Updates on hypoadrenocorticism - Veterinary Medicine
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Updates on hypoadrenocorticism
The lack of a stress leukogram in dogs with gastrointestinal signs may signal this potentially life-threatening disease. This review will help ensure that you aren't overlooking other clinical signs and that you know the latest about diagnosing and treating canine hypoadrenocorticism.



Glucocorticoid deficiency

Table 3: Diagnostic Test Results in Dogs with Hypoadrenocorticism*
There are two methods to assess adrenal function: dynamic testing and measurement of basal cortisol concentrations (Table 3).

ACTH stimulation test. Dynamic testing with an ACTH stimulation test is the gold standard for diagnosing cortisol deficiency.1 The test compares plasma cortisol concentrations before and after stimulation with synthetic ACTH (cosyntropin).1 Natural ACTH (ACTH gel) can also be used, but because of limited availability and the potential to induce immunologic reactions, cosyntropin is preferred.19

To perform an ACTH stimulation test, collect a blood sample to measure a baseline cortisol concentration. Then give 0.25 mg/dog of cosyntropin intramuscularly or intravenously, and collect a blood sample 60 or 90 minutes later to measure the post-ACTH cortisol concentration.1 In healthy dogs, similar post-cosyntropin serum cortisol concentrations are obtained regardless of whether cosyntropin is given intravenously or intramuscularly or whether samples are collected 60 or 90 minutes after cosyntropin administration.20 A post-ACTH plasma cortisol concentration < 2 μg/dl indicates a lack of an appropriate response and is diagnostic for hypoadrenocorticism.1

To minimize the cost of cosyntropin, an intravenous dose of 0.005 mg/kg may be used since this dose results in a similar degree of stimulation in healthy dogs and dogs with hyperadrenocorticism.19,21 Reconstituted cosyntropin can be stored frozen (-4 F [-20 C]) in plastic syringes for up to six months.22 Although no published data confirming this exist, some veterinarians store reconstituted cosyntropin in the refrigerator (39.2 F [4 C]) for up to 24 hours without a perceived change in potency.

Basal cortisol concentration. Measuring a basal cortisol concentration has been proposed as a diagnostic test for hypoadrenocorticism in dogs. In one study of 13 dogs with hypoadrenocorticism and 110 healthy dogs, a basal cortisol concentration ≤ 1 μg/dl had a sensitivity of 100% and specificity of 98.2% for hypoadrenocorticism.23 The same study found that using a cutoff of ≤ 2 μg/dl for the basal cortisol concentration had a negative predictive value of 100%.23 These data indicate that basal cortisol concentrations can be used to rule out hypoadrenocorticism in dogs with appropriate clinical signs that are not receiving drugs that could potentially alter cortisol secretion such as glucocorticoids, mitotane, trilostane, or ketoconazole. However, given the low disease prevalence of hypoadrenocorticism in dogs, this test had a poor positive predictive value.23 Since basal cortisol concentrations have a poor positive predictive value and hypoadrenocorticism requires life-long therapy, ACTH stimulation testing is still the test of choice for definitively diagnosing hypoadrenocorticism in dogs.

CAR. The ratio of basal cortisol concentration to endogenous ACTH concentration (CAR) is an additional method to diagnose primary hypoadrenocorticism.24 The reference interval CAR in healthy dogs is 1.1 to 26.24 Dogs with primary hypoadrenocorticism should have low cortisol and high ACTH plasma concentrations, resulting in a low CAR. In one study of 22 dogs with primary hypoadrenocorticism, the CAR was 0.003 to 0.17, well below the reference interval.24

This test allows for a specific diagnosis of primary hypoadrenocorticism in dogs with a single blood sample. Since endogenous ACTH concentrations will be low in dogs with secondary hypoadrenocorticism, CAR does not help differentiate normal dogs from dogs with secondary hypoadrenocorticism.

Endogenous ACTH concentrations. After definitive diagnosis, endogenous ACTH concentrations may be used to differentiate primary from secondary cortisol deficiency.1 Since dogs with primary glucocorticoid deficiency may develop a mineralocorticoid deficiency whereas dogs with secondary glucocorticoid deficiency should not, differentiating primary from secondary hypoadrenocorticism may help guide clinical monitoring.3,13 Dogs with pituitary dysfunction resulting in secondary hypoadrenocorticism should have low endogenous ACTH concentrations. On the other hand, dogs with primary hypoadrenocorticism should have a normally functioning pituitary gland, so their ACTH concentrations should be increased in response to hypocortisolemia.1

Mineralocorticoid deficiency

Mineralocorticoid deficiency is easily diagnosed based on recognizing hyperkalemia and hyponatremia (Table 3).1 Dogs with a cortisol deficiency that lack hyponatremia and hyperkalemia do not have a clinically important mineralocorticoid deficiency, so additional diagnostic testing for aldosterone deficiency is rarely indicated.

Measuring the basal aldosterone concentration is not a reliable way to diagnose aldosterone deficiency because of an overlap in the concentrations between healthy dogs and those with an aldosterone deficiency.24 The post-ACTH stimulation aldosterone concentration has been investigated as a means to assess zona glomerulosa function, but findings are inconsistent and vary with a dog's age.25,26

The main method of documenting mineralocorticoid deficiency, besides recognizing hyperkalemia and hyponatremia, is the aldosterone to renin ratio.24 The reference interval for this ratio in healthy dogs is 0.1 to 1.5.24 In a normal dog, hypovolemia stimulates renin with resultant aldosterone secretion. Dogs that have a mineralocorticoid deficiency due to adrenal dysfunction should have low aldosterone and high renin plasma concentrations and, consequently, a low aldosterone to renin ratio. In one study, dogs with primary hypoadrenocorticism (both glucocorticoid and mineralocorticoid deficiency) had ratios ranging from 0.002 to 0.08.24


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