Flashcards in Chapter 21: Adrenal Deck (112):
vascular supply: superior adrenal
inferior phrenic artery
vascular supply: middle adrenal
vascular supply: inferior adrenal
drainage of left adrenal vein
left renal vein
drainage of right adrenal vein
inferior vena cava
Innervation of medulla
sympathetic splanchnic nerve
innervation of adrenal cortex
no innervation of adrenal cortex
lymphatic drainage of adrenal
lymphatics drain to subdiaphragmatic and renal lymph nodes
what makes up the adrenals
made up of adrenal cortex and adrenal medulla
incidence of incidentaloma of adrenal mass on CT scan
1%-2% of abdominal CT scans show incidentaloma (5% are metastases)
two things to know about asymptomatic adrenal masses
- benign adenomas are common
- adrenals are also common site for metastases
what to do when you see an asymptomatic adrenal mass?
check for functioning tumor: urine metanephrines/vma/catecholamines, urinary hydroxycorticosteroids, serum K with plasma renin and aldosterone levels
- Consider CXR, colonoscopy, mammogram to check for a primary tumor
when is surgery indicated for asymptomatic adrenal mass?
ominous characteristics (non-homogenous), is > 4-6 cm, is functioning or is enlarging
how do you follow an incidentaloma?
need repeat imaging every 3 months for 1 year, then yearly
approach for adrenal CA resection
anterior approach for adrenal CA resection
Common metastases to adrenal
Lung CA (#1), breast CA, melanoma, renal CA
Management: cancer history with asymptomatic adrenal mass
what if you have isolated metastases to the adrenal gland?
some isolated metastases to the adrenal gland can be resected with adrenalectomy
layers of the adrenal cortex
GFR = salt, sugar, sex steroids
- Glomerulosa: aldosterone
- Fasciculata: glucocorticoids
- Reticularis: androgens / estrogens
precursor for androgens / cortisol / aldosterone
cholesterol -> progesterone -> androgens/cortisol/aldosterone
what enzyme do all zones of the adrenal cortex contain?
all zones have 21- and 11-beta hydroxylase
Released from the hypothalamus and goes to anterior pituitary gland
Corticotropin-releasing hormone (CRH)
Released from the anterior pituitary gland and causes the release of cortisol
Has a diurnal peak at 4-6 am
Inotropic, chronotropic, and increases vascular resistance; proteolysis and gluconeogenesis; decreases inflammation
Stimulates renal sodium resorption and secretion of potassium and hydrogen ion
What stimulates aldosterone secretion?
Stimulates by angiotensin II and hyperkalmeia, and to some extent ACTH
What is significant of excess estrogens and androgens by adrenals?
Almost always cancer
Enzyme defect in cortisol synthesis
Congenital adrenal hyperplasia
- MCC congenital adrenal hyperplasia
- Precocious puberty in males
- Virilization in females
- Increased 17-OH progesterone leads to increased production of testosterone
- Is salt wasting (decreased sodium and increased potassium) and causes hypotension
21-hydroxylase deficiency (90%)
Tx: 21-hydroxylase deficiency
HTN secondary to sodium retention without edema; hypokalemia; also have weakness, polydipsia, and polyuira
Hyperaldosteronism (Conn's syndrome)
#1 cause of primary hyperaldosteronism
Causes of primary hyperaldosteronism (Conn's syndrome)
Adenoma (85%), hyperplasia (15%), ovarian tumors (rare), cancer (rare)
Causes of secondary hyperaldosteronism (Conn's syndrome)
More common than primary disease
- Renal artery stenosis
- Liver failure
- Bartter's syndrome (renin-secreting tumor
Dx for primary hyperaldosteronism
- Salt load suppression test (best, urine aldosterone will stay high)
- Aldosterone:renin ratio > 20
- Labs: low K, high Na, high urine K, metabolic alkalosis
- Plasma renin activity will be low
Localizing studies for hyperaldosteronism (Conn's syndrome)
MRI, NP-59 scintigraphy (shows hyper functioning adrenal tissue; differentiates adenoma from hyperplasia; 90% accurate); adrenal venous sampling if others nondiagnostic
What do you need to consider for pre-op optimization in hyperaldosteronism?
Pre-op need control of HTN and K replacement
Hyperaldosteronism: adenoma tx
Hyperaldosteronism: hyperplasia treatment
Seldom cured (increased morbidity with bilateral resection)
- Try medial therapy first using spironolactone (inhibits aldosterone), calcium channel blockers, and potassium
- if bilateral resection is performed (usually done for refractory hypokalemia), patient will need fludrocortisone postoperatively
Adrenal insufficiency, Addison's disease
#1 cause hypocortisolism
Withdrawal of exogenous steroids
#1 primary disease: hypocortisolism
Causes of hypocortisolism (Addison's disease)
Withdrawal of exogenous steroids (#1), pituitary disease, adrenal infection / hemorrhage / metastasis / resection
Causes decreased cortisol (ACTH will be high) and decreased aldosterone
Hypocortisolism (adrenal insufficiency, Addison's disease)
Dx: hypocortisolism (adrenal insufficiency, Addison's disease)
Cosyntropin test (ACTH given, urine cortisol measured) - cortisol will remain low
Hypotension, fever, lethargy, abdominal pain, nausea and vomiting, decreased glucose, increased K
Acute adrenal insufficiency
Tx: acute adrenal insufficiency
Dexamethasone, fluids, and give cosyntropin test (dexamethasone does not interfere with test)
Hyperpigmentation, weakness, weight loss, GI symptoms, increased K, decreased Na
Chronic adrenal insufficiency
Tx: chronic adrenal insufficiency
- Most commonly iatrogenic
Most sensitive test hypercortisolism (Cushing's syndrome)
24-hour urine cortisol
1st thing to do in hypercortisolism (Cushing's syndrome)
Measure 24-hour urine cortisol (most sensitive test) and ACTH
- Low ACTH
- high Cortisol
Patient has a cortisol secreting lesion (eg, adrenal adenoma, adrenal hyperplasia)
- High ACTH
- High cortisol
Patient has a pituitary adenoma or an ectopic source of ACTH (e.g., small cell lung CA) -> move on to second part of workup (high-dose dexamethasone suppression test)
2nd portion of work up in hypercortisolism (high ACTH)
If ACTH is high, give high-dose dexamethasone suppression test
- if urine cortisol is suppressed -> pituitary adenoma
- if urine cortisol is not suppressed -> ectopic producer of ACTH (e.g. small cell lung ca
High dose dexamethasone suppression test:
- if urine cortisol is suppressed..
High dose dexamethasone suppression test:
- if urine cortisol is not suppressed
Ectopic producer of ACTH (e.g. small cell lung CA)
Can help localize tumors and differentiate adrenal adenomas from hyperplasia
#1 non-iatrogenic cause of Cushing's syndrome
Pituitary adenoma (Cushing's disease)
- 80% of cases
How will a pituitary adenoma look on low or high dose dexamethasone suppression test?
Cortisol should be suppressed with either or low or high dose dexamethasone suppression test
Pituitary adenomas: micro or maco?
How do you figure out which side of the pituitary is affected with a pituitary adenoma resulting in hypercortisolism?
Need petrosal sampling to figure out which side; MRI can also help
Tx: pituitary adenoma (Cushing's disease)
Most tumors removed with transsphenoidal approach; unresectable or residual tumors treated with XRT
#2 non-iatrogenic cause of Cushing's syndrome
What is ectopic ACTH most commonly from?
Small cell lung cancer
How will low- or high-dose dexamethasone suppression test look in ectopic ACTH production?
Cortisol is not suppressed with either low or high dose dexamethasone suppression test
How can you localize the lesion in ectopic ACTH production?
Chest and abdominal CT can help localize
Tx: Ectopic ACTH
Resection of primary if possible; medical suppression for inoperable lesions
#3 non-iatrogenic cause of Cushing's syndrome
Decreased ACTH, unregulated steroid production
- Tx: adrenalectomy
Tx: adrenal hyperplasia (macro or micro)
Metyrapone (blocks cortisol synthesis) and aminoglutethimide; bilateral adenalectomy if medical treatment fails
Rare cause of Cushing's syndrome
Consider in patients with ectopic ACTH from tumor that is unresectable (would need to be a slow growing tumor - rare) or ACTH from pituitary adenoma that cannot be found
When operating for Cushing's syndrome what is important post op?
Give steroids post op when operating for Cushing's syndrome
#1, #2, #3 causes Cushing's disease
1. Pituitary adenoma
2. Ectopic ACTH
3. Adrenal adenoma
Bimodal distribution (before age 5 and in the 5th decade); more common in females
- 50% are functioning tumors - cortisol, aldosterone, sex steroids
- Children display virilization 90% of the time (precocious puberty in boys, virilization in females); feminization in men; masculinization in women can occur
- Symptoms: abdominal pain, weight loss, weakness
- 80% have advanced disease at the time of diagnosis
Tx: adrenocortical carcinoma
Radical adenalectomy; debulking helps symptoms, prolongs survival
5-year survival rate adrenocortical carcinoma
From ectoderm neural crest cells
Pathway of catecholamine production
Tyrosine -> dopa -> dopamine -> norepinephrine -> epinephrine
Rate limiting step (tyrosine to dopa)
Enzyme that is an exclusive producer of epinephrine
- Only found in the adrenal medulla
PNMT (phenylethanolamine N-methyltransferase)
What does PNMT (phenylethanolamine N-methyltransferase)
Enzyme converts norepinephrine -> epinephrine
- Exclusively found in adrenal medulla, exclusive producer of epinephrine
What do adrenal pheochromocytoma produce?
Only adrenal pheochromocytomas will produce epinephrine
Breaks down catecholamines; converts norepinpehrine to normetanephrine, epinephrine to metanephrine
MAO (monoamine oxidase)
How is VMA (vanillylmandelic acid) produced?
Breakdown product of catecholamines (normetanephrine and metanephrine)
Where can you find extra-adrenal rests of neural crest tissue?
Usually in the retroperitoneum, most notably in the organ of Zuckerkandl at the aortic bifurcation
What is the origin of pheochromocytoma?
Chromaffin cells of the adrenal medulla
- Rare; usually slow growing; arise form sympathetic ganglia or ectopic neural crest cells
- Symptoms: HTN (frequently episodic), headache, diaphoresis, palpitations
What can pheochromocytoma be associated with?
MEN IIa, MEN IIb, von Recklinghausen's disease, tuberous sclerosis, Sturge-Weber disease
Laterality of pheochromocytoma
Right sided predominance
10% rule of pheochromocytoma
Malignant, bilateral, in children, familial, extra-adrenal
What is significant of extra-adrenal tumors in pheochromocytoma?
Extra-adrenal tumors are more likely malignant
Urine metanephrines and VMA
- VMA most sensitize test for diagnosis
- MIBG scan (norepinephrine analogue) - can help identify location if having trouble finding tumor with CT scan / MRI
- Clonidine suppression test: tumor does not respond, keeps cathetcholamines increased
- No venography -> can cause hypertensive crisis
Most sensitize diagnostic test in pheochromocytoma
What is a MIBG scan?
MIBG (norepinephrine analogue) -> can help identify location if having trouble finding tumor with CT scan / MRI
How is the clonidine suppression test useful in pheochromocytoma?
Tumor does not respond, keeps catecholamines elevated
Why no venography in pheochromocytoma?
Can cause hypertensive crisis
Preoperative management of pheochromocytoma
Volume replacement and alpha-blocker first (phenoxybenzamine -> avoids hypertensive crisis); then B-blocker if patient has tachycardia or arrhythmias)
Why do you ALWAYS give alpha blocker before beta blocker in pheochromocytoma?
Can precipitate hypertensive crisis (unopposed alpha stimulation, can lead to stroke) and heart failure
Adrenalectomy -> ligated adrenal veins first to avoid spilling catecholamines during tumor manipulation
How do you avoid spilling catecholamines during tumor manipulation in pheochromocytoma?
Ligate adrenal veins
Pheo: helps symptoms in patients with unresectable disease
Inhibits tyrosine hydroxylase causing decreased synthesis of catecholamiens.
What meds should you have ready during the time of surgery of pheochromocytoma?
Nipride, Neo-Synephrine, and anti arrhythmic agents (eg, amiodarone) ready during the time of surgery
Post op conditions to look for s/p adrenalectomy for pheochromocytoma
Persistent hypertension, hypotension, hypoglycemia, bronchospasm, arrhythmias, intracerebral hemorrhage, CHF, MI
Other sites of pheochromocytomas
Vertebral bodies, opposite adrenal gland, bladder, aortic bifurcation
Most common site of extra medullary tissue in pheochromocytoma
Organ of Zuckerkandl (inferior aorta near bifurcation)
What can cause falsely elevated VMA?
Coffee, tea, fruits, vanilla, iodine contrast, labetalol, alpha and beta blockers
Responsible for medullary CA of thyroid and extra-adrenal pheochromocytoma