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Adrenal pathology

What can you diagnose by measuring vanillyl mandelic acid in the urine?
pheochromocytoma and neuroblastoma

How much do the adrenals glands weigh? (each)

4-6 grams

What are epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine?
catecholamines

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?
90%

What are some of the sx of hypoadrenalism?
weakness, fatigue, hypotension, dizziness
anorexia, N/V/D, weight loss, abdominal pain
hyperpigmentation

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?
hypoadrenalism

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
thymoma
pheochromocytoma
gastrinoma
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?
iatrogenic

What are some of the sx of hyperadrenalism?
fat redistribution to trunk, face and cervical-thoracic junction
weakness, fatigue
flushed face (plethora), abdominal striae
easy bruising, poor wound healing
diabetes, HTN, osteoporosis
menstrual disorders, hirsutism
psychiatric abnormalities

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?
Conn syndrome

Ingestion of what common herb can mimic hyperaldosteronism?
licorice, glycyrrhiza

What else can induce excess aldosterone?
adrenal carcinoma
idiopathic adrenal hyperplasia

What kind of neoplasm makes catecholamines?
pheochromocytoma

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?
surgery

What's the #3 most common site for pheochromocytoma?
urinary bladder

What's the #1 site?
adrenal medulla!

What stains the catecholamines brown for ID?
dichromate fixative

What's the HTN like with a pheochromocytoma?
paroxysmal or constant
assoc w/ arrhythmias
CNS hemorrhage, headache, visual change
hyperglycemia, hypermetabolism

How do you diagnose a pheochromocytoma?
measure urinary catecholamines, metanephrine and VMA

What's 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?
Liddle's syndrome
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

ADDISON'S DISEASE
adrenal dysfunction common, Addison's rare
chronic primary adrenal insuff
ETIO:
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
SX:
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
LABS:
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
acute hypoadrenalism
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
circulatory collapse
extensive purpura, prostration, cyanosis
fever with low then high peaks repeating

CUSHINGS
more common
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
thymoma
pheochromatocytoma, makes catecholamines too
gastrinoma (carcinoid)
medullary carcinoma of thyroid
pituitary based: basophilic adenoma
adrenal based: diffuse hyperplasia gland up to 40 grams each
nodular hyperplasia, yellow nodules in cortex
SX
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
pendulous abdomen
poor wound healing, cortisol suppresses immune system
high BP
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!!
Dx:
24 hour urinary free cortisol
or ACTH
dexamethasone suppression test is high dose synthetic cortisol: does it suppress cort? yes-->pit, no-->ectopic
low ACTH means adrenal tumor

PRIMARY HYPERALDOSTERONISM
low renin levels
mostly in women 30-50
ETIO
adlosterone secreting adenoma = Conn syndrome
idiopathic adrenal hyperplasia is the big one
adrenal carcinoma
MORPH
small, solitary ademoma may not show on US or CT
SX
HTN--really high blood pressure
weakness
paresthesias, tingling, numbness
visual changes from pressure change
possible tetany dt Ca/Mg levels affected-->spasm
DX
low plasma renin and potassium
high sodium and aldosterone
TX
adenoma-->surgery
hyperplasia-->spironolactone med
a treatable cause of malignant HTN: curable

PHEOCHROMOCYTOMA
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
SX
paroxysms of HTN
afib
CNS hemorrhage

Comments

( 3 comments — Leave a comment )
newedition
Dec. 18th, 2009 06:39 pm (UTC)
Adrenal fatigue question
Hi, it's NewEdit.
I've been looking up information about this a lot lately and have two questions that I haven't been able to find the answer to. I wonder if you would know?

- Bovine/porcine adrenal gland extract is sometimes given for adrenal fatigue. But since the adrenal glands produce adrenaline, would taking this extract make a person feel overstimulated?

- In severe or prolonged adrenal fatigue, cortisol is low. From what I've read, cortisol and DHEA act in opposition. Yet DHEA is prescribed for adrenal fatigue. Would this further lower the cortisol level?
liveonearth
Dec. 19th, 2009 04:38 pm (UTC)
Re: Adrenal fatigue question
Hi there. The glandulars may contain a little cortisol, but so far I haven't seen it be overstimulating. The notion is that by consuming the gland you're taking in some of the nutrition that you need for your own adrenals to work better.

DHEA is not exactly "opposite" of cortisol. It is a steroid precursor of many other hormones. When one takes DHEA it is hard to say which hormones may increase as a result, because there are several pathways down which it may go. It depends on which enzymes work best, which varies by the individual and can be influenced by diet and lifestyle. That is why it is rarely prescribed and not recommended for people to just buy OTC to self-treat. It is prescribed for adrenal fatigue because cortisol is also a steroid, so it is supplying a precursor. If your issue was not one of lacking precursors, it won't help.

The best treatment I know for adrenal fatigue is eating regular small meals which contain protein, and keeping one's stress level to a minimum by living a predictable, scheduled life. This is not easy to do, but it definitely helps.
newedition
Dec. 22nd, 2009 02:31 pm (UTC)
Re: Adrenal fatigue question
Thanks for that information :-)
Happy holidays!
( 3 comments — Leave a comment )

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