We recently discussed a case of adrenal
insufficiency. Here is an overview and some key points about the presentation
and work-up for adrenal insufficiency (AI):
Signs
and symptoms: * they
are non-specific
History: Nausea, vomiting, anorexia, abdominal pain, presyncope, salt
craving (only in primary AI)
Physical
Exam: Evidence of volume depletion including
tachycardia and hypotension, hyperpigmentation (only in primary AI)
Labs: Normocytic anemia, hyponatremia, hyperkalemia (only in primary
AI), hypercalcemia, hypoglycemia
How
to diagnose AI:
·
In patients who are unstable,
with suspected severe adrenal insufficiency symptoms or adrenal crisis, the
JCEM guidelines recommend immediate therapy with IV hydrocortisone at an appropriate
stress dose prior to the availability of the results of diagnostic tests
o There is some practice variation and no universally accepted or
evidence-based “stress dose of steroids”
o Some reasonable doses can include hydrocortisone 100mg IV x1 then hydrocortisone
for a total of approximately 200mg IV/day (for example hydrocortisone 50mg IV
q6h or hydrocortisone 100 mg IV q8h) x 24 hours then reduce the doses based on
clinical picture)
o If there is a need to give a stress dose of steroids immediately due
to clinical instability but there is a plan to still test for AI after by
measuring serum cortisol, giving dexamethasone may be a good choice of steroid,
as it is not measured in the assays for serum cortisol (hydrocortisone will
interfere with the test and is measured in the cortisol radioimmunoassay).
·
Based on the most recent JCEM
guidelines, the recommended test to diagnose adrenal insufficiency is a corticotropin stimulation test (ACTH stim
test).
·
If a corticotropin stimulation
test cannot be performed, measure morning
(8am) serum cortisol
o If 8 am cortisol <140 140="" nbsp="" nmol="" span="">à
adrenal insufficiency
o If 8 am cortisol 140-500 nmol/L à indeterminate
à need further testing (ACTH stim test)
o If 8 am cortisol >500 nmol/L à
essentially rules out AI à in most cases no further testing necessary
Corticotropin
stimulation test (ACTH stim test):
How
to do it: There are 2 protocols of ACTH Stimulation
tests. Both use synthetic ACTH (cosyntropin) to assess the adrenal’s response
to ACTH.
Standard
high-dose ACTH stimulation test: Give cosyntropin
250 mcg IV and measure serum cortisol at time 0, 30, 60 mins post-injection.
Low-dose
ACTH stimulation test: Give cosyntropin 1 mcg IV
and measure serum cortisol at time 0 and 30 mins post-injection.
Notes:
* Can also measure ACTH before giving the
cosyntropin to help determine if it is primary or secondary AI
* Do the stimulation test in the morning as
cortisol responses are greatest in the morning. If you do it in the evening,
you could get a False Positive test in a normal individual.
* Theoretically the low-dose ACTH stim test
is a more sensitive test, especially
for secondary AI, as it is a more physiological dose of ACTH, but typically
high-dose ACTH stim test in the standard test that is done first (it is what is
recommended in JCEM guidelines)
*Hold oral contraceptives before ACTH Stim
tests, as the increased cortisol-binding globulins with oral contraceptive can affect
the results of the test (can lead to underestimation of hypocorticolism)
* If you suspect an adrenal crisis, do not delay glucocorticoid replacement
therapy while awaiting the results of ACTH stim test to confirm the
diagnosis. You can consider using dexamethasone as the initial steroid of
choice as it does not interfere with serum cortisol assays.
How
to interpret ACTH Stim test:
Peak serum cortisol >500 nmol/L at any
point during ACTH stim test (before or after cosyntropin injection at 30 or 60
mins) à no AI à no further testing necessary
Peak serum cortisol <500 500="" acth="" during="" nbsp="" span="" stim="" test="">à indicates adrenal insufficiency à
further testing to determine etiology
Determine
etiology:
ACTH Stim test confirms adrenal
insufficiency (cortisol remains <500 span="">à
measure serum ACTH
ACTH >2-fold the upper limit of the
reference range à consistent with Primary AI (including Addison’s disease) à further work up which may include CT adrenal, adrenal antibodies,
17-OH proesterone
ACTH in low/low-normal range à Secondary or tertiary AI à Pituitary
MRI, measure other pituitary hormones to rule out panhypopituitarism
Management
Acute management (adrenal crisis):
ABCs, IV
normal saline, electrolyte management, stress-dose steroids (no universally
accepted or evidence-based dose, one example is hydrocortisone 100mg IV x1 then
hydrocortisone for a total of approximately 200mg IV/day (for example
hydrocortisone 50mg IV q6h or hydrocortisone 100 mg IV q8h) x 24 hours then
reduce the doses based on clinical picture)
Chronic
management:
·
Glucocorticoid replacement: guidelines
suggest hydrocortisone (15-25mg) or cortisone acetate (20-35mg) daily in two or
three divided oral doses/day, with the highest dose given in the morning
·
Mineralocorticoid replacement:
Fludrocortisone (starting dose 50-100 mcg) and no salt intake restriction.
Monitor mineralocorticoid replacement based on clinical assessment (salt
craving, postural hypotension, electrolytes).
·
Other: medical alert identification,
patient education, patient education regarding stress dosing when sick (basics:
double or triple dose of oral steroid when sick until recovery (usually 2-3
days); if not tolerating PO intake, need to come to hospital for IV steroids),
education and consultation regarding peri-operative management.
References:
1.
Bornstein S et al. Diagnosis
and treatment of primary adrenal insufficiency: an endocrine society clinical
practice guildeline. J Clin Endocrinol Metab. 2016;101(2):364-89
2.
Klose M et al. Factors
influencing the adrenocorticotropin test: role of contemporary cortisol assays,
body composition, and oral contraceptive agents. J
Clin Endocrinol Metab. 2007;92(4):1326.
