the Management of Adrenal Lesions

Section 1: General remarks:

·       We recommend that patients with adrenal incidentalomas are discussed in a multidisciplinary expert team meeting, (a radiologist, an endocrinologist, and a surgeon), if at least one of the following criteria is met: 1) Imaging is not consistent with a benign lesion, (2) there is evidence of hormone excess (including mild autonomous cortisol secretion [MACS] in patients with clinically relevant comorbidities potentially attributable to cortisol), (3) adrenal surgery is considered and/or (4) evidence of significant tumor growth during follow-up imaging, (Good practice statement).

Section 2: Assessment of the risk of malignancy:

·       We recommend using CT as the first imaging modality if not yet performed to establish with the highest possible certainty if an adrenal mass is benign or malignant at the time of initial detection, (Strong recommendation, moderate certainty evidence, ⁽¹⁾).

·       We advise that if the CT is consistent with a benign adrenal mass, no further imaging is required, (Conditioned recommendation, moderate certainty evidence, ⁽¹⁾).

·       We advise performing an immediate additional imaging, if CT is equivocal with a tumor size < 4 cm, and the results of the hormonal work-up do not indicate significant hormone excess. Alternatively, interval imaging in 12 months by CT (or MRI) could be performed, (Conditional recommendation, very low certainty evidence, ⁽¹⁾).

·       If the adrenal mass is ≥ 4 cm and CT suggests that there is a relevant risk that this lesion is malignant, we advise discussing such cases in a multidisciplinary team meeting prior to surgery, (Good Practice Statement).

·       We suggest completely staging the patient (including at least thoracic CT and/or FDG-PET/CT, (Conditional recommendation, very low certainty evidence, ⁽¹⁾).

·       We recommend against the use of an adrenal biopsy in the diagnostic work-up of patients with adrenal masses unless there is a history of extra-adrenal malignancy, (Strong recommendation, moderate certainty evidence, ⁽¹⁾).

·       We advise measurement of sex steroids and precursors of steroidogenesis (ideally using multi-steroid profiling by tandem mass spectrometry) in patients in whom by imaging or clinical features an adrenocortical carcinoma is suspected, (Conditional recommendation, low certainty evidence, ⁽¹⁾).

Section 3: Assessment for hormone excess:

•   We recommend that patients with adrenal incidentalomas undergo a 1-mg overnight dexamethasone suppression test to exclude autonomous cortisol secretion, (Strong recommendation, moderate certainty evidence, (1)).

•   We recommend using post dexamethasone serum cortisol levels ≤50 nmol/L (≤1.8 µg/dL) as a diagnostic criterion for the exclusion of autonomous cortisol secretion, (Strong recommendation, low certainty evidence, ⁽¹⁾).

•   We recommend that in patients without signs and symptoms of overt Cushing’s syndrome a post-dexamethasone serum cortisol concentration above 50 nmol/L (> 1.8 µg/dL) should be considered as MACS. In these patients, we recommend that ACTH-independency should be confirmed, (Strong recommendation, low certainty evidence, ⁽¹⁾).

•   We recommend against considering patients with MACS (per definition without specific clinical signs of Cushing’s syndrome) as being at high risk for development of overt Cushing’s syndrome, (Strong recommendation, moderate certainty evidence, (1)).

•   We recommend screening patients with adrenal incidentaloma and MACS for hypertension and type 2 diabetes mellitus, (Strong recommendation, low certainty evidence, (1)).

•   We recommend discussing the option of surgery with the patient who has MACS in addition to relevant comorbidities and a unilateral adrenal mass. The proposal to perform surgery should be established within an expert multi-disciplinary group, (Strong recommendation, very low certainty evidence, (1)).

•   We advise excluding pheochromocytoma by measurement of plasma free metanephrines or urinary fractionated metanephrines in all patients with adrenal lesions, (Conditional recommendation, moderate certainty evidence, (1)).

•   We advise to measure VMA in urine to diagnose pheochromocytoma as an alternative to metanephrine, (Good practice statement).

•   In patients with concomitant hypertension or un-explained hypokalemia, we recommend use of the aldosterone/renin ratio to evaluate primary aldosteronism, (Strong recommendation, moderate certainty evidence, (1)).

Section 4: Surgical treatment:

•   We recommend adrenalectomy as the standard of care for unilateral adrenal tumors with clinically significant hormone excess. In patients with MACS, surgery can be considered in patients with relevant co-morbidities, (Strong recommendation, moderate certainty evidence, (1)).

•   We recommend against performing surgery in patients with an asymptomatic, non-functioning unilateral adrenal mass and obvious benign features on imaging studies, (Strong recommendation, low certainty evidence, (1)). If surgery is indicated for a benign adrenal mass causing hormone excess (including MACS), we advise that a minimally invasive approach is used, (Conditional recommendation, very low certainty evidence, (1)).

•   We advise performing minimally invasive adrenalectomy by an expert high-volume adrenal surgeon in patients with unilateral adrenal masses with radiological findings suspicious of malignancy and a diameter ≤6 cm, but without evidence of local invasion, (Conditional recommendation, very low certainty evidence, (1)).

•   We advise open adrenalectomy for unilateral adrenal masses with radiological findings suspicious of malignancy and signs of local invasion, (Conditional recommendation, very low certainty evidence, (1)).

•   We recommend perioperative glucocorticoid treatment at surgical stress doses in all patients undergoing surgery and a preoperative morning serum cortisol >50 nmol/L (1.8 µ/dL) after a 1 mg overnight dexamethasone test, (Strong recommendation, moderate certainty evidence, (1)).

•   We advise that patients with MACS (similarly to patients with adrenal Cushing's syndrome) that underwent surgery be followed by an endocrinologist until recovery of hypothalamic-pituitary-adrenal axis function has been documented, (Conditional recommendation, low certainty evidence, (1)).

Section 5: Follow-up of patients not undergoing adrenal surgery after initial assessment:

•   We advise against further imaging during follow-up in patients with an adrenal lesion with clear benign features on imaging studies, (Conditional recommendation, moderate certainty evidence, (1)).

•   In patients with an indeterminate adrenal mass (by imaging), opting not to undergo adrenalectomy following initial assessment, we advise repeating CT or MRI after 6-12 months to exclude significant growth. We advise surgical resection if the lesion enlarges by more than 20% in maximum diameter, (Conditional recommendation, very low certainty evidence, (1)).

•   We recommend against repeated hormonal work-up in patients with hormonal work-up results within the reference range at initial evaluation unless new clinical signs of endocrine activity appear, (Strong recommendation, low certainty evidence, (1)).

•   In patients with MACS, who do not undergo an adrenalectomy, we recommend only annual reassessment of comorbidities potentially attributable to cortisol, (Strong recommendation, low certainty evidence, (1)).