Adrenals

The adrenal glands are part of the endocrine system and help to produce several hormones. Glucocorticoids are released by the adrenal glands and are regulated by ACTH from the pituitary gland. The term corticosteroids is applied to hormones of the glucocorticoid class that are released from the adrenals.

The most important corticosteroids produced are cortisol and corticosterone. They help increase blood glucose levels by reducing glucose uptake in the cells, aid in gluconeogenesis and help to convert fatty acids back to glucose.

The adrenals also produce aldosterone, a mineralocorticoid (affects "minerals" also known as electrolytes) which regulates acid/base function of the kidney. It also helps to control the excretion of sodium, chloride and potassium.

Adrenal Insufficiency

The production of mineralocorticoids and/or corticosteroids becomes decreased. The cause of the decrease can be from bacteria or parasitic agents (Histoplasma, Cryptococcus) causing inflammation in the adrenals, hemorrhage (Waterhouse-Friderichsen syndrome due to massive sepsis), neoplasia, iatrogenic causes or may be idiopathic. Most dogs diagnosed with hypoadrenocorticism are young to middle-aged females (mean 4–5 years). Certain breeds seem to have a higher risk: standard poodles, West Highland terriers, bearded collies, Great Danes, Portuguese water dogs, Labrador retrievers, Rottweilers, and Wheaton terriers.

Roughly 90% of the adrenal function is compromised once clinical signs finally become evident. As the mineralocorticoids are decreased, the sodium, chloride and potassium levels within the body become unregulated. The kidneys no longer secrete appropriate amounts of potassium, which leads to hyperkalemia. The renal tubules do not reabsorb sodium and chloride as well, resulting in both being excreted rapidly in the urine. Aldosterone has a direct effect on the extracellular fluid because of a direct relationship with how much sodium is reabsorbed or excreted. Conversely, in the patients with hypoadrenocorticism, extracellular fluid volume will decrease as sodium decreases, thus causing the patient to become dehydrated. Any small change in sodium, even by a few milliequivalents on blood work, will stimulate thirst and water intake.

The hyperkalemia will often cause ECG changes resulting in high-peaked T waves and bradycardia. It can also cause abdominal pain, weakness (due to the cardiac effects), diarrhea, and in severe cases flaccid paralysis of the limbs, respiratory paralysis, circulatory and cardiac failure.

As the sodium decreases, the pet will become depressed, lethargic and cerebral edema may occur. Seizures and coma may occur, though these signs are often a reflection of how fast the sodium declined rather than the actual concentration. If the sodium decreases slow enough, the pet may have few clinical signs.

As the corticosteroid levels decrease, gluconeogenesis may not occur, which can result in a mild to moderate hypoglycemia leading to more lethargy of the pet.

Signs/Symptoms

Hypoadrenocorticism may occur acutely or chronically. If the pet has time to get used to the shifting electrolytes and decrease in hormones, then they typically present with more non-descript signs: weight loss, hypothermia, shivering, weakness, anorexia, lethargy, vomiting, polyuria and polydipsia. Some patients will also have weight loss, diarrhea and melena. Cats typically experience lethargy, anorexia, vomiting, weight loss, polyuria and polydipsia. When the body does not have a chance to get used to the decreases in hormones, the pet typically presents with severe dehydration, hypovolemic shock, and bradycardia.

Upon presentation pets are usually depressed and at least mildly dehydrated.

Pets that experience an acute onset of hypoadrenocorticism will often present with signs of hypovolemic shock: pale/tacky oral membranes, decreased capillary refill time, weak pulses, bradycardia, shaking, collapse, seizures or coma. These patients require emergency treatment.

Diagnosis

A complete blood count (CBC), blood chemistry panel, electrolyte panel, blood gas and ACTH stimulation test are all necessary if Addison's is suspected.

Typically, a mild anemia may be present, but may be masked by dehydration. The CBC is typically normal. On blood chemistry, hyponatremia, hyperkalemia and a sodium/potassium ratio less than 27:1 are usually present. Azotemia, hypocalcaemia and hypoglycemia are present in about 30% of pets. Pets may also experience metabolic acidosis and have a urine specific gravity <1.030.

Definite diagnosis requires the adrenocorticotropic hormone (ACTH) stimulation test. ACTH is a hormone produced in the pituitary gland that stimulates the adrenal glands to release cortisol and aldosterone. During the test, a small amount of synthetic ACTH (cosyntropin, Cortrosyn) is injected either IM or IV, and the amount of cortisol the adrenals produce in response is measured. In pets with hypoadrenocorticism, both the pre- and post-ACTH cortisol concentrations are usually less than 1 µg/dL, with some references stating that under 2.5 µg/dL is diagnostic.

There is a newer SNAP Cortisol test (IDEXX lab) that is available for in-house testing. It is fairly accurate in detecting ACTH, though the plasma ACTH detection is more accurate than the SNAP. Certainly, starting with the in-house is a great starting point to initiate treatment.

Treatment

An adrenal crisis is an acute medical emergency and requires the staff to work quickly in order for the patient to have the best chance of survival. Patients may present weak, ataxic, shaking, non-responsive and in shock. Dealing with the Addisonian crisis requires treating the patient's shock. Focus should be on treatment of the hypotension and hypovolemia.

A short, large-gauge, intravenous (IV) catheter should be placed and fluid therapy started. Since the patient is usually hypotensive and vasoconstricted, blood should be removed from the IV catheter once it is placed as subsequent venipuncture may prove challenging. If hypoadrenocorticism is suspected, then 0.9% sodium chloride (NaCl) should be considered choice because it offers a higher amount of sodium and lower amount of potassium compared to other isotonic crystalloids [Lactated Ringer's solution (LRS), Normosol-R (Norm-R)]. Any balanced isotonic crystalloid is an acceptable fluid choice in most Addison's disease patients.

Patients with severe hyperkalemia (severe bradycardia, ECG abnormalities), should be given regular insulin and dextrose to help decrease serum potassium levels. Calcium gluconate can also be given. While it does not decrease serum potassium levels it does protect the heart against the effects of hyperkalemia. Typically, these treatments are not needed as serum potassium is usually lowered fast enough through the dilution effects from the IV fluids.

Bicarbonate therapy is usually not necessary as the metabolic acidosis is usually mild. However, if the bicarbonate level remains less than 12 mEq/L even after fluid resuscitation, the bicarbonate administration should be considered.

If the patient is stable or after they are stabilized, the focus should shift to providing glucocorticoid replacement. All glucocorticoids react with the ACTH stimulation test except dexamethasone. Ideally, blood for the ACTH test should be performed before glucocorticoids are given. If the patient is not stable before the ACTH test can be completed, then dexamethasone sodium phosphate should be given IV. Dexamethasone is long acting, about thirty times more potent than hydrocortisone, but offers no mineralocorticoid activity.

If the pet is stable enough for the ACTH test to be completed, then prednisolone sodium succinate is the glucocorticoid of choice. Prednisolone is a glucocorticoid that has some mineralocorticoid activity. Some suggest hydrocortisone sodium succinate be administered instead of prednisolone because of its combination of mineralocorticoid and glucocorticoid activities. Hydrocortisone has only 25% of the glucocorticoid potency of prednisolone, but offers more mineralocorticoid effects than prednisolone.

Other treatments should be tailored to the pet's condition. Patient may need to be started on dextrose supplementation if they are hypoglycemic. Antibiotics should be considered in patients with severe melena or hemorrhagic diarrhea. Antiemetics can be administered to help combat nausea and vomiting. Colloids may need to be administered in patients with hypoalbuminemia and hypotension.

Nursing Care

Patients should be monitored for signs that they are not responding to the glucocorticoid therapy. This may include weakness, lethargy, anorexia, vomiting, ataxia, hypotension and/or tachy- or bradycardia. Physical exam parameters (heart rate, pulse, respiratory rate, effort, mucous membranes, capillary refill time) and blood pressure should be checked every 2–6 hours depending on how critical the pet is. If the patient was experiencing ECG abnormalities, then they should be placed on continuous ECG monitoring or have periodic ECG checks minimally every hour or two.

Pets should be weighed twice a day to monitor rehydration. Urine output should also be monitored to ensure the kidneys are functioning properly as well as for fluid therapy. Due to the severity of dehydration urine output may be lower than volume input until the pet is adequately hydrated.

Blood pressure is extremely important in hypoadrenocorticism patients and should be monitored minimally every 4–6 hours. Normalization of blood pressure, defined by a MAP of 80–120 mm Hg or systolic between 110–160 mm Hg, is the goal.

 Electrolytes, renal function and glucose should be all monitored regularly to assess the response to the glucocorticoid therapy.

Lastly, it is important that patients be given appropriate nutrition. Nurses need to tempt patients to eat and alert the veterinarian if the patient is nauseas or experiencing vomiting.

Long-Term Care

With diligent monitoring by the owner and appropriate medication, hypoadrenocorticism has a good prognosis. Therapy is required for life and dosage may need to be altered throughout the pet’s lifetime.

Patients will need to be given both mineralocorticoid and glucocorticoid supplements the rest of their lives. Oral prednisone or prednisolone is the glucocorticoid treatment of choice in both dogs and cats. In times of stress the prednisone may need to be increased. It is important that the dose is tapered to the lowest effective dose as high doses may result in hyperadrenocorticism. The decision to use glucocorticoids is based mainly on gastrointestinal signs.

The options for mineralocorticoid therapy are fludrocortisone acetate (Florinef) or desoxycorticosterone pivalate (DOCP). Only 50% of dogs on fludrocortisone require supplemental prednisone. Fludrocortisone is dosed orally and is given twice a day. It contains both glucocorticoid and mineralocorticoid properties. The most economical option is DOCP (Percorten®-V, Novartis) which requires the pet to have an injection every 21–30 days. It does not have any glucocorticoid activity. Almost all dogs on DOCP require prednisone at least every other day. Both DOCP and fludrocortisone should be tapered to effect.

References

References are available upon request.