Source: Textbook of Veterinary Internal Medicine, 4th edition, Chapter 19, pp. 1579-1591.
Hypoadrenocorticism can be one of the most diagnostically and therapeutically challenging, confusing, and frustrating diseases that a companion animal practitioner must face. The first human cases were described in 1855 by Thomas Addison, and this disease is often identified in the literature as "Addison's" disease. At about the same time, animal experiments verified that removal of the adrenal glands leads rapidly to death. It was not until the 1930s that crude aqueous extracts of adrenal glands were shown to prevent death in adrenalectomized cats. It was still several more years before sources of glucocorticoids and mineralocorticoids became commercially available, so that affected humans could now survive this previously fatal disease.
Hypoadrenocorticism is an uncommon endocrine disorder in dogs and rare in cats. The first canine case was reported in 1953, and the first reported case in a cat in 1983. The prevalence in dogs at one large veterinary hospital is said to be less than 1/1000. Since its initial recognition, several case series of dogs with Hypoadrenocorticism have been published. Only one series of 10 cats with this disorder has appeared.
Hypoadrenocorticism in dogs and cats is most often associated with diseases of the adrenal gland that result in combined deficiencies of glucocorticoids and mineralocorticoids (primary Hypoadrenocorticism). Less commonly, disruption of the hypothalamic-pituitary-adrenal axis occurs. this leads to deficient tropic hormone secretion of either corticotropin- releasing hormone (CRH) or adrenocorticotropic hormone (ACTH). Lack of pituitary stimulation of the adrenal cortex results in bilateral adrenal cortical atrophy and is classified as secondary Hypoadrenocorticism. Secondary Hypoadrenocorticism is only associated with signs of glucocorticoid deficiency.
Primary Hypoadrenocorticism, which is most often classified as idiopathic, is usually characterized histopathologically as bilateral adrenal atrophy with fibrosis. In some cases, significant infiltration of the adrenal cortex by lymphocytes and plasma cells has been seen, suggesting an immune-mediated basis for the disease. Two recent reports have identified through indirect immunofluorescence the presence of antiadrenal antibodies in the serum of two of three dogs with primary adrenal insufficiency. The third dog had an infiltrate of lymphocytes and plasma cells in its adrenal cortex at necropsy. One of these dogs was also severely hypothyroid and had antithyroid antibodies detected in its serum as well. Up to 50 per cent of humans with Hypoadrenocorticism are though to have an immune-mediated basis for their disease, and multiple endocrine organs are often involved simultaneously. In a survey of 45 dogs from the University of California, six were found to have at least one additional endocrinopathy. Four were hypothyroid, one had diabetes mellitus, and one had partial gonadal failure.
Other less common causes for spontaneous primary adrenal failure include infections (coccidioidomycosis, blastomycosis, or tuberculosis), hemorrhagic infarctions, metastatic neoplasia, trauma, and amyloidosis.
Genetic influences may play a role in some breeds of dogs. The only well-documented cases of familial Hypoadrenocorticism have occurred in standard poodles located on the East coast of the United States. Labrador retrievers and Portuguese water spaniels are also said to have familial tendencies for this disease.
Iatrogenic primary Hypoadrenocorticism may follow the administration of the adrenocorticolytic drug o,p'-DDD (mitotane), in the treatment of dogs for hyperadrnocorticism (Cushing's disease). Relative cortisol deficiency is common after treatment for this disease and is usually transient. However, combined mineralocorticoid and glucocorticoid deficiency occurs in approximately 5 per cent of treated dogs. Dogs suffering severe adrenal cortical destruction following o,p'-DDD therapy almost always have a permanent requirement for mineralocorticoid and glucocorticoid supplementation.
Two other therapeutic agents that may interfere with adrenal cortical function are ketoconazole and megestrol acetate. Both only interfere with the synthesis of glucocorticoids. Ketoconazole impairs the normal response of the adrenal cortex to ACTH but leaves basal concentrations unchanged. Adrenal reserve, as measured by ACTH stimulation testing, returns to normal within 3 weeks of discontinuation of ketoconazole administration.
Megestrol acetate has profound adrenal suppressive effects in cats. When given to normal cats at 5 mg/day for 16 days, ACTH response was severely impaired. Only three of seven cats had regained normal adrenal reserve capacity one month after the drug discontinued. None of the cats showed signs of cortisol deficiency, however.
Secondary Hypoadrenocorticism may be naturally occurring or iatrogenic. Naturally occurring secondary Hypoadrenocorticism is due to a lack of normal adrenal stimulation via CRH or ACTH and implies primary hypothalamic or pituitary failure. Most of these cases are the result of inflammation, tumors, trauma, or congenital defects of the hypothalamus or pituitary gland.
Iatrogenic secondary Hypoadrenocorticism is the most common cause for adrenal cortical nonresponsiveness in veterinary practice. it occurs following the administration of exogenous glucocorticoids. Exogenous glucocorticoids suppress normal pituitary ACTH production and this leads to bilateral adrenal atrophy. Secondary adrenal atrophy may develop after the administration of virtually any glucocorticoid used by veterinarians, including oral, injectable, and topical. Even otic and ophthalmic preparations can induce ACTH nonresponsiveness rapidly. Fortunately, the majority of dogs and cats receiving exogenous glucocorticoids do not develop signs of glucocorticoid deficiency when their medication is discontinued.
Although any glucocorticoid may inhibit ACTH release, long- acting depot preparations cause the most severe adrenal atrophy and result in long periods of adrenal hypofunction. Dexamethasone- containing preparations are 50 to 150 times as potent as endogenous cortisol in suppressing ACTH production.
Adrenal nonresponsiveness may occur within a few days following daily or repositaol glucocorticoid administration. Most dogs and cats have normal ACTH stimulation results within 2 weeks of steroid withdrawal. However, those who receive potent preparations or receive glucocorticoids for months or years may have prolonged periods before ACTH stimulation results normalize (weeks to months).
The adrenal glands are essential for life. they secrete a number of hormones that are required for normal functioning of an animal as well as for survival in stressful situations (cortisol, epinephrine, norepinephrine). The outer zona glomerulosa of the cortex is primarily involved with the synthesis and secretion of the mineralocorticoid, aldosterone. The middle zona fasciculata synthesizes and secretes glucocorticoids, of which cortisol is the most important in mammals. The inner zona reticularis of the adrenal cortex secretes primarily adrenal sex steroids. The androgens and estrogens secreted by the zona reticularis are of unknown clinical significance in animals. The adrenal medulla secretes the catecholamines, epinephrine and norepinephrine, which are not affected in Hypoadrenocorticism.
There is significant adrenal cortical functional reserve in animal and man. It is estimated that approximately 90 per cent of adrenal function must be compromised before clinical signs become evident. Approximately 10 per cent of animals with Hypoadrenocorticism have waxing/waning clinical courses, with signs only becoming evident following stressful situations (e.g., disease, trauma, surgery, kenneling). This probably reflects slight residual adrenal reserve that maintains them at rest in a nonstressful environment. As their glandular reserve progressively declines, they may develop an adrenal crisis with no obvious precipitating event.
MINERALOCORTICOIDS IN HEALTH AND DISEASE
Mineralocorticoids serve primarily to maintain sodium, chloride, and water balance. The primary adrenal mineralocorticoid, aldosterone, promotes renal reabsorption of sodium and chloride and their accompanying water in exchange for potassium and hydrogen ions. This effect is mediated primarily by the kidneys.
aldosterone release is controlled by three mechanisms working concurrently. The primary control is via the reninangiotensin- aldosterone system. Minor modifications in aldosterone secretion occur in response to hyperkalemia and also following an increase in plasma ACTH concentrations. Renin is stored in the cells of the juxtaglomerular apparatus of the kidney and is released in response to changes in extracellular volume. Anything that leads to hypotension or contraction in extracellular fluid volume will stimulate renin release (e.g., hemorrhage, dehydration, diuretic use, salt restriction). Renin acts on angiotensinogin in the circulation to release angiotensin I, an alpha-2 globulin. Angiostensin I is hydorlyzed by an angiostensin-converting enzyme in the lung to angiotensinII, a potent vasoconstrictor and the primary stiulus for aldosterone release. Angiotensin II has a direct effect on vasuclar smooth muscle, raising blood pressure. Aldosterone promotes active sodium, chloride, and water reabsorption, which expands the extracellular fluid (ECF) volume. Once blood pressure and ECF volume normalize, further renin release is inhibited.
An inability to release aldosterone has a number of adverse effects on the animal. the failure to conserve sodium and chloride leads to their loss as well as water depletion. The resulting hyponatremia and hypochloremia are typical of primary hypoadrenocorticism. A continuing loss of sodium, chloride and water causes a progressive decline in ECF volume, which results in dehydration, hyptension, an prerenal azotemia. In association with hypotension and dehydration, pituitary ADH release may be increased, promoting renal water reabsorption and thus further aggravating the hypnatremia. Untreated human patients have an impaired ability to excrete a free water load and are prone to water intoxication. Decreased tissue perfusion, prerenal azotemia, and failure to eliminate hydorgen ions in exchange for potassium - all lead to varying degrees of metabolic acidosis.
Polydipsia, polyuria, and low urine specific gravity in the face of clinical dehydration and azotemia are frequent abnormalities in both dogs and cats with hypoadrenocorticism. These findings probably reflect an ongoing solute diuresis of sodium chloride, and water secondary to hypoaldosteronism. Profound hypnaturemia also impairs the renal concentrating capacity through medullary solue washout, decreasing the maximal renal concentrating ability. Sodium and chloride account for approximately 50 per cent of the normal renal medullary solute gradient.
It has been proposed that severe hyponatremia may impair normal renal concentrating ability by interfering with ADH release. The primary stimulus fo rADH release is an increase in serum osmolality. since sodium and chloride account for the majority of ECF osmolality, severe decreases in these ions may impair normal osmotic stimuli for DAF release, promoting a dilute urine in the face of dehydration.
Failure to excrete potassium in exchange for sodium leads to hyperdalemia, on of the classic electrolyte abnormalities of adrenal insufficiency. Hyperkalemia not only is due to hypoaldosteronism bu is worsened by the decreased renal perfusion (*impairs excretion) and accompanying metabolic acidosis (promotes shift of potassium from intracellular to extracellular space). hperkalemia leads to decreased neuro-muscular excitability and impaired myocardial contractility. This may result in signs of muscular weakness, bradycardia and hypotension. As serum potassium concentrations approach 8 to 10 mEq/L, severe bradycardia and atrial arrest are seen. Ultimately, ventricular fibrillation or cardiac stand still results in death of the patient.
GLUCOCORTICOIDS IN HEALTH AND DISEASE
Glucocorticoids are synthsized primarily in the zona fasciculata of the adrenal cortex and have effects on nearly every tissue in the body. Their synthesis and secretion are under a relatively simple negative feedback mechanism between the hypthalamic-piuitary axis and the adrenal gland. when serum cortisol concentrations decline, hypthalamic CRH increases, thus stimulating increased production and release of pituitary ACTH. ACTH circulates to the adrenal cortex and increases production and release of cortisol. Increasing levels of cortisol inhibit CRH and ACTH release, which inhibits adrenal glucocorticoid production.
In primary hypoadrenocorticism, the lack of negative feedback by cortisol on the pituitary gland leads to chronically elevated concentrations of ACTH. In secondary hyoadrenocorticism, whether iatrogenic or naturally occurring, chronic lack of stimulation of the adrenal cortex by ACTH leads to severe adrnal cortical atrophy, nad endogenous ACTH concentrations are low. Thus, endogenous plasma ACTH concentrations are the best diagnostic test for differentiating primary from secondary hypoadrenocorticism.
In normal animals, glucocorticoids promote a general sense of well-being and stimulate appetite. They maintain fasting blood glucose values by promoting gluconeogenesis and hepatic glycogenesis, by impairing uptake of glucose by peripheral tissues, and by augmenting lipolysis. Glucocorticoids promote renal water elimination by increasing the GFR and inhibiting ADH effects on the kidney. They help to maintain normal serum calcium concentrations by augmenting renal excretion of calcium. they have anit- inflammatory and immunosuppressive effects on white blood cells while stimulating erythrocytosis. they protect organisms against shock, and maintain blood pressure by increasing vascular reactivity to catecholamines, preventing capillary dilatation, and impairing protein extravasation from capillaries.
Hypoadrenocorticism is primarily a disease of middle-aged female dogs. Most surveys indicate that from 70 to 85 per cent of affected dogs are female. The age of presentation ranges from 2 months to 9 years, with a mean of about 4 to 4.5 years of age. The majority of dogs are diagnosed while under 7 years of age. Although there is no increased risk based on breed or size, some evidence for familial tendencies exists in standard poodles, Labrador retrievers, and Portuguese water spaniels.
The clinical signs exhibited by dogs with hypoadrenocorticism usually reflect combined mineralocorticoid and glucocorticoid deficiencies. Hypoadrenocorticism is typically a disease associated with vague, nonlocalized clinical signs such as depression, lethargy, weakness, anorexia, and weight loss (Table 119-1). IN others, signs more typical of gastrointestinal (GI) diseases (vomiting, diarrhea) or renal diseases (polydipsia and polyuria) are seen. Additional abnormalities reported less often include shaking or tremors and a sensitive abdomen. The duration of clinical illness is generally about 2 weeks before presentation to a veterinarian. although it is commonly considered a disease that has a waxing and waning course as animals get into and recover from stressful situations, this observation is actually made by only 10 per cent of owners. Some animals will have received, and generally responded well to, supportive care for these signs in the recent past (fluids and glucocorticoids). Because signs of adrenal insufficiency mimic many other common diseases, the definitive diagnosis may be missed as animals are treated for these more commonly recognized disorders. They may actually present in what is perceived to be an "acute" adrenal crisis, when in actuality it is the end stage of progressively deteriorating adrenal gland disease.
PHYSICAL EXAMINATION FINDINGS
Physical examination findings are generally unrewarding in terms of leading to a specific diagnosis owing to the nonspecific nature of abnormalities induced by mineralocorticoid and glucocorticoid deficiencies. Depression, weakness, and dehydration are the most commonly identifed physical examination findings. Dogs in an adrenal crisis may be in shock, with only vague signs of illness noted previously. Approximately one-third of these dogs have bradycardia and/or weak pulses. although bradycardia is not pathognomonic for hypoadrenocorticism, its occurrence in a dehydrated, hypotensive animal with GI signns should arouse a strong suspicion that hypoadrenocorticism exists. Only occasionally will abdominal pain, hypothermia, or amaciation be found.
The definitive diagnosis of hypoadrenocorticism requires a thorough history, a careful physical examination, and complete laboratory screening. In animals suspected of having hypoadrenocorticism, a CBC, serum chemistry profile (including an electrolyte panel), and a urinalysis will be helpful in supporting the diagnosis. However, a definitive diagnosis is only established through an assessment of adrenal reserve capacity (ACTH stimulation test).
Alterations in the hemogram are much discussed but only occasionally of value in the diagnostic process. the changes seen are all secondary to glucocorticoid deficiency. a mild normocytic, normochromic anemia is common in dogs. It may be masked initailly by dehydration, only becoming evident following volume expansion. The packed cell volume then is usually in the 25 to 35 per cent range.
Ill animals with noninfectious diseases typically have a stress leukogram. This is characterized by a mature neutrophilia, eosinopenia, lymphopenia, and monocytosis. The dog or cat with hypodrenocorticism, lacking adequate cortisol reserve, would not be expected to develop this pattern in spite o being seriously "stressed". This would produce a hemogram characterized by a normal WBC count, with an eosinophilia and a lymphocytosis. In actuality, a "non-stressed" hemogram is uncommon in dogs with hypoadrenocorticism. Eosinophilia and lymphocytosis occur in only 10 to 15 per cent of affected dogs. However, the presence of a normal white count and normal numbers of eosinophils or lymphocytes in an ill animal is not normal, and hypoadrenocorticism should be considered.
Sodium an dPotassium Abnormalities. The patient with hypoadrenocorticism may have abnormalities in all the commonly reported electrolytes (sodium, potassium, chloride, calcium, phosphorus). typically, a presumptive diagnosis of hypoadrenocorticism is made based on the presence of hyponatremia, hypochloremia, hyperkalemia, and a sodium/potassium ratio less than 27:1 (Table 119-2). Normal sodium/potassium ratios range from 27:1 to 40:1, with a mean of 30:1. Most dogs with adrenal insufficiency have ratios less than 20:1. The presence of hyperkalemia and an abnormal sodium/potassium ratio-regardless of cause-warrants therapy to prevent life-threatening cardiac arrhythmias from developing. The most common diseases associated with hyperkalemia other than hypadrenocorticism are acute oliguric or anuric renal failure avere gastrointestinal disorders. All of these diseases benefit from judicious fluid administration while test to discriminate between them are performed.
Unfortunately, neither the presence of normal electrolytes nor a normal sodium/potassium ration can completely rule out a diagnosis of hypoadrenocorticism. Approximately 10 per cent of dogs with this disease have a normal sodium and/or a normal potassium levels. Clinical signs of so-called "atypical hypoadrenocorticism" are due primarily to cortisol deficiency and may be caused by either primary or secondary hypoadrenocorticism. Some dogs with primary hypoadrenocorticism initially have signs attributable only to severe cortisol deficiency, while mineralocorticoid secretion is adequate to maintain serum electrolytes in the normal range. Over time, electrolyte abnormalitites will develop the expected pattern. If naturally occurring or iatrogenic secondary hypoadrenocorticism is present, mineralocorticoid release is normal and electrolyte abnormalities never develop (Table 119-3). These latter cases required assessment of both ACTH stimulation and endogenous ACTH concentration for definitive diagnosis.
An abnormal sodium/potassium ratio is not pathognomonic for hypoadrenocorticism. Any disease associated with severe sodium depletion can cause the ratio to become subnormal, whereas diseases associated with hyperkalemia also produce ratios of <27:1 and may be misdiagnosed as hypoadrenocorticism (Table 119-4). It is important to differentiate nonadrenal from adrenal causes for hyperkalemia, because therapy for primary hypoadrenocorticism is needed permanently.
The most often recognized causes for non-adrenal-associated hyperkalemia include acute oliguric/anuric renal failure, chronic oliguric renal failure (less commonly), uroabdomen secondary to a reptured urinary bladder or ureter, postrenal uremia associated with urethral obstruction, severe gastrointestinal diseases, and metabolic acidosis (Table 119-4). GI diseases that may present with biochemical data resembling hypoadrenocorticism inclue infectious diarrheas (salmonellosis, trichuriasis, ancylostomiasis, parvovirus, distemper), perforated GI ulcers, gastric dilatation and volvulus, and severe malabsorption.
Less commonly, hyperkalemia may be associated with the use of therapeutic agents (potassium-sparing diuretics, non-steroidal anti- inflammatory drugs, angiotensin-converting enzyme inhibitors, and potassium-containing fluids). These causes should be readily identifiable.
Another less commonly recognized cause for both hyperkalemia and hyponatremia is seen in dogs with both chylous and nonchylous pleural effusions. The exact mechanism is unknown. Renal potassium excretion is impaired in spite of elevated serum aldosterone concentration in these animals.
Massive release of potassium to the extracellular space can occur in severe crush injuries, in association with aortic thrombosis in cats, or following rhabdomyolysis secondary to heat stroke or heavy excercies. It also occurs in association with severe hemolysis (rare) or in massive infections.
Pseudohyperkalemia has been seen in the Akita breed as a unique genetic abnormality. Their RBC's contain larger potassium concentrations than those of most dogs, and potassium concentrations increase after serum is left in contact with RBCs for 4 hours or more following collection. Pseudohyperkalemia may also occur in animals with severe leukocytosis (total WBC = >100,000/mm3) or in cases of severe thrombocytosis (platelets = 100,000/mm3). The potassium elevates in the serum as blood is clotting and is an in vitro phenomenon.
Hyponatremia can occur in many diseases other than hypoadrenocorticism (see Table 119-4). Severe hyponatremic states often result in a sodium/potassium ratio of less than 27:1, and hypoadrenocorticism must be considered in the differential diagnosis. Diseases associated with hyponatremia include GI losses secondary to vomiting, hemorrhagic gastroenteritis, and parvoviral enteritis, nephrotic syndrome and other edematous states, postobstructive diuresis, congestive heart failure, myxedema, diabetes mellitus, primary polydipsia, and inappropirate secretion of ADH. All of these diseases are differentiated from hypoadrenocorticism by their response to therapy and results of ACTH stimulation testing. Their clinical signs and other biochemical data overlap a great deal with those of primary hypoadrenocorticism and often cannot be differentiated on the basis of these data alone.
Calcium Abnormalities. Approximately one-third of dogs with hypadrenocorticism are hypercalcemic when they are hyperkalemic. In a review of 16 dogs whose hypercalcemia was associated with primary hypoadrenocorticism, the range of calcium concentrations was found to be from 12.0 to 14.9 mg/dl. The magnitude of the hypercalcemia correlated with the severity of their dehydration and other electrolyte abnormalities. Other causes for hypercalcemia must be considered as well and include pseudohyperparathyroidism, primary hyperparathyroidism, hypervitaminosis-D, acute and chronic renal failure, and intoxication with rodenticides containing vitamin D.
The hypercalcemia further complicates the process of establishing a diagnosis since hypercalcemia is seen much more often in patients with malignant disease, such as lymphosarcoma. Hypercalcemia induces polydipsia, polyuria, and varying degrees of renal failure-findings that also characterize hypoadrenocorticism.
Elevations in blood urea nitrogen (BUN) and creatinine and a reduction in renal concentrating ability are common in dogs with hypoadrenocorticism (see Tables 119-2 and 119-3). The mean BUN concentration in two large surveys was 83 mg/dl, with a range of 12 to 223. The BUN concentrations, coupled with a urine specific gravity that is often less than 1.030, and sometimes in the isosthenuric range in a dehydrated animal, may lead to the erroneous conclusion that primary renal failure exists. However, serum creatinine values are typically less elevated than the BUN concentrations, supporting the existence of a prerenal component. Values for creatinine typically range from 0.9 to 3.8 mg/dl (mean=2.2 mg/dl).
The elevations in BUN and crenine relfect the severe volume contraction, hypotension, and dehydration that are associated with hypadrenocorticism. The decreased urine specific gravity is related to the hypnatremia, meullary solute washout, and solute diuresis seen in this disease. The BUN and creatinine usually return to normal in 24 to 48 hours if appropriate fluid therapy is administered, even in cases with BUN concentrations over 200 mg/dl. Renal concentrating ability returns to normal in nearly all cases following appropriate medical management.
If hypotension is severe, renal ischemia may develop. The ischemia may induce a primary renal injury. Thus, a primary renal injury can be superimposed on a prerenal component, confounding both management and diagnosis.
Mild to moderate degrees of metabolic acidosis exist in many dogs with hypadrenocorticism. The acidosis is secondary to decreased renal H+ excretion in the mineralocorticoid-deficient animal. Decreased renal perfusion and hypotension may also contribute to the acidosis. Fortunately, the majority of animals do not require specific therapy for the acidosis. Adequate fluid resuscitation and mineralocorticoid replacement correct the abnormality in most cases.
Hypoglycemia (blood glucose = 70 mg/dl) is an uncommon laboratory finding in animals with hypoadrenocorticism in spite of the important role that cortisol plays in maintaining fasting blood glucose concentrations (see Table 119-2). Hypoglycemia is reported in from 8 to 37 per cent of dogs with this disease. It may be severe enough to cause weakness, tremors, and even convulsions. Occasionally, hyperglycemia is seen as well.
A number of dogs with primary hypoadrenocorticism have mild hypoalbuminemia. The serum concentration is usually 2.0 gm/dl (normal >2.7 gm/dl). In these cases, no other cause for the hypoalbuminemia can be identified, and it reverses with treatment for the hypoadrenocorticism. Hypoalbuminemia was noted in one of six dogs with hypadrenocorticism in one review. The exact mechanism remains speculative at this time, although it is known that glucocorticoids influence hepatic albumin synthesis, and a deficiency in cortisol may impair hepatic albumin production.
Survey radiographs are often obtained on dogs in an adrenoal crisis as part of the routine data base required in the evaluation of a critically ill dog. Thoracic radiographs may idenify the presence of microcardia due to the profound hypovolemia present in some patients. The cardiac silhouette appears small relative to the thoracic volume of the animal. The descending aorta appears flattened and of decreased diameter. The caudal vena cava also appears small. These findings are not diagnostic for hypadrenocorticism. They reflect the presence of shock and the severity of ECF volume contraction seen in these animals.
One additional radiographic observation that may be made is that of megaesophagus. Several reports have identified this abnormality in recent years. Some dogs have been asymptomatic (no regurgitation history), whereas others were evaluated primarily for signs of regurgitation. One animal had primary hypoadrenocorticism that was only associated with cortisol deciency. Replacment glucocorticoid therapy was associated with resolution of the megaesophagus.
The hyperkalemia associated with mineralocorticoid deficiency can have profound effects on myocardial contractility and the EKG. An EKG is an easy, inexpensive and rapid tool for assessing changes in serum potassium (K4) concentration in patients with hyperkalemia. When a bradycardia is identified on physical examination, and EKG is an efficeint means of deternining the presence of hyperkalemia. This is particularly true once clinicians become familiar with the electrocardiographic changes typical for this electrolyte abnormality. Therapy can then be instituted during the wait for laboratory values to be returned. An EKG is also an efficient aid to monitoring the initial therapeutic response of the patient.
EKG changes tend to parallel the severity of the serum potassium concentration. However, since hyponatremia, hypercalcemia, hypoxia, and metabolic acidosis can also affect myocardial performance, the severeity of EKG changes for a given potassium concentration varies from patient to patient. The primary effects of hyperkalemia are on electrical conduction through the myocardium and strength of contractions. Mild hyperkalemia (serum K+ = 5.5 to 6.5 mEq/L) is generally associated with a tall, "peaked" T wave. As the K+ concentration increases from 6.5 to 8.5 mEq/L, there is widening and flattening of the QRS complex, prolongation of the PR interval, decrease in P wave amplitude, and increase in duration of the P wave. At potassium concentrations of >8.5 mEq/L, atrial standstill, absence of P waves, and deviations of the ST segment from the base line are expected. At serum potassium concentrations of 11 to 14 mEq/L, ventricular asystole or ventricular fibrillation is common.
The frequency of ocurrence of EKG abnormalities was quantified in a large group of dogs with primary hypoadrenocorticism. Tall peaked T waves (>0.5 mV) in lead II occurred in 22 per cent of dogs. A decreased amplitude of the R wave (<0.5 mV) in lead II was observed in 22 per cent, and P waves were absent in 50 per cent of cases. The serum potassium concentration associated with an absence of P waves ranged from 8.6 to 11.3 mEq/L.
ADRENAL FUNCTION TESTING
Although results of a CBS, biochemical profile, urinalysis, and EKG may all be supportive of the diagnosis of hypoadrenocorticism, the definitive diagnosis requires an assessment of the integrity of the hypothalamic-pituitary-adrenal axis. This may be done in a number of ways, including basal plasma cortisol concentrations, 24-hour urinary 7-hydorxy-corticosteroid concentrations, ACTH stimulation testing, endogenous ACTH concentrations, and plasma aldosterone concentrations.
ACTH Stimulation Testing
Basal plasma cortisol concentrations are of little diagnostic value and should not be used as the sole criterion for establishing the diagnosis. Normal dogs can have basal cortisol values of zero, and dogs with hypoadrenocorticism occasionally have resting values within the low normal range. Assessing adrenal reserve capacity is the only way to diagnose this disease.
Performing an ACTH stimulation test is currently the best method for confirming the diagnosis of hypoadrenocorticism in dogs and cats. The test is run as soon as the diagnosis is suspected, regardless of the time of day. It is important to observe sample- handling instructions from the laboratory that will perform the hormone assays. Cortisol samples are usually stable in serum or plasma for as long as 5 days at room temperature. If the diagnosis is suspected and it is necessary to administer some sort of glucocorticoid before the test is completed, the recommended drug is dexamethasone, as it does not interfere with glucocorticoid assay. Most other synthetic glucocorticoids will be measured by the radioimmunoassay (RIA) techniques and confound the diagnostic process. It is generally of no increased risk to the patient with hypoadrenocorticism if only fluids (saline) are administered whle plasma cortisol values are awaited, to be follwoed by appropriate glucocorticoids as soon as the second sample is colledted (in 1 or 2 hours).
The test is performed in the following manner. Either animal- origin ACTH gel (Cortigel 40, Savage Labs, Melville, NY 11747) or synthetic ACTH, tetracosactrin (Cortrosyn, Organon Pharmaceuticals, West Orange, NJ 07052), may be used. The gel preparation is given at a dosage of 1 U/lb (2.2 U/kg) IM in both dogs and cats, and plasma samples are collected at 0 and 2 hours following administration in dogs and at 0, 60 and 120 minutes in cats. Awueous synthetic ACTH is given at 0.25 mg/dog or 0.125 mg/cat IM and plasma samples are collected at 0 and 1 hour postinjection in dogs, and 0, 30, and 60 minutes postinjection in cats.
Results of ACTH stimulation testing in dogs and cats with hypoadrenocorticism typically have resting levels in the low normal range that fail to increase following ACTH. Post-stimulation values are often similar to or below resting values. Some animals will have a slight increase in post-stimulation values, but in all reported cases in dogs, values have been below the minimum normal post-stimulation value (Table 119-5). Post-stimulation cortisol values are consistently less than 50 ng/ml (5.0 ug/dl) in dogs with hypoadrenocorticism.
Endogenous ACTH Concentrations
The results of ACTH stimulation testing will not differentiate primary from secondary hypoadrenocorticism. This requires measurement of endogenous plasma ACTH concentrations. Sample handling is critical for this hormone as it is much more labile than cortisol. It is imperative that the laboratory processing the sample provide handling instructions. Samples generally must be drawn and centrifuged immediately and stored frozen in plastic tubes.
Plasma endogenous ACTH concentrations are primarily of value in animals in which just glucocorticoid deficiency exists (ACTH stimulation test is nonresponsive, but electrolytes are normal). Some dogs with primary hypoadrenocorticism only have signs of glucocorticoid deficiency (i.e. lethargy, depression, anorexia, vomiting, diarrhea, and weakness). Their sodium, potassium, and chloride values are normal. Endogenous ACTH values should be high in dogs with primary hypoadrenocorticism, since no negative feeback from cortisol occurs. The presence of high endogenous ACTH concentrations confirms that the pituitary is functioning and that the primary lesion is located in the adrenal gland. These dogs should have serum electrolytes monitored every 3 to 4 months, as progressive destruction of adrenal tissue is to be anticipated. They would be expected to eventually develop minearlocorticoid deficiency and need replacement therapy. Progressive destruction of adrenal function does not always occur, however. In one reported case, a dog with pure glucocorticoid-deficient primary hypoadrenocorticism failed to develop electrolyte abnormalities even after several years of monitoring. It is being well managed with glucocorticoid replacement therapy alone.
The range of endogenous ACTH concentrations from 18 dogs with primary hypadrenocorticism was reported as 554 to 4950 pg/ml. Normal values are from 20 to 100 pg/ml. If both electrolytes and ACTH stimulation testing are abnormal, primary hypoadrenocorticism is confirmed, and endogenous ACTH concentrations become of academic interest.
Animals with pituitary failure causing their adrenal insufficiency should have low or undetectable endogenous ACTH concentrations, which leads to bilateral adrenal atrophy. This is true in both naturally occurring and iatrogenic secondary hypoadrenoncorticism in which endogenous ACTH concentrations were measured. Both dogs had values less than 20 pg/ml. These animals need only cortisol replacement therapy to control signs of their disease.
Plasma Aldosterone Assay
Measurement of plasma aldosterone concentrations may be of diagnostic value, but the assay is available commercially from few sources. It may be of interest to demonstrate normal results in dogs suspected to have secondary hypoadrenocorticism. It could also be of value in the rare situation in which an animal has hyperkalemia and hyponatremia, an abnormal sodium/potassium ratio, but normal ACTH stimulation results. Such an animal may have primary hypoadrenocorticism, but cortisol reserve is still normal.
Aldosterone release is measured as part of an ACTH stimulation test protocol. Limited numbers of dogs with primary hypoadrenocorticism have been tested, but all had low to non- detectable basal aldosterone concentrations and no repsonse following ACTH administration. Normal serum aldosterone values are reported to be 20.3 + 7 ng/dl before and 39.7 + 9.4 ng/dl one hour after 0.25 IU/lb (0.5 IU/kg) synthetic ACTH (Cosyntrosyn) was given IV, and 5 to 345 pg/ml before and 71 to 758 pg/ml 2 hours after 1 U/lb (2.2 U/kg) IM ACTH gel was administered.
Modified Thorn Test
A modified Thorn test has been proposed as a rapid method for supporting or refuting the diagnosis of hypoadrenocorticism during initial diagnostic evaluation of patients suspected of having this disease. The test is performed at the same time as ACTH stimulation testing is done for cortisol assays. This test is not recommended.
THERAPY OF HYPOADRENOCORTICISM
ACUTE ADRENAL CRISIS MANAGEMENT
Patients with the clinical, biochemical and electrolyte abnormalities compatible with acute hypoadrenocorticism should be treated as if they have the disease until they respond appropriately or the diagnosis is refuted. To delay therapy pending cortisol assays may lead to death of the patient. Patients with nonadrenal causes for their hyperkalemia will not be harmed by therapy. The primary goals of therapy are to correct hypvolemia and hyptension, to reestablish vascular responsiveness, to replace glucocorticoid deficits, and to correct electrolyte abnormalities, hypoglycemia, and acidosis (Table 119-6).
Management of Shock, Hyptension, an Hypovolemia
Death from hypadrenocorticism is usually secondary to vascular collapse and shock, not from profound hyperkalemia. Therefore, immediate intravenous fluid therapy is life-saving. Fluids not only increase the intravascular volume, raise blood pressure, and improve renal perfusion but also dilute out the extracellular potassium, reducing the risk of developping fatal cardiac arrhythmias.
Normal saline (0.9 per cent sodium chloride) is the fluid of choice. The primary electrolyte deficits are sodium and chloride, and the ideal fluid should be potassium-free. An intravenous line is established, and baseline samples are collected for a CBC, chemistry profile, resting cortisol, and a urine analysis. Saline is initially administered at 20 to 40 ml/lb (40 to 80 mg/kg) during the first hour. Total fluid requirements and rates of administration are determined by the degree of dehydration, maintenance needs, and ongoing losses, and they are adjusted accordingly. If the patient is found to be hypoglycemic, 50 per cent dextrose is added to the saline to make a 5 per cent solution (100 ml of 50 per cent dextrose per liter). Potassium-containing fluids such as lactated Ringer's solution are relatively contraindicated (K+ = 4 mEq/L). However, the serum potassium of the patient is usually much higher than the concentration in lactated Ringer's solution (LRS), and the volume expansion provided by LRS will dilute out the hyperkalemia. Administration of LRS is certainly preferable to giving no fluids at all. The patient's urine output needs to be monitored to be sure adequate urine production occurs once replacement fluids are begun.
Glucocorticoid replacement therapy can be delayed until a post- ACTH plasma cortisol sample is obtained (1 hour for synthetic ACTH and 2 hours for ACTH gel). Rapid volume expansion provides therapy for nearly all the acutely fatal complications associated with hypoadrenocorticism. If a steroid is given during the time ACTH stimuloation testing, it should be dexamethasone (see below for dosages). This glucocorticoid is not measured by most RIA techniques for cortisol.
The ideal glucocorticoid to utilize in an acute hypoadrenal crisis would be hydrocortisone hemisuccinate or hydrocortisone phosphate (see Table 119-8). These glucocorticoids possess both glucocorticoid and mineralocorticoid activity and are given at a dose of 1 to 2 mg/lb (2 to 4 mg/kg) IV initially, and repeated every 8 hours. Prednisolone sodium succinate can be used as an alternative rapid-acting glucocorticoid and is given at a dosage of 2 to 10 mg/lb (4 to 20 mg/kg) IV over 2 to 4 minutes. This dosage is repeated in 2 to 6 hours, depending on how well the patient is responding. Prednisolone sodium succinate also possesses some mineralocorticoid activity. Dexamethasone sodium phosphate may also be used as replacement glucocorticoid therapy during intial treatment at dosages of 0.25 to 1.0 mg/lb (0.5 to 2 mg/kg) initially. This dosage is reduced, once shock is reversed, to 0.02 to 0.05 mg/lb (0.04 to 0.1 mg/kg) twice daily and is added to the patients intravenous fluids.
Correction of sodium, chloride, and water deficits is accomplished by saline administration. Hyperkalemia is also improved by volume expansion and improved renal perfusion alone. There is no longer any rapid-acting parenteral mineralocorticoid preparation available. Dexoxycorticosterone acetate has been taken off the market. Hydrocortisone hemisuccinate or phosphate will provide adequate mineralocorticoid activity along with saline infusions to stabilize the hyperkalemia until oral daily mineralocorticoid or injectable monthly mineralocorticoids (desoxycorticosterone pivalate, Percorten-V) can be given. After initial shock dosages of hydrocortisone are administered, the dosage can be progressively reduced to 0.2 to 0.5 mg/lb (0.4 to 1.0 mg/kg) every 6 hours intravenously. This may be further reduced on day 2 to 0.05 to 0.1 mg/lb (0.1 to 0.2 mg/kg) every 6 hours. By day 3 the drug may be given at the same dosage with the frequency reduced to every 12 hours. Supplemental mineralocorticoid therapy will usually be needed when the dosage of hydrocortisone reaches this mainteance level.
Management of Life-Threatening Hyperkalemia
In some animals the hyperkalemia is so severe that alternatives to volume expansion and mineralocorticoid replacement alone must be considered. These alternative strategies for controlling hyperkalemia are rarely, if ever, needed. In addition to rapid volume expansion with 0.9 per cent saline, intravenous glucose, glucose plus regular insulin, sodium bicarbonate therapy, and intravenous 10 per cent calcium bicarbonate therapy may be considered.
Intravenous glucose is useful in managing hyperkalemia because as glucose enters cells, potassium follows, lowering its extracellular concentration. glucose may be given as a 10 per cent solution at a dosage of 2 to 5 ml/lb (4 to 10 ml/kg), which may be added to the saline and given over 30 to 60 minutes. Insulin is also known to promote the movement of extracellular potassium into cells. Regular insulin can be given either SQ or IV at a dosage of 0.03 to 0.06 U/lb (0.06 to 0.12 U/kg) to promote rapid potassium uptake by cells. For each unit of insulin given, 20 ml of 10 per cent dextrose are given to the patient to prevent hypoglycemia.
Alkalosis also promotes the transcellular movement of extracellular potassium into cells, reducing its cardiotoxic effects. Bicarbonate may be given at 0.25 to 0.5 mEq/lb (0.5 to 1.0 mEq/kg) as a slow IV bolus administration. Again, this should not be necessary in most hypadrenal patients.
Finally, calcium gluconate is known to protect against the effects of hyperkalemia on the myocardium. It can be given IV as a 10 per cent solution at 0.2 to 0.5 mg/lg (0.4 to 1.0 mg/kg) over a 10- to 20-minute period. Administration of calcium gluconate may provide time for other slower-acting therapies to be effective. Patients receiving intravenous calcium gluconate must have continuous EKG monitoring. If any new arrhythmias are noted, the infusion should be stopped.
The metabolic acidosis seen in patients with hypoadrenocorticism is usually mild and rarely needs to be treated specifially. Volume expansion, increased tissue perfusion, and improved renal function usually lead to correction of preexisting metabolic acidosis. If the total CO2 concentration (TCO2) is less than 12 mEq/L, judicious sodium bicarbonate therapy may be indicated. The base deficit is calculated as body weight (kg) x 0.5 x base deficit (mEq/L). In the absence of blood gas analysis for determination of the base deficit, it can be estimated as: base deficit = 22 - TCO2. One-fourth of the calculated bicarbonate deficit is given to the patient in the first 6 to 8 hours of therapy. It would be rare for nay more alkalinization therapy to be needed. Sodium bicarbonate therapy has an additional benefit in that it will help to promote the intracellular movement of potassium from the extracellular space, reducing its adverse physiologic effects.
Most patients improve significantly within hours after the administration of appropriate fluid, electrolyte, and glucocorticoid replacement therapy. Within 24 to 48 hours, most have stopped vomiting and diarrhea has ceased. Gradual reintroduction of oral food, water and medications can now be safely done. A rapid reversal of severe renal compromise, hypercalcemia, and hyperkalemia lends further support for the diagnosis if results of ACTH stimulation testing are still pending. Most other causes for these biochemical abnormalities will not respond this rapidly to the therapy described above.
In rare cases, renal function may not return rapidly to normal. In such animals it is liekly that the shock associated with hypoadrenocorticism induced severe reanl ischemia or that some preexisting primary renal disease was aggravated by hypovolemia and hyptension. In this situation, a rapid return to normal BUN or creatinine is not expected. These patients require much more judicious fluid administration, especially if they become oliguric.
MAINTENANCE THERAPY OF HYPOADRENOCORTICISM
Once patients stabilize following initial aggressive fluid, electrolyte, glucocorticoid, and acidosis therapy, maintenance therapy can be started (Table 119-7). In most animals with primary hypoadrenocorticism, both glucocorticoid and mineralocorticoid replacment therapy will be needed for life. In the rare animal with only glucocorticoid deficiency, no mineralocorticoids will be needed. Low dosages of glucocorticoids will control signs of their disease.
Oral glucocorticoid replacment therapy is continued for 3 to 4 weeks in most animals after the crisis is over. Prednisone or prednisolone may be given initially at 0.25 to 0.5 mg/lb/day (0.5 to 1 mg/kg) in divided doses every 12 hours. This dosage is gradually tapered off (decrease by 50 per cent per week) until the drug is discontinued entirely. The majority of dogs do well on replacement mineralocorticoid alone after the first few weeks of therapy if fludrocortisone acetate is used (Florinef). If dogs show signs of cortisol deficiency (anorexia, lethargy, depression), low dosages of prednisone or prednisolone can be started again. Daily maintenance needs for prenisone or prednisolone are approximately 0.1 mg/lb/day (0.22 mg/kg) in most dogs. All owners should be given a prescription for some sort of glucocorticoid to use in times of stress, regardless of whether the patient needs them daily.
Long-term mineralocorticoid replacement therapy can be provided by a number of means including oral fludrocortisone acetate, injectable desoxycorticosterone pivalate (DOCP), or surgically implanted DOCP pellets. The durg used most commonly is fludrocortisone acetate (Florinef). Fludrocortisone is a potent oral mineralocorticoid that is useful as daily replacement therapy. It is available in 0.1-mg tablets, and its mineralocorticoid potency is equivalent to that of natural aldosterone. It also has significant glucocorticoid activity. On a milligram basis, it is ten times as potent as cortisol. Thus, it provides for both the glucocorticoid and mineralocorticoid needs of most patients once the cortisol needs during an adrenal crisis are managed. It is administered at approximately 0.1 mg/10 lb body weight (0.1 mg/5 kg) in divided doses every 12 hours. Dosages are adjusted based on normalization of serum sodium and potassium concentrations. Electrolytes should be monitored every 4 to 7 days during the first week or two and then every 3 to 4 months during the first year of therapy. Dogs generally develop increased need for fludrocortisone during the initial 6 to 18 months of therapy. After that time, most have stable mineralocorticoid dosages. This increasing drug needmay be due to progression of adrenal inflammatory disease that was ongoing at the time of inital diagnosis.
Maintaining the serum potassium concentration in the high- normal range is the goal of therapy. The drug's cost and side effects (polyuria, incontinence) are limiting factors in the treatment of some dogs with hypoadrenocorticism. Particularly in giant breeds, the cost of daily fludrocortisone can be several dollars a day. By maintaining the serum potassium in the high- normal range, one can be sure the minimual amount necessary is being given, which helps to control long-term drug costs for the owner and is not associated with any increased clinical risk of relapse for the dog.
In some animals on large fludrocortisone dosages, polyuria can be profound and intolerable for owners, probably owing to the glucocorticoid activity inherent in this product. It has been suggested that this may be controlled by the use of oral hyrocortisone as replacement therapy for both glucocorticoids and mineralocorticoids. Hydrocortisone may be given at 0.0612 mg/lb (0.125 mg/kg), with two-thirds given in the morning, when steroid needs are greatest, and one-third given 12 hours later. In some dogs, supplemental fludrocortisone will still be needed, but at reduced dosages (0.05 to 0.2 mg/day).
In occasional animals, hyponatremia will persist in spite of normal serum potassium concentrations. In such cases, the addition of table salt to the diet should normalize the sodium concentrations without an increase in fludrocortisone dosages (a more costly alternative).
An alternative to daily oral fludrocortisone therapy is the use of injectable desoxycorticosterone pivalate (DOCP). DOCP is a long-acting ester of desoxycorticosterone in a microcrystalline suspension. Several recent reports have discussed its use as a replacement for daily fludrocortisone tablets. It was available commercially as Percorten pivalate until 1987, when commercial production was discontinued. Since that time it has only been available from the manufacturer upon individual request. The drug, Percorten-V, has gone through initial clinical trials and is awaiting approval by the FDA for use in dogs. The manufacturer anticipates approval of the drug for general use by veterinarians sometime in 1994 or 1995. At this time, it can only be obtained from the manufacturer by individual request. (Write CIBA Animal Health at P.O. Box 18300, Greensboro, NC 27419-1180 for information about obtaining DOCP for selected animals. Current costs are $62.00 per 100-mg vial[25 mg/ml].)
DOCP is useful for dogs that develop significant polydipsia and polyuria when receiving Florinef; for those that require large dosages, and thus incur high costs for control of their disease; or for animals in which fludrocortisone appears ineffective even in large doseages. DOCP is initially given at 1 mg/lb (2.2 mg/kg) IM once every 25 days. Serum should be collected after 14 days and again at 25 days for the first 2 to 3 months of therapy to determine whether dosage adjustments are needed. Occasionally, there are individual dosage variations with DOCP, and frequent monitoring, at least during the first few months of therapy, is of value. The goal is to maintain the dog on the smallest dosage needed to achieve normal serum electrolyte concentrtions and to prevent clinical signs of disease. If the sodium and potassium are normal at day 25 (the day of injection), the dosage may be decreased by 0.1 mg/lb (0.2 mg/kg) at each subsequent dosing interval until the lowest dosage that maintains normal electrolytes is obtained. As an alternative, the doing interval may be increased to 30 days and and electrolyte panel evaluated at the end of the new 30-day inter-injection interval.
In some dogs the duration of action is less than 25 days. If electrolytes are normal at 14 days, but not at day 25, the dosing interval should be shortened. Shorten the inter-injection interval to 21 days first. Rare animals need DOCP as often as every 14 days.
Current data suggest that approximately 15 per cent of dogs will require 0.5 mg/lb (1.1 mg/kg) every 25 days, and 30 per cent will require between 0.5 and 1.0 mg/lb (1.0 and 2.2 mg/kg). Over 50 per cent are well maintained on 1.0 mg/lb (2.2 mg/kg) every 25 days. Few require more than 1.0 mg/lb/injection (2.2 mg/kg).
Because DOCP has little or no glucocorticoid activity, supplemental glucocorticoid therapy should be combined with DOCP, at least initially. Interestingly, approximately 50 per cent of dogs do well with no supplemental glucocorticoids when maintained on DOCP alone. Initially, dogs are given approximately 0.1 mg/lb/day (0.22 mg/kg) of prednisone or prednisolone. This dosage may be gradually reduced and eliminated after several weeks if the dog has no clinical signs of disease (anorexia, lethargy, depression) in the absence of glucocorticoid supplementation. Some dogs do well when glucocorticoids are given only once every 2 to 3 days. Owners should have a supply of glucocorticoids available to give during stressful situations even if they are not needed on a daily basis. Glucocorticoid demands during stress are two to ten times those needed for maintenance.
Side effects associated with DOCP have been infrequent. Polydipsia and polyuria are occasionally seen. This most often results from combining glucocorticoids with the DOCP and responds to lowering the glucocorticoid dosage. In rare animals, lowering of the DOCP dosage results in elimination of these signs. One animal was reported to have a less favorable response to DOCP than Florinef, and one dog had an acute adrenal crisis in spite of having received the drug, and was considered a drug failure. Mild hypoalbuminemia has been noted in occasional dogs receiving DOCP (serum albumin 2.0 to 2.5 gm/dl).
The owner's main disadvantages in the use of DOCP are the need to return monthly for an injection and the costs of repeated examinations and laboratory work. Owners can be taught to give the injections at home and are seen only every 3 to 4 months once the patient is stable, to ensure that electrolytes are well maintained. Recent data also suggest that subcutaneous injections are as effective as IM injections, simplifying at-home management for owners.
The last method for mineralocorticoid replacement is that of DOCP pellets. DOCP pellets contain 125 mg of DOCP and are surgically implanted subcutaneously. They release approximately 0.5 mg of desoxycorticosterone acetate per implanted pellet per day and have a duration of action of approximately 10 months. The are costly, require more technical manipulations (surgery), and are the least reliable of the three methods available. They are not recommended for use at this time.
Therapy of Secondary Hypoadrenocorticism
Animals with spontaneous or iatrogenic secondary hypoadrenocorticism need only glucocorticoids to reverse their clinical signs. Dosages are similar to those recommended previously, starting at 0.25 to 0.5 mg/lb/day (0.5 to 1 mg/kg) and tapering to the lowest needed to control clinical signs of disease. Periodic reevaluation of serum electrolytes is indicated in animals thought to have naturally occurring secondary hypoadrenocorticism (pituitary disease) because some animals may actually have primary disease and have been misdiagnosed initially. They develop electrolyte abnormalities only late in their disease course. This is particularly true if endogenous ACTH concentrations are not available for analysis. In cases of iatrogenic hypoadrenocorticism, glucocorticoid dosages are gradually reduced to alternate-day therapy at low dosages until eventually no supplemental therapy is needed.
The long-term prognosis for animals with hypoadrenocorticism, once an adrenal crisis is controlled, is excellent. With appropriate glucocorticoid and or minerlocorticoid replacement, dogs and cats should be expected to live a normal life. Good communication between the veterinarian and the owner is critical for success, however. The importance of life-long therapy and the need for periodic physical examinations and biochemical evaluations must be emphasized to owners. In addition, owners need to know that their pet may deteriorate in high-stress situations if glucocorticoids are not increased. They also need to be educated about how to recognize signs of glucocorticoid defiency.
TABLE 119-1. HISTORICAL OWNER COMPLAINTS FOR DOGS WITH HYPOADRENOCORTICISM*
Weight loss 23
Polyuria (with or 15
Waxing-waning course 10
Sensitive abdomen 9
*Frequency of the various signs of canine hypoadrenocorticism as noted by the owners of these dogs. Results are a compilation of 100 personal and reported cases. From Feldman EC and Nelson RW: Canine and Feline Endocrinology and Reproduction. Philadelphia, WB Saunders, 1987, p. 199.
TABLE 119-2.SELECTED LABORATORY VALUES IN DOGS WITH PRIMARY HYOADRENOCORTICISM