CHAPTER 21- ADRENAL

inferior phrenic artery

aorta

renal artery

• right adrenal vein drains to - inferior vena cava
• left adrenal vein drains to- left renal vein

1) 1-2% of abdominal CT scans show incidentaloma (5% are metastases or primary adrenal tumors)

2) Benign adenomas are common

3) adrenals are also common sites for metastases

• 4) surgery is indicated if mass has:
• 1- ominous characteristics (nonhomogenous)
• 2- >4-6 cm
• 3- functioning
• 4- enlarging

5) need to follow every 3 months for 1 year, then yearly

• 6) Dx:
• 1- serum K
• 2- urine metanephrines/VMA/catecholamines
• 3- urinary hydroxycorticosteroids
• 4- plasma renin + aldosterone levels if HTN or decreased K
• 5- CXR
• 6- stool guiac and colonoscopy
• 7- mamogram

7) anterior approach for adrenal cancer resection

• 1) lung cancer (#1)
• 2) breast cancer
• 3) melanoma
• 4) renal Ca

Cancer history with asymptomatic adrenal mass- needs biopsy

• 1) from mesoderm
• 2)
• Glomerulosa: aldosterone
• Fasciculata- glucocorticoids
• Reticularis- androgens/estrogens
• 3) Cholesterol--> progesterone--> androgens/cortisol/aldosterone
• 4) all zones have 21 and 11-beta hydroxylase

• 1) no innervation to the cortex
• 2) medulla receives innervation from the splanchnic nerves

1) lymphatics drain to subdiaphragmatic and renal lymph nodes

• 1) corticotropin-releasing hormone (CRH) is released from the hypothalamus and goes to anterior pituitary gland
• 2) ACTH is released from the anterior pituitary gland and causes the release of cortisol
• 3) cortisol has a diurnal peak at 4-6am

• 1) Aldosterone stimulates:
• 1- renal sodium resorption
• 2- secretion of K, H, and ammonia

• 2) Aldosterone secretion is stimulated by:
• 1- angiotensin II
• 2- hyperkalemia
• 3- to some extent ACTH

almost always cancer

Enzyme defect in cortisol synthesis

• 1) 21-Hydroxylase deficiency:
• 1- 90%, most common
• 2- precocious puberty in males, virilization in females
• 3- increased 17-OH progesterone, leads to increased production of testosterone
• 4- is salt wasting (decreased sodium, increased potassium) and causes hypotension
• 5- Tx: cortisol, genitoplasty

• 2) 11-Hydroxylase deficiency
• 1- precocious puberty in males, virilization in females
• 2- increased 11-deoxycortisone
• 3- is salt saving (deoxycortisone acts as a mineralocorticoid) and causes hypertension
• 4- Tx: cortisol, genitoplasty

• 3) 17-hydroxylase deficiency
• 1- ambiguous genitalia at birth
• 2- salt saving

• 1) HTN secondary to sodium retention without edema
• 2) hypokalemia
• 3) also have weakness, polydipsia, polyuria

• 1)low renin
• 2) adenoma (80-90%)--> #1 cause of primary hyperaldosteronism
• 3) hyperplasia (10-20%)
• 4) ovarian tumors (rare)
• 5) cancer (rare)

• 1) high renin
• 2) more common than primary disease
• 3) Caused by:
• 1- CHF
• 2- renal artery stenosis
• 3- liver failure
• 4- pregnancy
• 5- diuretics
• 6- Bartter's syndrome (renin-secreting tumor)

• 1) urine aldosterone after salt load test (will stay high)
• 2) decreased serum K, increased urine K, increased serum Na, metabolic alkalosis
• 3) plasma renin activity will be low
• 4) Aldosterone: renin ratio >20

• 1) MRI
• 2) NP-59 scintigraphy (shows hyperfunctioning adrenal tissue; differentiates adenoma from hyperplasia; 90% accurate)
• 3) adrenal venous sampling if others nondiagnostic

• 1) adenoma- resection has good results with adrenalectomy
• 2) hyperplasia seldom cured (increased morbidity with bilateral resection)
• 1- try medical therapy first with hyperplasia using: spironolactone, calcium channel blockers, and potassium
• 2- if bilateral resection is performed (usually done for refractory hypokalemia) patient will need fludrocortisone postoperatively

• 1) adrenal insufficiency, addison's disease
• 2) #1 cause - withdrawal of exogenous steroids
• 3) #1 primary disease- autoimmune disease
• 4) Also caused by:
• 1- pituitary disease
• 2- infection
• 3- adrenal hemorrhage
• 4- adrenal metastasis
• 5- surgical resection or injury
• 5) get decreased cortisol and aldosterone
• 6) Dx: decreased serum Na, increased serum K, ACTH stimulation test

• 1) hypotension
• 2) fever
• 3) lethargy
• 4) abdominal pain
• 5) decreased glucose
• 6) decline in mental status
• 7) nausea/vomiting
• 8) increased K

• 1) dexamethasone
• 2) fluids
• 3) ACTH stimulation test (measure cortisol level after test)

most commonly iatrogenic

• 1st- 24 hr urine cortisol (most sensitive test)
• 2nd- low-dose overnight dexamethasone suppression test; look to see whether it suppresses cortisol production(measure in urine). If cortisol is low, the diagnosis is Cushing's disease (the pituitary adenoma was suppressed). If cortisol remains high, go to 3rd.
• 3rd- measure serum ACTH. If high, have either ectopic ACTH or pituitary tumor that was not suppressed with lose-dose overnight dexamethasone suppression test, go to 4th. If low ACTH, patient has cortisol-secreting tumor (ie. adrenal tumor or adrenal hyperplasia).
• 4th- if serum ACTH high--> high-dose overnight dexamethasone suppression test (positive=pituitary origin, negative=ectopic origin of ACTH). In 20% you still cannot tell; to to 5th
• 5th- CRH test--> pituitary adenomas will increase ACTH; ectopic producers will have no change in ACTH

• - MRI useful
• - NP-59 scintography localizes adrenal tumors and can help differentiate them from hyperplasia

• 1) #1 noniatrogenic cause of cushing's syndrome--> 70-80% of cases
• 2) cortisol should be suppressed with either low-or high-dose dexamethasone suppression test
• 3) mostly microadenomas
• 4) need petrosal sampling to figure out which side; MRI can help also
• 5) vertical incisions to find adenoma
• 6) Tx: most tumors removed with transsphenoidal approach; unresectable or residual tumors treated with XRT

• 1) #2 noniatrogenic cause of cushing's syndrome
• 2) most commonly from small cell lung cancer
• 3) cortisol is not suppressed with either low or high-dose dexamethasone suppression test
• 4) Chest and abdominal CT can help localize
• 5) Tx: resection of primary if possible; medical suppression or bilateral adrenalectomy for inoperable lesions

• 1) #3 noniatrogenic cause of cushing's syndrome
• 2) decreased ACTH, unregulated steroid production; does not suppress
• 3) Tx: adrenalectomy

• 1) rare cause of cushing's syndrome
• 2) Tx: radical adrenalectomy; debulking can help patients and prolong survival

Tx: bilateral adrenalectomy

• 1) ketoconazole and metyrapone- inhibit steroid formation
• 2) aminoglutethimide- inhibit cholesterol conversion
• 3) Op-DDD (mitotane)- adrenal-lytic, used for metastatic disease

• 1) may be needed in patients with ectopic ACTH from tumor that is unresectable or from pituitary adenoma that cannot be found.
• 2) need to remember to give steroids postoperatively

• 1) bimodal distribution (before age 5 and in the 5th decade)
• 2) more common in females
• 3) 50% are functioning tumors
• 1- cortisol
• 2- aldosterone
• 3- sex steroids
• 4) children display virilization 90% of the time (precocious puberty in boys, viriluzation in females)
• 5) feminization in men; masculinization in women can occur
• 6) Symptoms: abdominal pain, weight loss, weakness
• 7) 80% have advanced disease at time of diagnosis
• 8) Tx:
• 1- radical adrenalectomy
• 2- mitotane for residual or recurrent disease
• 9) 20% 5 year survival rate

• 1) from ectoderm neural crest cells
• 2) catecholamine production:
• tyrosine--> dopa-->dopamine--> norepinephrine--> epinephrine
• 3) Tyrosine hydroxylase- rate-limiting step (tyrosine to dopa)
• 4) PNMT- enzyme that converts norepinephrine to epinephrine (requires methylation)
• 1- enzyme is found only in the adrenal medulla (exclusive producers of epinephrine)
• 5) Only adrenal pheochromocytomas will produce epinephrine

• 1) converts norepinephrine to normetanephrine
• 2) epinephrine to metanephrine
• 3) VMA produced from these

• 1) usually in the retroperitoneum
• 2) most notably in the organ of Zuckerkandl

• 1) chromaffin cell
• 2) rare, usually slow growing, arise from sympathetic ganglia or ectopic neural crest cells
• 3) 10% rule:
• 1- malignant
• 2- bilateral
• 3- in children
• 4- familial
• 5- extra-adrenal

• 1) MEN IIa
• 2) MEN IIb
• 3) von Recklinghausen's disease
• 4) tuberous sclerosis
• 5) sturge weber disease

right-sided predominance

extra-adrenal tumors more likely malignant

• 1) HTN (frequently episodic)
• 2) headache
• 3) diaphoresis
• 4) palpitations

• 1) urine metanephrines and VMA- breakdown products of epi and norepinephrine
• 2) VMA most sensitive
• 3) MIGB scan (norepinephrine analogue)- can help identify location if having trouble finding tumor
• 4) clonidine suppression test- tumor does not respond, keeps catecholamines high
• 5) no venography- can cause hypertensive crisis
• 6) CT/MRI can help localize tumors
• 7) not able to localize--> still proceed with laparotomy

• 1) volume replacement
• 2) alpha-blocker first (phenoxybenzamine--> avoids hypertensive crisis)
• 3) then beta-blocker if patient has tachycardia/arrhythmias
• 4) need to be careful with beta-blocker and give after alpha-blocker--> can precipitate hypertensive crisis (unopposed alpha stimulation) and heart failure in patients with cardiomyopathy

• 1) check for other tumors at resection
• 2) ligate adrenal veins first to avoid spilling catecholamines during tumor manipulation
• 3) debulking helps symptoms in patients with unresectable disease
• 4) metyrosine- inhibits tyrosine hydroxylase causing decreased synthesis of catecholamines
• 5) should have the following ready during the time of surgery:
• 1- nipride
• 2- neo-synephrine
• 3- anti-arrhythmic agents (e.g. amiodarone)

• 1) persistent hypertension
• 2) hypotension
• 3) hypoglycemia
• 4) bronchospasm
• 5) arrhythmias
• 6) intracerebral hemorrhage
• 7) CHF
• 8) MI

• 1) vertebral bodies
• 2) opposite adrenal gland
• 3) bladder
• 4) aortic bifurcation

organ of zuckerkandle (inferior aorta near bifurcation)

• 1) coffee + tea
• 2) fruits
• 3) vanilla
• 4) iodine contrast
• 5) labetalol
• 6) alpha + beta blockers

responsible for medullary Ca of the thyroid and extra-adrenal pheochromocytoma

• 1) rare
• 2) benign
• 3) asymptomatic tumor of neural crest origin in the adrenal medulla or sympathetic chain

• Unilateral Adrenalectomy
• 1) aldosteronoma
• 2) cortisol-secreting adenoma (cushing's syndrome or subclinical cushing)
• 3) unilateral pheochromocytoma (sporadic or familial)
• 4) virilizing or feminizing tumors
• 5) non functioning unilateral tumor
• 1- size: >4-5cm
• 2- imaging features atypical for adenoma, myelolipoma, or cyst
• 3- adrenocortical carcinomas
• 4- solitary unilateral adrenal metastasis

• Bilateral Adrenalectomy
• 1) bilateral pheochromocytomas
• 2) cushing's syndrome from
• 1- bilateral nodular adrenal hyperplasia
• 2- ectopic ACTH-producing tumor unresponsive to primary therapy
• 3) cushing's disease (pituitary tumor) unsuccessfully treated by surgery/radiation