Chapter 21 - Adrenal Flashcards
Arterial supply of the adrenal?
Superior adrenal (from inferior phrenic), middle adrenal (from aorta), inferior adrenal (from renal artery)
Venous drainage of adrenal?
Left adrenal to L. renal vein, R. adrenal to IVC
What % of CT scans show incidentaloma?
1-2%. Next steps: biochemical testing, determine if malignant characteristics, follow or cut out.
When is surgery indicated for incidentaloma?
Ominous characteristics (nonhomogenous, high signal intensity, w/o loss on opposed-phase imaging, >20 HU), >4-6cm, functioning, enlarging
How often do you need to follow an incidentaloma?
Q3 months for 1 year, then yearly
How do you work up an incidentaloma?
Even if benign looking, get workup. For aldosterone, check BP and serum K (if HTN or low K, get plasma renin and aldosterone). For pheo, check urine metanephrines/VMA/catecholamines. For cortisol secreting tumor, check urinary hydroxycorticosteroids. CXR, stool guiac and colonoscopy, mammogram.
What are common mets to the adrenal?
Lung CA (#1), breast, melanoma, renal
What do you do for a patient with cancer history and an asymptomatic adrenal mass?
Biopsy. Biopsy not indicated for much else.
Adrenal cortex layers and products?
GFR = salt, sugar, steroids; glomerulosa (aldosterone), fasciculata (glucocorticoids), reticularis (androgens/estrogen)
Adrenal medulla receives innervation from what?
Splanchnics
What causes the release of cortisol from the adrenal cortex?
CRH (hypothalamus) - ACTH (anterior pituitary) - release of cortisol
When does cortisol peak?
Diurnal, 4-6am
What are the effects of aldosterone?
Stimulates renal sodium resorption and secretion of K+, H+, and ammonia
What stimulates secretion of aldosterone?
Angiotensin II, hyperkalemia, ACTH
What 3 deficiencies cause congenital adrenal hyperplasia?
21-hydroxylase deficiency(90%), 11-hydroxylase deficiency, 17-hydroxylase deficiency
Characteristics of 21-hydroxylase deficiency?
Precocious puberty in males, virilization in females; inc. 17-OH progesterone leads to inc. production of testosterone; salt wasting causing hypotension
Treatment for congenital adrenal hyperplasia?
Cortisol, genitoplasty
Characteristics of 11-hydroxylase deficiency?
Precocious puberty in males, virilization in females; salt saving causing hypertension
Characteristics of 17-hydroxylase deficiency?
ambiguous genitalia in males at birth; salt saving
Symptoms of hyperaldosteronism (Conn’s syndrome)?
HTN w/o edema, hypokalmia. Weakness, polydipsia, polyuria.
Causes of primary hyperaldosteronism (low renin)?
Adenoma (80-90%), hyperplasia, ovarian tumor, cancer
Causes of secondary hyperaldosteronism (high renin)?
CHF, renal artery stenosis, liver failure, pregnancy, diuretics
How is the diagnosis of primary hyperaldosteronism made?
Urine aldosterone after salt load (will stay high; ie not suppressible); low serum K, high urine K, high serum Na, metabolic alkalosis; aldosterone:renin ratio >20. CT to determine location. If not definitive, get adrenal vein sample.
What is the NP-59 scintigraphy?
Shows hyper functioning adrenal tissue, differentiates adenoma from hyperplasia
Treatment for adenoma causing hyperaldosteronism?
Adrenalectomy
Treatment for hyperplasia causing hyperaldosteronism?
Medical tx 1st with spironalactone, ca-channel blocker, potassium
What is the #1 cause of hypocortisolism (Addison’s disease)?
Withdrawal of exogenous steroids
What is the #1 primary disease causing hypocortisolism?
Autoimmune disease
Hormone/electrolyte aberrations with hypocortisolism?
Low cortisol and aldosterone; low serum Na, high serum K.
Symptoms of acute adrenal insufficiency?
Hypotension, fever, lethargy, abdominal pian, low glucose, depressed mental status, nausea/vomiting, high K+.
Treatment of adrenal insufficiency?
Dexamethasone, fluids, ACTH stim test
Most common cause of hypercortisolism (Cushing’s syndrome)?
Iatrogenic
How is the diagnosis of hypercortisolism made?
1st: 24h urine cortisol (most sensitive).
2nd: low dose overnight dexamethason suppression test (test urine to see if the cortisol has been suppressed - if low, Cushing’s disease, if high, go to 3).
3rd: serum ACTH (if high, ectopic ACTH or pituitary tumor and go to 4, if low ACTH, pt has cortisol-secreting tumor).
4th: serum ACTH high - high dose overnight dexamethasone suppression test (positive = pituitary, negative = ectopic).
5th: CRH test - pituitary adenomas will increase ACTH, ectopic producers will have no change in ACTH; MRI useful, NP-59 to localize and differentiate from hyperplasia.
1 noniatrogenic cause of Cushing’s syndrome?
Pituitary adenoma (70-80%)
Test findings with pituitary adenoma?
Cortisol should be suppressed with either low- or high-dose dexamethasone suppression test
Treatment of pituitary adenoma?
Transsphenoidal resection; unresectable or residual tumors treated with XRT. (Hypercortisolism w/ high ACTH suppressible w/ high dose)
2 noniatrogenic cause of Cushing’s syndrome?
Ectopic ACTH - most commonly from small cell lung cancer
Test findings with ectopic ACTH?
Hypercortisolism w/ elevated ACTH. Cortisol is NOT suppressed with either low-or high-dose dexamethasone suppression test.
Treatment of ectopic ACTH secreting tumor?
Resection of primary if possible; medical suppression or bilateral adrenalectomy for inoperable lesions
3 noniatrogenic cause of Cushing’s syndrome?
Adrenal adenoma
Test findings with adrenal adenoma causing Cushing’s?
Low ACTH, unregulated steroid production; does not suppress
Treatment for adrenal hyperplasia?
Bilateral adrenalectomy
Medical therapy for ectopic ACTH production or adrenocortical cancer (ACC) with residual or metastatic disease after resection?
Ketoconazole/metyrapone (inhibit steroid fomation), aminoglutethimide (inhibits cholesterol conversion), Op-DDD (adrenal-lytic, used for metastatic disease)
Postoperative care of bilateral adrenalectomies includes what?
Steroids
Age distribution of adrenocortical carcinoma?
Bimodal (before age 5, in the 5th decade)
% of adrenocortical carcinomas that are functional?
50% cortisol, aldosterone, sex steroids
Symptoms seen in children with adrenocortical carcinoma?
90% with virilization (precocious puberty in boys, virilization in females)
Symptoms of adrenocortical carcinoma?
Abdominal pain, weight loss, weakness
Treatment of adrenocortical carcinoma?
Radical adrenalectomy; mitotane for residual or recurrent disease
Survival rate of adrenocortical carcinoma?
20% 5-year survival
What is the adrenal medulla derived from?
Ectoderm neural crest cells
Steps of catecholamine production?
Tyrosine –> dopa –> dopamine –> norepinephrine –> epinephrine
What is the rate-limiting step in catecholamine production?
Tyrosine hydroxylase (tyrosine to dopa)
What enzyme converts norepi to epi (requires methylation)?
PNMT, found only in the adrenal medulla (only medulla tumors can secrete epinephrine)
What is the only tumor that will produce epinephrine?
Adrenal pheochromocytomas (ectopic will not)
What enzyme converts norepi to normetanephrine and epi to metanephrine?
Monoamine oxidase (MAO)
Where is extra-adrenal neural crest tissue found?
In the retroperitoneum, organ of Zuckerkandl
What do pheochromocytomas arise from?
Chromaffin cells; arise from sympathetic ganglia or ectopic neural crest cells
What is the 10% rule with pheos?
10% malignant, bilateral, in children, familial, extra-adrenal
What syndromes are pheos associated with?
MEN IIa, MEN IIb, von Recklinghausen’s disease, tuberous sclerosis, VHL, Sturge-Weber disease
Which side has more pheos?
Right side
Are extra-adrenal tumors more likely malignant or benign?
Malignant
Symptoms of pheos?
HTN (episodic), headache, diaphoresis, palpitations
How is the diagnosis of pheo made?
Urine mtanephrines and plasma VMA (VMA most sensitive), CT or MRI to localize, MIBG scan (norepi analogue) to localize if CT/MRI not definitive. FDG-PET only if suspicious for metastasis.
Is venography used for pheos?
NO, can cause hypertensive crisis
Preoperative treatment of pheos?
Volume replacement, alpha-blockers (phenoxybenzamine), then beta-blocker if pt has tachycardia or arrhythmias
What causes hypertensive crisis with pheos?
Unopposed alpha stimulation; can be precipitated by beta blockers given before alpha blockers; can cause heart failure in patients with cardiomyopathy
Treatment of pheo?
Resection, check for other tumors, ligate adrenal veins to avoid spilling catecholamines; debulking if unresectable; metyrosine (inhibits tyrosine hydroxylase)
What are frequent post op conditions following pheo resection?
Persistent hypertension, hypotension, hypoglycemia, bronchospasm, arrhythmias, intracerebral hemorrhage, CHF, MI
What are extra-adrenal sites of pheos?
Vertebral bodies, bladder, aortic bifurcation (organ of Zuckerkandl)
Where is the organ of Zuckerkandl?
Inferior aorta near bifurcation
What can falsely elevate VMA?
Coffee, tea, fruits, vanilla, iodine contrast, labetalol, alpha- and beta-blockers
What are ganglioneuromas?
Rare, benign, asymptomatic tumor of neural crest origin in the adrenal medulla or sympathetic chain
Indications for unilateral adrenalectomy?
Aldosteronoma, cortisol-secreting adenoma, unilateral pheo, virilizing or feminizing tumor, nonfunctioning tumor (>4-5cm, carcinoma, solitary unilateral mets)
Indications for bilateral adrenalectomy?
Bilateral pheos, Cushing’s caused by bilateral nodular adrenal hyperplasia or ectopic ACTH-producing tumor unresponsive to primary therapy
Biochemical diagnosis of pheo?
Plasma fractionated metanephrines and/or 24h urine catecholamines and metanephrines. Confirm one with the other.
Biochemical diagnosis of aldosteronoma?
Plasma aldosterone concentration and plasma renin activity, then determine ratio; urinary aldosterone and potassium on high-salt diet.
Biochemical diagnosis of Cushing’s disease from cortical adenoma?
24h urine free cortisol; overnight low-dose DMST; plasma ACTH
Biochemical diagnosis of adrenal cortical carcinoma?
24h urine cortisol, plasma DHEA level
Biochemical diagnosis of incidentaloma?
Low-dose DMST, plasma fractionated metanephrines/urine catecholamines; plasma aldosterone concentration and plasma renin activity if hypertensive or hypokalemic
