Adrenal

Jon Brown, DO and David Kashmer, MD MBA

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Adrenal cortex is mesoderm

Adrenal medulla is from neural crest ectoderm

Extra-adrenal locations for neural crest ectoderm include retroperitoneal rests and Organ of Zuckerkandl at aortic bifrucation

Has cortex (Greek for “bark” because it’s on the outside like bark of a tree) and medulla

Cortex is divided into

• Zona glomerulosa
• Makes mineralocorticoids (aldosterone)
• Conn’s syndrome is hyperaldosteronism
• Hypertension and hypokalemia, weakness, polydipsia and polyuria
• Salt load suppression test:  salt load patient and urine aldosterone stays high
• Aldosterone to renin ratio:  > 20:1
• Low serum K+, high serum Na+, metabolic alkalosis
• Primary Conn’s has low renin
• Adenoma is 85% of cases
• Secondary has elevated renin
• More common than primary, seen with CHF, renal artery stenosis

• Aldosteronoma
• Most commonly single adenoma (70%), may be bilateral hyperplasia (30%)
• HTN, hypokalemia, nonanion gap metabolic acidosis
• Serum aldosterone and serum aldosterone to renin ratio elevated
• If aldosterone:  renin elevated and discrete unilateral mass present, perform adrenalectomy
• If aldosterone:  renin elevated and no mass, or bilateral adrenal lesions are present, consider adrenal vein sampling.  If sampling localizes, remove ipsilateral adrenal
• If no localization, start spironolactone

• Aldosterone is released when stimulation occurs from renin-angiotensin-aldosterone system and decreased blood volume
• Give increased Na+ resorption at nephron (distal portion)
• H+ and K+ increased secretion
• Therefore, may cause HTN, hypokalemia, and metabolic alkalosis
• Zona fasciculata
• Glucocorticoids (cortisol)
• Pregnenolone converted to cortisol when stimulation from ACTH occurs via enzymatic conversions involving 3 hydroxylases:  21, 11 beta, and 17 alpha.

• Addison’s disease (low cortisol) most common cause is withdraw of exogenous steroids
• Most common PRIMARY cause is autoimmune disease
• May also be seen with decreased aldosterone
• Cosyntropin stim test to diagnose (give ACTH and measure serum cortisol)
• Acute adrenal insufficiency:  refractory hypotension (despite pressors and fluids) give dexamethasone (will NOT interfere with cosyntropin stim test) More on adrenal insufficiency later in section.
• Waterhouse-Friedrichson is adrenal insufficiency owing to adrenal hemorrhage.  May be seen with sepsis.
• Cushing’s syndrome (hypercortisolism) most commonly due to exogenous steroid dosing
• Measure 24-hour urine cortisol and ACTH
• If ACTH low and cortisol high patient has cortisol secreting lesion
• If ACTH and cortisol are high, patient has pituitary adenoma or an ectopic source of ACTH
• So, give high dose dexamethasone suppression test.  If urine cortisol decreases, patient has pituitary lesion.  If not, has ectopic ACTH production (eg small cell lung CA). 
• Zona reticularis

• Sex steroids (dihydroepiandrosterone)
• Results in eventual production of testosterone
• From DHEA or 17 alpha hydroxyprogesterone

• These catecholamines are produced from tyrosine.  Pathway is tyrosine to L DOPA to dopamine to norepinephrine then finally epinephrine. 
• Tyrosine to L DOPA is rate limiting step (tyrosine hydrolase)
• PNMT (phenylethanolamine N methyltransferase) converts norepi to epi
• PNMT enzyme is ONLY found in adrenal medulla
• Byproducts including vanillylmandelic acid (VMA) and homovanillic acid are made
• MAO (monoamine oxidase) enzyme converts breaks down catecholamines to produce these

Supplied by middle adrenal artery (from aorta), superior adrenal artery (from phrenic), and inferior adrenal artery (from renal artery)

Most blood that eventually cortex enters passes through medulla first

Usually one adrenal vein on each side:  on R drains to IVC, on L drains to renal vein

 

“Incidentaloma” at adrenal

• Adrenal lesion found when patient worked up for other things, eg pan-CT scan for trauma patient
• Lesions may be functional or non-functional and benign or malignant
• Malignancy risk by size
• Less than 4 cm has approx. 2% risk of cancer
• 4-6 cm has approximately 6% risk of cancer
• Greater than 6 cm has 25% risk of cancer
• 5% are metastastatic lesion
• Rule out functional mass first with urine metanephrines, VMA, catecholamines, urinary hydroxycorticosteroids, serum potassium levels, plasma renin, and plasma aldosterone levels
• Foreboding CT scan signs include lesion > 4-6 cm, enlarging lesion over time, non-homogenous appearance
• CXR, mammogram, and colonoscopy may be performed to check for primary tumor if metastasis suspected
• Metastases to adrenals:  lung CA most common, breast, melanoma, renal cell CA
• Biopsy lesions (especially if cancer history) AFTER ruling out functional lesion
• Non-functional lesions > 4-6 cm should be removed owing to cancer risk.  So rather than needle biopsy, remove lesion.  Use of laparoscopic approach has been decreasing the size criteria felt to be appropriate for resection.
• If you decide to follow an incidental adrenal lesion over time rather than resect, repeat imaging every three months for first year followed by yearly thereafter.

Congenital Adrenal Hyperplasia

• Most commonly due to lack of 21 hydroxylase
• Decreased aldosterone and decreased cortisol
• Virilization seen as well as hypotension
• Decreased Na+, increased K+
• Increased 17 alpha progesterone
• Increased androstenedione
• Increased testosterone

 

Adrenal insufficiency

• Seen in up to 30% of critically ill ICU patients
• Primary is due to failure of gland owing to stress, atrophy, hemorrhage (again Waterhouse-Friedrichsen syndrome), etc.
• Symptoms range from subtle (weight loss, hyperpigmentation, abdominal pain) to severe (hypotension despite pressors)
• May see decreased Na+, increased K+, nongap metabolic acidosis
• Perform cosyntropin stim test

 

Pheochromocytoma

• From chromaffin cells
• Right sided lesions are more common
• Extra-adrenal lesions are more commonly malignant
• Most common location is adrenal gland, but may be seen in Organ of Zuckerkandl
• 10% malignant, 10% bilateral, 10% familial (remember MEN syndromes), 10% seen in children, 10% extra-adrenal
• Associated with von Recklinghausen’s (chromosome 17 easily remember because “von Recklinghausen” has 17 letters in it), Sturge-Weber, and tuberous sclerosis
• MIBG scan will identify location if you are unable to see lesion on CT
• 24-hour urine metanephrines is the best test, also send VMA
• Lesion does NOT respond to clonidine suppression test
• Pre-op:  volume load patient first, give alpha blockade (prazosin, phenoxybenzamine), THEN add beta-blocker if arrhythmias or tachycardia seen.  Do NOT add beta blockade before alpha blockade or patient may develop hypertensive crisis with stroke, MI, heart failure
• Nipride and neosynephrine as well as anti-arrhythmics should be readily available during surgery
• During adrenalectomy, ligate adrenal vein first to avoid spilling catecholamines during lesion manipulation

Metyrosine inhibits tyrosine hydroxylase causing decreased catecholamine synthesis