K. Poppe Endocrinologie Adrenal masses K. Poppe Endocrinologie

Incidentaloma

Serendipitiously discovered by radiologic examinations (CT / MRI) Definition Mass lesion > 1 cm Serendipitiously discovered by radiologic examinations (CT / MRI)

Prevalence

Incidentaloma’s are bilateral in 10-15%

Work-up

Q1: Benign vs Malign?

W. Young NEJM 2007

Evaluate for malignancy Size and imaging characteristics (imaging phenotype) The maximum diameter is predictive of malignancy Adenocortical carcinomas - significantly association with mass size 90% > 4 cm - sensitivity 93 % - specificity 76 % The National Italian Study Groups

Benign 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

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 intermidiate intensity T-2 MRI Evidence of local invasion or Mets

MRI has advantages in certain situations: 1- Conventional spin-echo MRI - T1 and T2 - distinguish benign from malignancy and pheochromocytoma 2- Gadolinium-DPTA-enhanced MRI - adenoma : mild enhancement and rapid washout of contrast - malignancy : marked enhancement and a slower washout 3- Chemical shift imaging (CSI) - in-phase : water & lipid are aligned: signal intensity high - out of phase : opposite from each other: signal intensity low

Others Adrenal cysts Adrenal hemorrhage Myelolipoma

Others PET (Positron Emission Tomography) - fluoro-2-deoxy-D-glucose (FDG) - high sensitivity for detecting malignancy - however : 16% benign cortical lesions may have FDG-PET uptake - metomidate (MTO) : lack of MTO – specific to non-adrenal cortical origin (metastasis & pheochromocytoma) FDG-PET and MTO-PET are not routinely recommend ---> lack of data

Fine-needle aspiration biopsy Cannot distinguish a benign adrenal mass from adrenal carcinoma, but between an adrenal and a metastatic tumor. sensitivity of 81–96 % and a specificity of 99–100 % inconclusive biopsies were reported in 6–50 % Complications of FNAB is ranging from 2.8-14 % (pneumothorax, bleeding, infection, and pancreatitis). FNAB is useful in selected cases only: in patients with a history of an underlying extra-adrenal malignancy In case of inconclusive results of imaging tests if there is suspicion of a rare tumor (infiltrative, infection) ! It is mandatory to biochemically exclude a pheochromocytoma before FNAB is performed !

Q2: Functional ?

24-25 % = secreting

Hormonal hypersecretion is most likely if mass is ≥ 3 cm in diameter Occurs mostly within the first 3 years after diagnosis

Cushing’s disease 3 major causes: Cushing dsease 68 % Adrenal origin 20 % Para Neoplastic 12 %

Cushing

Cushing's syndrome. Howlett TA et al. Clin Endo Metab 1985 Symptoms Cushing's syndrome. Howlett TA et al. Clin Endo Metab 1985

Cushing’s syndrome 5-20 % of pt with adrenal incidentaloma are reported to have subclinical Cushing syndrome Subclinical Cushing's syndrome mild hypercortisolism without clinical manifestations of Cushing's syndrome

Hormonal evaluation Cushing's syndrome Lack of suppressibility of cortisol after 1 mg overnight dexamethasone intake (NL: cortisol < 1.8 mcg/dL ) Supranormal 24-hour urinary cortisol excretion Disturbed cortisol circadian rhythm (midnight salivary cortisol) Low baseline secretion of ACTH Confirmatory (second line) tests: Blunted plasma ACTH responses to CRH Overnight 8 mg dexamethasone

Diagnosis - Cushing

Pheochromocytoma Screening for pheochromocytoma is mandatory in all case because high rate morbidity and mortality It is symptomatic up to 15% of case

Pheo: Signs & Symptoms PHEO is easily suspected in someone with paroxysmal hypertension, resistant hypertension & in the presence of the so-called “Spells” the “5 P’s” Pressure (HTN) 90% Pain (Headache) 80% Perspiration 71% Palpitation 64% Pallor 42% Paroxysms (the sixth P!)

Plasma free metanephrines Screening test is measurement of plasma free or 24 hrs urines metanephrines Plasma free metanephrines sensitive 99 % specific 85-89 %

Confirmatory test

Primary Hyperaldosteronism (Conn’s syndrome) 1.6-3.8 % of adrenal incidentalomas Pts with hypertension should be evaluated Hypokalemia suggests hyperaldosteronism (~ 40 %), this means that a normal K+ doesn’t exclude it ! The best screening test is the ratio of the plasma aldosterone : renin activity (> 20)

Confirmatory test Saline infusion test — IV 2l NaCl 0,9 % / 4h (from 8 AM to noon) the PAC will fall below 5 ng/dL (139 pmol/L) in normal subjects, whereas values above 10 ng/dL (277 pmol/L) are consistent with primary aldosteronism. Ahmed AH et al. Seated saline suppression testing for the diagnosis of primary aldosteronism: JCEM 2014

Management of adrenal incidentaloma

Natural evolution Some adrenal incidentalomas followed for an average of 4 years can: increase (range 0–26%) decrease (~ 4%) and/or can develop hyperfunction (range 0–11%) EJE (2015) 173, 275–282

W.Young NEJM 2007;356:601-10

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

SUMMARY

Benign versus Malign ? Functional ? Bilateral ≠ Unilateral

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