Primary hyperaldosteronism in the cat: a series of 13 cases

Thirteen cases of feline primary hyperaldosteronism were diagnosed based on clinical signs, serum biochemistry, plasma aldosterone concentration, adrenal imaging and histopathology of adrenal tissue. Two cases presented with blindness caused by systemic hypertension, whilst the remaining 11 cases showed weakness resulting from hypokalaemic polymyopathy. Elevated concentrations of plasma aldosterone and adrenocortical neoplasia were documented in all cases. Seven cases had adrenal adenomas (unilateral in five and bilateral in two) and six had unilateral adrenal carcinomas. Three cases underwent medical treatment only with amlodipine, spironolactone and potassium gluconate; two cases survived for 304 and 984 days until they were euthanased because of chronic renal failure, whilst the third case was euthanased at 50 days following failure of the owner to medicate the cat. Ten cases underwent surgical adrenalectomy following a successful stabilisation period on medical management. Five cases remain alive at the time of writing with follow-up periods of between 240 and 1803 days. Three cases were euthanased during or immediately following surgery because of surgical-induced haemorrhage. One cat was euthanased 14 days after surgery because of generalised sepsis, whilst the remaining cat was euthanased 1045 days after surgery because of anorexia and the development of a cranial abdominal mass. It is recommended that primary hyperaldosteronism should be considered as a differential diagnosis in middle-aged and older cats with hypokalaemic polymyopathy and/or systemic hypertension and should no longer be considered a rare condition.     

Measurement of aldosterone in feline, canine and human urine

BACKGROUND: Systemic hypertension is an important problem in older cats associated with kidney disease and hypokalaemia, suggesting that excessive activity of the renin-angiotensin-aldosterone system might contribute to the hypertensive state. Fluctuations in plasma renin activity and plasma aldosterone concentrations complicate the interpretation of these assays. OBJECTIVES: The aim of this study was to determine whether measurement of urinary aldosterone excretion in cats aided the investigation of hypertension. METHODS: Urine concentrations of free (ethyl acetate extract) and 18-glucuronidated aldosterone (acid hydrolysis before extraction) were measured by radioimmunoassay in normal, normotensive and hypertensive azotaemic cats (n=11 per group). Urine samples from 11 healthy human volunteers and eight normal dogs were also analysed for comparison. Urinary aldosterone concentration was corrected for the urinary creatinine concentration. RESULTS: Cats excreted 7.3 times less free aldosterone than human beings, and no free aldosterone was detected in dog urine. Acid hydrolysis led to large increases in aldosterone recovery from both human beings and dog but not feline urine. No significant effect of hypertension or azotaemia on feline urinary aldosterone concentration was found. CLINICAL SIGNIFICANCE: Measurement of aldosterone in feline urine using the available methodology has limited or no utility in investigating feline hypertension.     

Urinary aldosterone to creatinine ratio in cats before and after suppression with salt or fludrocortisone acetate

Background: The endocrine diagnosis of primary hyperaldosteronism in cats currently is based on an increased plasma aldosterone to renin ratio, which has several disadvantages for use in veterinary practice. Objectives: To establish a reference range for the urinary aldosterone to creatinine ratio (UACR) and to determine whether oral administration of either sodium chloride or fludrocortisone acetate is effective for use in a suppression test. Animals: Forty‐two healthy cats from an animal shelter and 1 cat with primary hyperaldosteronism from a veterinary teaching hospital. Methods: Morning urine samples for determination of the basal UACR were collected from 42 healthy cats. For the suppression tests, urine samples for the UACR were collected after twice daily oral administration for 4 consecutive days of either sodium chloride, 0.25 g/kg body weight (n = 22) or fludrocortisone acetate, 0.05 mg/kg body weight (n = 15). Results: The median basal UACR was 7.2 × 10^?9 (range, 1.8–52.3 × 10^?9), with a calculated reference range of <46.5 × 10^?9. Administration of sodium chloride resulted in adequate salt loading in 10 of 22 cats, but without significant reduction in the UACR. Administration of fludrocortisone resulted in a significant decrease in the UACR (median, 78%; range, 44–97%; P < .001) in healthy cats. In the cat with an aldosterone‐producing adrenocortical carcinoma, the basal UACR and the UACR after fludrocortisone administration were 32 × 10^?9 and 36 × 10^?9, respectively. Conclusions and Clinical Importance: Using the UACR for an oral fludrocortisone suppression test may be useful for the diagnosis of primary hyperaldosteronism in cats.     

Primary hyperaldosteronism in two cats.

A condition of primary hyperaldosteronism resulting from an adrenal tumor in two cats is presented and was characterized by hypertension, hypokalemia, inappropriate kaliuresis, low normal plasma renin activity, and markedly increased serum aldosterone concentration. One of the two cats underwent a laparotomy, and in this case hypertension and hypokalemia resolved following the removal of an adrenal tumor.     

Primary hyperaldosteronism, a mediator of progressive renal disease in cats

In recent years, there has been renewed interest in primary hyperaldosteronism, particularly because of its possible role in the progression of kidney disease. While most studies have concerned humans and experimental animal models, we here report on the occurrence of a spontaneous form of (non-tumorous) primary hyperaldosteronism in cats. At presentation, the main physical features of 11 elderly cats were hypokalemic paroxysmal flaccid paresis and loss of vision due to retinal detachment with hemorrhages. Primary hyperaldosteronism was diagnosed on the basis of plasma concentrations of aldosterone (PAC) and plasma renin activity (PRA), and the calculation of the PAC:PRA ratio. In all animals, PACs were at the upper end or higher than the reference range. The PRAs were at the lower end of the reference range, and the PAC:PRA ratios exceeded the reference range. Diagnostic imaging by ultrasonography and computed tomography revealed no or only very minor changes in the adrenals compatible with nodular hyperplasia. Adrenal gland histopathology revealed extensive micronodular hyperplasia extending from zona glomerulosa into the zona fasciculata and reticularis. In three cats, plasma urea and creatinine concentrations were normal when hyperaldosteronism was diagnosed but thereafter increased to above the upper limit of the respective reference range. In the other eight cats, urea and creatinine concentrations were raised at first examination and gradually further increased. Even in end-stage renal insufficiency, there was a tendency to hypophosphatemia rather than to hyperphosphatemia. The histopathological changes in the kidneys mimicked those of humans with hyperaldosteronism: hyaline arteriolar sclerosis, glomerular sclerosis, tubular atrophy and interstitial fibrosis. The non-tumorous form of primary hyperaldosteronism in cats has many similarities with "idiopathic" primary hyperaldosteronism in humans. The condition is associated with progressive renal disease, which may in part be due to the often incompletely suppressed plasma renin activity.     

Aldosteronoma in a dog with polyuria as the leading symptom.

In a 10-year-old castrated male shorthaired German pointer polyuria was associated with slight hypokalemia, hypophosphatemia and alkalosis, as well as elevated plasma concentrations of a glucocorticoid-inducible iso-enzyme of alkaline phosphatase. Repeated measurements of urinary corticoids and normal suppressibility of the hypothalamus-pituitary-adrenocorticial axis excluded glucocorticoid excess.Urine osmolality (Uosm) did not increase during administration of the vasopressin analogue desmopressin. At the time water deprivation had caused Uosm to rise from 300 to 788 mOsm/kg, there was also plasma hypertonicity. During hypertonic saline infusion the osmotic threshold for vasopressin release was increased.The combination of elevated plasma aldosterone concentrations and unmeasurably low plasma renin activity pointed to primary hyperaldosteronism. As initially computed tomography (CT) did not reveal an adrenocortical lesion, the dog was treated with the aldosterone antagonist spironolactone. This caused Uosm to rise in a dose-dependent manner. However, well-concentrated urine was only achieved with doses that gave rise to adverse effects.Once repeated CT, using 2-mm-thick slices, had revealed a small nodule in the cranial pole of the left adrenal, unilateral adrenalectomy was performed which resolved the polyuria completely. Also the plasma concentrations of kalium, aldosterone and renin activity returned to within their respective reference ranges. The adrenocortical nodule had the histological characteristics of an aldosteronoma, with the non-affected zona glomerulosa being atrophic.In this dog with primary hyperaldosteronism the polyuria was characterized by vasopressin resistance and increased osmotic threshold of vasopressin release, similar to the polyuria of glucocorticoid excess. The possibility is discussed that the polyuria of glucocorticoid excess is actually a mineralocorticoid effect.     

Hyperadrenocorticism in cats: seven cases (1978-1987)

Hyperadrenocorticism was diagnosed in 7 cats with concurrent diabetes mellitus. Four cats had pituitary adenoma with bilateral adrenocortical hyperplasia, 1 cat had pituitary carcinoma with bilateral adrenocortical hyperplasia, 1 cat had adrenocortical carcinoma, and 1 cat had adrenocortical adenoma of the left adrenal gland. One year later, adrenocortical adenoma involving the right adrenal gland also was diagnosed in this cat. Clinical signs included polyuria and polydipsia (n = 7), development of pot-bellied appearance (n = 5), dermatologic alterations (n = 5), lethargy (n = 3), weight loss (n = 3), dyspnea/panting (n = 2), and recurrent bacterial infections (n = 2). In 6 cats, the diagnosis of hyperadrenocorticism was established before death on the basis of results of the ACTH stimulation test (n = 3) and the dexamethasone screening test (n = 5). Pituitary-dependent hyperadrenocorticism was differentiated from adrenocortical neoplasia on the basis of results of the dexamethasone suppression test (n = 4), endogenous ACTH concentration (n = 3), results of abdominal radiography and ultrasonography (n = 3), and exploratory celiotomy (n = 1). Four cats died or were euthanatized without treatment attempts. Treatment with mitotane followed by 60Co teletherapy was ineffective in one cat with pituitary adenoma. One cat with pituitary carcinoma died one week after bilateral adrenalectomy. Bilateral adrenocortical adenomas were removed surgically in the affected cat.     

Plasma renin activity and plasma concentrations of aldosterone, cortisol, adrenocorticotropic hormone, and alpha-melanocyte-stimulating hormone in healthy cats

A pathogenetic role of the renin-angiotensin-aldosterone system has been implicated in cats in both systemic arterial hypertension and hypokalemic myopathy. Yet, measurement of plasma aldosterone concentrations (PACs) and plasma renin activity (PRA) has not unequivocally pointed to hyperaldosteronism as a cause of these conditions. To obtain appropriate reference ranges, this study included a large number (130) of healthy house cats of different breeds without a history of recent illness and plasma concentrations of urea and creatinine below the upper limit of the respective reference ranges. In addition, the pituitary-adrenocortical axis was studied by measuring plasma concentrations of adrenocorticotropic hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), and cortisol. Reference ranges for PACs (110-540 pmol/L; 40-195 pg/mL), PRA (60-630 fmol/L/s; 0.3-3 ng/mL/h), and the aldosterone to renin ratio (ARR) (0.3-3.8) were very similar to those established in the same laboratory for humans in a supine position. No breed differences were found. The ARRs in neutered cats were significantly higher than in intact cats, primarily because of low PRA in neutered cats. The ARRs of cats > or = 5 years of age were significantly higher than those of cats < 5 years of age. The plasma concentrations of ACTH, alpha-MSH, and cortisol did not correlate significantly with PAC. Thus, although blood sampling was performed in cats in nonstandardized positions and was associated with a wide variation of stress responses, the references ranges of PAC, PRA, and ARR were similar to the relatively narrow limits established for humans under standardized conditions. The effects of neutering and aging on PRA and ARR warrant further investigation.     

Feline adrenal disorders

Although only recently discovered, feline adrenal disorders are becoming increasingly more recognized. Feline adrenal disorders include diseases such as hyperadrenocorticism (Cushing's syndrome) and hyperaldosteronism (Conn's syndrome). The clinical signs of feline hyperadrenocorticism, which include unregulated diabetes mellitus and severe skin atrophy, are unique to the cat. Other signs of feline hyperadrenocorticism, such as potbellied appearance, polydipsia, polyuria, and susceptibility to infections are also seen in dogs with hyperadrenocorticism. Conn's syndrome has only recently been described in the cat and is in fact more common in cats than in dogs. Characterized by severe hypokalemia, hypertension, and muscle weakness, Conn's syndrome may be misdiagnosed as renal failure. The clinician should become familiar with the clinical signs of adrenal disorders in cats and the common diagnostic tests used to diagnose these syndromes in cats as they differ from those in the dog. Treatment of feline adrenal disorders may be challenging; the clinician should become familiar with common drugs used to treat adrenal disorders in cats.     

Contrast-enhanced power and color Doppler ultrasonography of the pancreas in healthy and diseased cats

Background: The diagnosis of feline pancreatic disease is difficult, because clinical abnormalities and routine noninvasive diagnostic tests are unreliable. Objective: The purpose of this study was to investigate by Doppler ultrasonography if vascularity and blood volume differs in the otherwise ultrasonographically normal and diseased feline pancreas. Animals: Thirty‐six client owned cats. Methods: The pancreas was examined with B‐mode and contrast‐enhanced color and power Doppler ultrasonography. Doppler images were analyzed with a computer program: parameter fractional area represents a vascularity index and color‐weighted fractional area assesses blood volume. Results: Based on the B‐mode findings, the pancreas was considered normal in 11 clinically healthy cats and diseased in 25 cats of which 4 were clinically healthy and 21 had clinical signs consistent with pancreatic disease. Histologic or cytologic samples were taken in all diseased pancreata. Fifteen samples were of diagnostic quality: purulent or mixed cellular inflammation (8), nodular hyperplasia (4), and neoplasia (3) were identified. Vascularity and blood volume for all Doppler methods was significantly higher in cats with pancreatic disease. Significantly higher Doppler values were detected with power Doppler than with color Doppler, and with postcontrast color and power Doppler than with precontrast Doppler technologies. Conclusion: Contrast‐enhanced Doppler ultrasonography appears feasible in the feline pancreas. Significant differences were found between normal cats and those with evidence of pancreatic pathology. Further studies are needed to evaluate its use for the differentiation of pancreatic disorders and in cats suspected to have pancreatic disease but without B‐mode ultrasonographic changes of the pancreas.     

Entropion correction in dogs and cats using a combination Hotz-Celsus and lateral eyelid wedge resection: results in 311 eyes

A novel surgical combination technique for the correction of lateral lower lid entropion in dogs and cats is described, involving a combination of Hotz-Celsus and lateral eyelid wedge resection procedures. The technique was used to treat 311 eyes with lower lid entropion: 269 canine (109 bilateral, 51 unilateral) and 42 feline (16 bilateral, 10 unilateral). The most common canine breeds were the Shar Pei, Rottweiler, Bull Mastiff and Labrador Retriever. Domestic cats made up the majority of feline cases. The overall success rate for a single surgical procedure to correct lower lid entropion with this technique was 94.2% per eye.     

Increased mean arterial pressure and aldosterone-to-renin ratio in Persian cats with polycystic kidney disease

Polycystic kidney disease (PKD) in Persian cats has been increasingly reported and compared to human autosomal dominant polycystic kidney disease (ADPKD) in the last decade. In cats, however, few studies have dealt with the occurrence and hormonal determinants of hypertension, one of the most common extrarenal manifestations of ADPKD in humans. The purpose of this study was to compare Persian cats >4 years old with PKD to unaffected control cats with regard to blood pressure (BP), plasma renin activity (PRA), serum aldosterone concentration, plasma atrial natriuretic peptide (ANP) concentration, and aldosterone-to-renin ratio (ARR). Three gender- and age-matched groups were studied, each consisting of 7 cats: (1) a control group without cysts, (2) a group with mild PKD, and (3) a group with severe PKD (multiple cysts and renal enlargement). Mild renal insufficiency was found in only 1 of 14 cats with PKD. Cats with PKD had a higher mean arterial pressure (P = .04) and more often had a high ARR (P = .047) than did control cats. Tendencies toward higher diastolic and systolic arterial pressures (DAPs and SAPs, respectively) and lower PRAs were observed in cats with PKD compared to controls (.05 < P < or = .1). No significant differences were found between the groups in serum aldosterone and plasma ANP concentrations. None of the cats had echocardiographic evidence of cardiac hypertrophy. In conclusion, cats with PKD had a minor increase in mean arterial pressure compared to control cats, and half of the cats had a high ARR.     

Feline lung-digit syndrome: unusual metastatic patterns of primary lung tumours in cats

PRACTICAL RELEVANCE: Feline 'lung-digit syndrome' describes an unusual pattern of metastasis that is seen with various types of primary lung tumours, particularly bronchial and bronchioalveolar adenocarcinoma. Tumour metastases are found at atypical sites, notably the distal phalanges of the limbs; the weightbearing digits are most frequently affected, and multiple-digit and multiple-limb involvement is common. Often primary lung tumours in cats are not detected because of clinical signs referable to the primary tumour; rather, many cases present with signs referable to distant metastases. Other sites of metastases from feline primary lung tumours include the skin, eyes, skeletal muscle and bone, as well as multiple thoracic and abdominal organs. These lesions are thought to arise from direct arterial embolisation from the tumour. Indeed tumour embolisation to the aortic trifurcation is possible. PATIENT GROUP: Primary lung neoplasms are uncommon in the cat. Older animals are most affected (mean age at presentation 12 years, range 2-20 years). There is no apparent sex or breed predilection. CLINICAL CHALLENGES: Feline lung-digit syndrome presents a diagnostic challenge. Typically there is swelling and reddening of the digit, purulent discharge from the nail bed, and dysplasia or fixed exsheathment of the associated nail. While these signs might be suggestive of infection, this could be secondary to a digital metastatic lesion, particularly in a middle-aged or elderly cat. Radiographic evidence of extensive bony lysis of the distal phalanx, which can be trans-articular to the second phalanx, raises the index of clinical suspicion for metastasis of a primary pulmonary tumour. Thoracic radiography is warranted prior to any surgery or digital amputation as the prognosis is generally grave for cats with this syndrome, with a mean survival time of only 58 days after presentation. EVIDENCE BASE: This article reviews the previous literature and case reports of feline lung-digit syndrome and feline primary pulmonary neoplasia in general, discussing the course of this disease and the varying clinical presentations associated with different sites of metastasis.     

Feline systemic hypertension: Diagnosis and management

PRACTICAL RELEVANCE: the clinical importance of feline hypertension has been recognised for many years and most feline practitioners are quite familiar with this syndrome. Once systemic hypertension is identified, long-term management of the patient is needed to avoid catastrophic (eg, blindness due to retinal detachment) or subtle (eg, accelerated renal damage) target organ damage. PATIENT GROUP: feline systemic hypertension is most commonly a complication of renal disease and hyperthyroidism, both diseases of older feline patients. By 15 years of age, the probability of having at least one of these two diseases is high. As well cared for cats are living longer, optimal long-term management of feline hypertension in patients with concurrent diseases is an issue of clinical importance. CLINICAL CHALLENGES: obtaining accurate blood pressure measurements in patients that are anxious, fractious or just plain uncooperative remains a significant issue in feline medicine, as does confident analysis of results from these patients. DIAGNOSTICS: careful measurement of systolic blood pressure using Doppler or oscillometric techniques in conjunction with evaluation for evidence of hypertensive choroidopathy (funduscopic examination) and hypertensive cardiac changes (thoracic auscultation) are essential to the diagnosis of systemic hypertension in cats. Other diagnostic techniques, including evaluation of renal and thyroid function, are needed to detect the underlying disease condition. EVIDENCE BASE: numerous well-designed clinical studies have greatly advanced our understanding of the most appropriate methods of diagnosis and therapy of feline hypertension.     

Treatment of Aldosterone‐Secreting Adrenocortical Tumors in Cats by Unilateral Adrenalectomy: 10 Cases (2002–2012)

Background

Primary hyperaldosteronism (PHA) in cats occurs as a consequence of excessive hormone production by an adrenocortical tumor. Median survival time, association between tumor type and prognosis, and the likelihood that cats require continued medical therapy after surgery have not been systematically evaluated.

Objectives

To determine the median survival time of cats with PHA treated by unilateral adrenalectomy. To examine if tumor type, anesthesia time, or tumor location (left or right side) affect survival and if affected cats require continued postoperative treatment for persistent hypertension or hypokalemia.

Animals

Ten client‐owned cats.

Methods

Retrospective study. Cats were diagnosed with PHA based on clinical signs, increased plasma aldosterone concentration, and advanced imaging. Cats underwent unilateral adrenalectomy. Survival time (days alive after surgery) was determined for each cat. Factors affecting median survival time were investigated, including histopathology, anesthesia time, and location (side) of the tumor.

Results

Eight of 10 cats survived to discharge from the hospital post adrenalectomy. Overall median survival was 1,297 days (range 2–1,582 days). The only significant factor affecting median survival time was anesthesia time >4 hours. Tumor type and location (side) did not significantly affect median survival time. No cats required continued medical treatment for PHA.

Conclusions and Clinical Importance

Although PHA in cats is still considered an uncommon condition, it should be considered in middle to older aged cats with hypokalemic polymyopathy and systemic hypertension. Surgical correction by unilateral adrenalectomy is a viable approach to definitive treatment of PHA with no need for continued medical management.     

IMAGING FINDINGS IN PANCREATIC NEOPLASIA AND NODULAR HYPERPLASIA IN 19 CATS

Pancreatic neoplasia in cats is rare and associated with a poor prognosis, but pancreatic nodular hyperplasia is a common incidental finding. The purpose of this study was to describe radiographic and ultrasonographic findings in cats with pancreatic neoplasia or nodular hyperplasia. Fourteen cats (age 3-18 years) were diagnosed with malignant pancreatic tumors: carcinoma/adenocarcinoma (n = 11), lymphoma (n = 1), squamous cell carcinoma (n = 1), and lymphangiosarcoma (n = 1). The most common radiographic findings were an abdominal mass or mass effect (6/6) and lack of serosal margin detail (4/6). On ultrasound, the most common finding was a focal pancreatic mass or nodule, with a size range from 0.4 cm to more than 7.0 cm (8/14). Lymphadenopathy (7/14) and abdominal effusion (7/14) were frequently seen. Five cats (age 10-16 years) with adenomatous/nodular hyperplasia had an abdominal mass or mass effect as the most common radiographic finding (3/3). On ultrasound, all cats had multiple hypoechoic nodules between 0.3 and 1.0 cm associated with the pancreas. Other common findings were pancreatic thickening (2/5), lymphadenopathy (2/5), and abdominal effusion (2/5). The only imaging finding unique to malignant pancreatic tumors was the presence of a single pancreatic nodule or mass exceeding 2cm in at least one dimension (4/14). Although there was a tendency for neoplastic lesions to manifest as single larger lesions and for nodular hyperplasia to manifest as multiple smaller lesions, there was overlap of the imaging findings in both entities. Radiographs and ultrasound can complement but not replace cytology and histopathology in the diagnosis of feline pancreatic neoplasia.     

Radiographic signs in cats with nasal disease

Radiographic signs in 64 cats that had radiography as part of the diagnostic work-up for suspected nasal disease were reviewed in a blinded fashion. Final diagnoses in these cats were rhinitis in 27, primary nasal neoplasia in 21 and non-nasal disease in 16. The signs with highest predictive value for nasal neoplasia were displacement of midline structures (73%), unilateral generalised soft tissue opacity (70%), unilateral generalised loss of turbinate detail (69%) and evidence of bone invasion (64%). The only radiographic finding that occurred more frequently in cats with rhinitis was a nasal cavity within normal limits, and the predictive value of this sign was only 38%. Radiographic signs in cats with nasal neoplasia are similar to those reported in dogs, whereas the radiographic signs in cats with rhinitis are variable and non-specific, and may be absent.