Adrenal gland and paraganglia
Adrenocortical adenoma
Non-functioning adenomas / nodules

Author: Carmen Perrino, M.D. (see Authors page)

Editor: Debra Zynger, M.D.

Revised: 20 January 2016, last major update August 2014

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Non-functioning adenomas
Definition / General
  • Adrenal incidentaloma: adrenal masses discovered incidentally with imaging procedures performed in the work-up of clinical symptoms unrelated to adrenal disease (Endocrinol Metab (Seoul) 2013;28:20)
  • Benign adrenal cortical adenoma (ACA) is most common type of incidentally discovered adrenal mass, which is what this review will focus on
  • Metastases (especially from lung and breast) are second most common incidentally discovered adrenal mass
Terminology
  • Adrenal incidentaloma (described above)
  • Tumors may be adrenal cortical adenoma (ACA) or adrenal cortical carcinoma (ACC)
Epidemiology
  • Incidence has been increasing due to increasing utilization of imaging, estimated 0.2 to 0.4% in general population (Endocrinol Metab (Seoul) 2014;29:5)
  • Incidence increases with age, reported in <1% of patients under 30 years and in up to 7% of patients over 70 years (Indian J Endocrinol Metab 2013;17:S59)
  • Slight female predominance
  • Average age early 60s
Sites
  • Incidental ACA can arise from all 3 layers of the adrenal cortex
  • However, any adrenal lesion incidentally discovered can be called an "incidentaloma," and therefore may arise from adrenal cortex or medulla
Pathophysiology
Etiology
  • May be due to a variety of adrenal lesions including ACA (most common), ACC, pheochromocytoma, metastases, ganglioneuroma, myelolipoma, lipoma, benign cyst (Indian J Endocrinol Metab 2013;17:S59)
Clinical Features
  • Usually no detectable clinical features
  • Approximately 10% of ACAs may be functional, with patients having subclinical cortisol/aldosterone/sex hormone production (Endocrinol Metab (Seoul) 2013;28:20)
Diagnosis
  • Adrenal lesion discovered with imaging used to work-up unrelated clinical symptoms, therefore usually no detectable hormonal abnormalities or clinical symptoms (Pol J Radiol 2013;78:47)
  • Work-up may include observation (serial imaging, laboratory tests) or fine needle aspiration/core biopsy (rarely indicated, mainly for ruling out non-adrenal metastases) (J Clin Endocrinol Metab 2010;95:4106)
Laboratory
  • Battery of endocrine tests usually within normal limits, although a minority may have subclinical hormone production with slight abnormalities
    • Suggested endocrine tests include: dexamethasone suppression test, ACTH levels, plasma free metanephrine/normetanephrine, 24 hour total urinary metanephrines, ratio plasma aldosterone:plasma renin (Indian J Endocrinol Metab 2013;17:S59)
  • Adrenal tumors in patients with previously unrecognized clinical symptoms attributable to the tumor are not considered incidentalomas (Pol J Radiol 2013;78:47)
Radiology Description
  • Un-enhanced computed tomography (CT) densitometry: high intracytoplasmic lipid and low Hounsfield unit (HU) measurement (< 10 HU) favors adenoma (Endocrinol Metab (Seoul) 2013;28:20)
    • Initial imaging modality of choice in work-up of adrenal incidentaloma
  • Delayed-contrast enhanced CT: fast enhanced washout (> 50% at 10 minutes after injection of contrast medium consistent with benign) (Endocrinol Metab (Seoul) 2013;28:20)
Prognostic Factors
Case Reports
Treatment
  • Goal is to identify subclinical cortisol or aldosterone secreting lesions, identify pheochromocytoma, resect non-functional lesions suspicious for ACC on imaging (BMC Surg 2013;13:57)
  • Most adrenal lesions >4 cm should be removed regardless of imaging findings because of increased risk of ACC (BMC Surg 2013;13:57)
  • If large (>4 cm), functional, worrisome characteristics on imaging: surgical resection
  • If small (<4 cm), non-functional, benign features on imaging: clinical observation and follow-up (exact guidelines not well established)
    • Repeat laboratory studies to assess functional status, yearly for 4 years
    • Repeat CT scan 6-12 months after diagnosis, if no increase in size then no further follow-up needed
Clinical Images

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Adenoma-massive

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Ganglioneuroma

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Hemangioma

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Hemangioma-cavernous


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Myelolipoma

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Oncocytic neoplasm

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Oncocytoma

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Schwannoma

Gross Description
  • Round to oval
  • Smooth, well-delineated margin
  • Average size 2-3 cm, typically measuring up to 5-6 cm
Gross Images

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Adenoma

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Adenomatoid tumor

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Ganglioneuroma

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Hemangioma


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Myelolipoma

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Oncocytic Neoplasm

Micro Images

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Giant non-functional adrenal adenoma

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Adenomatoid tumor

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Ganglioneuroma

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Hemangioma-cavernous


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Myelolipoma

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Oncocytic neoplasm

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Oncocytoma


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Schwannoma

Cytology Description
Negative Stains
  • EMA, CEA, B72.3, S100, chromogranin (stains adrenal medulla), vimentin, carbonic anhydrase IX (CAIX)
Differential Diagnosis