HYU Onc - Adrenal Flashcards
Adrenal in relation to Gerota’s
Located within a compartment of Gerota’s fascia
Arterial supply to adrenal
3 arteries
inferior phrenic –> superior adrenal artery
aorta at SMA –> middle adrenal artery
renal artery –> inferior adrenal artery
Venous supply to adrenal on right
right adrenal = ‘vein of death’
comes from IVC and/or right renal vein
Venous supply to adrenal on left
comes from left renal vein +/- inferior phrenic vein
Ddx benign adrenal mass
Adrenal adenoma (~15% metabolically active –> cortisol and/or aldosterone production)
Pheo (90% benign)
Myelolipoma
Oncocytoma
Ganglioneuroma
Cyst
Hemorrhage
Ddx malignant adrenal mass
ACC
Met lesion
Staging of ACC
T1: <5 cm, confined to adrenal
T2: > or = 5cm or functional sympathetic paraganglioma, confined to adrenal
T3: Local invasion into surrounding tissues
Stage I: T1N0M0
Stage II: T2N0M0
Stage III: T3N0M0, T1-3N1M0
Stage IV: M1 disease
Radiographic assessment of adrenal mass
- Noncon CT?
- Best studies and parameters?
Assess intracytoplasmic lipid content: high lipid is associated with low attenuation (<10 HU) on noncon CT
- On MRI, associated with opposed phase chemical shift
- These are both diagnostic for adrenal adenoma
~30% of adenomas are lipid poor and don’t exhibit <10 HU on CT or signal drop out on MRI –> Get CT Washout Imaging
Washout parameters for adrenal adenoma vs cancer
- CT?
- MRI?
> 60% absolute washout
40% relative washout
- These are both highly specific for adrenal adenoma
Cancer is greedy and retains contrast, so it won’t wash out
MRI drop out indicates presence of fat and therefore a benign mass
Myelolipoma HU/appearance on imaging (CT and MRI)
Macroscopic lipid of -10 to -20 HU on noncon CT is diagnostic
Benign, 90% metabolically silent
High T1 signal on MRI
***On MRI, fat is bright on T1 and H20 is bright on T2
ACC appearance on imaging
Mean enhancement on noncon CT is 39 HU
Generally >4cm masses with heterogeneous appearance, calcifications, necrosis
Pheo appearance on imaging
> 10 HU on unenhanced CT
Enhance to >100 HU with contrast
Well circumscribed, light-bulb sign on T2 MRI
(ACC and metastatic lesions can also be bright on T2)
Relative adrenal mass resection indications
Metabolic activity or concern for malignancy (~20% of incidentalomas)
>4 cm mass in young, healthy patients
>6 cm mass and NOT myelolipoma in all surgical candidates (1/3rd of these will be malignant)
General metabolic evaluation for adrenal masses
Test Cortisol and Catecholamine for All, Aldosterone and Sex Steroids for some
Cortisol Testing
- Most common - what is positive/negative and why?
- Alternatives
Low dose dexamethasone suppression test (corticosteroid)
- 1 mg dexamethasone at 11 PM (OCPs cause FPs) given to suppress ACTH secretion from the anterior pituitary
- If 8 AM serum cortisol is <5 mcg/dL, it rules out an ACTH-independent glucocorticoid secretion by an adrenal nodule (which would not respond to ACTH suppression)
- AKA test is positive if cortisol remains HIGH despite dex SUPPRESSION
-* Don’t perform if pheo suspected (>10 HU on imaging) as this can trigger catecholaminergic crisis
Alternatives:
- Late night (11pm) salivary cortisol (if testing is normal, you know ACTH hyperproduction is not etiology)
- 24-hour urinary cortisol (obtain 2 or more collections to reduce risk of FN)
What is next testing once hypercortisolemia is identified?
Get late-afternoon serum ACTH to determine if the process is ACTH dependent (>10 pg/mL) or independent (<5pg/mL)
Catecholamine Testing
Pheo screening
- Performed with plasma-free metanephrines (preferred)
–> Can be drawn at same time as AM cortisol
–> No caffeine for 24 hours
–> FPs can be caused by TCAs, MAOIs, SSRIs, tylenol
–> draw in supine position after patient has been resting for 20 minutes
–> positive result is 4x normal value
- Can also use 24-hour total urinary fractionated metanephrines
*24 hour urine tests require normal renal function to be worthwhile
Pheo rule of 10s
Roughly 10% (each) of pheos are:
- Normotensive
- Bilateral
- Familial
- Malignant
- Pediatric
- Extra-adrenal
- Multiple
Aldosterone Testing
- When test for this?
- What are we testing for?
- What is a positive screening test?
If a patient has HTN and hypoK, correct hypoK and stop potentially interfering medications (spironolactone, eplerenone) for 6 weeks
- Screen for primary hyperaldosteronism (Conn’s syndrome) with morning/sitting plasma aldosterone (>15 ng/mL is a positive test) and renin levels (aldosterone to renin ratio (ARR) >20-30 is a positive test)
If aldosterone screening test is positive?
Confirm Conn’s with 24 hour urine study with salt loading
- Urine sodium >14 mcg and urine K+ >30 mEq/24 hour are positive tests
- Can also do fludrocortisone suppression or captopril challenge
If confirmatory test is positive, get AVS (could have bilateral lesions even in setting of unilateral adenoma)
A functional adenoma is treated with adrenalectomy, but bilateral adrenal hyperplasia is treated with an aldosterone receptor antagonist like spironolactone or eplerenone
When do you do Sex Steroid Testing?
If there is a strong suspicion for ACCn (stigmata of feminization or virilization), can test for sex steroids to use as a form of surveillance after resection
(DHEA, 17-OH progesterone, androstenedione, testosterona, 17B-estradiol)
Adrenal mass follow-up?
All adrenal masses should have at least 2 years follow-up imaging (CT at 6, 12, 24 months)
Metabolically silent adrenal masses:
< 3 cm –> no metabolic follow-up needed
> 3 cm –> 20% can have hormonal hypersecretion at follow-up –> annual metabolic evaluation for 4 years
Adrenal layers, origin, and production, superficial to deep
Cortex (mesoderm)
Zona glomerulosa –> mineralocorticoids (aldosterone)
Zona fasiculata –> glucocorticoids (prednisone)
Zona reticulata –> Sex hormones
Medulla (ectoderm/neural crest, innervated by preganglionic sympathetic neuron)
- Chromaffin cells produce norepinephrine and epinephrine
–> dietary precursors are tyrosine and phenylalanine –> broken down by catechol-o-methyl transferase (COMT) and monoamine oxidase (MAO) into normetanephrine, metanephrine, and VMA
Hyperaldosteronism
- Primary is called?
- Primary vs. secondary
- Testing
- When surgery?
Primary hyperaldo = Conn’s syndrome
-70% aldosteronoma, 30% bilateral adrenal hyperplasia
- Causes suppression of renin and angiotensin, but not usually sustained abnormalities in K, Na, or volume status
In secondary aldo, increased renin is root problem
If hyperaldo is confirmed and there ISN’T a 1+ cm lesion on a unilateral adrenal on CT, get adrenal venous sampling (AVS) to see if there is a functional adenoma that can be treated with surgery, or if there is no difference in aldosterone between each side (waranting K sparing diuretics and HCTZ if there is HTN)
Most common cause of hypercortisolism?
Cushing’s Disease
- Excessive anterior pituitary secretion of ACTH
- Diagnose with head imaging +/- inferior petrosal vein sampling
High dose dexamethasone WILL suppress ACTH secretion by pituitary in setting of Cushing’s Disease (and therefore suppress urinary 17-hydroxycorticosteroids) but WON’T in setting of tumor or ectopic ACTH producer
Cushing’s Syndrome
- What is it?
- Causes?
Hypercortisolism
Can be caused by adrenal tumor, ectopic ACTH production, or Cushing’s disease
High dose dexamethasone WILL suppress ACTH secretion by pituitary in setting of Cushing’s Disease (and therefore suppress urinary 17-hydroxycorticosteroids) but WON’T in setting of tumor or ectopic ACTH producer
ACC tends to secrete ketosteroids and DHEA in addition to cortisol and leads to more pronounced hirsutism compared to other adenomas
How is Cushing’s Syndrome diagnosed?
- Increased cortisol
- Test serum ACTH to determine ACTH-dependent or not
What do you do with with continued hypercortisolemia after adrenalectomy?
Likely from other adrenal
- Start metyrapone (Metopirone)
–> Blocks conversion of 11-deoxycortisol to cortisol
Iodocholesterol scanning
Can be used to find ectopic steroid producing tumors
What is Nelson’s Syndrome?
- How to diagnose?
- Mechanism?
- Treatment?
HA and visual field changes caused by pituitary tumor
10-30% of patients who have had BILATERAL adrenalectomy for Cushing’s Syndrome later develop pituitary tumors that secrete ACTH and are almost always chromophobe adenomas
Dx = MRI brain, ACTH level
Mechanism = decreased negative feedback from cortisol –> increased corticotropin releasing hormone (CRH) from posterior pituitary –> increased stimulation of anterior pituitary –> tumor growth
Treatment= radiation, surgery, or pharmacotherapy (octreotide, temozolomide, pasireotide)
Neuroendocrine tumor arising from neural crest tissue outside of the adrenal?
Paraganglioma
Most sensitive test for pheo?
Plasma free metanephrines (normetanephrine, metanephrine, vanillylmandelic acid)
Catecholamines are paroxysmal, so they are less reliable (epi, norepi, dopamine)
What substances can cause FP of plasma free metanephrine testing?
TCAs, MAOIs, caffeine, nicotine, acetaminophen
For the medications, need to stop for 1-2 weeks before testing
How to differentiate between pheochromocytoma and essential hypertension?
Oral clonidine test
- Norepi drops significantly in essential HTN only
What to do when continued HTN after adrenalectomy for pheo?
Repeat plasma free metanephrine levels
- If still elevated, MIBG scan to identify additional lesions (which occur in 10-20% of patients with pheo)
What imaging can be used to evaluate for metastases when met pheo is suspected?
Ga-68 Dotatate PET/CT scan
- High affinity for somatostatin receptor
What % of ACCs are functional?
80%
Most common secretions: glucocorticoids, androgens, precursors, estradiol, aldosterone
5-year survival for ACC?
35% for clinically localized
50% for pathologically confined
If large ACC suspected on imaging - how to complete workup?
Get chest imaging to complete staging
Consider systemic therapy prior to other intervention
Metastatic ACC treatment?
Some combination of mitotane, cisplatin, etoposide, doxorubicin, streptozotocin
What therapy to consider after adrenalectomy for ACC?
Adjuvant mitotane
What imaging to get when concern for ACC?
FDG (fluorodeoxyglucose) PET
Periop management for adrenalectomy?
- Cushing’s?
- Pheo?
- Conn’s?
Cushing’s:
- stress-dose steroids and tight glycemic control
Pheochromocytoma:
- Alpha-blockers (phenoxybenzamine or doxazosin) and hydration
- if inadequate to control HTN, add metyrosine
–> this is an inhibitor of tyrosine hydroxylase, the rate limiting step in catecholamine synthesis
- If still inadequate, add Ca++ channel blocker
If BP drops after adrenal vein ligation, first line is NS bolus. Norepi next if needed, though rarely required.
Conn’s: K-sparing diuretics (spironolactone, eplerenone, amiloride, triamterene)
Postop steroids could be required in any patient due to preop contralateral adrenal suppression
Adrenal Insufficiency
- What? Primary vs secondary?
- Presentation?
- Labs?
- Treatment? Acute vs long term?
Deficiency of glucocorticoid and mineralocorticoids due to primary (AI, infectious or hemorrhagic causes) or secondary (mets, surgical removal, pituitary disease, exogenous steroids) causes
Presents acutely or chronically with hypotension, fever, lethargy, nausea, anorexia
Send CMP, ACTH, cortisol
Don;t wait on results
Give 3L D5NS and IV corticosteroids (hydrocortisone or dexamethasone)
COnfirm dx with ACTH-stim test (cortisol doesn’t rise much in setting of AI)
Begin steroid therapy (fludrocortisone) after Dx
Mitotane
Steroidogenesis inhibitor
Cytotoxic for adrenal cortex
Used for advanced ACC
Metyrosine
Tyrosine hydroxylase inhibitor and anti-HTN
Used for pheo if alpha-blockade is insufficient because tyrosine is a precursor molecule in catecholamine synthesis
Metyrapone
Inhibitor of (11-deoxycortisol –> cortisol)
Used if hypercortisolemia after adrenalectomy persists to decrease cortisol production of contralateral adrenal
MIBG scan - when to use?
(Stands for metaiodobenzylguanidine)
Scan used to identify additional catecholamine sourced of plasma free metanephrine levels remain elevated after adrenalectomy for pheo
(e.g. another pheo, paraganglioma, metastatic pheo)
If patients have a positive MIBG scan and unresectable or metastatic disease, can use Iodine-131-MIBG, a radioactive pharmaceutical
Best predictor for malignant risk of adrenal mass?
Size
Best predictor of overall survival after adrenal mass resection?
Margin status
Newly diagnosed adrenal mass on US - Next imaging?
Get noncon CT because if adrenal mass is adenoma (<10 HU), can be saved contrast load
Incidentally found 2 cm, 5HU adrenal mass. Next step?
Metabolic workup
Indications for partial adrenalectomy?
Solitary adrenal gland, bilateral disease, familial syndromes
Most common cancers to met to adrenal?
Lung, breast, kidney, melanoma, lymphoma
History of lung cancer with new large adrenal mass not consistent with adenoma. Next step?
Biopsy to determine if met
Inadvertent renal devascularization during adrenalectomy?
Small injuries (~3cm of parenchyma or less) can be observed
Larger injuries may require attempt at revascularization
