Ch57 adrenal carcinoma, Incidentaloma

• Presence of irregular borders
• Irregular enhancement
• Calcifications
• Necrotic areas with cystic degeneration.
• Mean attenuation on noncontrast CT scan in ACC is significantly higher (39 HU) compared with adenomas (8 HU).

Over 90% of ACCs are greater than 5 cm

Bilateral and bulky disease (>4 cm) is necessary to produce biochemical evidence of adrenal insufficiency. 

More than 50% of newly discovered adrenal lesions in patients with a history of previous malignancy represent metastatic disease; nevertheless, metabolic work-up in these patients is recommended.

Unsuspected adrenal masses greater than 1 cm in diameter identified on cross sectional imaging performed for seemingly unrelated causes

Unenhanced CT -  Low attenuation (<10 HU) on unenhanced CT corresponds to high intracytoplasmic lipid content and is diagnostic for an adrenal adenoma.

Enhanced CT - the diagnostic information that can be obtained from attenuation values of these single-phase studies (approximately 1 minute after the contrast bolus) is limited. 

CT Washout Study - Approximately 30% of adrenal adenomas exhibit an attenuation of greater than 10 HU on unenhanced CT due to their lower lipid content. These “atypical adenomas” are indistinguishable from nonadenomas using noncontrast CT density measurements alone. Fortunately lipid-poor adenomas possess identical properties to lipid-rich adenomas regarding their rapid loss (washout) of enhancement following CT contrast load.

The high diagnostic accuracy provided by biochemical evaluation and cross-sectional radiographic imaging of adrenal incidentalomas limits the indications for the routine use of functional imaging.

Radiolabeled cholesterol analogue 131I-6β-iodomethyl-norcholesterol (NP59) can help determine whether or not an adrenal lesion originated in the adrenal cortex or is from another source. 

11C-metomidate is radiotracer used to identify tumors of adrenocortical origin. Metomidate is an inhibitor of 11β-hydroxylase and aldosterone synthase that is preferentially taken up by adrenocortical cells. 

MIBG is a functional and structural analog of norepinephrine - uptake by medulla

• Masses >6 cm - should be considered malignant until proven benign, which generally requires definitive resection.
•  
• 4 - 6 cm - rate of malignancy is estimated to be only 6%

Nonetheless, in otherwise healthy individuals with acceptable perioperative risk profile, most experts recommend 4 cm as the cutoff diameter that warrants resection.


Incidence of benign adrenal adenomas increases with age; therefore adrenal lesions in younger patients, even those less than 4 cm, must be managed with greater caution than similar lesions in an older age group. Likewise, lesions greater than 4 cm in older patients with significant comorbidities may be better served with observation than resection.

Kinetics of growth should be followed. Current recommendation is to resect masses that grow over 1 cm; however, incidence of malignancy among these patients is low.

The role for adrenal biopsy has been limited for the following reasons:

• (1) modern imaging in the context of clinical characteristics affords superb diagnostic capabilities,
• (2) histologically adenomas cannot be reliably differentiated from adrenal carcinomas, and
• (3) adrenal biopsy is not without risk

Adrenal biopsy should be pursued only when limitations of imaging have been reached and when the physician and patient are certain that the result of biopsy will influence management

The NIH consensus statement recommends metabolic testing for all adrenal incidentalomas.

• Test all new adrenal masses for cortisol and catecholamine hypersecretion.
• In patients with a history of hypertension, aldosterone hypersecretion should also be assessed.

• (1) an overnight low-dose dexamethasone suppression test (OST)
• (2) a late-night salivary cortisol test, and
• (3) a 24-hour urinary–free cortisol evaluation

Practice guidelines issued by the Endocrine Society in 2008 recommend that the dexamethasone suppression test or the late-night salivary cortisol test supplant the 24-hour urinary–free cortisol evaluation in initial metabolic screening of patients with incidentalomas

The patient is given a prescription for 1 mg of dexamethasone and instructed to take it between 11 PM and 12 AM. The next morning, a serum cortisol is obtained between 8 AM and 9AM.

50% false-positive rate in women using oral contraceptives, because the contraceptives increase total (but not bioavailable) cortisol levels by raising the patient’s cortisol-binding globulin concentrations

Today the screening test of choice for Conn syndrome is a morning plasma aldosterone (ng/dL) to renin (ng/mL/hr) ratio (ARR). An ARR of 20 (some suggest 30) along with a concomitant aldosterone concentration above 15 ng/mL are indicative of Conn syndrome. 


Potassium sparing diuretics such as amiloride, and especially mineralocorticoid receptor blockers such as spironolactone, alter the renin-angiotensin-aldosterone system and will affect test results. These agents should be stopped approximately 6 weeks prior to testing

Routine testing of incidentalomas for sex hormones is currently not recommended

• Free-fractionated plasma metanephrines, and 
• 24-hour urinary–fractionated metanephrine tests

Indeed, the 2005 International Symposium on pheochromocytoma concluded that one of these two tests should be used for initial diagnosis and screening for  pheochromocytoma

• As in all 24-hour urine collections, the patient is instructed to discard the morning’s first voided urine and begin to collect all subsequent voided samples. The last sample that is collected is the first morning’s void of the following day. Creatinine levels in the collection must be checked to verify completeness of the collection.
• The test is most accurate in patients with normal renal function.
• Tricyclic antidepressants and phenoxybenzamine should be stopped.