Feline Hyperthyroidism and its Relation with Renal Function
Sylvie Daminet, DVM, PhD, DACVIM, DECVIM-CA
Professor, Internal Medicine, Dept. Small Animal Medicine, Ghent University, Merelbeke, Belgium

Feline hyperthyroidism and chronic renal failure (CRF) are common diseases in older cats. Further, renal function is profoundly influenced by thyroid status in several species. In cats, several studies have shown a marked decline of renal function after treatment of hyperthyroidism. This has been documented with all treatments routinely available for treatment of feline hyperthyroidism.

Physiological Interactions Between Thyroid Hormones and Renal Function

Through their ino- and chronotropic effects, excessive thyroid hormone concentrations can lead to an increased cardiac output (CO). Further, hyperthyroidism diminishes peripheral vascular resistance by dilating arterioles of the peripheral circulation. This leads to a stimulation of the renin-angiotensin-aldosterone system, which contributes to the increased CO. As a consequence of these processes, an increased RBF is observed. Opposite changes are described in hypothyroid humans and rats.

The increased GFR associated with hyperthyroid states is thought to result from the increased CO and intrarenal vasodilatation and leads to a decline in BUN and serum creatinine concentrations. Opposite changes are observed in hypothyroidism (human) and studies have shown a normalisation of GFR, BUN and creatinine values after successful treatment of hypo- or hyperthyroidism in human medicine.

Considerations and Clinical Implications in Hyperthyroid Cats

It is important to underline that CRF and hyperthyroidism are both frequently encountered diseases in geriatric cats. Therefore, finding both diseases in one cat is not uncommon. Also, clinical signs of both diseases can overlap. Further as shown in table 1, renal function will decline after treatment of hyperthyroidism in cats. This can unmask renal failure in some cats. Decreased muscle mass associated with emaciation and therefore decreased production of creatinine can contribute to the declined serum creatinine concentrations observed in untreated hyperthyroid cats. The presence of a hyperthyroid state could contribute to the development or progression of CRF. Systemic hypertension can lead to intraglomerular hypertension, hyperfiltration and contribute to the development of glomerulosclerosis.

In the study of Adams et al. (1997), 9 out of 22 hyperthyroid cats had concurrent CRF at presentation. Another study on a larger number of cases (n=167) reported that 14% of hyperthyroid cats had pre-existing renal disease (Milner et al., 2006). Approximately 30% of hyperthyroid cats are azotemic after therapy of hyperthyroidism.

Assessment of complete blood count, chemistry, urinalysis and blood pressure are important in hyperthyroid cats prior to treatment. Indeed, careful evaluation of BUN, creatinine and urine specific gravity (USG) are required prior to instituting therapy for hyperthyroidism as these results will influence the initial choice of therapy for hyperthyroidism. Medical, surgical and 131I therapy are available and effective in the treatment of hyperthyroidism. Thyroidectomy and 131I are considered definitive and irreversible treatments. Daily oral administration of methimazole (MMI) is reversible.

Pre-existing renal failure in a newly diagnosed hyperthyroid cat: First, in such a case, the diagnosis of mild hyperthyroidism can be somewhat complicated by a decline in thyroid hormones (euthyroid sickness) within the reference range. Second, given the further decline in GFR to be expected after resolution of the hyperthyroid state, it is wise to start an azotemic hyperthyroid cat with a reversible anti-thyroid therapy (trial therapy). Often, methimazole is used (orally or transdermal), at a low starting dose (i.e., 1.25 mg orally once a day). This allows assessing the impact of anti-thyroid therapy on renal function. These patients should be monitored every 2 weeks. Dosage adjustments should be made prudently. The presence of overt signs of thyrotoxicosis (heart murmur, emaciation, proteinuria) underlines the importance of treating the hyperthyroidism. Management of CRF is also warranted. If the patient stabilises and renal function remains stable after reestablishment of a euthyroid state, a more definitive treatment, such as 131I, can still be considered. If renal function declines significantly after methimazole treatment is instituted, it seems wise to maintain the cat on a reversible anti-thyroid therapy, which can be adjusted individually as needed. In some cats, maintenance of a mild hyperthyroid state may be beneficial.

Development of renal failure after treatment of hyperthyroidism: Resolution of the hyperthyroid state can unmask renal failure. Excess thyroid hormones increase GFR and treatment of hyperthyroidism will decrease glomerular filtration, leading to an increase in BUN and creatinine values. Approximately 30% of the patients develop overt CRF after treatment of hyperthyroidism. This underlines the importance of appropriate monitoring after therapy of hyperthyroidism.

Predicting which non azotemic cats will develop renal failure after treatment of hyperthyroidism is currently difficult. Pre-treatment values of serum creatinine, BUN, USG and urine protein to creatinine ratio (UPC) did not appear to be predictive for the development of post-treatment renal failure in several studies. However, there are some reports of hyperthyroid cats with isostenuric urine prior to treatment who developed post-treatment azotemia. It seems reasonable (although not evidence-based) to recommend a trial therapy in any hyperthyroid cat presented with one or more of the following: BUN or serum creatinine values at the high end of the reference interval, a low USG, an increased UPC or marked ultrasonographic kidney abnormalities. Currently the most useful predictive parameter seems to be GFR measurement. A low pre-treatment GFR was predictive of the development of CRF in several studies. However, measurement of GFR is often impractical in a clinical setting. Usefulness of urinary markers of early renal disease is currently being investigated.

Keeping in mind the negative effects on renal function, described in rats and humans in hypothyroid states, it seems important to avoid a hypothyroid state after treatment of hyperthyroidism in cats.

The relationship between kidney disease and hyperthyroidism in cats is complex. It can be challenging to accurately diagnose and treat cats with concurrent CRF and hyperthyroidism. Follow-up of all cats treated for hyperthyroidism is important as a significant amount will develop CRF.

Table 1. Follow-up of renal function after treatment of hyperthyroidism in cats.

Hyperthyroid: HT, Methimazole: MMI, thyroidectomy: SX, Radioactive iodine: 131I. Mean values for USG, GFR and creatinine are given prior to and after therapy of hyperthyroidism.

Author
et al.

Number HT cats
Evaluation period

Therapy

USG
ml/kg/min

GFR

Creatinine
mg/dl

Graves
1994

n=13
(+ 11 controls)
30 days

SX

1038rightwards arrow1030

2.51±0.69
rightwards arrow1.4±0.41

1.26±0.34rightwards arrow2.05±0.60

DiBartola
1996

n=27 131I
n=9 MMI
n=22 SX
90 days

131I
MMI
SX

1046rightwards arrow1043
1042rightwards arrow1037
1033rightwards arrow1033

Not performed

1.3±0.4rightwards arrow2±0.6
1.7±0.9rightwards arrow2.7±2.5
1.7±0.6rightwards arrow2.4±0.8

Adams
1997

n=22
30 days

131I

1032rightwards arrow1028

2.2rightwards arrow2 (day 6)

1.3±0.6rightwards arrow1.9±0.7

Becker
2000

n=12
(+22 controls)
6 weeks

MMI

1041rightwards arrow1033

3.83±1.82
rightwards arrow2.02±0.81

1.32±0.21rightwards arrow1.81±0.96

References

1.  Adams WH, Daniel GB, Legendre AM, Gompf RE, Grove CA. Changes in renal function in cats following treatment of hyperthyroidism using 131I. Vet Radiol & Ultrasound 1997; 38: 231-238.

2.  Becker TJ, Graves TK, Kruger JM, Braselton WE, Nachreiner RF. Effects of methimazole on renal function in cats with hyperthyroidism. J Am Anim Hosp Assoc 2000; 36: 215-223.

3.  Bhatti S., Van Neste A., Waelbers T., Daminet S., Peremans K.: Treatment of feline hyperthyroidism with radioactive Iodine (131I) in Belgium: a retrospective study. Poster. EAVDI 2005.

4.  den Hollander JG, Wulkan RW, Mantel MJ, Berghout A. Correlation between severity of thyroid dysfunction and renal function. Clin Endocrinol 2005; 62: 423-427.

5.  DiBartola SP, Broome MR, Stein BS, Nixon M. Effect of treatment of hyperthyroidism on renal function in cats. J Am Vet Med Assoc 1996; 208: 875-878.

6.  Graves TK, Olivier NB, Nachreiner RF, Kruger JM, Walshaw R, Stickle RL. Changes in renal-function associated with treatment of hyperthyroidism in cats.Am J Vet Res 1994; 55: 1745-1749.

7.  Langston CE, Reine NJ. Hyperthyroidism and the kidney. Clin Tech in Small Anim Pract 2006; 21: 17-21.

8.  Milner RJ, Channell CD, Levy JK, Schaer M. Survival times for cats with hyperthyroidism treated with iodine 131, methimazole, or both: 167 cases (1996-2003). J Am Vet Med Assoc 2006; 228: 559-563.

9.  Slater LA, Neiger R, Haller M, Mueller W, Stevens KB, Church DB. Long-term changes in glomerular filtration rate in hyperthyroid cats following treatment with iodine-131. In: Proceedings ECVIM-CA Congress, Uppsala, Sweden, 2003, p. 154.

10. Syme HM, Elliott J. Evaluation of proteinuria in hyperthyroid cats. J Vet Intern Med 2001; 15, p. 299.

11. Syme HM, Elliott J. Prevalence and significance of proteinuria in cats with hyperthyroidism. In: Scientific Proceedings BSAVA Congress, Birmingham, England, 2003, p. 533.

Speaker Information
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Sylvie Daminet, DVM, PhD, DACVIM, DECVIM-CA
Dept. Small Animal Medicine
Ghent University
Merelbeke, Oost-Vlaanderen, Belgium


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