Flashcards in Adrenal Dysfunction Deck (26):
Contrast the venous drainage of left and right adrenals.
left adrenal vein drains into the left renal vein, the right adrenal vein drains directly into the IVC
When are levels of cortisol highest?
highest around 6-9am and lowest around 2p, there is variability in pulses but the pattern is generally biphasic
What enzyme does the zona glomerulosa lack?
17-hydroxylase (also not in the placenta?)
What are the clinical features of primary adrenocortical insufficiency?
glucocorticoids: weakness, fatigue anorexia, weight loss, GI disturbances
mineralcorticoids: hypotension, salt craving, postural symptoms, hyperkalemia
excess ACTH/MSH: hyperpigmentation
What are the common a rare causes of primary adrenocortical insufficiency?
major: autoimmune (80%), TB (20%)
rare: adrenal hemorrhage, infarction, fungal infections, metatastic disease, amyloidosis, sarcoid, HH, radiation, surgical adrenalectomy
How do the symptoms of secondary adrenal insufficiency differ from those of primary insufficiency?
similar but usually less pronounced (serum cortisol may be normal or low) esp. those symptoms related to low mineral corticoids because those are normally maintained by RAAS in absence of ACTH
hyponatriemia can be due to ADH/ACTH ratio
(acute syndrome can be caused by pituitary apoplexy)
What is Waterhouse Friedricksen Syndrome?
caused by infarction of the adrenal gland often accompanies meningococcal infection
What is a distinguishing symptom of adrenal hemorrhage.
usually commonly associated with pain, whereas chronic damage is unlikely to present with pain (flank/abdomen) as well as other symptoms shared with low levels of glucocorticoids
How do you distinguish between primary or secondary adrenocortical insufficiency from lab tests.
start with a serum cortisol (check when they are naturally low if concerned about hyposecrtion)
secondary test include rapid ACTH stimulation test (and measure cortisol) to determine if the adrenal gland is working
Name an iatrogenic cause of secondary adrenocortical insufficiency.
giving steroids (stop ACTH stimulation with negative feedback)
What are medical treatments for maintenance of therapy for adrenocortical insufficiency?
hydrocortisone (identical to cortisol), higher dose in AM
fludrocortisone- mineralcorticoid properties PO in AM
patient education re: ID bracelet and cortisol dose adjustment
monitor weight, blood pressure, electrolytes
What are features of Cushing's syndrome?
Contrast Cushing Syndrome and Cushing disease.
Cushing disease is specifically the condition of pituitary dysfunction causing low levels of glucocorticoids and cushingoid features
Cushing's syndrome can have many causes
Contrast ACTH dependent and independent causes of Cushing syndrome.
dependent: (central-ish) Cushing disease, ectopic corticotropin syndrome, ectopic CRH syndrome
independent: (adrenal-ish) adrenal adenoma, adrenal carcinoma, macro nodular hyperplasia
What types of tumors cause ectopic ACTH syndrome?
small cell carcinoma of the lung (50%)
pancreatic islet tumors
(can present with sudden onset DM, HTN, very high ACTH and hypercalemia)
How do you differentiate between pituitary and ectopic causes of excess CRH/ACTH?
pituitary tumors often show suppression when dexamethasone is administered (some overlap)
ectopic tumors will not respond to CRH stimulation where as those with Cushing disease do respond
pituitary tumors present with a gradient if bilateral simultaneous blood sampling of inferior petrosal sinuses is performed (**with CRH stimulation)
What are different ways you can detect excess cortisol?
24hr. cortisol urine collection
salivary cortisol around midnight (after low-key evening)
How does the level of ACTH secretion vary with whether the ectopic source of ACTH is benign or malignant?
much higher levels are see in malignant tumors v. benign
What treatments are indicated for Cushing's disease?
TSS, pituitary irradiation and total bilateral adrenalectomy (in that order)
caution: removal of adrenal gland can sometimes remove negative feedback and lead to expansion of tumor and Nelson's syndrome (hyper pigmentation)
What treatments are indicated for adrenal tumor?
surgical resection of tumor, for carcinomas, cure is often not possible, +/- adrenal enzyme inhibitors
What treatments are indicated for ectopic sources of excess glucocorticoids?
surgical resection if tumor can be found, octreotide scans helpful (often difficult with NET), adrenal enzyme inhibitors may be used in malignant disease and indolent tumors may be related by medical or surgical adrenalectomy
What DNA segment does the GR receptor bind to within the nucleus after being activated?
GR translocates, dissociated from HSP and binds to GRE segments of gene to regulate transcription.
How do steroids interfere with the immune system?
GR binding creates a product that slows the metabolism of INFkB binding protein, INFkB protein is inactive when bound to the carrier protein, reducing inflammatory response
What is unique about the pharmacology of fludrocortisone?
potent mineral corticoid activity with negligible glucocorticoid actions
What are the most potent forms of glucocorticoids?
dexamethasone (strongest, no MR activity)