Adrenal Tumors Flashcards
What are the criteria for calling an adrenal tumor an incidentaloma?
Over 1 cm in size
What type of screening should you do for solid adrenal masses?
You should get functional testing done
What characterizes a benign adrenal adenoma?
On CT the Hounsfield units should be under 18 or CT contrast washout at 60% at 15 minute mark.
What are 3 primary functional adenomas?
Cushing’s Syndrome, Conn syndrome, and Pheochromacytoma
What is unique about adrenal cortical adenomas?
Majority are functional
What is the risk of malignancy by size of adrenal incidental mass?
< 4 cm is 2%
4-6 cm is 6%
>6 cm is 25%
3 key symptoms/signs for diagnosis of Conn Syndrome
Refractory HTN, Muscle cramping/fatigue, and profound hypokalemia if placed on diuretic.
What makes a tumor benign vs malignant when it comes to aldosterone secreting adenomas.
Benign are under 3 cm while malignant are over 3 cm.
What types of labs would you expect for an aldosterone tumor?
Na - high K+ - low H+ - low (alkalosis) Renin - low Aldosterone - high
What is the screening regimen for Conn syndrome?
Serum potassium (< 3) and aldosterone:renin ratio (<20:1)
What’s the difference between primary and secondary hyperaldosteronism
Primary has low renin, secondary has high renin.
How do you go about confirming hyper aldosterone?
You get urinary aldosterone excretion +/- w/sodium loading for 3 days.
How do you lateralize the etiology of the tumor when not clear on imaging?:
Get adrenal venous sampling.
How would you classify the position of the adrenal glands?
Retroperitoneal within Gerota’s fascia
What are the typical size and weight of adrenal glands?
Weight 5-7 grams
Size 4-6cm by 2-3 cm
From what specific origin does the adrenal cortex arise?
It arises from the intermediate mesoderm of the urogenital ridge
When does the adrenal cortex arise?
It arises between 5-8 weeks
When it the function of the adrenal cortex?
Purely endocrine in function
What are the 3 zones within the Adrenal Cortex and what do they do ?
GFR
Glomerulosa - salty (aldosterone/mineral corticoids)
Fasciculata - sweet (glucocorticoids/cortisol)
Reticularis - sex (estrogens/androgens)
From where does the adrenal medulla hail?
Comes from the neural crest cells that are adjacent to the sympathetic ganglia
When does the adrenal medulla arise?
It arises in the 9th week
How much of the gland does the medulla account for? What cells compose it?
10 percent of the gland, and chromaffin cells
What innervation level innervates the chromaffin cells in the medulla?
T11-12
What hormones get secreted from the medulla?
Catecholamines like epinephrine, norepinephrine, and dopamine
From what amino acid are catecholamines derived from
Tyrosine
When autopsies are done, what percent of individuals are found to have incidentalomas?
9% in autopsy series
What percentage of adrenal incidentalomas are deemed to be metabolically active?
20% roughly
Patient comes in with an adrenal incidentaloma, what are your first two steps? What do you do if they are hypertensive too ?
First step is to do a History and Physical including BP and HR
Second step is to do a 1mg overnight dexamethasone suppression test, plasma metanephrines, or 24 hour urine catecholamine test.
If patient is hypertensive you want to do a plasma renin activity and aldosterone renin ratio test too
Patient with an adrenal incidentaloma is found to be non-functional, what are your next 2-3 steps?
If its nonfunction, assess size
- If over 5cm, surgical resection
- If under 5cm then imaging characteristics
- If suspicion –> FNA/Biopsy and possible resection
What happens if you have an adrenal incidentaloma and it’s under 5cm and looks benign on imaging?
Re-image at 6 months or 12 months with biochemical assessment yearly for 4 years –> if it grows over 1cm or is functional, resect.
Patient comes in with adrenal incidentaloma, is found to be functional, what are your next 2 steps?
Confirmation test followed by resection
When would you not get biochemical evaluation of an adrenal lesion?
If it’s an obvious myelolipoma
What makes an obvious myelolipoma on imaging?
Low CT attenuation of -10 to -20 Hounsfield units or presence of microscopic fat.
What are your 3 options for testing for cortisol hypersecretion?
- 1mg dexamethasone suppression test (OST)
- Late night salivary cortisol test (SCT)
- 24 hour urinary free cortisol evaluation
How does salivary cortisol test compare to dexamethasone suppression test?
Salivary is easier for patients but suppression test is more sensitive in detecting subclinical Cushing syndrome
How does the 1mg dexamethasone suppression test work?
Give 1mg at 23:00 the night prior and check morning serum cortisol levels at 08:00 - You have a putative diagnosis of Cushing Syndrome if serum cortisol levels are greater than 5 micrograms/dL
What is the gold standard for diagnosis of Cushing syndrome?
24 hour urinary free cortisol is the gold standard but is more time intensive and inconvenient. Also likely higher chance of lab error if not collected properly.
What percentage of folks will have excess aldosterone and have refractory hypertension ?
10% of folks
What are the classic 3 symptoms of conn syndrome? How often do folks have all 3 ?
Classically hypertension, hypokalemia and alkalosis. 40% of folks will have normal potassium though.
What’s your first test when wanting to rule out Conn syndrome?
You want an Aldosterone to Renin ratio in the morning.
What is a positive aldosterone to renin ratio? What else is needed to confirm diagnosis of primary hyperaldosteronism
Over 20 WITH concomitant aldosterone concentration over 15 ng/mL suggest primary hyperaldosteronism
If you want an accurate Aldosterone to Renin ratio what 2 drugs need to be stopped and how long before the test.
Need to stop K+ sparring diuretics and Mineralocorticoid receptor blockers 6 weeks before testing.
Let’s say you get a positive aldosterone : renin ratio, what’s your next test?
Next test should be 24 hour urine study with salt loading
What do you always need to do if you have positive aldosterone hypersecretion?
Test laterality by adrenal venous sampling.
What percentage of patients with adrenal incidentalomas have pheochromocytomas?
4-5 percent of these patients will have PHEs
Patient has a solid adrenal mass, what are your options for testing for PHE biochemically?
You can do a plasma free metanephrines and normetanephrine level and you can also do 24 hour urinary metanephrines and fractional catecholamine.
Which is more sensitive and why? Metanephrines testing vs catecholamine?
Metanephrines because it’s metabolically synthesized continuously vs in pulses.
What 5 classes of drugs need to be reviewed as these can falsely elevate catecholamine levels?
Levodopa, monoamine oxidase inhibitors, benzodiazepines, tetracycline and rapid withdrawal from clonidine.
What folks need genetic testing when it comes to pheochromocytoma?
Those under 50, family history, extra-adrenal pheochromocytoma
What genetic testing is warranted when you are working up PHE patients that meet criteria?
Look for the RET gene, VHL, or succinate dehydrogenase genes
What percentage of folks will have adrenocortical carcinoma within the adrenal incidentaloma?
3 percent of folks
Should you do testing for excess sex hormones if you find an adrenal incidentaloma?
No, unless you suspect adrenocortical carcinoma (62-79% have elevated sex hormones), obvious virilization, and over 5 cm in mass
What sex hormones will you work up if they meet criteria and they have an adrenal incidentaloma ?
Test for DHEA, and 17-ketosteroids. If they are a woman with virilization you should get testosterone and 17beta estradiol if a man and has feminization.
What is the goal of imaging in the workup of adrenal masses?
Differential between an adrenal adenoma, carcinoma, pheochromocytoma, and metastatic lesions
What imaging can help diagnose an adrenal adenoma?
Lipid density on non-contrast CT
In phase and out phase on MRI
contrast washout kinetics on contrast enhanced CT
What attenuation on non-contrast CT are considered adenomas?
Below 10 HU on non-contrast CT
What does washout kinetics look like for a benign adrenal adenoma, how is this done?
Looks like more than 50% washout on delayed scan while not on metastatic lesions, carcinomas and PHE
You get a CT immediately after IV contrast and then again after 10-15minutes
How do you diagnose PHE on CT
They will measure greater than 10 HU on unenhanced CT and will enhance greater than 100 HU on contrast studies. They will often have a well circumscribed appearance with or without a necrotic or cystic element.
How do you diagnose PHE on MRI?
On MRI you get a classic light bulb signal on T2. Not as sensitive as previously thought.
What additional testing can you do if you suspect an extra-adrenal location?
Meta-iodonbenzylguanidine scan
How do you diagnose an adrenocortical carcinoma on CT? What about the HU ?
Usually larger than 4cm with heterogenous appearance on CT with calcifications and necrosis often present.
HU on non-contrast CT are usually greater than 25 with less than 50% washout at 10min post-contrast imaging.
How do you tell the difference between a lipid poor adenoma and an adrenal carcinoma?
Lipid poor adenoma will have HU between 20-40 but washout over 50% whereas adrenal carcinomas washout is always under 50%
Difference between an adrenal mass under 4cm to that of one over 6cm?
Under 4cm is only a 2% chance of being an adrenal carcinoma but over 6cm it’s over 25%.
What should you do for all adrenal masses between 4-6cm ?
Remove unless clearly a myelolipoma
What should you do about functional masses that cause Cushing’s, conn or are pheochromocytomas?
Adrenalectomy to avoid long term sequelae of hormonal imbalance or risk of metastasis
What should you do if a patient has Cushing’s but is not a candidate for surgery?
They should get either aminoglutethimide, metyrapone or ketoconazole while watching for adrenal insufficiency
What if a patient has subclinical Cushing syndrome, what should you do?
Only do surgery if worsening HTN, abnormal glucose tolerance, or osteoporosis.
What do you do for those with primary hyperaldosteronism?
Adrenalectomy with adrenal venous sampling to locate the functionality of the side. Especially in case of bilateral adrenal hyperplasia.
What should you give patients prior to an adrenalectomy?
Mineralcorticoid receptor antagonist with antihypertensive medication and restore potassium levels
What can be used to predict the resolution of antihypertensive medications in patients following an adrenalectomy?
You can use the Aldosteronoma Resolution score
How should you treat patients with Aldosterone secreting tumors who are not surgical candidates?
Spironolactone or eplerenone (latter has less side effects because it is a corticosteroid based competitive mineralocorticoid receptor antagonist with little androgen activity
What are the hypertension presentation of PHE patients?
30-50 percent come with paroxysmal HTN and the rest sustained.
Common clinical manifestation of PHE patients?
HTN, pallor, headache, sweating, and palpitations
How do you know if a pheochromocytoma is malignant or not?
To be malignant it has to have extracapsular invasion into adjacent structures or distant metastatic disease.
What are the 5 most common sites where you get Mets from a pheochromocytomas?
Bone, Lung, Liver, Regional Lymph Node, and Peritoneum.
What is the operative mortality of pheochromocytoma resection?
Just under 3 percent
What should you start before surgery for a PHE?
7-14 days before give alpha blocker like phenoxybenzamine, then add beta blockade with atenolol or metoprolol if they become tachycardia or develop an arrhythmia.
What are alternatives to alpha blockade preoperatively for PHE?
You can try calcium channel blockade.
What about fluids for PHE patients?
They need intra-vascular expansion due to the chronic vaso-constricted state.
Intra-operatively your patient develops a hypertensive spike during a PHE resection, what are your 4 options?
Nitroprusside, Nicardipine, Nitroglycerine, or Phentolamine
Patient with PHE intraoperatively develops a tachyarrhythmia what are your options?
Esmolol or Lidocaine
What happens once you ligate the adrenal vein?
Large hypotension so you will need fluids and an alpha agonist.
What’s the follow up following a PHE resection?
Lifelong due to a 16% recurrence rate. So at least annual follow up.
Gold standard surgery for adrenal carcinoma?
Open adrenalectomy to allow en bloc excision
