Editing Diagnosis and Evaluation of Adrenal Mass (section)

== Diagnosis and Evaluation ==

* '''<span style="color:#ff0000">2011 CUA: ALL incidental adrenal masses (excluding myelolipomas, hemorrhages, and cysts) initially require a comprehensive workup, including thorough clinical, radiologic and hormonal evaluations''' to distinguish benign from malignant processes, as well as non-functioning from hyperfunctioning tumours.</span>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3147036/ §]

=== UrologySchool.com Summary ===

* '''<span style="color:#ff0000">History and Physical Exam</span>'''
* '''<span style="color:#ff0000">Labs (3)</span>'''[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3147036/ §]
*# '''<span style="color:#ff0000">Low-dose dexamethasone suppression test or 24-hour urinary cortisol to rule out hypercortisolism AND</span>'''
*# '''<span style="color:#ff0000">24-hour urinary metanephrines and/or catecholamines to rule out pheochromocytoma +/-</span>'''
*# '''<span style="color:#ff0000">Aldosterone-renin ratio in patients with hypertension to rule out hyperaldosteronism</span>'''
* '''<span style="color:#ff0000">Imaging (1)</span>'''
*#'''<span style="color:#ff0000">Unenhanced CT</span>'''
*#* '''<span style="color:#ff0000">If attenuation ≥ 10HU, obtain contrast enhanced CT with adrenal washout</span>'''

=== History and Physical Exam ===

*'''Most patients are asymptomatic'''
*'''<span style="color:#ff0000">Screen for signs and symptoms related to disorders of</span>'''
** '''<span style="color:#ff0000">Adrenal hyperfunction</span>'''
**# '''<span style="color:#ff0000">Hypercortisolism (9)</span>'''
**##'''<span style="color:#ff0000">Central obesity</span>'''
**##'''<span style="color:#ff0000">Moon facies</span>'''
**##'''<span style="color:#ff0000">Buffalo hump</span>'''
**##'''<span style="color:#ff0000">Facial plethora</span>'''
**##'''<span style="color:#ff0000">Menstrual disturbances</span>'''
**##'''<span style="color:#ff0000">Hirsuitism</span>'''
**##'''<span style="color:#ff0000">Proximal muscle weakness</span>'''
**##'''<span style="color:#ff0000">Easy bruisability</span>'''
**##'''<span style="color:#ff0000">Abdominal striae</span>'''
**##'''<span style="color:#ff0000">Systemic manifestations include dyslipidemia, insulin resistance, and hypertension</span>'''
**# '''<span style="color:#ff0000">Hyperaldosteronism: hypertension</span>'''
**#*Hypertension classified as
**#** Elevated blood pressure: SBP 120-129 mm Hg; DBP < 80 mm Hg
**#** Stage 1 hypertension: SBP 130 - 139 mm Hg; DBP 80 - 89 mm Hg
**#** Stage 2 hypertension: SBP ≥140 mm Hg; DBP ≥ 90 mm Hg
**# '''<span style="color:#ff0000">Pheochromocytoma (3):</span>''' 
**##'''<span style="color:#ff0000">Headache</span>'''
**##'''<span style="color:#ff0000">Episodic sudden perspiration</span>'''
**##'''<span style="color:#ff0000">Tachycardia</span>'''
**# '''<span style="color:#ff0000">Adrenal sex steroid hypersecretion</span>'''
** '''<span style="color:#ff0000">Adrenal malignancy</span>'''

=== Labs ===

* See 2011 CUA Incidental Adrenal Mass Guideline [https://test.urologyschool.com/index.php/CUA:_Adrenal_Mass_(2011) Notes]
* '''<span style="color:#ff0000">Hypercortisolism'''
** '''<span style="color:#ff0000">Assessed by overnight low-dose (1 mg) dexamethasone suppression test</span>''' (sensitivity: 85-90 specificity: 95-99)
*** Consideration can be given to using the 24-hour urine free cortisol (sensitivity: 80-98, specificity: 45-98) for screening, with the low dose 1 mg dexamethasone suppression test used to differentiate Cushing’s from subclinical Cushing’s syndrome if the cortisol level on the 24-hour test is elevated.
*** Further [https://www.ncbi.nlm.nih.gov/pubmed/31069279 details on hypercortisolism testing]
* '''<span style="color:#ff0000">Pheochromocytoma'''
** '''<span style="color:#ff0000">Assessed by 24-hour urine metanephrines and catecholamines'''
*** '''Fractionated plasma metanephrines''' is a newer test that may be more sensitive, but less specific. As such, its use '''should be reserved for confirmatory testing as opposed to primary screening'''.
**** Plasma metanephrine testing may not be widely available outside select centers, therefore 24-hour urinary metanephrines is suggested for initial screening.
* '''<span style="color:#ff0000">Hyperaldosteronism'''
** '''<span style="color:#ff0000">Assessed in hypertensive patients by upright plasma aldosterone concentration to plasma renin ratio (ARR).'''
*** '''Pre-testing considerations'''
****'''Mineralocorticoid receptor blockers (e.g. spironolactone) and some diuretics, particularly potassium sparing diuretics (e.g. amiloride, triamterene) and potassium wasting diuretics (e.g. furosemide, HCTZ, indapamide), should be discontinued at least 4 weeks prior to the ARR'''
**** If ARR results are not diagnostic and hypertension can be controlled with relatively noninterfering antihypertensives, withdrawal of other potentially interfering medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, dihydropyridine calcium channel antagonists, β-blockers, central α-2 agonists and non-steroidal anti-inflammatory drugs) for at least 2 weeks prior to a repeat ARR is recommended.
**** '''Patients should be informed to liberalize salt intake leading up to the test to ensure accurate results'''
*****Acute fluctuations in dietary sodium are reported to not affect the diagnostic accuracy of the ARR
** '''Normokalemia occurs in up to 50% of patients with hyperaldosteronism.'''
*** Traditionally, hyperadlosteronism has been clinically associated with hypertension and hypokalemia
* '''<span style="color:#ff0000">Adrenal Sex Steroid Hypersecretion'''
** '''<span style="color:#ff0000">Routine testing of incidentalomas for sex hormones is not currently recommended'''
*** '''Hypersecretion of adrenal sex steroids by adrenal masses, especially incidentalomas, is exceedingly rare and typically present with concomitant clinical symptoms (i.e., feminization or virilization)'''
**'''Assessed with (2):'''
**#'''Serum DHEA-S'''
**#'''24-hour urine 17-ketosteroids'''
* '''<span style="color:#ff0000">Confirmatory hormonal testing for all positive screening tests is recommended to limit false positive results and unnecessary surgery'''

=== Imaging ===

==== CT ====
* '''<span style="color:#ff0000">Unenhanced CT scan is the first test</span>'''
** '''Myelolipoma, cysts and hemorrhages have distinct features on imaging'''
**'''Most easily interpreted test for intracellular lipid'''
*** '''<span style="color:#ff0000">Adenomas typically contain a greater proportion of intracellular fat</span>''' in comparison to malignant incidentalomas.
** '''<span style="color:#ff0000">If attenuation of a region of interest over a mass on unenhanced CT</span>'''
***'''<span style="color:#ff0000"><10 HU, diagnostic for an adrenal adenoma (corresponds to high intracytoplasmic lipid content)</span>'''
**** '''<span style="color:#ff0000">This cutoff has ≈70% sensitivity and 98% specificity for the diagnosis of adrenal adenomas</span>'''
***** '''<span style="color:#ff0000">≈30% of adrenal adenomas exhibit an attenuation >10 HU on unenhanced CT owing to their lower lipid content</span>'''
****** '''These “atypical adenomas” or "lipid-poor adenomas" are indistinguishable from non-adenomas on non-contrast CT density measurements alone'''
*** '''<span style="color:#ff0000">>10 HU, obtain contrast enhanced CT with washout</span>'''
**** Contrast enhanced CT with washout has excellent sensitivity and specificity in differentiating between adenomas and non-adenomatous incidentalomas
*****The diagnostic information from a single-phase enhanced CT scan for adrenal lesions is quite limited, as there is considerable overlap in post-contrast attenuation of adenomas and non-adenomas
**** '''Phases of adrenal CT study (3):'''
****# '''Non-contrast 5-mm images through the adrenal'''
****# '''Enhanced (1-minute post-bolus imaging)'''
****# '''15-minute washout imaging'''
**** '''<span style="color:#ff0000">Delayed (washout) imaging indicative of adrenal adenoma</span>'''
***** '''<span style="color:#ff0000">Absolute percent washout > 60%</span>''' ([Enhanced − delayed]/[Enhanced − unenhanced] × 100%)
***** '''<span style="color:#ff0000">Relative percent washout (RPW) > 40%</span>''' ([Enhanced − delayed]/ [Enhanced] × 100%)
****** '''Lipid-poor adenomas possess identical properties to lipid-rich adenomas regarding their rapid loss (washout) of enhancement after CT contrast'''
****** RCC metastases and HCC mets may exhibit washout characteristics similar to those of lipid-poor adenomas
* '''<span style="color:#ff0000">Characteristics of pheochromocytoma and malignant processes include (5):</span>'''
*# '''<span style="color:#ff0000">Size (>3 cm)</span>'''
*# '''<span style="color:#ff0000">Heterogenous texture</span>'''
*# '''<span style="color:#ff0000">Increased vascularity</span>'''
*# '''<span style="color:#ff0000">Attenuation of >10 HU on unenhanced CT</span>'''
*# '''<span style="color:#ff0000">Decreased contrast washout''' at 10 to 15 minutes</span>

==== MRI ====
* '''Similar to CT scan, chemical-shift MRI uses the lipid-rich property of most adenomas to differentiate benign from malignant'''
* '''CT with washout is considered the gold standard and is better than chemical shift MRI for identifying adenomas'''

==== Ultrasound ====
* '''Suboptimal imaging modality for detecting and characterizing adrenal lesions'''

==== Functional imaging ====
* '''The role of functional imaging for the diagnosis of pheochromocytoma is limited, given that most pheochromocytomas can be accurately diagnosed with cross-sectional imaging and metabolic evaluation for catecholamines and their metabolites.'''

==== PET ====
* '''2-[18F] FDG-PET scan can be useful in detecting metastasis in patients with a history of malignancy''', as metabolically-active lesions typically have increased uptake of FDG versus benign lesions.

=== Adrenal biopsy ===

* '''<span style="color:#ff0000">Currently NOT recommended for the routine workup of adrenal incidentaloma</span>'''
** Limited role in contemporary era:
**# Modern imaging in the context of clinical characteristics affords superb diagnostic capabilities
**# Histologically, adenomas cannot be reliably differentiated from adrenal carcinomas
**# Risks of biopsy
* '''Should be pursued if diagnosis remains equivocal and the result of biopsy will influence management.'''
** '''Most useful in patients with primary malignancies that have potentially recurred in the adrenal gland and whose management will be affected by the biopsy results.'''
* '''<span style="color:#ff0000">ALWAYS exclude possibility of pheochromocytoma before biopsy''' '''to avoid potentially life-threatening hemorrhage and hypertensive crisis'''