Hypoadrenocorticism occurs as a result of a deficiency in glucocorticoids and, in some cases, mineralocorticoids.
Hypoadrenocorticism occurs as a result of a deficiency in glucocorticoids and, in some cases, mineralocorticoids. Primary hypoadrenocorticism is the result of destruction of the adrenal cortices. Secondary hypoadrenocorticism occurs as a result of insufficient ACTH secretion from the hypothalamus leading to atrophy of the adrenal cortices and glucocorticoid deficiency.
Normally neural stimulation of the hypothalamus produces corticotrophin-releasing hormone (CRH). Corticotropin-releasing hormone stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. ACTH exerts its effects on the adrenal cortex and stimulates the zona fascisulata to release cortisol, the zona reticularis to release androgens and the zona glomerulosa to release mineralocorticoids. ACTH's primarily effects are on cortisol release. Cortisol provides a negative feedback to ACTH and CRH. Glucocorticoids are involved in many normal physiologic responses in the body.
Mineralocorticoid release form the zona glomerulosa is primarily mediated by the renin angiotensin aldosterone system and only minimally by ACTH. Renin is released from the juxtaglomerular apparatus of the kidney into circulation as a result of sympathetic stimulation, hypotension, hyponatremia and hypochloremia. Renin then converts circulating angiotensinogen to angiotensin I. Angiotensin converting enzyme in the pulmonary vascular endothelium converts angiotensin I to angiotensin II. Angiotensin II then stimulates aldosterone secretion from the zona glomerulosa. In the absence of ACTH, atrophy of the zona glomerulosa can occur and mineralocorticoid deficiency result. Mineralocorticoids are primarily involved in water and electrolyte balance.
The majority of dogs with hypoadrenocorticism have idiopathic atrophy of the adrenal cortices likely secondary to immune-mediated destruction. Hypoadrenocorticism may also occur as a result of adrenolytic therapy. Infarcts, trauma and neoplasia are rare causes of adrenal insufficiency. Occasionally dogs can develop hypoadrenocorticism as a part of a polyglandular syndrome that might also involve hypothyroidism, diabetes mellitus or hypoparathyroidism.
Hypoadrenocorticism can occur in any breed but there may be an increased incidence in West Highland white terriers, Great Danes and standard poodles amongst other breeds. Females are affected more frequently and intact females have an even higher incidence. Affected dogs have been reported up to 14 years of age but the disease is more common in young and middle-aged dogs.
The history can be variable. The classic history is of waxing and waning lethargy, inappetence, vomiting and diarrhea that often responds to symptomatic treatment. There is often a stressful event that precipitates these episodes. Dogs may also present for weakness, polyuria, polydipsia, muscle wasting, regurgitation and seizures. These signs may be present for weeks to months. A more acute presentation may also occur in which dogs present in hypovolemic shock. These dogs may or may not have a history of more chronic signs. In acute disease anorexia, vomiting, diarrhea, melena and collapse are more common.
Dogs may be weak, lethargic, have a poor coat or coat color change, muscle wasting, and abdominal pain. In a more acute presentation the dog may be laterally recumbent, with pale tacky mucous membranes, increased capillary refill, poor pulse quality, bradycardia and hypothermia.
The most common finding on the CBC is a mild non-regenerative anemia. In many cases the absence of a stress leukogram (lymphopenia, eosinopenia) is noted. The classic electrolyte abnormalities are increased potassium, decreased sodium and decreased chloride. These occur due to mineralocorticoid deficiency because of a lack of aldosterone and its effects on the renal tubules. Increased BUN and creatinine are primarily prerenal. It is possible that these dogs can develop acute renal failure if their prerenal factors (hypovolemia, hypotension) are not addressed in a timely fashion. Liver enzymes may be normal or mildly increased likely due to poor perfusion of the liver. Hypoglycemia may also be seen with cortisol deficiency. A mild hypercalcemia is fairly common and the exact cause unknown. A mild hypoalbuminemia is also seen frequently and likely due to increased losses in the intestinal tract. A metabolic acidosis occurs secondary to decreased hydrogen ion excretion (aldosterone deficiency), poor tissue perfusion (generates lactic acid) and decreased renal excretion of acids.
Thoracic radiographs might reveal microcardia, decreased diameter of the caudal vena cava and megaesophagus. On abdominal ultrasound, adrenal glands might be normal or occasionally, small in size.
Hyperkalemia can cause several electrocardiographic changes including bradycardia, a spike T wave, shortening of the Q-T interval, increased duration of the QRS, decreased to absent P wave, prolonged P-R interval and atrial standstill.
The ACTH stimulation test is the only test available to diagnose this disease. It is important to note that a single baseline cortisol is inadequate for diagnosis and may be normal in dogs with hypoadrenocorticism. Blood for a baseline cortisol is taken followed by administration of synthetic ACTH given IV at 5 mcg/kg with a second sample obtained an hour later. There should be no stimulation and cortisol levels are almost always less than 2.0 µg/dl.
This test can be done to differentiate primary form secondary hypoadrenocorticism. In primary hypoadrenocorticism ACTH is increased because of a lack of feedback. With secondary hypoadrenocorticism ACTH is low to undetectable.
Aldosterone can also be used as a differentiating test but is more difficult to interpret than endogenous ACTH. Aldosterone is measured prior to and 1 hour after synthetic cortrosyn is administered as described above. In normal dogs aldosterone should increase two-fold. In dogs with primary hypoadrenocorticism, there will be little to no increase in aldosterone. In cases of secondary hypoadrenocorticism, aldosterone concentrations will be variable. Basal and post-ACTH levels may be undetectable or subnormal.
In hypovolemic shock it is important to address hypotension and hypovolemia. Typically this is done with shock rates (80 – 90 ml/kg/hr) of crystalloids until fluid deficits are corrected. Sodium chloride is frequently used. If bradycardia and moderate to severe hyperkalemia (> 8.0 mEq/L) is present then 10% calcium gluconate can be administered at 0.5 ml/kg over 15 minutes to help maintain a normal membrane potential. Regular insulin (0.2 U/kg) and dextrose 1g/kg can be given IV to move potassium intracellularly. Sodium bicarbonate at 2 mEq/kg can be given as an alternative for translocation. Fluid diuresis will aid in elimination of potassium through the kidneys.
Glucocorticoids should be given as soon as possible. Dexamethasone sodium phosphate is recommended because it will not interfere with the ACTH stimulation test. Initially high doses of glucocorticoids are used. Dexamethasone sodium phosphate is given at 0.5 mg/kg initially. This can be followed up by hydrocortisone sodium succinate at 0.5 mg/kg/hr CRI or prednisolone sodium succinate 1 mg/kg BID to TID. Parenteral glucocorticoids are given until the dogs is no longer vomiting and eating regularly then switched to prednisone at 0.5 mg/kg BID. Maintenance doses of glucocorticoids can be as low as 0.1 mg/kg/day but it might take several weeks until the dog can be safely weaned to this dose.
Mineralocorticoids are not necessary in an acute crisis but should be given as soon as a mineralocorticoid deficiency is diagnosed. Options for mineralocorticoid replacement are desoxycorticosterone pivalate (DOCP) or fludrocortisone acetate. DOCP is given at 2.2 mg/kg SC or IM injection every 2 to 6 weeks. Monitoring electrolytes every 1 to 2 weeks will help determine dosing intervals. Initially IM administration of DOCP might be preferred due to possibilities of poor perfusion in acute disease. Fludrocortisone is an alternative in a dog that can take oral medications. Fludorcortisone is given at 0.02 mg/kg once to twice daily. DOCP has very little glucocorticoid activity so supplementation with glucocorticoids is necessary. Fludrocortisone can occasionally be administered without glucocorticoids but in both instances glucocorticoids should be given initially and then tapered to the lowest dose necessary to maintain appetite and normal activity levels while minimizing signs of glucocorticoid excess. Sodium and chloride often remain low despite normal potassium. Salt can be supplemented to help normalize sodium and chloride but is usually not necessary long term.
H2 antagonists and sucralfate are commonly administered in acute hypoadrenal crisis particularly if there is hematemesis or melena that may be due to gastrointestinal ulceration. Glucose is supplemented as needed for hypoglycemia.
The disease carries a good to excellent prognosis with treatment. Many dogs with atypical hypoadrenocorticism may eventually develop mineralocorticoid deficiency so electrolytes should be checked periodically.