pheochromocytoma and neuroblastoma
How much do the adrenals glands weigh? (each)
What are epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine?
What are a few things that can destroy the adrenal glands?
neoplasm, infiltrative disease, fungal infections, hemorrhage, AI and AIDS
TB used to do it and is on the rise
What do you call the syndrome in which bleeds destroy the adrenals?
Waterhouse Friedrichsen syndrome
adrenals are sacs of clotted blood
begins in medulla, spreads to cortex
rapid onset of shock dt infx (bact septicemia) of insuff, death in hours-days if untx
Who can experience Waterhouse Friedrichsen syndrome?
newborns (dt traumatic delivery), children, adults
What sign may be seen on the skin?
DIC with extensive purpura
What color are adrenals with Waterhouse-Friedrichsen syndrome?
red-black (dt hemorrhage)
How much of the adrenal cortex must be gone before there are adrenal sx?
What are some of the sx of hypoadrenalism?
weakness, fatigue, hypotension, dizziness
anorexia, N/V/D, weight loss, abdominal pain
What do the labs show in hypoadrenalism?
low Na, Cl, bicarb, glucose and cortisol
high potassium and ACTH
What adrenal situation do you expect with low chloride, bicarbonate, glucose and sodium?
What is meant by Cushing's syndrome?
increased cortisol from any cause
What can produce ACTH--besides the anterior pituitary?
small cell carcinoma of the lung
carcinoid of the bronchus, pancreas
medullary carcinoma of the thyroid
What is meant by Cushing's disease?
high cortisol due to pituitary adenoma
Who gets pituitary adenomas?
young adults, female 5:1
What's the most common cause of excess cortisol?
What are some of the sx of hyperadrenalism?
fat redistribution to trunk, face and cervical-thoracic junction
flushed face (plethora), abdominal striae
easy bruising, poor wound healing
diabetes, HTN, osteoporosis
menstrual disorders, hirsutism
How do you diagnose Cushing sydrome??
cortisol: elevated throughout 24 hours
What result will you have with a dexamethasone suppression test if the cortisol is ectopic?
it will not be supppressed by the dexamethasone
If dexamethasone suppression test results in suppressed cortisol, what caused the Cushings?
the anterior pituitary
If someone presents with HTN, weakness, paresthesias, visual changes and tetany, what might you suspect?
hyperaldosteronism-->low renin and potassium, high sodium and aldosterone
If a person has low renin and potassium, and high sodium, what do you expect of the aldosterone level?
it would be high in hyperaldosteronism, pt will have HTN
What syndrome involves an aldosterone secreting adenoma?
Ingestion of what common herb can mimic hyperaldosteronism?
What else can induce excess aldosterone?
idiopathic adrenal hyperplasia
What kind of neoplasm makes catecholamines?
What are the top three locations for pheochromocytomas?
wherever there are chromaffin cells left in the body
#1 adrenal medulla, (85%)
#2 Organ of Zuckerkandl
#3 urinary bladder
#4 and 5: prostate, behind liver, where else???
What is the Organ of Zuckerkandl?
1) the most common extra-adrenal site of pheochromocytoma
2) The Organ of Zuckerkandl (or paraaortic bodies) is a chromaffin body derived from neural crest located at the bifurcation of the aorta or at the origin of the inferior mesenteric artery. Its physiological role is thought to be of greatest importance during the early gestational period as a homeostatic regulator of blood pressure, secreting catecholamines into the fetal circulation. The organ begins to regress late in the third trimester, continuing until after birth, to form the aorticosympathetic group of the adult paraganglia.
What are the main catecholamines?
most abundant: epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine
What amino acids are the precursors of catecholamines?
phenylalanine and tyrosine
What is spironolactone?'
Tx for hyperplasia of the adrenals according to SSL, below stuff according to wikipedia:
a synthetic 17-lactone drug
a competitive aldosterone antagonist (in kidney)
a potassium-sparing diuretic
used primarily to treat CHF, ascites, HTN, low-renin HTN, hypokalemia, and Conn's syndrome
on its own, only a weak diuretic, can be combined with other diuretics
***~1/100 person w/ HTN has elevated levels of aldosterone;
in these persons the antihypertensive effect of spiro. may exceed that of other antihypertensives even combined
anti-androgen effect-->used to treat hirsutism
also hormone therapy for male-->female transsexual/transgender
also used for treating hair loss and acne in women
can be used as a topical medication for treatment of male baldness
What's the Tx for adenoma according to SSL?
What's the #3 most common site for pheochromocytoma?
What's the #1 site?
What stains the catecholamines brown for ID?
What's the HTN like with a pheochromocytoma?
paroxysmal or constant
assoc w/ arrhythmias
CNS hemorrhage, headache, visual change
How do you diagnose a pheochromocytoma?
measure urinary catecholamines, metanephrine and VMA
Vanillyl mandelic acid
a metabolite of norepinephrine
found in the urine, along with other catecholamine metabolites: homovanillic acid (HVA)
timed urine tests: quantity (concentration μg /24 h) is assessed, creatinine clearance, concentration of cortisols, catecholamines, and metanephrines
also used to diagnose neuroblastomas, and to monitor treatment
***Norepinephrine breaks down into normetanephrine and VMA***
What are chromaffin cells?
neuroendocrine cells in the medulla of the adrenal gland and in symathetic ganglia
derived from the embryonic neural crest
EMBRYONIC DEVELOPMENT: in the fifth week of (human) fetal development neuroblast cells migrate from the neural crest to form the sympathetic chain and preaortic ganglia-->migrate a second time to the adrenal medulla. Also settle near the sympathetic ganglia, vagus nerve, paraganglia, and carotid arteries.
A few extra-adrenal chromaffin cells also reside in bladder wall, prostate, and behind liver.
I betcha that the prostate and retro-liver are 4th and 5th most likely locations for pheochromocytomas, whaddaya think??
What is Conn syndrome?
aldosterone secreting adenoma
What can cause severe hypertension in infancy?
rare autosomal dominant disorder characterized by early hypertension assoc w/ low plasma renin
metabolic alkalosis due to hypokalemia
hypoaldosteronism (low secretion of aldosterone)
one of several conditions known as pseudohyperaldosteronism
abnormal kidney function: excess resorption of sodium and loss of potassium
Tx: low sodium diet, potassium-sparing diuretic drugs
Etio: epithelial sodium channel mutated so it is no longer degraded correctly by the ubiquitin proteasome system-->increased activity-->increased sodium reabsorption-->hypertension.
NOTES TAKEN DURING CLASS ON HYPO AND HYPER ADRENALISM
HYPO AT BIRTH
congenital hypoplasia very rare, deadly if not treated
hyper pigmentation dt high ACTH from anterior pituitary-->MSH-->darker skin
adrenal failure in newborn, muscular dystrophy
adrenal dysfunction common, Addison's rare
chronic primary adrenal insuff
dstrx of adrenals by neoplasm, infiltrative dz, fungal, TB, hemorrhage, AI, AIDS
infilt: hemochromatosis, amyloidosis
fungal: histiomycosis, coccydiomycosis
TB was big cause back when, still is outside US but it's coming back
waterhouse frederickson syndrome dt hemorrhage
AI, glands are small, thin, pancake flat
have dz when 90% of gland lost
all zones of cortex are lost, atrophied
infiltrates: lymps, plasma cells, macrophages
hyperpigmented buccal mucosa, gums, skin, areas with pressure or friction, nipples, freckling, hair can get darker, scars too, skin creases
LOW BP, dizziness
emaciated, muscular weakness esp proximal muscles
appetite loss, vomiting and diarrhea, abd pain
low blood sugar
very low Na (normal 135-145, addisons may have below 120)
low Cl, bicab, glucose, cortisol
high potassium, ACTH
WATERHOUSE FRIDERICHSEN SYNDROME
sacks of clotted blood
newborns, children, adults
newborns have low prothrombin levels so more in them
ETIO: overwhelming bact septicemia, hypotension,
shock, traumatic delivery, DIC w/ extensive purpura (also assoc w/ infx or delivery)
adrenals are sacs of clotte blood
begins in medulla and spreads to cortex
rush to ER
rapid onset of shock dt infx of insuff
red-black disoloration dt hemorrhage
meningococcus is a common cause
extensive purpura, prostration, cyanosis
fever with low then high peaks repeating
production of cortisol from any cause
ETIO: iatrogenic, pituitary adenoma (5:1 females, young adult)
adrenal cortex neoplasms: adenoma, cancer, hyperplasia
"disease" is from adenoma, "syndrome" from any other source
mb assoc with other AI: SLE
could be dt ACTH from tumor instead of ant pit:
small cell carcinoma of lung
carcinoid tumor of bronchus, pancreas
pheochromatocytoma, makes catecholamines too
medullary carcinoma of thyroid
pituitary based: basophilic adenoma
adrenal based: diffuse hyperplasia gland up to 40 grams each
nodular hyperplasia, yellow nodules in cortex
florid red face, plethora = excess blood and tissue, florid is just face
round face, buffalo hump, truncal/central obesity
striae, atrophy of skin, atrophy of ligaments
wasting of extremities, skeletal muscles, thin arms and legs
poor wound healing, cortisol suppresses immune system
bruisability, vessel walls more fragile, collagen resorbed
osteoporosis, codfish compression of vertebrae
high blood sugar, insulin resistance, maybe high testosterone
menstrual disorders, hirsutism
psychiatric abnormalities: insomnia, mania, anxiety, psychosis
may present with psychosis!!
24 hour urinary free cortisol
dexamethasone suppression test is high dose synthetic cortisol: does it suppress cort? yes-->pit, no-->ectopic
low ACTH means adrenal tumor
low renin levels
mostly in women 30-50
adlosterone secreting adenoma = Conn syndrome
idiopathic adrenal hyperplasia is the big one
small, solitary ademoma may not show on US or CT
HTN--really high blood pressure
paresthesias, tingling, numbness
visual changes from pressure change
possible tetany dt Ca/Mg levels affected-->spasm
low plasma renin and potassium
high sodium and aldosterone
a treatable cause of malignant HTN: curable
very rare but you need to know it
forms catecholamines: epi, norepi
locations: (3) adrenal medulla (most common: 85%), also Organs of Zuckerkandle (neural tube-->neuroendocrine tissue along aorta, aka para-aortic nodes), urinary bladder
dichromate stains catecholamines brown
paroxysms of HTN