ADRENAL INCIDENTALOMAS Societatea Endocrinologilor din Republica Moldova Dumitru

ADRENAL INCIDENTALOMAS Societatea Endocrinologilor din Republica Moldova Dumitru Harea Asist. univ.

https: //www. guideline. gov 2012

“Medical science has made such tremendous progress that there is hardly a healthy human left. ” Aldous Huxley

• An adrenal incidentaloma is an adrenal mass detected on imaging not performed for suspected adrenal disease. • The imaging study is not done for symptoms related to adrenal hormone excess or an otherwise suspected adrenal mass, but rather for the evaluation of symptoms that are not obviously related to an adrenal problem, such as abdominal or back pain or kidney stones. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. 2016. www. eje-online. org

Are outside the definition of an adrenal incidentaloma: • screening imaging in patients with a hereditary syndrome leading to adrenal tumors • adrenal masses discovered on an imaging study performed during tumor evaluation for extra-adrenal malignancies (‘tumor staging’ or follow-up) Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. 2016. www. eje-online. org

Size of adrenal incidentalomas • have not considered adrenal incidentalomas smaller than 1 cm. • perform additional diagnostic work-up only in lesions ≥ 1 cm unless clinical signs and symptoms suggestive of adrenal hormone excess are present. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. 2016. www. eje-online. org

• Bening • Malignant From the: • Adrenal cortex • Medulla • Extra-adrenal origin • Unilateral • Bilateral Hormonally • Active • inactive Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. 2016. www. eje-online. org

incidence and prevalence • Autopsy studies suggest a prevalence of clinically unapparent adrenal masses of around 2% (range 1. 0– 8. 7%), which increases with age. • Radiological studies report a frequency of around 3% in the age of 50 years, which increases up to 10% in the elderly. In childhood, adrenal incidentalomas are extremely rare. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. 2016. www. eje-online. org

adrenal incidentaloma - frequency of the different underlying tumor types Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. 2016. www. eje-online. org

adrenal incidentaloma in adults Adrenal incidentaaloma in adulst – management recommendations by the Polish Society of Endocrinology. Endokrynologia Polska Vol 67, Nr 2/2016

For diagnostic and therapeutic purposes, in patients with incidentaloma, two major goals should be set forward: • To establish if an adrenal mass is benign or malignant (The diagnosis of all adrenocortical carcinoma cases). • The diagnosis of all hormonally active tumours. Adrenal incidentaaloma in adulst – management recommendations by the Polish Society of Endocrinology. Endokrynologia Polska Vol 67, Nr 2/2016

Which imaging examinations should be performed in adrenal incidentaloma patients? • The main goal of imaging examinations is the differentiation between adenomas and “non-adenomas” which require further diagnostic steps. • For the differentiation of malignant from benign adrenal tumors, there are three main imaging techniques in current use: § computed tomography (CT), § magnetic resonance imaging (MRI) § positron emission tomography with 18 F-2 -deoxy-d-glucose (mostly combined with CT; FDGPET/CT). Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. 2016. www. eje-online. org Adrenal incidentaaloma in adulst – management recommendations by the Polish Society of Endocrinology. Endokrynologia Polska Vol 67, Nr 2/2016

• CT and MRI are techniques mainly aiming to identify benign lesions, therefore representing tools designed for the exclusion of adrenal malignancy. • Conversely, FDG-PET/CT is mainly used for the detection of malignant disease Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. 2016. www. eje-online. org

Unenhanced adrenal CT • First-line imaging examination in adrenal tumour diagnostics - unenhanced high-resolution CT (layers < 3 mm). • Advantage: low price, short duration, and no necessity to use a contrast medium. • It is possible to asses such tumour features as the size (additionally, in further tests it is possible to assess its growth dynamics), shape, radiation attenuation coefficient (in Hounsfield units [HU]), and structure homogeneity (including calcifications, necrotic areas). Adrenal incidentaaloma in adulst – management recommendations by the Polish Society of Endocrinology. Endokrynologia Polska Vol 67, Nr 2/2016

Unenhanced adrenal CT • The basic examination interpretation: values smaller or equal to +10 HU represent a high lipid content and are typical for adenomas. Further imaging tests are usually not necessary. • If the values exceed 30 HU it may suggest a pheochromocytoma or a malignant tumour (ACC or adrenal metastases). Adrenal incidentaaloma in adulst – management recommendations by the Polish Society of Endocrinology. Endokrynologia Polska Vol 67, Nr 2/2016

Adrenal CT — examination with contrast medium administration (washout assessment) • In numerous health centres it constitutes a first-line examination in adrenal tumour diagnosis. It is also performed when the unenhanced CT is ambiguous in terms of the tumour nature (adenoma or “nonadenoma”), primary localisation (e. g. liver hilar tumour, pancreatic tumours), and infiltration of the surrounding tissues. • In comparison to unenhanced CT, on the basis of this examination it is possible to assess the absolute and relative washout values features of the surrounding tissues infiltration, as well as the presence of liver metastases. • Basic interpretation: adenomas are characterised by faster washout – the attenuation coefficient returns quickly to basic values. Adrenal incidentaaloma in adulst – management recommendations by the Polish Society of Endocrinology. Endokrynologia Polska Vol 67, Nr 2/2016

Adrenal MRI contrast medium) (most frequently without • It is performed when unenhanced adrenal CT is ambiguous in terms of the tumour character. • It is recommended if iodine-containing contrast medium administration is contraindicated. • MRI without contrast medium is the method of choice in adrenal tumours during pregnancy. Adrenal incidentaaloma in adulst – management recommendations by the Polish Society of Endocrinology. Endokrynologia Polska Vol 67, Nr 2/2016

Adrenal MRI contrast medium) (most frequently without • MRI is characterised by high sensitivity in the diagnosis of lipid-poor adenomas (90%). • MRI allow for the assessment of lipid content in the adrenal tumours with higher sensitivity than unenhanced CT. • Basic interpretation: in the majority of cases, visual assessment (qualitative) allows us to distinguish lipid-containing tumours from other lesions. • In fact, myelolipomas are easy to diagnose in MRI Adrenal incidentaaloma in adulst – management recommendations by the Polish Society of Endocrinology. Endokrynologia Polska Vol 67, Nr 2/2016

Characteristic features of adrenal tumours in imaging examinations Adrenal incidentaaloma in adulst – management recommendations by the Polish Society of Endocrinology. Endokrynologia Polska Vol 67, Nr 2/2016

Adrenal biopsy • Indications - are very limited. • May be considered in selected patients with suspected adrenal metastases of an unknown primary localisation, lymphoma, or adrenal tuberculosis if the diagnosis would change the course of treatment. • A suspected pheochromocytoma or ACC constitute contraindication for biopsy. Adrenal incidentaaloma in adulst – management recommendations by the Polish Society of Endocrinology. Endokrynologia Polska Vol 67, Nr 2/2016

Surgery

What are the indications for the surgical treatment of an incidentaloma? oncological recommendation • imaging examinations suggest a malignant lesion • Additional criteria include: • Tumour size (diameter > 5 cm); • Fast or very fast tumour growth endocrinological recommendations • with confirmed hormonal activity • All cases of a suspected pheochromocytoma • ACTH — independent Cushing’s syndrome. • Primary hyperaldosteronism. • Hyperandrogenic syndrome associated with adrenal tumour

Follow-up of patients not undergoing adrenal surgery after initial assessment Imaging tests • Basic tests monitoring tumour size: US of the abdominal cavity and noncontrast adrenal CT. • US - larger than 3 cm in diameter localised in the right adrenal gland. • Tumor ≤ 3 (4) cm in diameter and clear benign features - every 12 months. • larger tumours, or those with a less characteristic phenotype - every 3– 6 months within the first year, and later every 12 months. • not oncologically suspicious and is stable, monitoring may be ceased after four years - the risk of malignant transformation is practically non-existent.

Follow-up of patients not undergoing adrenal surgery after initial assessment Hormonal tests • selective hormonal assessment every 12 months. • new clinical signs of endocrine activity appear or there are comorbidities (e. g. worsening of hypertension and type 2 diabetes, obesity, osteoporosis) • Tumours larger than 3 cm are more frequently hormonally active than smaller lesions • The risk of an excessive hormonal secretion by an adrenal tumour reaches a plateau after 3– 5 years; further control is not necessary. • The risk of developing pheochromocytoma in an initially unsuspicious adrenal tumour is very low

Patients with bilateral adrenal incidentalomas • each adrenal lesion - the same imaging protocol as for unilateral adrenal masses to establish if either or both are benign or malignant. • clinical and hormonal assessment, indication for surgery and follow-up identical with unilateral adrenal incidentaloma • 17 -hydroxyprogesterone - to exclude congenital adrenal hyperplasia • testing for adrenal insufficiency - if suspected on clinical grounds or if imaging suggests bilateral infiltrative disease or hemorrhages.

Adrenal incidentalomas in young patients in children, adolescents, pregnant women and adults <40 years: • urgent assessment of an adrenal mass - higher likelihood of malignancy • use of MRI rather than CT

Conclusion Adrenal incidentaloma is an abnormal lesion ≥ 1 cm in diameter, found incidentally during imaging examination. Every focal lesion in adrenals found in US requires confirmation by CT or MRI. The main goal of imaging tests is the differentiation between adenomas and “nonadenomas” requiring further diagnosis for ACC, adrenal metastasis or pheochromocytoma. Basic imaging tests include: unenhanced adrenal CT, adrenal CT with contrast medium (washout assessment), and adrenal MRI (most frequently without contrast medium). In all adrenal incidentaloma patients, notwithstanding the clinical picture and concomitant diseases, tests for pheochromocytoma and hypercortisolism are recommended. Tests for primary hyperaldosteronism are indicated in patients with diagnosed hypertension and hypokalaemia.

Conclusion Adrenal incidentaloma is an abnormal lesion ≥ 1 cm in diameter, found incidentally during imaging examination. Every focal lesion in adrenals found in US requires confirmation by CT or MRI. Control tests (imaging and laboratory) in patients not qualified for surgical treatment should be planned individually taking into considerations such features as: tumour size and growth dynamics, clinical manifestations, hormonal test results, and concomitant diseases.

Conclusion Adrenal incidentalomas with malignancy features in the imaging test (oncological recommendations), as well as those with diagnosed hormonal activity (endocrinology recommendations), require surgical treatment. The principal surgical procedure is videoscopic/laparoscopic adrenalectomy. Hormonally active adrenal tumours (especially suspected pheochromocytoma) require pharmacological treatment prior to surgery. Control tests (imaging and laboratory) in patients not qualified for surgical treatment should be planned individually taking into considerations such features as: tumour size and growth dynamics, clinical manifestations, hormonal test results, and concomitant diseases.