentalomas have hormonal abnormality. Hormonal hypersecretion is most likely in mass are at least 3 cm in diameter. Occurs mostly within the first 3 years after diagnosis.

85 percent of the masses were non fuctioning. 9 percent secreted sufficient cortisol to produce subclinical Cushing's syndrome . 4 percent were pheochromocytomas (less than half caused hypertension) . 2 percent were aldosteronomas .

A careful personal and family history, review of systems, PE. At minimum for the following condition. Pheochromocytoma Cushing syndrome (including subclinical disease) Primary aldosteronism (only if hypertensive)

Pheochromocytoma 3-10% of adrenal incidentalomas prove to be pheochromocytomas. Screening for pheochromocytoma is mandatory in all case. Because high rate morbidity and mortality. It is symptomatic up to 15% of case.

Screening test is measurement of plasma free metanephrines or 24 hr urine metanephrine . Plasma free metanephrines is 99% sensitive. Not very specific 85-89%

Cushing syndrome 5-20% of pt with adrenal incidentaloma are report to have subclinical Cushing syndrome. Subclinical Cushing's syndrome mild hypercortisolism without clinical manifestations of Cushing's syndrome . most frequent hormonal abnormality detected in patients with adrenal incidentalomas .

Lack of supression interfering condition. In 2002 ,a National institutes of Health consensus panel recommened a 1 mg over night dexamethasone supression test. Lack of supression interfering condition. Decrease dexamethason absorbtion. Drug : barbiturate, phenyltoin, carbamazepine, rifampicin. Increase concentration of corticosteroid-binding globulin Pseudo Cushhig state

Hormonal evaluation in subclinical Cushing's syndrome showed the following Low baseline secretion of corticotropine (ACTH) in 79 percent Lack of suppressibility of cortisol secretion after 1 mg dexamethasone in 73 percent Supranormal 24-hour urinary cortisol excretion in 75 percent

Disturbed cortisol circadian rhythm in 43 percent Blunted plasma ACTH responses to corticotropin-releasing hormone in 55 percent

If the post-overnight DST Then baseline serum ACTH, two-day high-dose DST is indicated to confirm the excess hormone secretion.

Primary Hyperaldosteronism 1.6-3.8% of adrenal incidentalomas. Pt with hypertension should be evaluated for primary aldosteronism. Hypokalemia suggest aldosteronism. Normal K not exclude. The best screening test is the ratio of the plasma aldosterone to the plasma renin activity.

Management of adrenal incidentaloma

Clinical and CT apperance True cyst adrenolipoma Metastasis carcinoma FNAB investigation Metastasia CA resect Aspirate? Treatment or F/U Resect if appropriate Repeat CT at 1 yr

Diagnosis unclear BP serumK Catecholamine Overnigth 1 gm DST Urine 17 OHCS 17KS Non fuctioning functioning FNA < 6 CM > 6CM Adenal tissue resect resect Repeat CT at 2,8,18 mo

subclinical Cushing's syndrome and unilateral adrenalectomy? absence of a prospective randomized study candidates for adrenalectomy. who have attributable to excess glucocorticoid secretion (eg, recent onset of hypertension, diabetes, obesity, and low bone mass) lack of suppression to both an overnight DST) and a two-day high-dose DST.

Bilateral adrenal masses The management of bilateral adrenal masses is different from that for unilateral masses.

SUMMARY All patients should be evaluated for subclinical hormonal hyperfunction and cancer. History and physical examination are important in the initial assessment.

Benign cortical adenoma. A homogeneous adrenal mass <4 cm in diameter, with a smooth border, and an attenuation value <10 HU on unenhanced CT, and rapid contrast medium washout (eg, >50 percent at 10 minutes)

The imaging suggest adrenal carcinoma or metastases include: irregular shape. inhomogeneous density. high unenhanced CT attenuation values (>20 HU), delayed contrast medium washout (eg, <50 percent at 10 minutes), diameter >4 cm, and tumor calcification. Other characteristics are described above.

Pheochromocytoma should be excluded by measuring 24-hour urinary fractionated metanephrines and catecholamines. Subclinical Cushing's syndrome should be ruled out by the 1-mg overnight dexamethasone. primary aldosteronism. should be screen in patient is hypertensive by a plasma aldosterone-to-plasma renin activity ratio and plasma potassium concentration

Recommend surgery: pheochromocytoma, aldosteronoma. Suggest surgery for patients with subclinical Cushing's syndrome who are younger and who have disorders potentially attributable to autonomous glucocorticoid secretion.

Suggest surgery for patients with adrenal masses greater than 4 cm in diameter . If there is evidence of metastasis and after excluding pheochromocytoma with biochemical testing, suggest performing a diagnostic CT-guided FNA biopsy .

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