Horse or zebra? A case of feline hyperaldosteronism

CAse RepORt

Horse or zebra? A case of feline hyperaldosteronism

gRACe kAeMpeR BVsc

(dist.)

Introduction

Hyperaldosteronism is the most common adrenal endocrine disease in cats (Kooista 2020). the true frequency is difficult to determine, as it is generally regarded to be underdiagnosed (Schulman 2010). this case study examines the presenting signs, diagnosis, and treatment of feline hyperaldosteronism; and proposes that this not uncommon endocrine disease should be routinely put on differential diagnosis lists when presented with hypertensive or hypokalaemic cats, rather than considered a ‘zebra’.

Case history

A 12-year-old female spayed domestic short hair cat presented for acute onset of blindness. the cat had mildly increased water intake, but there were no other significant historical findings.

Clinical findings

on physical exam, there was bilateral mydriasis, and menace and pupillary light reflexes were absent. there was no pain on ocular retropulsion. ophthalmoscopic examination revealed regions of retinal haemorrhage. Systemic arterial blood pressure was measured as 280 mmHg using a Doppler flow detector, therefore hypertensive retinopathy was diagnosed. the physical exam was otherwise within normal limits. An in-house biochemistry renal panel (Kidney Profile Plus; Abaxis, Griesheim, Germany) revealed moderate hypokalaemia of 2.8 (reference range 3.7–5.8) mmol/L, and mild elevations in the concentration of urea and content of tCo2. the concentration of creatinine was within normal limits, as were other electrolytes.

Contact: gracekaemper.bayvets@gmail.com Hypertensive retinopathy and hypokalaemia were the key clinical findings. Hypertension can be idiopathic but is more commonly secondary to another pathology (Acierno et al. 2018). In cats, the most common causes are hyperthyroidism, chronic kidney disease, hyperaldosteronism, protein losing nephropathy, and less commonly diabetes mellitus (Acierno et al. 2018). the combination of hypertension and hypokalaemia made hyperaldosteronism the most likely differential.

Further diagnostic findings

Hyperthyroidism was ruled out by a normal concentration of free thyroxine (t4) (t4/Cholesterol test; Abaxis) in serum. In-house urinalysis collected by cystocentesis showed a urine specific gravity of 1.043, negative glucose, 2+ protein and an inactive sediment; thereby ruling out chronic kidney disease, protein-losing nephropathy and diabetes mellitus. Although there was moderate proteinuria, this was most likely secondary to hypertension rather than the cause. An aldosterone assay was run on frozen serum resulting in a concentration of 1,430 pmol/L. A study by Yu et al. (1998) found the median plasma aldosterone concentration of healthy cats was 161 pmol/L. As the upper value set by the laboratory for healthy domestic cats was 700 pmol/L, this result confirmed the diagnosis of primary hyperaldosteronism.

treatment

While waiting for the results of the aldosterone assay, symptomatic treatment with 0.65 mg/cat amlodipine (Amodip 1.25 mg; CEVA Animal Health Pty Ltd, Glenorie, Australia) once daily and oral potassium gluconate supplementation at 0.5 mEq/kg (Kaminox 2 mEq/2mL; VetPlus Ltd, Docklands, uK) were initiated. the amlodipine dose was increased to 1.25 mg/cat once daily after 1 week due to insufficient response. two weeks after starting treatment, the diagnosis of hyperaldosteronism was confirmed, and spironolactone (Spiractin 25mg; Mylan New Zealand Ltd, Auckland, NZ) was initiated at a dose of 2 mg/kg twice daily. At this point, systolic blood pressure had decreased to a mean of 148 mmHg, which fell within the ideal range. However shortly after beginning treatment with spironolactone, the cat developed acute forelimb pain and lethargy due to hypokalaemic myopathy. Persistent hypokalaemia of 3.2 mmol/L was confirmed despite oral supplementation. Intravenous potassium supplementation was provided with 10 mEq/L potassium chloride (Biomed Ltd, Auckland, NZ) and Metabolase (Ethical Agents Ltd, Auckland, NZ) added into a constant rate infusion of 0.9% NaCl at 9 mL/hour. treatment was unsuccessful and the cat entered cardiac arrest.

Discussion

Hyperaldosteronism is the most common adrenal endocrine disease in cats (Kooistra 2020). However, the true frequency is difficult to determine, as it is generally regarded to be underdiagnosed (Schulman 2010). Lo et al. (2014) estimate that primary adrenal tumours make up 0.2% of all neoplasms in cats. Many studies argue that hyperaldosteronism should be considered as a differential when middle-aged to older cats present with either hypertension or hypokalaemia (Ash 2005, Kooistra 2020). one proposed reason for underdiagnosis is that chronic kidney disease is blamed for hypertension and hypokalaemia, and no further diagnostics are performed (Javardi et al. 2005). In reality, hyperaldosteronism can accelerate the progression of CKD and the two diseases are present concurrently in a proportion of azotaemic cats (Javardi et al. 2005). Aldosterone is secreted from the zona glomerulosa in the adrenal cortex. In a healthy animal, its release is regulated by

the renin-angiotensin system (involved in blood volume homeostasis) and serum potassium concentration. Aldosterone acts at the distal convoluted tubule to increase sodium resorption and potassium secretion, thereby decreasing water loss in urine and maintaining blood volume. It also increases blood pressure by increasing systemic vascular resistance. Primary hyperaldosteronism leads to an increase in circulating aldosterone, causing the classic clinical signs of hypertension and hypokalaemia. unlike Cushing’s disease (hyperadrenocorticism), hyperaldosteronism is caused by hyperplasia or functional tumours of the adrenal gland, not by pituitary lesions. these adrenal tumours are most commonly unilateral but can be bilateral (Kooistra 2020). Common presenting clinical signs associated with hypokalaemia include polymyopathy, episodic muscle weakness, muscle pain, and/or ventroflexion of the neck. this muscle weakness can progress to difficulty breathing and paresis. Clinical signs are seen when blood potassium falls below 2.5 mmol/L (Kooistra 2020). Blindness secondary to hypertension is another common presenting sign. Not all cats will present with signs of both hypertension and hypokalaemia (Kooistra 2020, Ash et al. 2005). Some cats are polyuric/polydipsic however this is suspected to be due to secondary renal disease (Ash et al. 2005). Secondary hypertensive cardiomyopathy can also be seen (Bento et al. 2016). there are a range of confirmatory diagnostics. this author found measurement of serum aldosterone concentration to be a cheap, readily available, straightforward and reliable test, especially in the absence of referral ultrasonography. the disadvantage of testing serum aldosterone is that it is highly labile, therefore a frozen serum sample must be sent to the diagnostic laboratory. Additionally, it is only available at human laboratories, and there can be a delay in receiving results. Both an elevated or a high-normal aldosterone concentration in the face of hypertension/hypokalaemia, are suggestive of primary hyperaldosteronism due to negative feedback mechanisms (Kooistra 2020). other diagnostic methods include the measurement of the serum aldosterone to renin ratio, urinary aldosterone to creatinine ratio, and dynamic aldosterone secretion testing (fludrocortisone suppression test or telmisartan suppression test) (Kooistra 2020). Abdominal ultrasound is the diagnostic test of choice, when available, as it is non-invasive and allows for determination of unilateral versus bilateral adrenal abnormalities (Kooistra 2020). the normal dorsoventral length of the adrenal gland in cats is 4 mm (Moore et al. 2000). Gold standard treatment for unilateral hyperaldosteronism is unilateral adrenalectomy. However, this is a difficult, referral procedure with a high intra-operative complication rate. In a retrospective study of ten cats by Lo et al. (2014), two cats were euthanised prior to discharge due to surgical complications, which included haemorrhage, hypotension and sepsis. the remaining eight cats required no further medical treatment for hyperaldosteronism. the median survival time was nearly 1,300 days. Although few owners are willing to pursue this route due to cost and risk, the clinical outcomes can be excellent. Medical management, as described in this case study, is centred on spironolactone 2 mg/kg twice daily. Amlodipine at 0.625–1.25 mg/cat is given once daily to reduce blood pressure, aiming for systolic blood pressure <150 mmHg. oral potassium supplementation with potassium gluconate at 0.5 mEq/kg is often required (Kooistra 2020). Survival time for conservative treatment ranges from months to years (Bento et al. 2016). When reflecting on management of this case, the poor outcome was likely due to long-term uncontrolled hypokalaemia. this cat would have benefited from I/V potassium supplementation at the initial consult. Studies show there is poor oral absorption of potassium in cats with hyperaldosteronism (Ash et al. 2005). Further questioning of the owners also revealed that they struggled to give Kaminox routinely, further reducing the efficacy of oral treatment. Additionally, due to the marked hypertension, amlodipine could have been started on the higher dose of 1.25 mg/cat, rather than titrating up (Acierno et al. 2018). In conclusion, hyperaldosteronism should be considered whenever patients present with hypertension or hypokalaemia, especially in poorly responsive renal cases, as hyperaldosteronism may be the underlying cause. Diagnosis can be made in general practice without referral, utilising either ultrasonography or serum aldosterone. When picked up early enough, these cases can be very rewarding; and with greater awareness of the disease, frequency of diagnosis in general practice is likely to increase.

Acknowledgements

thanks to my colleagues at Bay Vets for their support and trust; and to Sandra Forsyth at SVS laboratories for her diagnostic advice.

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