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Urinary dilemmas in feline hyperthyroidism (Proceedings)
A guide to feline hyperthyroidism dilemmas
• Older cats with hyperthyroidism frequently have concurrent renal disease or UTI.
• Concurrent diseases can suppress total thyroid hormone measurements in cats and confuse the diagnosis of hyperthyroidism.
• GFR is increased by the hyperthyroid state and declines over the first month after treatment.
• Hyperthyroid cats with concurrent renal disease require a trial treatment period with reversible anti-thyroid medications in order to determine the likely effects of definitive treatment on renal function.
• Systemic hypertension and proteinuria may resolve after treatment of hyperthyroidism.
• Hyperthyroid cats with concurrent chronic kidney disease, persistent systemic hypertension or proteinuria require specific management of these disorders in addition to management of hyperthyroidism.
• UTI in hyperthyroid cats should be managed as complicated UTI.
Polyuria/polydipsia in cats
Although cats may not demonstrate polyuria/polydipsia in as dramatic a fashion as dogs, a change in water intake or increase in urine in the litter box warrants further investigation. Owners will readily notice a change in habits if a cat begins to empty the water bowl or seeks water from other sources, such as a dog bowl, sink, faucet or shower. Polyuria is confirmed by documenting dilute urine in several random samples. Recall that normal cats usually concentrate urine to a specific gravity much greater than 1.035.
The most common causes of PU/PD in cats include chronic kidney disease, hyperthyroidism and diabetes mellitus, all diseases of geriatric cats that can co-exist in an individual cat. In hyperthyroidism, it is thought that changes in medullary blood flow alter distal concentrating mechanisms. Psychogenic polydipsia may result from thyrotoxicosis in some cats as well. A data base including biochemical data, thyroid hormone measurement and urinalysis is usually adequate for diagnosis of pu/pd in cats.
Hyperthyroidism and renal function
High circulating thyroid hormone directly impacts renal blood flow and the hemodynamic forces favoring glomerular filtration. Filtration forces and tubular functions are increased. In the short term, hyperfiltration will preserve total GFR even if the kidneys have lost functional nephrons. In cats with marginal renal function, treatment of hyperthyroidism may remove these positive forces and reveal ("unmask") the biochemical or clinical effects of the underlying renal dysfunction. On the other hand, sustained glomerular hypertension is a known mechanism perpetuating renal disease in many species. Systemic hypertension associated with untreated hyperthyroidism also is damaging to renal and other capillary beds and is a risk factor for progressive dysfunction.
Concurrent hyperthyroidism and chronic kidney disease
Chronic kidney disease is usually discovered by finding alterations in renal structure, urine concentrating ability, biochemical indicators (BUN, creatinine) or persistent proteinuria. In a hyperthyroid cat, however, urine specific gravity is a unreliable indicator of renal function; BUN and creatinine can be affected by dehydration (or conversely, decreased by muscle wasting and malnutrition). Likewise the stage or degree of renal disease cannot be determined by the level of azotemia in a CKD cat with concurrent hyperthyroidism. Other clues become important in determining the relative contribution of renal disease to the cat's illness: patient history, prior laboratory findings, kidney size or architecture. Measures of GFR can provide more objective information, although GFR is affected by thyroid hormone levels. GFR measurements lower than 2.25 ml/min/kg as measured by DTPA scintigraphy are associated with worsening of renal parameters after radioiodine treatment in hyperthyroid cats. Plasma clearance methods are becoming more practical for veterinary practice and can be used to provide some objective measure of renal function in questionable cases. GFR can be expected to decline to some degree in all cats after definitive treatment of hyperthyroidism (radioiodine, surgical thyroidectomy), but the decline appears to stabilize at about 4 weeks post-treatment.
Hyperthyroidism, hypertension and proteinuria
Because older cats often suffer from hypertensive disorders (hyperthyroidism, diabetes mellitus, chronic kidney disease, or idiopathic hypertension), serial monitoring of blood pressure, fundic examination and urine protein:creatinine ratio should be part of the management strategy. UPC serves as a key marker for the risk of, and progression of CKD in cats. Specific management of proteinuria may be required in cats with persistent, significant proteinuria (UPC > 0.4) despite control of underlying hyperthyroidism or hypertension.
Hyperthyroidism and urinary tract infection
Bacterial urinary tract infections are rare in young cats, but the risk increases in older cats and in cats with concurrent diseases. In two studies, 12 - 21% of cats with hyperthyroidism had a positive urine culture. Risk also can be considered greater in cats with concurrent CKD or diabetes mellitus. Urine cultures certainly should be performed during the initial diagnostic evaluation of cats with suspected hyperthyroidism, and periodically (every 3 – 6 months) in cats treated with methimazole. Many of these cats are asymptomatic, and may or may not have any other indications of infection on routine urinalysis or sediment examination.
Because of the presumed change in host defenses, UTI in hyperthyroid cats should be treated as a complicated UTI. Antimicrobial treatment should be chosen based on culture and susceptibility results; treatment should extend for 3 – 6 weeks, depending on the degree of illness and control of concurrent disease. Follow-up urine culture should be completed during and following treatment to ensure eradication of the organism. In cats with concurrent CKD, eradication of upper tract infection can be particularly challenging.
Concurrent disease and thyroid hormone measurements
Hyperthyroidism can be diagnosed in most affected cats with a single total T4 (TT4) measurement. In geriatric cats with chronic kidney disease, hypertensive disease, urinary tract infection, or any other nonthyroidal illness, TT4 may be suppressed into the reference range, making confirmation of hyperthyroidism more difficult. In these situations, additional diagnostic information can be gained by repeating the TT4, adding a free T4 measurement, or performing the T3 suppression test or scintigraphy. Addition of feline TSH measurement (where available) also increases diagnostic accuracy (the TSH is lower than normal in hyperthyroid cats). Endocrinologic results should always be correlated with clinical findings in order to best assess the patient.
Table 1: Data base for evaluating urinary system in hyperthyroid cats
Treatment dilemmas and recommendations
Treatment strategies will depend on the individual cat. Specific treatments can be applied for systemic hypertension, urinary tract infection, dehydration or electrolyte abnormalities. Cats with evidence of chronic kidney disease are likely to benefit from dietary and other modifications as indicated for renal disease.
In most cats, even those with significant renal dysfunction, treatment of hyperthyroidism will improve their overall health and help correct associated cardiac, vascular or urinary disorders. However, abrupt reduction in renal blood flow can be dangerous, especially in the fragile cat. In all cases in which renal function is questionable, a titratable treatment with reversible anti-thyroid medication is recommended (See table 2). Unfortunately, there are few additional therapeutic options for cats that do not tolerate methimazole. Carbimazole or ipodate may be available in some areas. Propranolol or atenolol can be used for symptomatic treatment of hyperthyroidism if no other treatments are tolerable or wise.
Most importantly, the cat's azotemia and other biochemical findings, hydration and clinical status should be evaluated during a period of euthyroidism gained by methimazole treatment. Repeated CBC, chemistry and TT4 measures are completed every 2 to 3 weeks in order to assess response to therapy and to monitor for increasing azotemia or other adverse effects.
Table 2: Approach to therapy of concurrent hyperthyroidism and CKD