CUSHING SYNDROME AND CUSHING DISEASE Flashcards
what hormone does the zona glomerulosa release?
mineralcorticoids: aldosterone
what hormone does the zona fasciculata release?
glucocorticoids: cortisol, corticosterone, cortisone
what hormone does the zona reticularis stimulate?
androgens that stimulate masculinization-> dehydroepiandrosterone
what hormone does the adrenal medulla secrete?
stress hormones that stimulate the sympathetic ANS: epinephrine and norepinephrine
what does the hypothalamus do in the HPA axis?
it secreted CRH that stimulates the release of ACTH from the anterior pituitary gland
when ACTH is released in the HPA axis, what does ACTH do next?
like CRH, ACTH follows the circadian rhythm
ACTH increases in the early morning hours before awakening with peak levels in the morning around 8:00 and decrease in the evening
what does the adrenal gland (cortex) do in the HPA axis?
what things are secreted from adrenal gland-only two
the zona fasciculata (cortisol) and zona reticularis (androgens) are stimulated by ACTH
what is the zona glomerulosa (aldosterone) stimulated by?
it is primarily regulated by the renin-angiotensin system and potassium levels
what is cushing syndrome?
a constellation of clinical abnormalities caused by chronic high blood levels of cortisol
what is primary hypercortisolism?
increased production of glucocorticoids by adrenal glands
tumor- adrenal adenoma or adrenal carcinoma
what is secondary hypercortisolism?
- cushings disease which is a subtype of cushings syndrome
- increased pituitary ACTH production leading to
adrenal gland hyperplasia (most likely d/t pituitary
adenoma)
- increased pituitary ACTH production leading to
- ectopic ACTH syndrome
- increased ACTH production outside the pituitary and
adrenal glands (paraneoplastic syndromes- SMALL
CELL LUNG CANCER )
- increased ACTH production outside the pituitary and
are primary and secondary hypercortisolism endogenous or exogenous?
endogenous
is endogenous or exogenous the most common form of hypercortisolism and what is the reason?
exogenous- medical use of glucocorticoids
what does exogenous cortisol cause at the level of the hypothalamus and anterior pituitary?
a negative feedback that leads to decreased CRH and ACTH
what occurs during long-term exogenous glucocorticoid use?
- cortisol will not be released by the body
- atrophy of the zona fasciculata
what occurs when a patient abruptly discontinues exogenous glucocorticoid use?
the body cannot produce enough cortisol and adrenal insufficiency will occur leading to an adrenal crisis
what is ACTH independent cushings syndrome?
the adrenal glands produce cortisol without stimulation from ACTH
what is ACTH dependent cushings syndrome?
the body makes too much ACTH which in turn increases the production of cortisol
what is the clinical presentation of cushings?
moon face
truncal (central) obesity
prominent supraclavicular and dorsal cervical fat pads (buffalo hump)
thin distal extremities and fingers
proximal muscle wasting
recurrent opportunistic or bacterial infections such as crypto neoformans, or candida species
thin and atrophic skin
violaceous striae wider than 1 cm (abdomen)
does cushings syndrome cause hypo or hypertension?
atrial hypertension
what does the increased blood pressure in cushings syndrome lead to?
pseudohyperaldosteronism
what are the different diagnostic tests for high cortisol/ cushings?
- 24-hr urine for free cortisol level
- dexamethasone suppression test
- plasma ACTH levels
- CRH stimulation test
- serum or saliva cortisol measurement at midnight to assess the normal fall of cortisol
what high cortisol result will you seen in a 24-hr urine for free cortisol level ?
> 4 times the upper limit of normal cortisol levels
what is the dexamethasone suppression test?
- 1-2 mg of dexamethasone is given orally at 11 pm (normally should decrease ACTH) and serum cortisol is measured at 8 am the next morning (normally should decrease serum cortisol)
- increase cortisol levels= positive test and further testing is needed
what is the plasma ACTH level test?
it is measured to determine the cause of cushing syndrome
what is the CRH stimulation test?
patient is given synthetic CRH
what does an increase in ACTH and cortisol during the CRH stimulation test mean, and what are the next steps?
- cushings disease
- order an MRI of the brain w/ contrast
what does no increase in ACTH and cortisol during the CRH stimulation test mean, and what are the next steps?
- ectopic ACTH secretion
- order a CT scan of the chest, abdomen, and pelvis
what if there is an increase in levels during the plasma ACTH level test?
- high levels -> pituitary (cushings disease or ectopic source)
what if there is a decrease in levels during the plasma ACTH level test?
- low levels -> primary adrenal cause (adenoma, carcinoma, exogenous glucocorticoids)
what is the first diagnostic thing you should do before testing?
exclude exogenous glucocorticoid use
what are the treatment options/types for hypercortisolism?
- stopping exogenous glucocorticoids- gradual
withdrawal - pituitary, adrenal, or ectopic ACTH-producing tumor
treatments - adrenalectomy
- nonresectable tumor treatments
what is the treatment for pituitary, adrenal, or ectopic ACTH-producing tumors?
- surgical removal
- radiation
what will patients with an adrenalectomy require?
glucocorticoid replacement therapy
what are the treatments for nonresectable tumors?
- glucocorticoid receptor antagonists
- adrenal enzyme inhibitors
- dopamine agonists
what is an example of a glucocorticoid-receptor antagonist and its MOA?
mifepristone- blocks effects of cortisol in tissues
what is an example of a adrenal enzyme inhibitors and its MOA?
ketoconazole and metopirone- decrease cortisol production
what is the MOA of a dopamine agonist?
inhibits ACTH secretion
what is a pheochromocytoma?
a catecholamine-secreting tumor that mimics over-activity of the sympathetic nervous system
where do the majority (90%) of pheochromocytomas originate?
in the adrenal medulla where catechomaines are
what is the BIG 3 clinical presentation of pheochromocytoma?
- HA
- tachycardia/palpitations
- sweating
what are the non- big 3 clinical presentations of pheochromocytoma?
- HTN (sustained or paroxysmal)- most common symptom
- elevated metabolic rate
- hyperglycemia
- nervousness
what is the most common symptom of pheochromocytoma?
HTN (sustained or paroxysmal)
what is the treatment of pheochromocytoma?
surgical resection
