Hypoadrenocorticism

Chapter 76 Hypoadrenocorticism



Jamie M. Burkitt, DVM, DACVECC



KEY POINTS



• Hypoadrenocorticism is uncommon in the dog and rare in the cat.

• Primary hypoadrenocorticism is due to failure of the adrenal glands, whereas secondary hypoadrenocorticism is due to pituitary or hypothalamic malfunction.

• Young to middle-aged female dogs are predisposed.

• Certain breeds are overrepresented, but most dogs with Addison’s disease are of mixed breeding.

• Diagnosis is challenging because signs and clinicopathologic findings of hypoadrenocorticism mimic many other disease processes.

• Definitive diagnosis is by adrenocorticotropic hormone (ACTH) stimulation test, ideally coupled with an endogenous ACTH concentration.

• Treatment of the animal in crisis consists of aggressive, appropriate fluid resuscitation followed by hormone replacement.

• Electrocardiographic (ECG) changes associated with hyperkalemia can be life threatening and must be treated promptly and appropriately.

• Cats may require 3 to 5 days for a good clinical response to therapy.

• Long-term prognosis is very good with lifelong hormone supplementation.


INTRODUCTION


The adrenal cortex is responsible for secreting many important hormones including cortisol and aldosterone. Cortisol is a glucocorticoid released in small amounts in a circadian rhythm, and in larger amounts during times of physiologic stress. It has many important homeostatic functions including regulation of carbohydrate, lipid, and protein metabolism; modulation of immune system function; ensuring proper production of catecholamines and function of adrenergic receptors; and stabilizing cell membranes. Serum cortisol concentration is determined by the hormonal cascade and negative feedback mechanisms of the hypothalamic-pituitary-adrenal axis. The hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH in circulation stimulates the zona fasciculata and zona reticularis of the adrenal cortex to produce and release cortisol. Cortisol has negative feedback action on both the hypothalamic release of CRH and the pituitary release of ACTH. Thus, when circulating cortisol concentration is low, CRH and ACTH will increase, stimulating the adrenal glands to produce more cortisol. The increased serum cortisol concentration inhibits the release of more CRH and ACTH.


Aldosterone is a mineralocorticoid released from the zona glomerulosa of the adrenal cortex under the influence of a complex hormonal cascade that starts in the kidney. Its main purposes are to maintain normovolemia and enhance potassium excretion. When effective circulating volume is depleted, glomerular filtration decreases. The macula densa, a group of specialized cells in the distal portion of the thick ascending loop of Henle, senses decreased filtrate (specifically chloride) delivery. The macula densa then induces renin release from the nearby juxtaglomerular cells of the afferent arteriole serving that nephron. Renin cleaves the circulating hormone angiotensinogen into angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme located in the lung, on endothelial cells throughout the body, and in many other organs. Angiotensin II stimulates the zona glomerulosa to release aldosterone, which stimulates cells of the renal collecting duct to reabsorb sodium and excrete potassium. Sodium reabsorption leads to water retention and thus augmentation of effective circulating volume. The adrenal cortex also releases a significant amount of aldosterone in response to hyperkalemia and a minimal amount in response to ACTH.


Hypoadrenocorticism, also called Addison’s disease, is an uncommon disease in dogs and is rare in cats. Primary hypoadrenocorticism is caused by adrenal gland dysfunction, whereas secondary hypoadrenocorticism occurs when hypothalamic or pituitary malfunction prevents the release of CRH or ACTH, respectively. In most cases, patients with primary hypoadrenocorticism will have both glucocorticoid and mineralocorticoid insufficiency. However, there are many reports of dogs with atypical primary hypoadrenocorticism who have only glucocorticoid insufficiency.1-4 Dogs with atypical primary hypoadrenocorticism may progress to mineralocorticoid deficiency within months of initial diagnosis.1,2,4 Because aldosterone release is mediated primarily by the renin-angiotensin cascade and serum potassium concentration, patients with secondary hypoadrenocorticism do not usually have the classic electrolyte abnormalities seen in patients with typical primary hypoadrenocorticism (see Clinicopathologic Findings).



WHO IS AFFECTED?


Hypoadrenocorticism usually occurs in young to middle-aged dogs, and females are more commonly affected than males.2,4-7 Although the average age of onset is approximately 4 years,4-7 naturally occurring hypoadrenocorticism has been documented in dogs as young as 4 months,5,8 as well as in geriatric dogs. The most commonly affected pure breeds vary somewhat by report and include the Portuguese Water Dog, Great Dane, West Highland White Terrier, Standard Poodle, Wheaton Terrier, and Rottweiler.5 It is important to note that mixed breed dogs are more commonly affected than any individual breed.4,5 Primary hypoadrenocorticism has been reported in fewer than 40 cats. There appears to be no sex predilection in this species, and most are domestic shorthaired or longhaired cats.4,9-13 Most cats are young to middle aged, with ages ranging from 1.5 to 14 years.11



ETIOLOGY


The cause of naturally occurring primary hypoadrenocorticism in dogs and cats is unknown, but the most widely accepted theory is one of immune-mediated destruction of the adrenal cortices.4,6 In support of this theory, young to middle-aged female dogs are most commonly affected by both Addison’s disease and established immune-mediated diseases, and naturally occurring primary hypoadrenocorticism in humans is caused by immune-mediated destruction of the adrenal cortices. On necropsy, adrenal glands of affected animals are atrophied and fibrosed, consistent with prior immune-mediated destruction.4,6,9,11 Other documented causes of primary hypoadrenocorticism in dogs and cats include adrenal neoplastic infiltration,14,15 trauma,16 suspected hemorrhage or hypoperfusion,17 and iatrogenic destruction due to mitotane18 or trilostane19 therapy for hyperadrenocorticism. Adrenal infiltration with infectious organisms has also been implicated.4


Secondary hypoadrenocorticism is due to hypothalamic or pituitary malfunction; decreased CRH or ACTH secretion causes decreased adrenal cortisol production. The most common cause of secondary hypoadrenocorticism is steroid withdrawal after long-term glucocorticoid therapy.4,20 Long-term steroid administration causes negative feedback on the hypothalamus and pituitary, significantly decreasing ACTH production, which leads to adrenal cortical atrophy. Other documented causes of secondary hypoadrenocorticism in dogs and cats include hypothalamic or pituitary neoplasia,21 trauma,22 and iatrogenesis (surgical).



CLINICAL PRESENTATION


The most important thing to remember about hypoadrenocorticism is that the clinical picture is vague and mimics other disease processes, most of which are significantly more common than Addison’s disease. The classic signs and basic diagnostic test results in the hypoadrenal patient are generally nonspecific, and the vast majority of Addisonian patients will not have all the classic signs. Therefore the clinician must always remember to place hypoadrenocorticism on the rule-out list for the patient that has any of these clinical signs.



History


The history for patients with Addison’s disease is often vague and nonspecific, and usually includes decreased appetite, lethargy, gastrointestinal (GI) disturbance, and weight loss. GI bleeding manifested by hematemesis, hematochezia, or melena may be present.1,3,4,7,23 Other historical findings may include polyuria, polydipsia, weakness, shaking, pain, muscle cramps, and other nonspecific problems.1,4-6,24 Because the clinical signs are often vague, patients may be brought for treatment in acute crisis without specific prior clinical signs. Thus the absence of such signs does not exclude hypoadrenocorticism as a diagnosis.

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Hypoadrenocorticism

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