Feline nightmare case number one: A 14-year-old cat with acute onset of blindness (Proceedings)

A 14 year old, male intact, DSH cat is presented for acute onset of blindness. There are no other striking historical findings. Physical examination findings reveal a 4/9 body condition score, heart rate of 180, normal mucous membranes, normal hydration, possibly small kidneys on palpation, and a 3/6 systolic murmur with the point of maximal intensity at the left sternal border. Ocular examination reveals bilateral retinal detachment. Palpation of the central neck revealed a small goiter most easily palpable on the left lobe of the thyroid gland

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

Results

Urinalysis

• Color – pale, clear

• Protein – negative

• Glucose – 1+

• Bili – negative

• Ketones – negative

• Specific gravity – 1.021

CBC (reference interval in parentheses)

• Hct – 44%

• WBC – 22.8 x 103 (5.5 – 19)

• Segs – 84%

• Bands – 0%

• Lym – 5%

• Eos – 1%

• Mono –10%

Chemistry Profile (normal ranges indicated)

• Albumin – 3.0 g/dl (2.7-3.8)

• Calcium – 10.9 mg/dl (8.4-10.8)

• Chloride – 114 mEq/L (112-1240

• Cholesterol –102 mg/dl (63-130)

• Creatinine – 0.8 mg/dl (0 – 1.5)

• Glucose – 195 mg/dl (65-129)

• Phosphorus – 3.6 mg/dl (4.0-7.0)

• Potassium –3.9 mEq/L (3.8-5.4)

• Sodium – 155 mEq/L (144-156)

• TCo2 14 mM (13-25)

• T Bili – 0.1 mg/dl (0.0-0.3)

• BUN – 40 mg/dl (14-34)

• ALP – 89 U/L (6-93)

• ALT – 110 U/L (1-64

Total T4 = 34 nmol/L (17 – 48)

Thoracic Radiography: Evidence of mild cardiomegaly

Systolic Blood Pressure – 260 mmHg

Questions To Consider:

• Is the glucosuria significant?

• Is the urine concentrated enough?

• What is the significance of the neutrophilia?

• What is the significance of the hematocrit?

• Does the elevated BUN indicated renal failure?

• Is the hyperglycemia significant?

• Why is the ALT activity increased?

• Does the normal T4 rule out hyperthyroidism?

• Have any causes of systemic hypertension been excluded?

• What is the next diagnostic step

Case Outcome

The following causes of hypertension were considered:

• Systemic hypertension

o By far the most common cause in cats

• Hyperviscosity

• Vasculitis/Chorioretinitis

o Immune-mediated

o SLE

• Sub-retinal hemorrhage

• Coagulopathy

Ruleouts for hypertension in this cat

• Hyperthyroidism

• Chronic Renal Failure

• Hyperaldosteronism

• Pheochromocytoma

• Diabetes does not seem to cause hypertension in cats

o Senello et al. JAVMA 2003;223:198

Some subtle findings that increased the suspicion for hyperthyroidism were the hematocrit of 44% (abnormally high for a sick, older cat, but commonly found in hyperthyroidism cats), the relative increase in BUN vs creatinine (increased protein catabolism leads to BUN elevation unrelated to renal function in hyperthyroid cats), and the increased alanine aminotransferase activity (thought to be due to metabolic stress on hepatocytes).

Repeating of the total T4 measurement, free T4, thyroid scintigraphy, and T3 suppression testing were considered to further investigate occult hyperthyroidism.

Further Results

The free T4 concentration was elevated, and the fructosamine concentration was in the normal range, so a diagnosis of hyperthyroidism was made

The Effects of Treatment on Renal Function

Investigators have shown consistently that treatment of hyperthyroidism can have deliterious effects on renal function in cats, and that feline hyperthyroidism can mask underlying chronic renal insufficiency.1-4 Post-treatment renal failure is common, occurring in 17% to 38% of cats treated for hyperthyroidism.1,3,4 Treatment of hyperthyroidism by bilateral surgical thyroidectomy causes a consistent, and sometimes disastrous, drop in glomerular filtration rate (GFR)1 . The same is true for radioiodine treatment and methimazole.2-4 This clinical problem has led to the use of "methimazole trials" prior to radioiodine or surgical thyroidectomy. Especially in cats with impaired renal function, methimazole is often considered the most logical first-line treatment for hyperthyroidism because it can be reversed if renal failure ensues.4,5

Which cats should undergo methimazole trials?

There are many different recommendations for how and when methimazole trials should be performed. Unfortunately, there are few published data to guide these decisions. For example. Veterinarians, general practitioners and specialists alike, commonly recommend methimazole trials only for cats with questionable renal function. There is a commonly held belief that cats with well-concentrated urine (urine specific gravity > 1.035) have adequate renal function and do not run a significant risk of post-treatment renal insufficiency and that methimazole trials are not needed in these cats.6,7 There are no published data to support this opinion, and its wisdom should be questioned. First, urine specific gravity is an unreliable predictor of renal function in cats because thyroid hormone can cause polydipsia and polyuria as a primary effect, regardless of renal function. Second, urine specific gravity is not a measure of GFR, but rather an indicator of renal tubular function. It is unknown if hyperthyroid cats with concentrated urine are at a lower risk of post-treatment renal failure. We looked at 24 hyperthyroid cats developing overt renal insufficiency within 2-3 months of radioiodine treatment in our hospital, 13 (54%) had urine specific gravity measurements greater than 1.035. Five of those cats (21%) had urine specific gravity measurements above 1.050 (unplublished data). We suspect, therefore, that urine specific gravity should not be used as a predictor of post-treatment renal status in hyperthyroid cats, and that a methimazole trial should be recommended for any hyperthyroid cat that can tolerate the drug.

How long should a trial run?

There are no published studies that have determined the best length of time for a methimazole trial. Studies in which GFR has been measured in cats treated for hyperthyroidism have typically examined renal function before and 30 days after treatment.1,3,4 It is not known whether there is a further decline in GFR after this initial treatment period, or whether the decline in GFR is permanent. My opinion is that a 30-day period is adequate, but that is based on clinical experience rather than on scientific results. It should also be noted that a good response to a trial with methimazole does not guarantee that a given cat will not experience overt renal insufficiency with subsequent radioiodine treatment. In our hospital we have seen several cats with hyperthyroidism well-controlled on methimazole and with well-concentrated urine and normal serum creatinine and urea nitrogen concentrations, that developed overt renal insufficiency shortly after radioiodine therapy. Some have speculated that a more gradual drop in circulating thyroid hormone concentrations with anti-thyroid drugs vs. radioiodine may explain this situation. Also, methimazole may have some renal protective effects in cats as has been shown in other species.8,9

Are there predictors of renal failure?

Despite the recommendation of some experts, there is no strong evidence to support the notion that cats with urine specific gravity measurements about 1.035 are not at risk for renal insufficiency following treatment of hyperthyroidism, but it is unknown whether there are other predictors. Our group has examined many cases of post-treatment renal failure looking for pre-treatment predictors, and we have not been able to find anything useful. Investigators have reported that pre-treatment GFR measurement may be useful as a predictor of post-treatment renal status in hyperthyroid cats.3 In one report cats that underwent treatment for hyperthyroidism and did not develop renal insufficiency all had pre-treatment GFR measurements of greater than 2.25 ml/kg/min. The authors concluded that pre-treatment GFR was a valuable predictor of post-treatment renal insufficiency. We looked back at our original published reports of GFR in cats with hyperthyroidism, and found that 3 of 5 hyperthyroid cats experiencing post-treatment renal insufficiency had pre-treatment GFR's greater than 2.5 ml/kg/min.1 We found no significant difference between GFR in cats that did or did not experience post-treatment renal insufficiency. Because of these two conflicting reports, it is probably unwise to consider a given cat safe from harm if the pretreatment GFR is >2.25 ml/kg/min. Differences in methods of determining GFR may account for these disparate reports, but we do not believe there is adequate published evidence to rely on GFR measurement to predict post-treatment renal insufficiency in hyperthyroid cats. Furthermore, measurement of GFR in cats is difficult. Most accepted methods of GFR estimation are not available to the majority of small animal practitioners, so a methimazole trial would be considerably more practical.

How is a methimazole trial performed?

While the time necessary to see if treatment of hyperthyroidism will cause overt renal insufficiency has yet to be determined, there is adequate evidence to suggest that 30 days is a reasonable time. A common mistake, however, is failure to recheck serum thyroid hormone concentrations during the trial. Because the half-life of T4 in the cat is less than 8 hours, I typically recheck cats one week after starting a trial. If the T4 is not in the lower half of the normal range (optimal for hyperthyroidism control), the dose is increased and the on-month period is started again. Often the dose of methimazole needs to be adjusted to achieve euthyroidism, and the goal is to have euthyroidism for a month, not just methimazole for a month. Because of the danger of developing other side effects to methimazole ( eg. vomiting, hepatopathy, blood dyscrasia) cats should be re-evaluated at 2-week intervals while on a methimazole trial.

Final Outcome

The cat showed no signs of renal insufficiency following the methimazole trial and was treated with radioiodine as a permanent treatment for hyperthyroidism. Shortly thereafter, the cat developed overt renal failure. Subsequently, the cat was treated with varying combinations of thyroid hormone replacement and antihypertensive drugs.