Adrenal Insufficiency Flashcards
Causes of Primary Adrenal Insufficiency
- Autoimmune
- Infection - Tb worldwide; HIV pts w/ CMV or mycobacterium avium in US
- Infiltration
- Bilateral adrenal apoplexy (hemorrhage)
- Surgical resection
- Metabolic
- Congenital adrenal hyperplasia syndromes
- Drugs - Etomidate (anesthetic) & ketaconazole - inhibit 11 beta hydroxylase
- Abiraterone (anti-adronergic for prostate cancer) - blocks 12alpha hydroxylase
- Adrenoleukodystrophy
Autoimmune Adrenalitis
- humoral and cellular immune damage –> fibrosis and atrophy
- most common are antibodies against 21 hydroxylase (most common primary)
- Isolated, sporadic (50%)
- Polyglandular Syndromes (50%)
- I - Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy; auto rec AIRE gene mutation; primary hypoparathyroidism and mucocutaneous Candida b/f age 10; autoimmune adrenalitis at 10-15
- II - Schmidt’s Syndrome- primary adrenal insufficiency often first (20-40 yr) then autoimmune thyroid disease and poss DM Type 1
Bilateral Adrenal Apoplexy
- ACUTE; extreme stress causes inc press in adrenal vessels + underling predisposition to bleeding or thrombosis –> hemorrhage into both adrenals AND hypotension (no cortisol)
- Can be seen in bacterial sepsis (N meningitidis, pseudomonas, staph) - Waterhouse-Fridericksen Syndrome
Congenital Adrenal Hyperplasia Syndromes (3 forms)
- auto recessive dec cortisol synthesis –> inc ACTH to comp –> adrenal hyperplasia –> inc hormones proximal to missing enzyme and dec hormones distal to missing enzyme
1- Most common is dec or no 21 hydroxylase –> needed for cortisol and aldosterone so both are dec; but inc DHEA and androsteredione
- Females w/ this syndrome can have excess androgens leading to hirsutism, amenorrhea, acne, ambiguous genitalia if severe
2- 11betahydroxylase def - later step in cortisol and aldo synthesis so still neither of them but get inc DOC in addition to inc androgens
3- 17alpha hydroxylase def - needed for cortisol and androgen synthesis; dec androgens (hypogonadism) and inc DOC
**DOC activates MR in kidney so HTN and hypokalemia
Adrenoleukodystrophy
X linked rec
-defective beta oxidation of FAs –> lipid build up in adrenals and brain
Causes of Secondary Adrenal Insufficiency
- Suppression of HPA axis
- Usually from withdrawal of exogenous GC tx (most common overall)
- Primary adrenal tumor
- High dose megestrol or opioids
- Hypopituitarism - hypothalamus or pituitary problem
- Masses, head injury, aneurysm, infarct (Sheehan’s)
- Autoimmune hypophysitis (worse on check pt inhib)
- 75% of endogenous secondary adrenal insufficiency due to pituitary adenomas
Withdrawal from Exogenous GCs
- When using GCs, no ACTH needed so zona fasciculata and reticularis atrophy
- Can take a yr after meds to recover (hypothal –> pit –> adrenal)
Presentation of Primary v Secondary Adrenal Insufficiency
- In both primary and secondary … (dec cortisol)
- Weak, wt loss, anorexia, nausea, vomit, ab pain, constipation, diarrhea, sex dysfunction (all non-specific)
- High suspicion if hypotension, hyponatremia, hypoglycemia
- Just chronic primary … (dec aldosterone too) hyperkalemia, acidosis, hyperpigmentation, salt craving
- Primary are volume contracted while secondary usually not
- Adrenal medulla / catecholamine synthesis can be impaired w/ no clinical manifestations b/c ANS compensates
What is an adrenal crisis and how do you treat?
- When those w/ adrenal insufficiency have cardio collapse
- Marked hypotension that will not response to pressors or volume loading
- Fever, ab pain, hypoglycemia, delirium
- Tx = high dose GCs (inc sensitivity to pressors)
Dx of Primary and Secondary Adrenal Insufficiency
- Screen - meas cortisol and ACTH in AM (peak) or in periods of stress
- Confirm - ACTH stimulation test (give ACTH then check for inc cortisol 30-60 min later)
- Primary - will have little or no inc cortisol
- Secondary - will have detectable but still sub-normal inc in cortisol
**Cannot be used if acute onset of secondary adrenal insufficiency b/c it takes weeks for ACTH def to produce adrenal atrophy (test will be normal; test does not eval hypothalamus or pituitary)
3 Commonly Used GC Replacements
- Hydrocortisone - shortest acting (6-10 hrs) so give 2/3 dose in morning and 1/3 dose in afternoon (diurnal pattern)
- Prednisone - intermediate acting (12-36 hrs) also give 2/3 then 1/3
- Dexamethasone - long acting (24-72 hrs) and very potent so not used for chronic therapy b/c causes over-replacement; given once daily
**Must inc dose in times of stress (high initial dose then quick taper)
Which GC for kids? Which for pregnancy?
- Kids - use hydrocortisone b/c even prednisone causes over-replacement
- Pregnancy - use hydrocortisone (inactivated by placenta HSD11beta2 (dexamethasone is not)
Tx for Adults w/ Congenital Adrenal Hyperplasia
- usually prednisone b/c longer acting than hydrocortisone for more continuous suppression of plasma ACTH (prevent/reverse hyperplasia) but also safer than dexamethasone
Mineralocorticoid Replacement
- only used in primary adrenal insufficiency
- Can maintain high salt diet to comp for Na lost in urine OR give replacement (fludrocortisone - slow onset so use IV w/ NaCl and hydrocortisone if emergent vol depletion)
