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Hypoadrenocorticism (Addison's disease)

Simply put, Addison's disease is a deficiency of hormones secreted by the adrenal cortex. An uncommon disease, it affects dogs of any age sex or breed, although there is a slight female predisposition in the dog, and is even more rare in cats. It can be classified into 2 categories, primary and secondary hypoadrenocorticism, and directly affects 2 hormones in the body.

Cortisol (a glucocorticoid) is responsible for the body's carbohydrate, lipid and protein metabolism, maintenance of normal blood pressure, and to counteract the effects of stress. The effects of cortisol deficiency may include gastrointestinal bleeding, diarrhea, lethargy, mental depression and impaired tolerance to stress.

Aldosterone (a mineralocorticoid) regulates extracellular fluid, and potassium, sodium and chloride balance in the body. It is the main source of regulation of the body's serum electrolyte levels.

Primary hypoadrenocorticism is caused by destruction or atrophy of the adrenal cortex itself, and affects both glucocorticoid and mineralocorticoid activity in the body. This is typically immune mediated damage but can be caused by a wide range of factors such as adrenalectomy, idiopathic adrenal atrophy and tumor. Iatrogenic hypoadrenocorticism can be precipitated by exogenous steroid or mitotane therapy in the treatment of hyperadrenocorticism (the opposite of Addison's disease) called Cushing's disease.

Secondary hypoadrenocorticism is caused by a deficiency of ACTH (adrenocorticotropic hormone) from the pituitary gland and affects only the body's glucocorticoid production. This can be induced by tumor, trauma, lesions, or idiopathic pituitary atrophy. ACTH from the pituitary gland stimulates the production of cortisol by the adrenal gland. If the pituitary is damaged and does not produce endogenous ACTH, or if the adrenal cortex itself is damaged, the body's cortisol level drops.

It should be noted that neither primary, nor secondary hypoadrenocorticism has any effect on the adrenal medulla (the source of epinephrine), except in the case of adrenalectomy.


Although very non-specific, hypoadrenocorticism is usually presented as the owners complaining of anorexia, vomiting, diarrhea, weight loss, lethargy and weakness. Physical examination by the veterinarian.may show mental depression, dehydration, bradycardia and slow capillary refill time.


The current definitive diagnostic tool for the diagnosis of hypoadrenocorticism is a blood profile followed by an ACTH stimulation test. The blood profile may show reduced sodium and chlorine, with increased potassium and calcium.

There are 2 possible preparations for conducting this test, natural ACTH gel, or synthetic ACTH, called cosyntropin.

If the natural gel is used, warm it to body temperature and administer IM to the patient at 2.2 U/kg.

Measure serum cortisol levels at 1 and 2 hours post ACTH.

If cosyntropin is used, administer 0.25 mg IV to the dog, and measure serum cortisol 1 hour later. (1. If cosyntropin zinc hydroxide is used, it should be administered by IM injection. 2. Actual values will differ from lab to lab. Best to leave it to the lab to convey what is a normal value. Regardless of the type of ACTH used, a baseline serum cortisol level is taken and compared to the levels taken at later intervals. If the basal cortisol level is low, or low normal, and the post ACTH level shows little or no response, then the animal has hypoadrenocorticism. There is no danger in conducting this test on a normal dog, as the body employs an automatic feedback system to limit production of endogenous ACTH.

Interpreting Test Results

The ACTH stimulation test does not differentiate between primary or secondary hypoadrenocorticism as it only measures serum cortisol. It merely tells us that there is a deficiency in cortisol produced by the adrenal gland, and the origin of the problem must be found. A direct measurement of endogenous ACTH is used to determine pituitary function, although complex sample handling and price makes this cost-prohibitive to most owners. It is usually simpler to measure serum electrolytes, as this can be traced to the adrenal cortex. A dog with secondary hypoadrenocorticism (where only cortisol is affected) will show little or no increase in serum cortisol after being injected with ACTH, and will not show abnormalities in serum sodium or potassium. Electrolyte management or mineralocorticoid therapy is not required, however it must be determined if the problem exists in the adrenal cortex, or in the pituitary gland. If endogenous ACTH shows a normal or high level, then the pituitary cannot be responsible for the low cortisol, and the adrenal gland must be at fault. The only determination left is whether or not the adrenal gland is also in need of mineralocorticoid supplementation. This is done by measuring serum sodium and potassium.

A dog with primary hypoadrenocorticism (where cortisol and electrolytes are affected) will show little or no response to the ACTH stimulation test and will also present with an increase in serum potassium (>4.5 mmol/L) a decrease in serum sodium (<137 mmol/L) and a sodium/potassium ratio of less than 27:1 . An ACTH test will have no effect on serum electrolytes. This dog will require mineralocorticoid replacement therapy combined with glucocorticoid therapy.

Specifics About Percorten-V

Dogs that suffer from chronic electrolyte imbalances due to problems with adrenal function are destined for long term mineralocorticoid therapy with a drug such as Percorten-V. Percorten-V(desoxycorticosterone pivalate, or DOCP) acts to replace aldosterone in the body, effectively reproducing the function of the compromised adrenal gland in returning serum levels of sodium and potassium back to acceptable norms. It has no effect on glucocorticoid activity, and prednisone is the most common form of supplementation for dogs with primary hypoadrenocorticism. Percorten-V is available in 4 ml suspension vials at a concentration of 25 mg/ml . It is initially given at a dose of 1 mg/lb. (2.2 mg/kg) I.M. once every 25 days. Success is measured by normalizing the levels of serum potassium and sodium. Blood values should be checked at 14 and 25 day intervals and the dosage can be adjusted as necessary. If sodium/potassium levels are normal by day 25, dosage can be reduced by 0.1 mg/lb. (0.2 mg/KG) at each dosage interval, or by prolonging the interval between dosing. Hypernatremia or hypokalemia may be indications of a higher dose than is necessary.


True adverse reactions are infrequent. They tend to be the result of overdosing the dog, which would have the effect of making serum sodium too high and potassium too low. This could easily be detected by a blood screen and the dose can be reduced or the interval increased. Percorten-V does increase venous return to the heart and should not be used in animals with congestive heart failure or edema. It's success is dependent on a functioning kidney. Safety in pregnant animals has not been established. Once diagnosed and stable, with periodic blood monitoring, the prognosis is usually excellent, and dogs with hypoadrenocorticism can live normal lives on Percorten-V.

Normal dog (Range) Dog #1 On Present-
Dog #1, 1 Hour Post ACTH Dog #2 On Present-
Dog #2, 1 Hour Post ACTH Dog #3 On Present-
Dog #3, 1 Hour Post ACTH
137- 15 141 147 54 55 129 130
2.9 - 4.5 3.5 3.7 6.5 6.6 4.0 3.4
15 - 120 4 5 6 5 55 120
7 - 40 35 34 24 25 28 28
27:1 - 40:1 30:1 31:1 15:1 14:1 35:1 36:1

Dog #1 presented with normal electrolytes, yet an abnormal cortisol, and a basal ACTH that appears normal. After the injection of ACTH his cortisol is still below normal. We may then conclude that this dog must be suffering from secondary hypoadrenocorticism due to a problem with the adrenal cortex and not the pituitary. His adrenal gland is receiving adequate ACTH from the pituitary , which we know because the endogenous ACTH value tells us the pituitary is functioning normally, yet the adrenal gland cannot produce cortisol, therefore the adrenal gland is the source of the deficiency. Treatment would consist of glucocorticoid therapy only, with periodic monitoring of the electrolytes.

Dog # 2 presents with abnormal electrolytes and cortisol. Blood values show us that the dog has hyponatremia and hyperkalemia. The cortisol is also below normal. The ACTH stimulation test shows the dog does not respond, we also note that his endogenous ACTH is normal, therefore we know he has primary hypoadrenocorticism related to the adrenal cortex because he is producing the ACTH necessary for the adrenal to produce cortisol, yet the adrenal gland is not responding. Treatment would consist of Percorten-V for hormone replacement therapy, and prednisone as a glucocorticoid replacement.

Dog #3 Presented as normal, and the ACTH test shows a response in cortisol from the adrenal gland. The ACTH shows that his pituitary is functioning normally. This dog appears healthy with no sign of compromised adrenal, electrolyte, or pituitary function.

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