Adrenal Insufficiency Flashcards
cortisol binds ___ in plasma
CBG
(also albumin to lesser extent)
primary vs secondary adrenal insuf clinical presentation differ because
in primary, aldosterone is also absent
adrenal venous drainage
right adrenal vein to posterior IVC
left directly to left renal vein
ACTH secreting neoplasms in Cushings have a higher set point for ____
glucocorticoid negative feedback
earliest biochemical finding in cushings
lack of nadir or cortisol secretion late at night
pathophysicology ACTH independent hypercortisolism
solitary tumor or bilateeral adrenal nodular disease
ACTH low in patients due to corisol negative feed back, making contralteral adrenal small
lab abnls in adren insuf
hyperkalemia (primary)
hypercalcemia, hypoglycemia (rare in adults)
lymphocytosis
Rx cause of pituitary disease related secondary adrenal insufficiency
ipilimumab
Primary adrenal insufficiency =
Secondary adrenal insufficiency =
Teritiary adrenal insufficiency =
impaired production of cortisol from adrenal cortex due to dysfunctional adrenal gland
diseases of pituitary (ACTH def)
diseases of hypothalamus (CRH def)
2 caveats for cortisol testing outcomes
- chronically ill may have low binding proteins - low total cortisol with normal free levels
(estrogen, contraception may increase cortisol levels reflecting increase in binding proteins with no adrenal dyfunction
- adrenal androgen production is a sensitve marker of adrenal reserve and normal levels are very rare in adrenal insuff
concurrent disorders common with adrenal insuff
critical illness with hypotension
pituitary diseasse
TBI
Brain radiation
explanation of skin pigmentation changes with marke ACTH elevation
presence of alpha melanocyte stimulating hormone amSH within peptide hormone complex POMC from which ACTH is processed from
Rx causes of adrenal insuff
Withdrawal from corticosteroids
narcotics (supress CRH/ACTH)
Ketoconazole, etomidate, mitotane (adrenostatic/lytic)
mifepristone (glucocorticoid receptor antagonist)
presenting symptoms adrenal insufficiency
fatigue, low energy
nausea/vomiting/weight loss
hypotension > dizzyness, orthostasis
increased skin pigmentation and salt craving (primary)
response to acute adrenal crisis
Admin hydrocortisone 100mg IV every 6hrs for 24hr
once stable, taper 50mg every 6 hours and then taper to maintenance
porgesterone compound used to stimualte apetite and cause suppression of ACTH and cortisol
megestrol acetate
congenital causes of adrenal insuf
congenital adrenal hyperplasia
adnrenoleukodystrophy (X-linked with accumulation of very long chain FAs in adrenals and brain)
normal cortisol response to ACTH//Cosyntropin
peak resposne at 30 or 60 min >18ug/dL (500nmol/L)
Treatment and Rx for Cushings syndrome
Surgery (ressection or bilateral adrenalectomy if refractory)
Radiotherapy
Pasireotide - somatostating receptor antagoinist
Metyrapone - 11-betahydroxylase inhibitor (p450 c11)
Mifepristone - glucocorticoid receptor antagonist
cortisol exerts ___ feedback on CRH/ACTH
negative
presenting symptoms that raise suspicion for Cushings
Weight gain (truncal)
SUpraclavicular and dorsocervical fat
facial rounding and plethora
proximal muscle weakness
Hirsutism, angrogen excess in females
Wide violaceous stria
Easy bruising, cutaneous atrophy
Cognitive difficulty, depression, psychosis
Cortisol mechanism of action
Binds gluccocorticoid receptor >
> dissociation of heat shock proteins + dimerization >
> dimers translocate to nucleus > enhance glucocorticoid related genes.
in 17-hydroxlyase deficiency, ____ makes up for deficiency of corisol
corticosterone
causes of primary adrenal insuf
Autoimmune
Adrenal hemorrhage (associated with coagulopathis, bilateral)
Infectious (TB, histoplasmosis, coccidiomycosis, HIV)
Genetic
Infiltrative (amyloidosis, hemochromatosis)
Drugs (ketoconazole, metyrapone, mititoane, etomidate)
(Autos Are Infectious, Impressive Diversions)
injectable hydrocortisone for emergent use
Solu-Cortef
if in suspected ACTH dependent Cushings, if MRI of pituitary is normal or equivocal >
outcomes?
bilateral pitrosal sinus sampling with ACTH admin
no gradient = occult ectopic ACTH
gradient = cushings disease
Drugs associated with primary adrenal insuf
Ketoconazole
metyrapone
mitotane
etomidate
diagnostic tests for cushings
Late night salivary cortisol - lack of nadir
Overnight dexmethasone supression test - normal suppression = cortisol
24 hour urine free cortisol (poor senstivity)
ACTH is processed from ___ inside the pituitary gland corticotropj
POMC
initiating process in cortisol synthesis
cholesterol import into mitochondrion via StAR protein
first step in DDx for Cushings
outcomes?
measure plasma ACTH
Low = independent Cushings > Adrenal CT
Normal or elevated = ACTH dependent > MRI of pituitary
glucocoritcoid receptor antagonist used for endogenous hypercortisolism
mifepristone
in kidney, cortisoal metabolized to cortisone via
and converted back to cortisol via ____ inside the _____
11B-HSD2
back via 11B-HSD1 in liver and visceral fat
aldosterone pathway in zona glomerulosa is stimulated by
ang II
Potassium
ACTH
diagnoses that raise suspicion for Cushings
Diabetes/HTN/metabolic syndrome
Osteoporosis
Adrenal nodules
intitial evalulation of suspected adrenal insuff
follow-up
morning cortisol
cosyntropin stimulatory test of adrenal reserve
steroid production in zona fasciculate controlled by
ACTH (via hpyothalamus)
CRH
AVP
(also negative feedback(
lab findings Primary vs secondary adrenal insuf
Pimary High ACTH
HIGH PRA
low Aldosterone
**Secondary: **low-normal ACTH
normal PRA
normal aldosterone
