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Feline hyperthyroidism

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Feline hyperthyroidism is a disorder of the endocrine system in domestic cats (feline, adjective derived from the Latin felis, meaning "cat"). It is characterized by hyperthyroidism and is the most common hormonal disorder (endocrinopathy) in cats over ten years of age. In contrast, hyperthyroidism is much less common in other pets. The disease often manifests itself as weight loss despite increased food intake, is usually detected by blood tests, and is easily treatable.

Occurrence

Feline hyperthyroidism was first described in 1979[1] and has been increasingly diagnosed in cats since then. It is unclear whether the disease is truly a recent phenomenon, or whether the increasing monitoring of the cat population for this disease is leading to the discovery of more cases.[2] The disease is the most common endocrine disorder in cats over ten years of age. All cat breeds are susceptible to the disease, with no evidence of a predisposition for certain breeds or a gender-specific association.

Pathogenesis

In contrast to hyperthyroidism in humans, the disease is almost exclusively due to benign thyroid enlargement. The most common form of thyroid tumor is adenomatous hyperplasia, which is characterized by the proliferation of glandular cells. Less frequently, autonomous adenomas may also occur.[3] In approximately 70% of cases, multiple small foci are observed, while in the remaining cases, a single focus is evident.[2] It is noteworthy that thyroid cancer can also cause hyperthyroidism in rare cases. However, this is a very rare occurrence in cats, with less than 5% of thyroid diseases being attributed to this phenomenon. To date, there is no evidence that immune-related hyperthyroidism, as observed in humans (Hashimoto's thyroiditis, Graves' disease), has been described in cats.

As a result of the changes, there is an increased release of the thyroid hormone thyroxine and, in three-quarters of cases, triiodothyronine (another thyroid hormone). The release of these hormones in affected cats is independent of thyrotropin (TSH), which normally regulates the thyroid gland.

What triggers these adenomas is still unknown. Mutations in the thyrotropin receptor genes may be responsible for the unregulated growth of the cells.[3] Diet and environmental factors, as well as genetic factors, may play a role.[4] According to epidemiologic studies, the feeding of commercial cat food is a risk factor for the development of the disease, which is attributed to the high content of thyroid-enlarging (strumigenic) substances such as soy isoflavones or phthalates.[5][3] Cats fed canned food are 2.5 to 5 times more likely to develop hyperthyroidism.[6] In addition, environmental factors such as the use of certain litters may also play a role in the development of the disease.[7][8] Polybrominated diphenyl ethers (PBDEs), which are used as flame retardants in textiles (they are now banned in the EU and some US states), could also be involved in the pathogenesis due to their endocrine effects: The chronically increased TSH production could lead to hypertrophy of the thyroid follicles.[6]

Clinical picture

The clinical picture is very variable and also depends on the degree of hyperthyroidism. In the end, most of the observed symptoms are signs of forced metabolic processes in the affected animals caused by the excess of thyroid hormones.

The most common sign is weight loss, which occurs in 88% of hyperthyroid cats. Other signs with a frequency of about 50% include palpable enlargement of the thyroid gland (the healthy thyroid gland is not palpable in cats), heart palpitations and murmurs, and increased food intake and even binge eating.[9] The excess of thyroid hormones can cause the clinical picture of hypertrophic (more common) or dilated (rare) heart muscle disease. This condition is also called thyrotoxic cardiomyopathy. The hypertrophic form is often reversible after successful treatment of hyperthyroidism.

Other symptoms occasionally seen with hyperthyroidism include increased stool volume, vomiting, increased thirst and urination, increased activity (much less common is decreased activity with rapid fatigue), behavioral changes (anxiety or increased aggressiveness), decreased food intake, shortness of breath, and skin changes (shaggy coat, hair loss, increased claw growth).[9] Hypertension is seen in 5-20% of hyperthyroid cats, but a clear cause-and-effect relationship has not been established.[6] There is one case report of polyneuritis of the cranial nerves with motor deficits in the head.[10]

Hyperthyroidism may also be the cause of life-threatening arterial thromboembolism. In 1.7% of cats with thromboembolism, hyperthyroidism was not previously known. This results in sudden hind limb paralysis and severe pain.[11]

Diagnosis

Based on the clinical picture, a number of other diseases in older cats should be considered, such as diabetes, chronic kidney disease, heart disease, liver failure, digestive disorders and chronic intestinal inflammation, and intestinal lymphoma. Rare feline diseases such as exocrine pancreatic or adrenal hypofunction should also be considered. Therefore, the diagnosis can only be made with hormone testing or scintigraphy (see below).[4]

Laboratory tests

The blood count often shows an increase in white blood cells (leukocytosis) and a decrease in eosinophil granulocytes (eosinopenia) and lymphocytes (lymphopenia) as a result of the stress response to high thyroxine levels. Red blood cell count and hemoglobin content are in the upper normal range. There is usually a slight to moderate increase in the activity of various enzymes (ALAT, ASAT, LDH, AP) in the serum. The fructosamine level is reduced due to the increased protein metabolism and is usually below 200 µmol/l.[3]

Blood urea and creatinine levels may be elevated as a result of the renal dysfunction often associated with hyperthyroidism.[4][9] However, the coexistence of hyperthyroidism and chronic kidney disease may be masked to some extent because thyroxine increases metabolism and cardiac output, improving blood flow to the kidneys. This increases the glomerular filtration rate, which favors the excretion of toxic metabolites. Paradoxically, therefore, renal insufficiency may become clinically manifest after treatment of hyperthyroidism. According to Egner and Carr[12], these laboratory changes, together with positive palpatory findings, are evidence of the disease.

Special thyroid function tests must be carried out for further diagnosis.

The initial step should be to determine the serum concentration of thyroxine (T4). However, in veterinary medicine, the total thyroxine concentration is typically determined, rather than that of free (non-protein-bound) thyroxine (fT4). Nevertheless, the latter is more sensitive.[13] The normal range for T4 in cats is between 1.1 and 4.5 µg/dl, for fT4 between 1.0 and 2.8 ng/dl when determined by equilibrium dialysis.[2] In approximately 20% of animals, the T4 level is normal despite the presence of disease, which may be due to fluctuations in the hormone level during the course of the day or a reduction in the T4 level as a result of other secondary diseases. The measurement of fT4 has a sensitivity of 95%, but 20 to 30% of thyroid-healthy cats also have elevated fT4 levels. Therefore, if fT4 levels are elevated, total T4 must also be measured, which should be in the upper reference range in animals with hyperthyroidism.[14] Furthermore, various medications, including glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), phenobarbital, and trimethoprim-sulfonamide combinations, can influence T4 levels.[3] In the event of a clinical suspicion, it is advisable to repeat the determination at a later date.

Another method is the thyroid suppression test. In this procedure, a synthetic triiodothyronine (T3, typically Liothyronine) is administered to the cat over two days. A cat with a healthy thyroid gland will respond to this treatment by reducing the secretion of TSH (negative feedback), which will result in a decline in the T4 concentration. However, as the hyperthyroidism has already led to a permanently low TSH level, the administration of T3 in sick cats does not result in a reduction in TSH and T4.[4]

Another diagnostic procedure is the TRH stimulation test. In this test, the cat is administered thyrotropin-releasing hormone (TRH), which leads to a significant increase in the T4 concentration in healthy cats. In diseased animals, on the other hand, there is no or at most a slight increase.[15] However, this test sometimes has considerable side effects in cats (salivation, vomiting, palpitations, defecation), which is why it is rarely used. The TSH test, which determines the serum content of thyrotropin, a hormone that regulates the thyroid gland, is now also available for cats.[2] As in humans, early forms of hyperthyroidism can be detected based on low or unmeasurable TSH levels. However, the TSH stimulation test, which functions in a similar manner to the TRH function test, is no longer conducted as TSH is no longer available on the market.

Imaging procedures

Thyroid sonography, a diagnostic technique that has been utilized in human medicine for decades, has only recently been employed in veterinary medicine, primarily for research purposes. The primary reasons for this are the high equipment requirements and the associated high equipment costs. High-resolution linear transducers with at least 7.5 MHz, preferably 10 to 13 MHz, with a small contact surface are utilized.[16] Sonography can be employed to diagnose thyroid enlargement in all hyperthyroid cats, whereas the diagnostic reliability of palpation is only 84%, even among experienced veterinarians.[17] Thyroid scintigraphy is a valuable diagnostic procedure, yet it is only available in a limited number of veterinary clinics. In this procedure, a cat is administered a radionuclide (e.g., the iodine isotope 131I or the technetium isotope 99mTc), and its accumulation in the adenomas is then visualized. The principal advantage of this method is that the precise location of the tumors in the thyroid gland can be determined, which is advantageous with regard to surgical therapy. On rare occasions, additional thyroid tissue may colonize outside the thyroid gland (ectopia, particularly in the mediastinum) and become diseased as a result of disorders during organogenesis. Such displaced thyroid tissue can only be detected by scintigraphy.[18]

To date, Magnetic Resonance Imaging (MRI) and Computer Tomography (CT) have not been employed for thyroid diagnostics in cats. Furthermore, such equipment is only accessible at large veterinary clinics.

Therapy

Currently, three therapy options are available for hyperthyroidism in cats: the use of thyrostatic drugs, surgical removal of the diseased thyroid tissue, and radioiodine therapy. Regardless of the procedure selected, subsequent treatment of concomitant and secondary diseases (e.g., kidney damage, high blood pressure, heart disease) is typically necessary.[12] In order to ascertain the potential adverse effects of reduced thyroid hormone levels on renal function, a 30-day course of medication is recommended prior to the implementation of more radical measures such as thyroidectomy or radioiodine therapy.[6]

Thyreostatics

Therapy with thyrostatic agents is relatively straightforward and is therefore the most commonly used. Thyrostatic drugs inhibit the formation of thyroid hormones, but, in contrast to other methods, do not eliminate the pathologically altered tissue. Nevertheless, these drugs can usually be used in long-term therapy without any problems or can also be used to stabilize patients before a surgical procedure. In veterinary medicine, thiamazole (syn. methimazole, trade names Felimazole, Felidale and Thiamatab) or carbimazole (trade name Vidalta) are employed. Carbimazole is rapidly converted into methimazole when administered orally.[19] According to the manufacturer, side effects (including vomiting, lethargy, itching, liver disease, and blood count changes) occur in approximately 20% of cats, particularly with long-term treatment. However, these typically resolve once the drug is discontinued. Additionally, thiamazole cannot be used in cats with concomitant liver disease, diabetes, or blood clotting disorders.

Iopanoic acid may also be employed in the event of intolerance to thiamazole. It inhibits the conversion of T4 to T3 and has a negligible incidence of side effects.[12]

Thyroidectomy

Although surgical removal (thyroidectomy) is an effective treatment, it is also associated with a high risk of complications, particularly in cats with severe hyperthyroidism, due to the inherent risks associated with anesthesia. Prior to the surgical procedure, it is common practice to administer thyrostatic drugs. There are several techniques for the removal of the thyroid gland, with the objective of preserving the epithelial cells to the greatest extent possible. Additionally, there is a potential risk of injury to crucial cervical nerves (recurrent laryngeal nerve, vagosympathetic trunk) during surgery. A total thyroidectomy results in a deficiency of thyroid hormones, which must be compensated for by lifelong administration.[20] In the event of unilateral removal, a transient hypothyroidism frequently develops postoperatively, although this is typically not a cause for concern.[4] Furthermore, there is a risk of recurrence with surgical removal, particularly in the presence of ectopic thyroid tissue.[21]

Radioiodine therapy

Radioiodine therapy is the treatment of choice due to its efficacy and tolerability. A single treatment is typically sufficient, eliminating the need for long-term drug treatment (which can be problematic in some cats) and the risks associated with surgical removal.[22] However, it is associated with significant radiation protection requirements and is currently only available at two veterinary facilities in Germany. In addition to the limited availability, the associated costs and the need for hospitalization represent a disadvantage. In close consultation with the responsible supervisory authorities, it has been possible to reduce the required duration of hospitalization from approximately three weeks to a few days.[23] The necessary duration of hospitalization is determined by dosimetry and is seven to ten days.[5]

Thermal or chemical destruction of the thyroid gland

Destruction of the thyroid tissue using a radiosurgical device under ultrasound control (thermal ablation) or by injection of 96% ethanol (chemical ablation) is practically no longer relevant. Both forms of treatment have increased side effects such as laryngeal paralysis or Horner's syndrome.[5]

References

  1. ^ M. E. Peterson et. al: Spontaneous hyperthyroidism in the cat. In: Proc. Am. College Vet. Intern. Med. 1979, p. 108.
  2. ^ a b c d R. Hämmerling: Die feline Hyperthyreose. In: Der praktische Tierarzt. 86(5), 2005, p. 320–324. ISSN 0032-681X
  3. ^ a b c d e Eva Höfel, Thomas Rieker: Hyperthyreose – Aktuelles zur Pathogenese und Diagnose. In: Fachpraxis. No. 63, 2013, p. 6–11.
  4. ^ a b c d e M. E. Peterson: Hyperthreodism. In: Stephen J. Ettinger, Edward C. Feldman: Textbook of veterinary internal medicine. 5th edition. Volume 2, Saunders, 2000, ISBN 0-7216-7256-6, pp. 1400-1419.
  5. ^ a b c Andrea Monika Mathes, Reto Neiger: Hyperthyreose der Katze. In: Kleintierpraxis. 55, 2010, p. 685–698.
  6. ^ a b c d Thomas Graves: Aktuelle Aspekte der Hyperthyreose bei der Katze. In: Vet. Focus. 19.3, 2009, p. 2–5.
  7. ^ R. W. Nelson, C. G. Couto (Ed.): Feline Hyperthyreose. In: Innere Medizin der Kleintiere. 1st edition. Urban & Fischer, München/ Jena 2006, ISBN 0-323-01724-X, p. 758–772.
  8. ^ P. H. Kass et. al: Evaluation of environmental, nutritional, and host factors in cats with hyperthyroidism. In: J. Vet. Int. Med. 13(4), 1999, p. 323–329. ISSN 0891-6640
  9. ^ a b c J. D. Broussard et. al: Changes in clinical and laboratory findings in cats with hyperthyreodism from 1983 to 1993. In: J. Am. Vet. Med. Assoc. 206(3), 1995, p. 302–305. PMID 7751233.
  10. ^ C. T: Holland et al.: Multiple cranial nerve motor defects, resembling polyneuritis cranialis, in a cat with hyperthyreodism. In: Aust. Vet. J. Volume 100, No. 4, 2022, p. 146–149.
  11. ^ Kieran Borgeat et al.: Arterial thromboembolism in 250 cats in general practice: 2004-2012. In: Journal of veterinary internal medicine. Volume 28, No.1, 2014 Jan-Feb, p. 102–108, doi:10.1111/jvim.12249, PMID 24237457, PMC 4895537 (free full text).
  12. ^ a b c Beate Egner, Anthony P. Carr: Hyperthyreose bei der Katze – Welche Rolle spielen ACE-Hemmer? In: kleintier konkret. 11, 2008, p. 11–14.
  13. ^ M. E. Peterson: Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. In: J. Am. Vet. Med. Assoc. 218(4), 2001, p. 529–536. PMID 11229503.
  14. ^ Stephanie Nather et. al: Hyperthyreose der Katze. In: Kompendium Kleintier 2017, p. 52–57.
  15. ^ M. E. Peterson et. al: Use of the thyrotropin releasing hormone stimulation test to diagnose mild hyperthyreodism in cats. In: J. Vet. Intern. Med. No. 4, 1999, p. 279–286. ISSN 0891-6640
  16. ^ C. Poulsen Nautrup et. al: Schilddrüse und Nebenschilddrüsen. In: C. Poulsen Nautrup, R. Tobias (Ed.): Atlas und Lehrbuch der Ultraschalldiagnostik bei Hund und Katze. 2nd edition. Published by Schlütersche publishing company, Hannover 1998, ISBN 3-87706-663-1, p. 113–116.
  17. ^ W. Kraft et. al: Symptome bei Hyperthyreose der Katze: eine retrospektive Studie. In: Kleintierpraxis. 44(10), 1999, p. 719–732. ISSN 0023-2076
  18. ^ M. E. Peterson, D. V. Becker: Radionuclide thyroid imaging in 135 cats with hyperthyroidism. In: Vet. Radiol. 25(1), 1984, p. 23–27. ISSN 0196-3627
  19. ^ M. E. Peterson, D. P. Aucoin: Comparison of disposition of carbimazole and methimazole in clinically normal cats. In: Res. Vet. Sci. 54(3), 1993, p. 351–355. PMID 8337482.
  20. ^ C. D. Welches et. al: Occurence of problems after three techniques of bilateral thyroidectomie in cats. In: Vet. Surgery. 18(5), 1989, p. 392–396. PMID 2815557.
  21. ^ E. C. Naan et. al: Results of thyroidectomy in 101 cats with hyperthyroidism. In: Vet. Surg. 35(3), 2006, p. 287–293. PMID 16635010.
  22. ^ M. E. Peterson: Radioiodine treatment of hyperthyroidism. In: Clin. Tech. Small Anim. Pract. 21(1), 2006, p. 34–39. PMID 16584029.
  23. ^ M. Puille et. al: Radiojodtherapie bei Katzen: Strahlenschutz der Kontaktpersonen. In: Tierärztl Prax. 33 (K), 2005, p. 291–295. ISSN 1434-1239

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