Diagnosis and Management of Geriatric Canine Endocrine Disorders

Veterinary Research Communications, 27 Suppl. 1 (2003) 543–554 © 2003 Kluwer Academic Publishers. Printed in the Netherlands Diagnosis and Management of Geriatric Canine Endocrine Disorders A.Boari* and G. Aste Department of Veterinary Clinical Sciences, Internal Medicine Section, School of Veterinary Medicine, University of T eramo, V iale Crispi 212, 64020, T eramo, Italy *Correspondence: Department of Veterinary Clinical Sciences, Internal Medicine Section, School of Veterinary Medicine, 64020 T eramo, Italy E-Mail: [email protected] Keywords: dog, endocrinology, geriatric INTRODUCTION Ageing is defined as a complex biological process resulting in the progressive reduction of an individual’s ability to maintain homeostasis under internal physiological and external environmental stress, thereby decreasing the individual’s viability and increasing its vulnerability to disease. As in other organ systems, normal ageing of the endocrine system is characterized by a progressive loss of reserve capacity, resulting in a decreased ability to adapt to changing environmental demands. This loss of homeostatic regulation reflects important alterations in hormonal synthesis, metabolism, and action, but since the functional reserve for endocrine organs is much greater than the resting level, clinical change is generally not evident except under severe stress (Chastain, 1996). During the clinical evaluation of geriatric patients with endocrine disease, it should be considered that manifestations of endocrine disease may often be altered or masked by coexisting illnesses and medication used to treat comorbidities. Endocrine diseases are very common in the ageing dog and they are mainly represented by hypothyroidism, hyperadrenocorticism, phaeochromocytoma, hyperparathyroidism, diabetes mellitus, and insulinoma. Among these disorders only the endocrinopathies that require a challenging diagnostic and therapeutic approach will be considered in the present report. THE HYPOTHALAMO–PITUITARY–THYROID AXIS Hypothyroidism is generally considered to be the most common manifestation of the effects of ageing on the hypothalamo–pituitary–thyroid axis (Quadri and Palazzolo, 1991). Most cases (>95%) are caused by primary hypothyroidism due to lymphocytic thyroiditis or idiopathic thyroid atrophy (Kemppainen and Clark, 1994; Graham 543 544 et al., 2001). Canine thyroiditis is believed to be immune-mediated and antithyroglobulin antibodies are present in about 50% of hypothyroid dogs (Beale et al., 1990; Graham et al., 2001). Dermatological manifestations are the most common findings, occurring in about 85% of cases, and may include a dry and scaly coat, bilateral symmetrical and nonpruritic truncal alopecia, rat tail, hyperpigmentation, myxoedema and recurrent pyoderma (Dixon et al., 1999). Mental dullness, obesity, lethargy, exercise intolerance, heat-seeking, ocular abnormalities, reproductive disfunction, laryngeal paralysis, weakness, vestibular deficits and lower motor neuron signs are other manifestations attributed to hypothyroidism. Routine laboratory tests may reveal mild non-regenerative anaemia, hypercholesterolaemia and hypertriglyceridaemia (Panciera, 1994) but these abnormalities are neither specific for hypothyroidism nor consistently found. A definitive diagnosis of hypothyroidism can be difficult because of the many clinical abnormalities associated with thyroid hormone deficiency, and the lack of readily available diagnostic tests with high sensitivity and specificity. In addition to the age-related decline of the hypothalamo–pituitary–thyroid axis (Quadri and Palazzolo, 1991), breed, age, non-thyroid illness, drug administration and the presence of autoimmune thyroid disease can also affect thyroid function tests (Ferguson and Peterson, 1992). There are several known diseases that can cause the non-thyroidal illness syndrome (hyper- and hypo-adrenocorticism, hepatic disease, renal failure, heart failure, diabetes mellitus, diabetic ketoacidosis, chronic infectious and cancer cachexia), and the severity of illness and nutritional status instead of a specific disease appear to be the major factors associated with a decrease in thyroid hormones (Ramsey et al., 1997; Scott-Moncrieff et al., 1998). Drugs that may decrease thyroid hormone concentration include corticosteroid, diazepam, mitotane, furosemide, sulphonamides, phenobarbital, primidone, salycilates, dopamine, and phenothiazines (Gulikers and Panciera, 2002). Concentrations of total thyroxine (T4), free T4 by dialysis, and thyroid-stimulating hormone (TSH) are the functional thyroid tests most commonly used by veterinarians. Total T4 concentration is an excellent screening test for thyroid disfunction. A dog with a T4 concentration well within the reference range may be assumed to be euthyroid, unless anti-T4 antibodies are causing a spurious increase in the T4 value. This is uncommon, because anti-T4 antibodies are detected in only 0.8% of canine serum samples. In general, most dogs (>95%) with hypothyroidism have low circulating levels of total T4 but a low total T4 value is not necessarily diagnostic for hypothyroidism. As previously mentioned, the best use of the total T4 measurement is to exclude hypothyroidism, a decision made on finding a normal total T4 concentration in suspect dogs. A decrease in T4 concentration is not specific for the diagnosis of hypothyroidism. In fact decreased T4 may be normal for that individual (due to normal daily fluctuation in serum T4), it may result from non-thyroidal illness, or it may be secondary to drug administration. If the total T4 value is low or borderline low, free T4 by dialysis can be determined using that same sample. 545 The measurement of free T4, from a diagnostic viewpoint, gives a more accurate assessment of thyroid status and is less affected by non-thyroidal illness. This test is currently the best single test to detect canine hypothyroidism. However, false positive results can occur in dogs with hyperadrenocorticism and in dogs receiving phenobarbital or glucocorticoids (Ferguson and Peterson, 1992; Dixon and Mooney, 1999; Gulikers and Panciera, 2002). Measurement of the endogenous TSH concentration has recently become available but, unfortunately, the results, when considered alone, fail to identify about onequarter of patients with hypothyroidism. In fact concentrations of TSH are not elevated in approximately 20–35% of hypothyroid dogs (Scott-Moncrieff et al., 1998). Conversely, TSH concentrations are occasionally high in euthyroid dogs, but all of them had a total T4 value in the normal range. Because of the presence of false positive and false negative results, the measurement of canine TSH alone is not recommended in the diagnosis of hypothyroidism in dogs. In conclusion, the probability of an accurate diagnosis (hypothyroid or euthyroid) is significantly increased when the results of two or more tests agree. Hypothyroidism is very likely in a dog with typical clinical signs, a low free T4 by dialysis (or low total T4) and a high TSH concentration. Once hypothyroidism has been detected in an individual, a lifelong therapy must be instituted. The treatment of choice is a L-thyroxine preparation (0.02 mg/kg orally twice daily to start); and then the dose and the frequency should be adjusted based on result of therapeutic monitoring. Therapeutic success should be judged first on clinical grounds and then on measurements of serum T4 following the achievement of steady state concentrations. Serum T4 concentrations should be within the reference range immediately before the administration of a dose (pre-pill value) and should be at the high end, or slightly above the reference range, 4–6 hours after the administration of a dose (post-pill value). Once clinical signs have resolved, most dogs should be tried on once-daily L-thyroxine to see if this more convenient protocol adequately maintains clinical euthyroidism. Both clinical and pharmacological responses to hormone supplementation are important aspects of therapy. Neither parameter should be used on its own. Serum T4 concentrations should be measured at 6–8 week intervals during the first 6–8 months of treatment. Once adequate T4 levels are documented, the frequency of measurement of serum T4 may be decreased to once or twice a year. THE HYPOTHALAMO–PITUITARY–ADRENAL AXIS It is generally recognized that the incidence of hyperadrenocorticism (HAC) or Cushing’s disease in dogs increases with age, indicating that the hypothalamo– pituitary–adrenal axis is another major target of age-associated changes in this species (Quadri and Palazzolo, 1991; Rothuizen et al., 1991). The median age of onset of HAC is 10 years and over 75% of dogs with HAC are older than 9 years of age 546 (Reusch and Feldman, 1991). In pituitary-dependent HAC (PDH), which accounts for approximately 85% of cases, a pituitary tumour autonomously secretes corticotrophin (ACTH). Adrenal tumours (AT), which account for the remaining 15% of HAC cases, secrete cortisol autonomously. A bilateral adrenocortical neoplasia has only rarely been observed in the dog (Feldman and Nelson, 1996a). No matter the location of the underlying abnormality, clinical signs are relatively similar in all forms of HAC, with few exceptions. A large pituitary tumour can cause neurological signs such as stupor, disorientation, head pressing, pacing, circling, alterations in behaviour, seizures, ataxia and blindness, while a large AT may cause signs of a space-occupying nature. Most dogs with HAC are presented for evaluation of polyphagia, polyuria/ polydipsia (PU/PD), lethargy or weakness, panting, weight gain (usually a pendulous abdomen) or dermatological abnormalities including alopecia, comedones, hyperpigmentation and calcinosis cutis (Feldman and Nelson, 1996a). A detailed history and careful physical examination are essential to evaluate dogs suspected of having HAC, both to exclude non-adrenal illness and to identify any complications of HAC that may be present. In fact many non-adrenal diseases cause clinical signs similar to those seen in dogs with HAC. There are many diagnostic tests available to distinguish normal dogs from those with HAC, but it has been observed that the predictive value for HAC of a positive screening test result increases in direct proportion to the number and severity of clinical signs and biochemical changes typically occurring in the disease. The most consistent routine hematological and serum findings with HAC are a stress leukogram, markedly increased levels of serum alkaline phosphatase (ALP), alaninotransferase (ALT) activities, hypercholesterolaemia and lipaemia. Dogs with HAC usually have dilute urine. The incidence of urinary tract infection is very high (about 50%) in dogs with HAC even in absence of an active sediment (Feldman and Nelson, 1996a). Once a strong clinical suspicion of HAC is established, and the patient has been evaluated for the presence of non-adrenal diseases, performing a specific screening test for HAC is appropriate. Screening tests are designed to diagnose HAC and therefore to determine whether it is present or not. Tests that fit this category are the urine cortisol:creatinine ratio test (UCCR), low-dose dexamethasone suppression test (LDDST), and the corticotrophin (ACTH) stimulation test. In geriatric dogs, because of the high possibility of the presence of a concurrent non-adrenal disease, it has been recommended that positive results of the tests must be viewed in the light of the history and clinical signs of each dog. False positive results may occur frequently with the three common tests for HAC when dogs with non-adrenal diseases are tested. Testing a sick dog for HAC is inappropriate and should be avoided, if possible. The urine cortisol:creatinine ratio test (UCCR), because of his high sensitivity (close to 100%) but low specificity (20–25%) is indicated as a good test to rule out the diagnosis of HAC but never to rule it in (Behrend and Kemppainen, 2001). The ACTH stimulation test is commonly used as a screening test and it is also used 547 in order to distinguish spontaneous from iatrogenic HAC and obtain valuable baseline information for monitoring mitotane treatment. The test cannot distinguish between a PDH and an AT. Cortisol concentration should be measured before and 1 or 2 hours after intravenous or intramuscular administration of 0.125 mg of synthetic ACTH, respectively. The overall sensitivity of the ACTH stimulation test in diagnosing HAC is approximately 85%. However, in dogs with adrenal tumours the sensitivity is only 60%. There are many possible explanations for this finding, but it has recently been demonstrated that several dogs with AT and normal ACTH stimulation test results showed an increase in 17-hydroxyprogesterone, and other sex hormone concentrations (Norman et al., 1999; Syme et al., 2001). In these atypical cases adrenal tumours were producing hormones that probably inhibited cortisol production by normal adrenal tissue. The specificity of the ACTH stimulation test in a group of dogs with a concurrent illness is very low (Kaplan et al., 1995). The low dose dexamethasone suppression test (LDDST) is considered by many internists and dermatologists to be the test of choice for the diagnosis of HAC in dogs (Behrend et al., 2002). Serum cortisol should be measured before and at 4 and 8 hours after the administration of dexamethasone sodium phosphate (0.01 mg/kg, IV). The sensitivity of the LDDST is approximately 95%. Following administration of dexamethasone, inadequate serum or plasma cortisol concentration is found in about 100% of dogs with an adrenal tumour and in 90–95% of dogs with PDH. An additional 30% of dogs show cortisol suppression at 4 hours with a rise in the serum cortisol value by 8 hours after dexamethasone administration. This escape from suppression is diagnostic for PDH, and further tests to determine the cause of the HAC are not usually necessary. The specificity of the LDDST is quite low, especially when measured in a population of sick dogs. For this reason a diagnosis of HAC should never be based only on results of a LDDST in a dog with non-adrenal disease. The final step in diagnosis of hyperadrenocorticism is determining whether the cause is pituitary, adrenal or both. Determining the location is important in planning treatment and in formulating a prognosis. Currently available tests for discrimination between PDH and AT include the high dose dexamethasone suppression test (HDDST), plasma ACTH concentration, abdominal ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI). The HDDST is performed similarly to the LDDST with respect to timing. Dexamethasone is administered at the dose of 0.1 mg/kg IV. Adrenocorticotropic hormone production by pituitary tumours is suppressed by negative feedback if a large enough dose of dexamethasone is used and, as a result, plasma cortisol concentration is also suppressed. Typically suppression up to 50% of the baseline concentration or a cortisol concentration less than 30 nmol/L is considered consistent with PDH (Feldman et al., 1996a). However, approximately 30% of dogs with PDH do not suppress (Reusch and Feldman, 1991; Feldman et al., 1996). Cortisol concentration can be rarely suppressed by administration of high doses of dexamethasone to dogs with AT (Behrend et al., 2002). 548 Plasma endogenous ACTH concentration is a very specific test for discrimination between PDH and AT. The measurement of a single endogenous ACTH concentration was correct in localizing the source of HAC in 70% to 91% of dogs; this value increased to 98% when a repeat sample was taken from an animal that initially had non-diagnostic results (Reusch and Feldman, 1991). Endogenous ACTH concentrations are normal to elevated in dogs with PDH, whereas ACTH concentrations are usually low or undetectable in dogs with AT. Abdominal ultrasound is the most sensitive means of identifying adrenal tumours and permits evaluation of size and tissue texture, the presence of metastatic disease, invasion of the vena cava; it can also provide more information on other system involvement. In dogs with PDH, bilateral adrenal enlargement may be found. In the evaluation of AT the tumour may be hypo-, iso-, or hyperechoic compared to the renal cortex, or it can have mixed echogenicity. The adrenal gland may also appear simply enlarged. In the rare recurrence of bilateral ATs, such an appearance can be mistaken for bilateral adrenal hyperplasia, falsely providing a diagnosis of PDH. Ultrasound cannot differentiate a functional adrenocortical from non-functional tumour, adrenal adenoma from carcinoma, a phaeochromocytoma, a metastatic lesion or a granuloma (Behrend and Kemppainen, 2001). A study recently demonstrated that endogenous ACTH concentrations and adrenal ultrasonography used together can differentiate accurately between PDH and ADH, although neither is of value alone in the diagnosis of HAC (Gould et al., 2001). The treatment of hyperadrenocorticism can be performed by pharmacological control, surgical correction, or a combination of both. There are three treatments commonly used in the management of PDH in dogs in European countries: mitotane (o,p∞-DDD), ketoconazole, and trilostane. The method of choice for us for PDH is selective destruction of the adrenal cortex using mitotane, attempting to destroy most of the cortisol-producing areas of the adrenal cortex while preserving some ability to produce cortisol and mineralocorticoids. This method uses an initial ‘loading’ dose of 30–50 mg/kg per day in divided doses until a response is noted, while monitoring clinical signs daily and ACTH response tests every 7–10 days as needed. The dog is then maintained on 50 mg/kg per week (maintenance dosage). The specific protocol has been very well described by Feldman and Nelson (1996a) and requires fairly close attention to detail. With this protocol most of the dogs with HAC have a good improvement in clinical signs and only few have a fair response. With this protocol it is imperative that clients understand HAC as well as the potential problems with mitotane therapy. Before and during the administration of mitotane owners should monitor clinical signs such as the dog’s attitude, appetite, and water intake. Awareness of these signs helps to determine whether drug administration should be stopped before completion of the 10-day induction period and when monitoring by the corticotrophin stimulation test is needed. The goal of treatment with mitotane is to achieve a ACTH stimulation test results that suggests relative, but not complete, hypoadrenocorticism (Kintzer and Peterson, 1991). Dogs have individual sensitivity to mitotane during the induction 549 period, and the length of daily treatment needed to adequately reduce the adrenal reserve can range from 5 days to 2 months. For this reason the only way to identify the moment at which the adequate total induction dosage of mitotane has been administered is to closely monitor clinical signs (decreasing appetite, anorexia, vomiting, weakness) in combination with ACTH stimulation test, weekly, or as needed. Side effects are relatively common and should be anticipated during mitotane administration, especially during induction of mitotane. Lethargy, weakness, anorexia, vomiting and diarrhoea are the most common adverse effects observed and they are mainly correlated with a fall in cortisol concentration and less with direct effect of the drug. The most serious adverse effect associated with mitotane administration is the development of total or near total adrenocortical destruction with concomitant glucocorticoid and mineralocorticoid deficiency and hyperkaliaemia and hyponatraemia (Addison’s disease). In the rare recurrence of this endocrine emergency, mitotane should be discontinued, and an appropriate glucocorticoid, mineralocorticoid and fluid replacement therapy should be immediately instituted. When treating dogs with AT (subjects with unresectable tumour, gross metastatic disease, refusal of surgery by the owner) mitotane should be employed as a true chemotherapeutic agent, with the goal being the destruction of all tumour tissue (indicated by undetectable basal and post-ACTH serum cortisol concentrations). Initially, mitotane should be given at a dosage of 50–75 mg/kg per day for 10 to 14 days or longer. Concurrent prednisone supplementation at 0.2 mg/kg per day is indicated throughout the period of mitotane administration. The therapeutic objective would be undetectable to low concentrations of both basal and post-ACTH serum cortisol (<25 nmol/L). Once undetectable to low-normal serum cortisol concentrations are documented, an initial maintenance mitotane dose of 75–100 mg/kg per week in divided doses, together with daily maintenance glucocorticoid supplementation, are recommended. In general, dogs with AT require higher maintenance dosages of mitotane than do dogs with PDH. If iatrogenic Addison’s disease does develop, mitotane should be discontinued and appropriate supplementation with glucocorticoid and mineralocorticoid is instituted. Ketoconazole, an imidazole derivative, is an orally active broad spectrum antimycotic drug that, at high doses, interferes with steroid biosynthesis. Ketoconazole is an effective reversible enzyme blocker which can be effective in both pituitary- and adrenal-dependent diseases. The initial dose is 5 mg/kg bid PO, increasing by 5 mg/kg per dose every 2 weeks up to a maximum dose of 20 mg/kg bid (Feldman and Nelson, 1996a). Clinical signs are evaluated and the ACTH stimulation test is initially performed every 2 weeks to monitor the dog’s response to the drug. Trilostane is a synthetic orally active steroid analogue. It can act as a competitive inhibitor of the 3-beta-hydroxysteroid dehydrogenase enzyme system and it thereby inhibits the synthesis of several steroids, including cortisol and aldosterone. This blockage is reversible and seems to be dose-related. Several reports suggest that trilostane offers an acceptable alternative to mitotane in the treatment of canine PDH (Neiger et al., 2002; Ruckstuhl et al., 2002). However, the optimal dose rate and 550 frequency of administration need to be determined from pharmacokinetic studies. It is very important to monitor the clinical and biochemical effects of therapy and to adjust the trilostane dose to achieve optimal control. The ACTH stimulation test is the test of choice and it should be performed at 10–14 days, 30 days and 90 days after starting therapy. It is quite important that ACTH stimulation tests are performed 4–6 hours after trilostane administration and interpreted in the light of the history and the findings of a thorough physical examination. Serum biochemistry should be performed periodically to check for hyperkaliaemia. PRIMARY HYPERPARATHYROIDISM (PHPTH) Primary hyperparathyroidism is generally caused by neoplasia of the parathyroid glands with excessive synthesis and secretion of parathyroid hormone (PTH). This hormone excess is usually due to a solitary adenoma. The clinical signs of primary hyperparathyroidism result from hypercalcaemia, bone reabsorption, and calcium nephropathy resulting from excessive secretion of PTH, and they essentially involve the gastrointestinal, urinary and neuromuscular systems (Feldman and Nelson, 1996b). Clinical signs usually tend to be mild, insidious and non-specific and they are due to hypercalcaemia. Polydipsia and/or polyuria and/or haematuria, as well as stranguria, are the most common clinical signs (70%) and listlessness has been observed in almost 50% of dogs. The physical examination is usually unremarkable for dogs with PHPTH and affected parathyroid tissue is not palpable. Hypercalciuria results in calcium phosphate or oxalate uroliths and thus in increased incidence of urinary infection. Since hypercalcaemia is the best single diagnostic tool for PHPTH, a complete and accurate physical examination is imperative. In fact several of the causes of hypercalcaemia in dogs (lymphosarcoma, apocrine gland carcinoma of the anal sac, mammary gland carcinoma, vaginal sarcoma and multiple myeloma) may be strongly suspected or considered less likely after examination. Hypercalcaemia is usually persistent and serum calcium levels often exceed 15 mg/dl. These high values of calcium are mainly consistent with malignancy and hypervitaminosis D. Ionized calcium is always increased in PHPTH dogs. A low or low-normal serum phosphorus concentration is common for PHPTH dogs because of the effects of PTH on renal tubular phosphorus reabsorption. The serum PTH concentration is typically midnormal to exceedingly increased but should always be evaluated relative to serum calcium levels. Ultrasonography of the neck can aid in detecting parathyroid tumours larger than 1 cm in diameter. Ultrasonic scanning of the abdomen should also be a routine component of the diagnostic evaluation of hypercalcaemic dogs. The urinary tract, especially the bladder, should be evaluated for calculi, which are common in dogs with PHPTH. 551 The primary mode of therapy for severe hypercalcaemia should be aimed at correcting the cause. In canine PHPTH, hypercalcaemia is not usually an acute or severe problem. The calcium X phosphate product is rarely above 60. Products greater than 60 to 80 are likely to be associated with nephrotoxicity. In fact hypercalcaemia caused by PHPTH, because it is associated with low or low-normal phosphate concentration, is less dangerous and worrisome than hypercalcaemia associated with renal failure or hypervitaminosis D. The latter two disorders are almost always accompanied by hyperphosphataemia, a problem that amplifies the potential for soft tissue calcification associated with hypercalcaemia. It is sometimes necessary to administer symptomatic treatment for correcting hypercalcaemia. Such measures may include fluid diuresis and administration of furosemide and glucocorticoids. Surgical removal of the parathyroid neoplasm is the treatment of choice for dogs with PHPTH. Before surgery, an evaluation of renal function and thoracic radiographs for metastasis of parathyroid carcinoma or for cranial mediastinal ectopic parathyroid neoplasms is recommended. Enlarged glands should be removed; however, if all are enlarged, then three glands should be removed, leaving one cranial parathyroid gland. Transient but serious hypocalcaemia may develop 12–96 hours after the operation because the source of excess PTH has been removed, with unaccommodated parathyroid tissue remaining, and because of rapid calcium uptake by mineral-starved bones. Due to the risk of postsurgical hypocalcaemia, prophylactic postsurgical dihydrotachisterol has been recommended. The dose suggested is 0.02 mg/kg per day bw per 3 days, then 0.01 mg/kg per day per week; the dosage is then reduced by 25–50% per week, and the medication is discontinued after 2–3 months. Serum calcium levels should be maintained between 7.5 and 9.0 mg/dl by adjusting oral doses of calcium gluconate and vitamin D. Percutaneous ultrasoundguided chemical parathyroid ablation has recently been proposed as a safe and effective alternative to surgery in the treatment of dogs with PHPTH (Long et al., 1999). The response to these procedures is identical to surgical removal, at a lower cost, no surgical risk and minimal anesthetic risk. PHAEOCHROMOCYTOMA Phaeochromocitoma (Phaeo) is an uncommon endocrine tumour of neuroectodermderived chromaffin cells of the adrenal gland, which are capable of producing, storing, and secreting catecholamines. The tumour does not usually metastasize and is locally invasive into the vena cava, kidney and liver. Metastasis has been seen in the lung, liver, spleen, kidney bone, heart, and pancreas (Gilson et al., 1994b). A variety of vague and non-specific clinical signs (weakness, collapse, vomiting, PU/PD, weight loss, respiratory distress, tachycardia, cardiac hypertrophy, congestive heart failure with ataxia and seizures) attributed to excessive secretion of catecholamines or local invasion of surrounding structures, has been reported in dogs (Maher and McNiel, 1997). In ageing dogs, clinical signs can be typical of more 552 commonly diagnosed disorders. Many of these concomitant diseases have been the primary focus of the clinician, and symptoms of an underlying phaeochromocytoma have been either overlooked or ascribed to the more recognizable disorder. A high frequency of concurrent neoplasia (50% of affected dogs) has been reported (Gilson et al., 1994b; Feldman and Nelson, 1996c; Barthez et al., 1997). Frequently, the diagnosis of Phaeo is not made clinically but only on necropsy (Gilson et al., 1994b). The challenge of diagnosis stems from the ambiguity of clinical signs, the lack of specificity on routine diagnostic tests, the presence of other conditions obscuring the diagnosis and, possibly, the secretion of biologically active hormones other than catecholamines (Maher and McNiel, 1997). Results of routine laboratory work including complete blood count, biochemical profile, and urinalysis are rarely helpful in establishing a diagnosis. Although hypertension is the most common single finding in humans with Phaeo, there has been a relative paucity of blood pressure determinations in reports of dogs with Phaeo (Barthez et al., 1997). Repeated blood pressure evaluations may be necessary to document hypertension in some patients. Specific diagnostic techniques for Phaeo are aimed at identifying elevated levels of circulating catecholamines or urinary metabolites of catecholamine. However these techniques have been infrequently used in the canine patient (Maher and McNiel, 1997). Abdominal ultrasonography is an effective diagnostic tool that may be superior to radiography in evaluating the adrenal area and detecting adrenal masses (Feldman and Nelson, 1996b). An adrenal mass can be detected in 50% to 83% of cases of canine Phaeo (Gilson et al., 1994b; Feldman and Nelson, 1996c; Barthez et al., 1997). Ultrasonography may be helpful in detecting abdominal metastasis and local invasion into the kidney or caudal vena cava. Phaeo has been found incidentally in a large number of dogs during abdominal ultrasonography (incidentaloma) (Barthez et al., 1997; Myers, 1997). This finding also emphasizes the importance of performing a complete ultrasonographic examination regardless of clinical signs and presumptive diagnosis. Limited availability, expense, and the need for general anaesthesia limit the use of computerized tomography and magnetic resonance imaging in dogs. The treatment of choice for pheochromocytoma is surgical excision. 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