Adrenal AxisTesting: Making the Diagnosis Cynthia R. Ward, VMD ...

Adrenal AxisTesting: Making the Diagnosis
Cynthia R. Ward, VMD, PhD, Dipl. ACVIM
Professor of Medicine
Chief of Staff Inpatient Medicine
University of Georgia School of Veterinary Medicine
April, 2011
I. Regulation of Secretion of glucocorticoids - corticosterone and cortisol
A. hypothalamic-pituitary-adrenal (HPA) axis - classic endocrine
feedback loop
a. CRH (hypothalamus)
b. ACTH (pituitary)
c. Cortisol (adrenals)
d. Cortisol negative feedback on CRH and ACTH release
II. Diseases of the Adrenal Cortex and how to diagnose them
A. Hypoadrenocorticism
a. primary disease - destruction of the adrenal cortex
b. iatrogenic
i. mitotane (Lysodren)
ii. trilostane (Vetoryl) – can also cause adrenal necrosis
iii. abrupt withdrawal of glucocorticoids
iv. bilateral adrenalectomy
B. Diagnosis
a. Decreased Na:K ratio - less than 25-27 consistent with addison’s disease
b. ACTH-stimulation test – definitive test
i. normal pre 1-4 mcg/dl cortisol
ii. normal post 10-18 mcg/dl cortisol
iii. Addisons: pre and post sample

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1. rationale: gives cortisol estimation since last time dog urinated - so
usually get an estimate of plasma cortisol over several hours
2. procedure: collect urine sample (preferably owners collect at home);
urine cortisol measured and compared to creatinine to normalize
for urine concentration
3. interpretation - if morning urine (really should be 3 on separate days)
sample(s) less than 10 (or use your lab’s reference ranges) then
animal probably doesn’t have Cushing’s. If > 10 then you need to
do another screening test. Very sensitive; not specific
b. ACTH-stimulation test
1. rationale: stimulate gland to determine hormonal reserve;
if gland is hyperfunctioning you should get an exaggerated
response
2. interpretation:
(1) normal pre 1-4 mcg/dl cortisol
normal post 10-18 mcg/dl cortisol
(2) gray area post sample (may/may not be
hyperadrenocorticism)18-22 mcg/dl
(3) post > 22 mcg/dl think hyperadrenocorticism
3. uses:
(1) test of choice for diagnosing iatrogenic
hyperadrenocorticism
(2) screening test for hyperadrenocorticism – is a more
specific test in animals with concurrent disease
(3) monitoring lysodren therapy
(4) 60-75% sensitive
(5) 85-90% specific
c. Low Dose Dexamethasone Suppression Test (LDDS)
1. rationale: take advantage of the normal negative feedback
mechanism in the HPA axis. If you can’t suppress
the system normally, then suspect hyperadrenocorticism
2. procedure:
(1) get baseline cortisol
(2) give 0.01 mg/kg dexamethasone IV
(3) get 4 and 8 hour post-injection cortisol samples
(4) can use dexamethasone SP or dexamethasone in
polyethylene glycol
3. interpretation:
(1) look at the 8 hour post-injection sample first; in a
normal animal it should be below the normal range; the
gray area in which you can’t make a diagnosis is 1.0-1.4
ug/dl; greater than 1.4 mcg/dl is consistent with
hyperadrenocorticism
(2) the 4 hr post-injection sample is used as a
discriminating test (to tell whether there is an adrenal tumor or
PDH)
4. advantages:
(1) more sensitive for diagnosis of hyperadrenocorticism
85-95% sensitive

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(2) by getting the four hour sample, can also use as a
discriminating test for hyperadrenocorticism (i.e.
tell whether hyperadrenocorticism is due to a
pituitary or adrenal tumor)
5. disadvantages:
(1) 8 hour test
(2) may be less specific in animals with concurrent disease
(i.e. get false positives) 70-75% specific
6. uses:
(1) screening test for hyperadrenocorticism
(2) discriminating test for hyperadrencorticism
3. Discriminating Tests for Adrenal Function
(tests to differentiate pituitary- versus adrenal-dependent hyperadrenocorticism)
a. Low Dose Dexamethasone Suppression test – 4 hour sample
b.. Endogenous ACTH levels
i. measure on a single blood sample
ii. if how – adrenal tumor
iii. if very high – PDH
iv. significant overlap between normal and dogs with PDH
c. Ultrasound
i. look for adrenal tumors and contralateral adrenal atrophy
ii. look for bilateral adrenal enlargement
iii.look for potential metastatic disease
d. High Dose Dexamethasone Test (HDDST)-no longer recommended
ACTH-Stimulation Test
1. Synthetic ACTH (cortrosyn)
2. ACTH gel – compounded by compounding pharmacy (be careful)
3. Cortrosyn
a. 5 mcg/kg cortrosyn IV (or IM)
b. adrenal hormone(s) that you want to measure before and 45-60 min after
injection
c. Can reconstitute and freeze cortorsyn in aliquots. Stable for 6 months.
4. ACTH gel – trust your pharmacy
a. 2.2 U/kg IM or check with your pharmacy
b. Adrenal hormone(s) measured pre and 2 hours post injection
C. Feline Adrenal Axis Testing
a. LDDST – use 0.1 mg/kg of dexamethasone (instead of 0.01 mg/kg of
dex for a dog); use the same criteria for diagnosing
hyperadrenocorticism
b. ACTH-stimulation test
i. 5 ug/kg synthetic ACTH IV
ii. Cortisol levels at 60 and 90 minutes
iii. Cortisol above 16 ug/dl (slightly lower than dogs) consistent
with hyperadrenocorticism
iv. Low sensitivity (~50%)
c. Adrenal ultrasonography