Difficult feline medicine cases (Proceedings)

August 1, 2011

Article

Hyperaldosteronism is uncommon in dogs, but may be more common in cats than previously thought. Disorders of aldosterone deficiency have been recognized in combination with general adrenocortical insufficiency (Addison's disease), and will not be discussed here.

Clinical case one

A 13-year-old, castrated male domestic shorthair cat was presented for evaluation of acute onset of neurological signs. The owner complained that the cat was disoriented, uncoordinated, and was having trouble walking. The cat was kept as an indoor pet. All vaccinations were current. The diet consisted of a mixture of free-choice adult dry maintenance food and a small amount daily of canned food (a variety of flavors). Two other cats in the household were reported to be normal. The owner reported the cat's appetite had been mostly normal, but the owner thought the cat may have been drinking more than usual.

On physical examination, the cat was depressed and seemed ataxic. The body condition score was 3/9. There was pronounced cervical ventroflexion. The cat was mildly dehydrated, with a normal body temperature. The heart rate was 155 bpm, and there was a grade 2/6 systolic murmur, with a point of maximum intensity heard at the left sternal border. Abdominal palpation revealed a large urinary bladder, but no obvious abnormalities. The cat seemed to resent palpation of any part of the body. There was no palpable goiter

A neurological exam was done. The cat was depressed, but mentally appropriate, and irate. All cranial nerves were normal. Proprioception was normal. All spinal reflexes were intact, but were subjectively diminished. Based on the neurological findings, it was determined that rather than being ataxic or disoriented, the cat was profoundly weak.

According to the owner, the cat had never been unfriendly or uncooperative during veterinary visits in the past.

Some initial questions

1. What are causes of weakness? (Consider neurological disease, metabolic disease, cardiopulmonary disease, muscle disease, orthopedic disease.)

2. What is the significance of the heart murmur? Are there signs of heart failure?

3. What is the significance of the heart rate?

4. Should you be concerned about possible PU/PD at this point? What physical examination findings fit with this problem?

5. Are you concerned about the cat's behavior?

6. What is your initial problem list?

The initial workup included: urinalysis, serum chemistry profile, CBC, total T4, thoracic radiographs, and systolic blood pressure measurement.

Results

Urinalysis

• Color – pale, clear

• Protein – trace

• Glucose – negative

• Bili – negative

• Ketones – negative

• Specific gravity – 1.016

CBC (reference interval in parentheses)

• Hct – 44%

• WBC – 18.8 x 103 (5.5 – 19)

• Segs – 79%

• Bands – 0%

• Lym – 13%

• Eos – 1%

• Mono –7%

Chemistry Profile (normal ranges indicated)

• Creat = 1.9 mg/dL (0.8 – 1.4)

• BUN = 84 mg/dL (7 – 36)

• Albumin = 3.6 g/dL (2.7-3.8)

• Calcium = 9.2 mg/dL (8.7-11.9)

• Phos = 2.5 mg/dL (3.7– 9.0)

• Na+ = 155 mmol/L (144-156)

• K+ = 2.0 mmol/L (3.8 – 5.4)

• Chlor = 120 mmol/L (112-124)

• Gluc = 178 mmol/L(65-120)

• ALP = 89 U/L (6-93)

• ALT = 44 U/L(1-64)

• GGT = 0 U/L (0-3)

• Tbili = 0.1 umol/L (0 – 0.3)

• Chol = 120 mmol/L (70-198)

• TCO2 = 21 mmol/L (15 – 27)

› Total T4 = 24 nmol/L (17 – 48)

› Thoracic Radiography: Evidence of cardiomegaly

› Systolic Blood Pressure – 190 mmHg

Questions to consider

1. Is the hyperglycemia significant?

2. Is the azotemia pre-renal, renal, or post-renal?

3. What are causes of hypokalemia?

4. What is the significance of the hematocrit?

5. Does the normal T4 rule out hyperthyroidism?

6. Does the systolic blood pressure of 190 mmHg confirm hypertension.

7. What is the significance of the low total CO2?

8. Is the mild hypophosphatemia of clinical interest?

9. What further tests would you perform?

Fundic examination revealed small retinal hemorrhages, but not large areas of detachment. Based on this, the hypertension was considered a significant finding.

Ruleouts for hypertension in this cat

• Hyperthyroidism

• Chronic renal failure

• Hyperaldosteronism

• Pheochromocytoma

• Essential hypertension

• Increased intracranial pressure

Ruleouts for hypokalemia

• Urinary Potassium Loss

o Renal disease

o Diuretics

o IV fluids

o Increased aldosterone

• Insufficient potassium intake

o Anorexia

o Dietary deficiency

• Gastrointestinal potassium loss

o Vomiting

o (severe diarrhea)

o GI obstruction

• Translocation of potassium from extracellular to intracellular fluid

o Alkalemia

o Insulin administration

o Glucose administration

o Bicarbonate administration

Case development:

Hypertension was suspected immediately following the physical examination (based on the heart murmur and relatively slow heart rate). The most interesting finding on the serum chemistry profile was the hypokalemia. The level of hypokalemia was severe. The azotemia was mild, and severe renal disease was not considered likely in this cat. Also, the finding of hypophosphatemia did not fit was the clinical picture of renal failure. Because the total CO2 was low, serum bicarbonate was considered to be low, making alkalosis an unlikely cause of hypokalemia in this case. There were no gastrointestinal signs to explain the hypokalemia. Primary hyperaldosteronism was considered the most likely cause of the clinical problems observed. Mild azotemia could be accounted for by hypokalemic nephropathy, and the cat's behavior may have been a response to muscle pain which occurs in hypokalemic myopathy.

Further tests:

Abdominal ultrasound: To examine kidneys and adrenal glands primarily. The kidneys appeared normal. A large tumor associated with the left adrenal gland was observed.

Serum aldosterone measurement: 3300 pmol/L (upper limit of normal is 300 pmol/L)

Diagnosis and Discussion:

Based on these results a diagnosis of hyperaldosteronism was confirmed. Some subtle findings that increased the suspicion for hyperthyroidism were the abnormally normal hematocrit (expected to be lower in a sick, older cat) and the relatively higher increase in BUN compared to creatinine. Primary hyperaldosteronism is considered a rare disorder in cats. Aldosterone secretion is influenced by serum potassium and renin concentrations. Aldosterone enhances sodium retention and facilitates potassium excretion in the kidney. Clinical signs of hyperaldosteronism are due to hypokalemia, hypertension, and less commonly, sodium retention. Although sodium is retained in hyperaldosteronism, water is retained as well, resulting in normal serum sodium concentrations in most patients. The azotemia in the cat was considered to be of renal origin, and hypokalemia causes a unique nephropathy in cats, which may have explained the azotemia. Azotemia is normally accompanied by hyperphosphatemia as well (due to decreased glomerular filtration), so the finding of a low serum potassium in this case increased the suspicion for hyperaldosteronism.

Hyperaldosteronism may be more difficult to diagnose in milder cases, but it should be considered whenever hypertension is encountered in a cat. Plasma renin activity is measured in the diagnostic work-up of hyperaldosteronism in people. In primary hyperaldosteronism, plasma rennin activity should be low, while aldosterone is high, and the plasma renin:aldosterone ratio is commonly used to diagnose human hyperaldosteronism. Plasma renin in cats has not been as well-studied, and the test is not widely available. Recently the urinary aldosterone:creatinine ratio has been proposed as a screening test for hyperaldosteronism in cats.

Hyperaldosteronism is usually associated with a unilateral adenoma of an adrenal gland. In human medicine, bilater adrenal hyperplasia is more commonly associated with hyperaldosteronism, and this occurs in cats as well. When an adrenal tumor is demonstrated, the treatment of choice is adrenalectomy. Adrenalectomy is not always possible, especially when the right adrenal gland is involved (because of the proximity of the caudal vena cava, which is sometimes invaded by an aggressive adrenal tumor).

Medical management of hyperaldosteronism is also possible, and entails the following components:

• Potassium supplementation (potassium gluconate is usually used, and dosages changes are based on serum potassium monitoring).

• Sprinolactone: This is an aldosterone antagonists that interferes with the action of aldosterone on the distal nephron and helps prevent renal potassium loss.

• Angiotensin-converting enzyme inhibitors: These drugs are used to treat hypertension and to block production of aldosterone. It is unknown whether these drugs have the desired effect on aldosterone secretion in the cat

• Amlodipine: A calcium-channel blocker that is more effective than ACE inhibitors in the treatment of hypertension in the cat.

Case outcome

• The owners declined adrenalectomy and elected medical management

• The cat was treated with oral potassium supplementation, spironolactone, enalapril, and amlodipine.

• Clinical signs subsided within one week.

• At the time of this writing, the cat has been doing well for 17 months.

Clinical case two:

Signalment: 15-year-old female spayed DLH cat

History

• One-day of lethargy, anorexia, and inability to use the hind legs.

• One-year history of PU/PD

• Diet of Fancy Feast

Physical exam

• T = 99F, P = 148 bpm, R = 36 rpm

• III/VI left parasternal murmur

• L kidney > R kidney

• Profound weakness in rear limbs

• Motor activity present

• Cranial nerves normal

• Non-painful, femoral pulses OK, toes pink

CBC

• Hct = 27%

• Normocytic, normochromic

• 60,700 retics

Systolic blood Pressure = 160 mmHg

Urinalysis

• USG = 1.016

• pH = 6

• Protein = 100

• Glucose =100

• Quiet sediment

Serum Chemistry

• Creatinine = 350 uM/L mg/dl (90 – 210)

• BUN = 64.1 mg/dl (14 – 34)

• Globulin = 62 g/L (26 – 51)

• Albumin = 43 g/L (27 – 38)

• Phosphorus = 2.8 (0.8 - 3)(0.7-2.6)

• Potassium = 2.7 meq/L (3.8 – 5.4)

• Glucose = 16 mM/L

• Total T4 = 31.5 nmol/L (17 - 49)

Summary of Results

• Azotemia

• Panhyperproteinemia

• Hyperglycemia

• Hypophosphatemia

• Isosthenuria

• Proteinuria

• glycosuria

Questions

1. If this is renal azotemia with dehydration, why is the phosphorus low?

2. What's the reason for the hind limb weakness?

3. Is this cat diabetic?

Subsequent developments

• Intravenous LRS + 24 mEq/L KCL given

• Increased respiratory effort developed over ensuing 8 hours

• Progressed to cyanosis, HR of 88 bpm, temp of 92.7F

• EKG showed only bradycardia and occasional VPC

Recheck of some values

• Sodium = 154 mEq/l

• Potassium < 2 mEq/L

• Venous pH = 6.887

• Base excess = -11mmol/l

• pCO2 = 115 mmHg

Assessment

• Mixed acidosis

• Hypoventilation

• Worsening hypokalemia

• Hypernatremia

Our Plan

• Anesthesia and Positive Pressure Ventilation

• Active warming

• KCl infusion

• EKG, temp, blood pressure, pulse ox, and end tidal CO2 monitoring

One Hour Later . . . .

• O2 saturation declines to 90%

• Muffled lung sounds

• Thoracocentesis yielded 300 ml air

• Arterial Blood Gases on 100% O2

• pH = 7.125

• pCO2 = 42.1 mmHg

• pO2 = 144 mmHg

• Bicarb = 14 mEq/l

• Base excess = -15 mmol/L

We had initially made a tentative diagnosis of chronic renal failure with secondary hypertension, dehydration and electrolyte loss, but did not know the cause of the hindlimb weakness. Hyperglycemia in this cat may have been due to diabetes mellitus, which was consistent with the polyuria, polydipsia, glycosuria and proteinuria, however stress hyperglycemia could not be ruled out. Initial treatment involved intravenous fluid therapy, but within 8 hours of admission the cat's clinical status had deteriorated. She developed respiratory distress, and electrolye and venous blood gas analysis revealed mild hypernatremia (sodium 154 mEq/L), severe hypokalemia (potassium < 2mEq/L) and a marked mixed acidosis (pH 6.887, pCO2 115 mmHg, base excess –11 mg/dL). Arterial blood gas analysis performed after thoracocentesis (FiO2 100%) showed pH 7.125, pCO2 42.1 mmHg, pO2 144 mmHg, bicarbonate 14 mmol/L, base excess –15 mmol/L and SO2 98%, indicating metabolic acidosis and relative hypoxemia despite positive pressure ventilation. The acidosis was most likely due to decreased oxygen delivery to tissues secondary to hypoperfusion and hypoxemia with production of acid in anaerobic glycolysis. When the pneumothorax continued and the cat declined further, the owners elected euthanasia.

The gross necropsy findings showed a right adrenal gland tumor. Both kidneys were abnormal, but consistent with chronic disease. A lung tumor was also found, and. the pneumothorax may have been due to parenchymal rupture secondary to increased pressure on weakened pulmonary tissue due to the focal lung mass. On histopathology, the adrenal mass was interpreted as a cortical adenoma. The kidneys had interstitial inflammation and membranous glomerulonephritis with glomerulosclerosis and medullary tubular mineralization. We measured the concentration of aldosterone on a banked serum sample. The resting serum concentration of aldosterone was > 3329 pmol/L, consistent with hyperaldonsteronism

Primary hyperaldosteronism is a rare disorder in cats. Although not reported with primary hyperaldosteronism, profound hypokalemia has been associated with respiratory failure in clinical studies of cats. The progressive clinical signs in this cat, from weakness and lethargy to acute respiratory failure, were exacerbated by the initial treatment. The ventilatory failure may have been due to an acute decrease in the serum potassium concentration and intravenous fluid therapy may have exacerbated potassium loss by increasing glomerular filtration rate and delivery of potassium to the distal tubule, where the effects of aldosterone would further enhance potassium excretion. Hypokalemia develops when there is depletion of total body potassium stores or when extracellular potassium is redistributed into cells. Redistribution of extracellular potassium may occur with insulin administration or with a metabolic alkalosis. Decreased potassium intake may occur with inappetance. Potassium loss occurs with most commonly through the kidneys. Osmotic diuresis, diuretics, renal tubular acidosis, and, as in this case, hyperaldosteronism can be the underlying causes of renal potassium loss.

Aldosterone secretion is influenced by serum potassium and renin concentrations. Aldosterone enhances sodium retention and facilitates potassium excretion in the kidney. Clinical signs of hyperaldosteronism are due to sodium retention, and include polyuria, polydipsia and hypertension.

Reports cats with hypokalemia associated with aldosterone-secreting adrenal tumors are rare. This case was reported in the Journal of Veterinary Emergency and Critical Care. For complete information on this case, please see:

Haldane S, Graves TK, Bateman S, Lichtensteiger CA. Profound hypokalemia causing respiratory failure in a cat with hyperaldosteronism. J Vet Emerg Critical;17(2):202-207, 2007