Hypoadrenocorticism
History. A concerned client presents her 1 -year-old spayed female Samoyed with the complaint of severe weakness, inappetence, and vomiting since the previous day.
Clinical Examination.
The dog is lethargic, weak, and extremely dehydrated. The heart rate is normal, but pulses are weak. No other abnormalities are detected on physical examination. Samples of blood and urine are collected immediately for a complete blood count, serum chemistry profile, and urinalysis, and then an intravenous catheter is placed to start volume replacement therapy with a balanced electrolyte solution. The urinalysis is normal, with a specific gravity of 1.025. Abdominal radiographs are normal, but the thoracic radiographs demonstrate a small cardiac silhouette and small thoracic vessels. The serum creatinine level is 2.5 mg/dL (normal, 0.6-1.2 mg/dL), serum K+ level is 6.5 mEq/L (normal, 3.6-5.6 mEq∕L), serum Na* is 129 mEq/L (normal, 141-155 mEq/L), serum CΓ is 97 mEq/L (normal, 103-115 mEq/L), and serum HCO3- is 12 mEq/L (normal, 18-24 mEq/L).Comment. The dog has hypoadrenocorticism. The metabolic disturbances result from a deficiency of the mineralocorticoid hormone aldosterone. In a normal animal, aldosterone stimulates Nat,K'-ATPase activity and enhances the apical plasma membrane Na* and K* permeability in the connecting segment and the collecting duct, thereby enhancing Na+ reabsorption and Kt secretion. In the absence of aldosterone, Na+ conservation and K* secretion in these segments are impaired. Cl and waler follow the path of Na+ and also are excreted excessively by the kidney. Hyperkalemia (high serum K’ level) has profound effects on excitable tissue, including nerve and muscle cells, and results in muscle weakness, decreased cardiac output, hypotension, and cardiac arrhythmias.
The loss of Na' and water results in volume depletion and decreased size of the heart and thoracic blood vessels and exacerbates the hypotension and poor tissue perfusion.Poor perfusion of the kidneys is probably the major cause of the elevated serum creatinine level (azotemia) because inadequate renal blood flow and reduced glomerular capillary hydrostatic pressure prevent adequate glomerular filtration. This is called ρrerenal azotemia. In most cases of prerenal azotemia the urine is maximally concentrated in an attempt to retain fluid and restore blood volume, but in hypoadrenocorticism, this response is often blunted, possibly by the hyponatremia (reduced serum Na* level) or by the absence of glucocorticoids, which have been shown to have a permissive effect on maximal urine concentration (see Chapter 43). The decreased serum bicarbonate level indicates metabolic acidosis, which is the result of both the diminished renal ability to secrete H' and reabsorb HCO3- (see Chapter 44) and the increased production of acid from poorly perfused tissue.
Treatment. Prompt treatment is important for the animal’s survival because the hyperkalemia and acidosis can cause fatal cardiac arrhythmias. Volume repletion with normal saline and correction of the base deficit (low serum HCO5" level) often stabilizes the animal. Replacement therapy with mineralocorticoid hormones (e.g., desoxycorticosterone acetate, desoxy- Corticosterone pivalate, fludrocortisone acetate) restores apical Na+ channel and basolatcral Na*,K"-ATPase activity and should be started as soon as possible. Frequently, glucocorticoid hormones are given early to treat shock even before the electrolyte status is known; these hormones are beneficial for two reasons. First, hypoadrenocorticism usually results in glucocorticoid deficiency, sometimes manifested by hypoglycemia, and replacement therapy is indicated. Second, the mineralocorticoid activity in many glucocorticoid preparations may be beneficial in correcting the hyperkalemia and hyponatremia.
A definitive diagnosis may be obtained by an adrenocorticotropic hormone (ACTH, corticotropin) challenge test, which maximally stimulates the release of cortisol from the adrenal gland and shows little or no response in animals with hypoadrenocorticism.
Chronic maintenance usually involves oral therapy with fludrocortisone acetate; the proper dosage is determined by periodic evaluations of the serum K* and Na* levels. Chronic replacement of glucocorticoids is also recommended.