Primary Hyperaldosteronism in the Cat

WHAT IS YOUR DIAGNOSIS? An 11 year, male neuter, domestic shorthair cat was presented to the R(D)SVS Internal Medicine Service for investigation with a three month of polydipsia and polyuria. There had been a mild decrease in amount eaten. Defecation was normal. There has been a decrease in exercise tolerance and the cat was less willing to play or jump up onto higher surfaces. On clinical examination, the cat was quiet but alert with a body condition score of 4/9. Mucous membranes were slightly tacky but skin turgor was normal. The heart rate was 186 bpm with no arrhythmia, murmur or pulse deficits. The respiratory rate was 46 breaths/minute, with no adventitious lung sounds. A craniodorsal abdominal mass was noted on palpation. The hocks were slightly lowered in a partial plantigrade stance. Peripheral lymph nodes were unremarkable and the rectal temperature was 39.0°C. A blood sample was taken for routine haematology and serum biochemistry (results below). Systolic blood pressure was elevated at 200 mmHg. Haematology Parameter Result Reference Range RBC (x 1012/l) 6.2 5.5-10 PCV (%) 30 24-45 Hb (g/dl) 11 8-14 MCV (fl) 42 39-55 MCHC (%) 31.0 30-36 TWBC (x 109/l) 9.7 7-20 Neutrophils (x 109/l) 2.8 2.5-12.8 Lymphocytes (x 109/l) 6.0 1.5-7.0 Monocytes (x 109/l) 0.38 0.07-0.85 Eosinophils (x 109/l) 0.1 0-1.0 Basophils (x 109/l) 0 0-0.2 Platelets (x 109/l) 320 300-600 page 1 of 5 Serum biochemistry Parameter Result Reference Range Total protein (g/l) 75 69-79 Albumin (g/l) 31.0 28-39 Globulin (g/l) 44 23-50 Bile acids (μmol/l) 6.9 0-7 Total bilirubin (μmol/l) 4.2 0-6.8 Urea (mmol/l) 9.8 2.8-9.8 Creatinine (μmol/l) 170 40-177 Glucose (mmol/l) 6.9* 3-5 AP (iu/l) 26 10-100 ALT (iu/l) 69 6-83 Sodium (mmol/l) 152 145-156 Chloride (mmol/l) 120 117-140 Potassium (mmol/l) 2.4* 4-5 Inorganic phosphate (mmol/l) 1.59 1.4-2.5 Total calcium (mmol/l) 2.34 2.1-2.9 Serum T4 values and blood gas analysis results were within reference intervals. Urinalysis: USG 1.025, pH 6.5, otherwise unremarkable 1) What are your differential diagnoses for hypokalaemia in the cat? 2) What other diagnostic evaluations would you perform? 3) How would you treat this cat? page 2 of 5 1) The differential diagnoses for hypokalaemia in the cat include: a) Decreased intake including anorexia, low potassium content of diet, intravenous fluid therapy with low/no potassium supplementation (especially if also anorexic) b) Translocation of potassium between blood and intracellular fluid including metabolic alkalosis (rarely clinically significant), insulin administration, bicarbonate administration, refeeding syndrome c) Increased renal loss including chronic renal failure, diabetic ketoacidosis (especially during treatment phase), primary hyperaldosteronism(Conn’s syndrome), post-obstructive diuresis, renal tubular acidosis and diuretic administration d) Increased gastrointestinal loss i.e. vomiting and diarrhoea e) Miscellaneous e.g. hypokalaemic polymyopathy of young Burmese cats, hyperthyroidism, lab error In this patient, the cat was still eating a commercial feline diet sufficiently well enough to make decreased intake an unlikely cause of the measured hypokalaemia. There was no evidence of gastrointestinal loss or any reason for a transcellular shift. Therefore, it is likely that the hypokalaemia was secondary to excessive urinary losses. The cat did not have azotaemia or blood glucose above the renal threshold ruling out renal failure or diabetes mellitus. The combination of hypokalaemia and hypertension, in a cat with an abdominal mass raised the index of suspicion for a diagnosis of hyperaldosteronism. 2) Raised aldosterone in cats can be due to hyperkalaemia, hypovolaemia (activation of the renin-angiotensin-aldosterone system (RAAS)) or hyperaldosteronism. This cat was hypokalaemia rather than hyperkalaemic. Activation of the RAAS causes an increase in both renin and aldosterone while in hyperaldosteronism renin is reduced or normal but aldosterone is elevated. Therefore, testing renin and aldosterone concurrently is useful for diagnosis. In this cat the values were as follows and were supportive of a diagnosis of Conn’s syndrome: • Renin 0.22 ng/ml/hr (0.14-3.85) • Aldosterone >4000 pmol/l (195-390) Hyperaldosteronism in cats is due either to a neoplasm or hyperplasia of the zona glomerulosa of the adrenal gland. Therefore, imaging of the adrenal glands (ultrasound or CT) is indicated (Figure 1). No metastases were detected. page 3 of 5 Figure 1. Note large partially mineralised adrenal mass that the level on the right hand side at the level of the left kidney. 3) The primary treatment is control of hypokalaemia using spironolactone (aldosterone receptor antagonist) 2-4 mg/kg/day and potassium supplementation (potassium gluconate/potassium chloride) if needed. If persistent hypertension is present then the addition of amlodipine is indicated. Once stabilised, the treatment of choice is adrenalectomy for confirmed unilateral hyperaldosteronism. Discussion Hyperaldosteronism is thought to be the most common adrenocortical disease in cats. Untreated, it can cause severe muscle weakness, arrhythmias, hypertension and chronic renal failure. It should be considered in any cat with hypokalaemia or hypertension, particularly in middle aged and geriatric cats. Hyperaldosteronism maybe underdiagnosed partly due to blood pressure not always being routinely monitored in cats and because of the association between chronic kidney disease and hypertension/hypokalaemia means further diagnostic testing is not undertaken. The plasma aldosterone:renin ratio is currently the best screening test for feline hyperaldosteronism but was not necessary in this case as the renin and aldosterone results in themselves were not equivocal. Disease due to bilateral hyperplasia (rather than unilateral neoplasia) is more likely to result in a more borderline aldosterone result and therefore the ratio is more likely to detect disease in those cases. Any elevation in aldosterone in the face of hypokalaemia should be considered inappropriate. page 4 of 5 References Andrew R, Harvey AM, Tasker S. Primary hyperaldosteronism in the cat: A series of 13 cases. Journal of Feline Medicine and Surgery 2005; 7: 173-182 Djajadiningrat-Laanen S, Galac S, Kooistra H. Primary hyperaldosteronism : Expanding the diagnostic net. Journal of Feline Medicine and Surgery 2011; 13: 641-650 Lo AJ, Holt DE, Brown DC, Schlicksup MD, Orsher RJ, Agnello KA. Treatment of aldosterone-secreting adrenocortical tumors in cats by unilateral adrenalectomy: 10 cases (2002-2012). Journal of Veterinary Internal Medicine 2014; 28: 137-243 The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. www.ed.ac.uk/vet/hfsa-int-med page 5 of 5