The Adrenal Incidentaloma :The Evidence Based Management Algorithm

1. The Adrenal Incidentaloma The Evidence
Based Management Algorithm
Dr Amit Agrawal, MCh
All India Institute of Medical Sciences, Bhopal

2. Adrenal Incidentaloma
 Definition
 “An adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for
suspected adrenal disease”
 Autopsy-2.3%
 Abdominal computed tomography scan-0.5-2%
 Advances in imaging (including CT, MRI, US) may reveal even higher numbers
• Fassnacht M, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline
in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016 Aug;175(2):G1-G34.
• Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence and natural history of adrenal incidentalomas. Eur J
Endocrinol. 2003 Oct;149(4):273-85.

3. Adrenal Incidentalomas: Key Questions
•What is the prevalence?
•Benign versus malignant, functional versus non-functional?
•What investigations?
•How to confirm the diagnosis?
•What treatment medical or surgical?
•When to operate and how to operate?
•How to follow benign non-functioning incidentalomas?
•Special considerations (elderly versus age <40 years)
• Fassnacht M, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in
collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016 Aug;175(2):G1-G34.
• Lee JM, et al; Korean Endocrine Society, Committee for Clinical Practice Guidelines. Clinical Guidelines for the Management of
Adrenal Incidentaloma. Endocrinol Metab (Seoul). 2017 Jun;32(2):200-218.

4. Diagnostic Evaluation
 Detailed clinical and endocrine Evaluation
 Hormonally active or nonfunctioning?
 Malignant or benign?
 Goal: determine if patient has pheochromocytoma, subtle glucocorticoid excess, primary aldosteronism,
virilizing or feminizing tumors.
 History of or episodic hypertension, tachycardia, profuse sweating
 Hirstuism, striae, central obesity, gynecomastia
 Radiological investigations (CT, MRI, USG)

5. Adrenal imaging (CT, MRI and USG)
 For the differentiation of malignant from benign adrenal tumors
 CT and MRI are techniques to identify benign lesions
 FDG-PET/CT for the detection of malignant disease (positron emission tomography with 18F-2-deoxy-D-
glucose)
 Ultrasound
◦ Operator dependent
◦ Compounding factors: obesity, overlying gas
◦ Decreased sensitivity compared to CT/MRI
 Blake MA, et al. Distinguishing benign from malignant adrenal masses: multi-detector row CT protocol with 10-minute delay. Radiology 2006 238 578-585.
 Ilias I, et al. The optimal imaging of adrenal tumours: a comparison of different methods. Endocrine-Related Cancer 2007 14 587-599.
 Mackie GC, et al. Use of [18F]fluorodeoxyglucose positron emission tomography in evaluating locally recurrent and metastatic adrenocortical carcinoma.
Journal of Clinical Endocrinology and Metabolism 2006 91 2665-2671
 Groussin L, et al. 18F-Fluorodeoxyglucose positron emission tomography for the diagnosis of adrenocortical tumors: a prospective study in 77 operated
patients. Journal of Clinical Endocrinology and Metabolism 2009 94 1713-1722

6. FNAC
CT or USG guided
◦ Sensitivity 81-100%
◦ Specificity 83-100% to diagnose malignancy
◦ Higher sensitivity and accuracy if mass > 3 cm or needle > 19 gauge
Risk of needle-track metastases from FNA biopsy of adrenal carcinoma not known
Fassina AS, Borsato S, Fedeli U. Fine needle aspiration cytology (FNAC) of adrenal masses. Cytopathology. 2000
Oct;11(5):302-11. doi: 10.1046/j.1365-2303.2000.00261.x. PMID: 11014657.

7. Assessment of the risk of malignancy
 At the time of initial detection whether an adrenal mass is benign or malignant
 Initial imaging i.e.. non-contrast CT show a homogeneous and lipid-rich and therefore benign adrenal
mass (Hounsfield units <10) smaller than 4 cm, no further imaging
Fassnacht M, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice
Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016
Aug;175(2):G1-G34.

8. Assessment for hormone excess
 Careful clinical examination for symptoms and signs of adrenal hormone excess
 1 mg overnight dexamethasone suppression test to exclude cortisol excess in all patients
 Investigations to exclude pheochromocytoma (plasma-free metanephrines or urinary fractionated
metanephrines)
 Concomitant hypertension or unexplained hypokalemia: Aldosterone/renin ratio to exclude primary
aldosteronism
 Sex hormones and steroid precursors where clinical or imaging features suggest adrenocortical
carcinoma
Fassnacht M, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice
Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016
Aug;175(2):G1-G34.

9. Surgical treatment
 An asymptomatic, non-functioning unilateral adrenal mass and obvious benign features on imaging studies- no
surgical intervention
 Adrenalectomy as the standard of care for unilateral adrenal tumours with clinically significant hormone excess
 Laparoscopic adrenalectomy-unilateral adrenal masses with radiological findings suspicious of malignancy and
a diameter <6 cm, but without evidence of local invasion
 Open adrenalectomy for unilateral adrenal masses with radiological findings suspicious of malignancy and
signs of local invasion
 An individualized approach in patients that do not fall in one of the above-mentioned categories (©OOO).
 Perioperative glucocorticoid treatment to manage major surgical stress doses as recommended
Fassnacht M, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical
Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J
Endocrinol. 2016 Aug;175(2):G1-G34.

10. Patients not undergoing adrenal surgery
 Most adrenal lesions remain stable, but 5-25% enlarge and 3-4% decrease in size
 Imaging – if not excised, lesion should be re-evaluated with CT in 6-12 months
 An adrenal mass <4 cm with clear benign features on imaging – no further imaging studies
 Indeterminate adrenal mass on imaging opting not to undergo adrenalectomy - repeat non-contract CT
or MRI after 6-12 months to follow the growth
 If the lesion enlarges by more than 20% -surgical resection
Fassnacht M, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice
Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016
Aug;175(2):G1-G34.

11. Patients with bilateral adrenal
incidentalomas
 Each adrenal lesion needs to be assessed and managed as for unilateral adrenal masses (to establish
whether these are benign or malignant)
Fassnacht M, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice
Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016
Aug;175(2):G1-G34.

12. Young or elderly patients
 Urgent assessment of an adrenal mass in children, adolescents, pregnant women and adults <40 years
of age because of a higher likelihood of malignancy.
 Preferred use of MRI for imaging
Fassnacht M, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice
Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016
Aug;175(2):G1-G34.

13. History of extra-adrenal malignancy
 Measurement of plasma or urinary metanephrines to exclude pheochromocytoma
 Additional hormonal work-up based on an individualized approach
 FDG-PET/CT, for further investigations
Fassnacht M, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice
Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016
Aug;175(2):G1-G34.

14. Algorithm for the management of
adrenal incidentalomas
Caiafa RO, Izquierdo RS, Villalba LB, Cerqueda MS, Molina CN. Diagnosis and management of adrenal
incidentaloma. Radiología (English Edition). 2011 Nov 1;53(6):516-30.

15. Summary and conclusions
 Patients with adrenal incidentaloma needs multidisciplinary expert team
approach if
 Imaging is not consistent with a benign lesion
 Evidence of hormone excess
 Evidence of significant tumour growth at follow-up
 Adrenal surgery is considered
Fassnacht M, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice
Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016
Aug;175(2):G1-G34.

16. Summary and conclusions
Need to make all efforts make a decision whether the adrenal mass is benign or malignant to avoid
cumbersome and expensive follow-up imaging in patients with benign disease
In most cases, adrenal incidentalomas are non-functioning adrenocortical adenomas
> 6cm: Excise the lesion
< 4 cm: low risk, unlikely to have malignant potential, not resected
Lesions between 4 and 6 cm, either close follow-up or adrenalectomy
◦ Adrenalectomy strongly considered if rapid growth rate, decreased lipid content on imaging or other imaging
findings suggestive of malignancy
Nonfunctional Lesions
◦ Management is not straightforward
◦ Silent Pheochromocytoma: high risk for hypertensive crisis
◦ Benign vs Malignant is another challenge

17. Summary and conclusions
 The literature on adrenal incidentaloma has increased in the last several years, however there is lack of
lack of controlled studies making diagnostic and treatment strategies difficult.
 Long term large, multicenter cohort study to understand the spectrum and behaviour of adrenal
incidentalomas
 Randomized trials to assess the management protocols