Thursday, September 13, 2012

Alternative Medical Treatments for Hyperthyroid Cats


Occasionally, alternative medical therapies are required in cats with hyperthyroidism because of adverse reactions to methimazole or for other specific reasons (usually cat owner preference for a “natural” treatment method). For the most part, these alternative therapies should be used for the short-term and only recommended prior to a more permanent treatment option.

Beta-Adrenoceptor Blockers (Propranolol and Atenolol)
Propranolol and atenolol are the most frequently used beta-adrenoceptor blocking agents in hyperthyroid cats (1-5). The basis for use of beta-adrenergic blocking agents (beta blockers) is that excessive thyroid hormone mimics many of the effects of excess adrenalin. Beta blockers act to block the action of endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline), which mediates the fight-or-flight response.

Propranolol and atenolol are used to symptomatically control the tachycardia (rapid heart rate), tachypnea (rapid respiratory rate), hypertension and hyperexcitability associated with hyperthyroidism. Although traditionally considered to have no discernable effect on serum thyroid hormone concentrations, propranolol may inhibit peripheral conversion of T4 to T3.

These drugs are recommended when rapid control of clinical signs is desirable and may be used either in combination with stable iodine or methimazole. Alone, they are a useful treatment option for cats awaiting radiation therapy or in those cases in which there is a delayed return to normal thyroid function after treatment because neither have any direct effect on the thyroid gland.

Stable Iodine
Iodine solutions, such as saturated potassium iodide solutions (SSKI) or potassium iodide-iodine (Lugol's solution), were used extensively in the 19th century as treatment for human endemic goiter. In the 1920s and 1930s, iodine solution were thought to be useful both as adjunct and sole therapy for  hyperthyroidism. Today, iodine continues to be used, but it has only a minor role in the treatment of hyperthyroidism, both in human patients and cats.

Iodine has several effects on thyroid function. Large doses of stable iodine (I-127) acutely decrease the rate of thyroid hormone synthesis and release although these effects are erratic, inconsistent, short-lived and escape from inhibition can occur (6). In addition stable iodine is contraindicated prior to the administration of radioactive iodine. The drug is associated with a high incidence of adverse reactions (excessive salivation and partial to complete loss of appetite) purportedly because of its brassy taste (2,3). Placing the dose in a gelatin capsule can reduce the prevalence of these side effects.

For these reasons, iodine is never used as sole therapy but can be given together with beta-adrenoceptor blocking agents in a staged regimen for short-term pre-operative treatment (2,7). Using this combination results in reference range serum total T3 concentrations in most cats and therefore clinical improvement, although serum total T4 concentrations only decrease in approximately one third of cats.

Calcium Ipodate and Iopanoic Acid
Oral cholecystographic agents have been widely used in the past as a dye for radiological visualization of the gall bladder. A number of oral cholecystographic agents (e.g. calcium ipodate) decrease T4 production, an effect presumably mediated by release of iodine as the drug is metabolized, and also acutely inhibit peripheral T4 to T3 conversion (8).

The latter effect has been clearly demonstrated in hyperthyroid cats where administration of calcium ipodate was associated with clinical improvement and normalization of serum total T3 concentrations in over 60% of cases (9). Waning of the effect is possible after three months of therapy.

Therefore, calcium ipodate is only likely to serve as an alternative to stable iodine in the short-term preparation for surgery. Calcium ipodate is no longer widely available. Similar agents such as iopanoic acid (10) and diatrizoate meglumine have been used at the doses described. All of these drugs are quite expensive to use on a long-term basis and are of only limited effectiveness.

L-Carnitine
Carnitine is an amino acid that can ameliorate hyperthyroid symptoms in human patients (11), and I have used this as an adjunct therapy in hyperthyroid cats as well. Daily doses up to 250 mg per day appear safe in cats, and we have occasionally used doses as high as 500 mg per day in cats with no untoward effects.

The primary effect of L-carnitine appears to be on peripheral tissues, not on the thyroid gland itself (12). The drug’s effects are related to its ability to inhibit the entry of both T4 and T3 into the cell nucleus. Although L-carnitine acts to reduce symptoms of hyperthyroidism, it does not change the circulating T4 and T3 concentrations, reduce thyroid tumor volume or size, or prevent adenomatous transformation into thyroid carcinoma (11).

Alternative/Complementary Therapies
Some of the alternative medicine approaches that have been claimed effective in treating cats with hyperthyroidism include the following (13,14):
  • Traditional Chinese Medicine, including herbs and acupuncture
  • Bugleweed/Lycopus
  • Lemon balm/Melissa officinalis 
  • Homeopathic drugs
Resthyro is one common herbal therapy marketed as a natural product for cat hyperthyroidism support. This popular product is loaded with a powerful combination of seven different herbal extracts. Together, it is claimed through many testimonials that these herbs are very effective in helping with the symptoms of feline hyperthyroidism. An “all-natural product,“ it is clamed that Resthyro has no known side effects and is “gentle” enough for long-term use. The ingredients and actions are as follows:
  • Eleutherococus Senticosus: helps manage thyroid hormone levels.
  • Bugleweed: helps control TSH; helps ease tension and irritability. 
  • Lemon Balm: aids in managing thyroid activity; supports normal digestion; calms nervous tension and excitability. 
  • Hawthorn: heart and vascular tonic, helps maintain cardiovascular structures and functions. 
  • Skullcap: a natural sedative; moderates nerve transmissions; supports kidney function. 
  • Valerian: helps control inflammation, relaxes spasms and helps manage pain.
  • Glycerin based formula 
Personally, I have never seen a cat treated with one of these natural alternative medications that was cured or has clinical signs resolve, at least on a long-term basis. Most of the active ingredients in the herbs act by supposedly lowering TSH secretion, but circulating TSH is already low in these cats with hyperthyroidism (3,4). It is also important to remember that cats with hyperthyroidism usually have one or more thyroid adenomas and, less commonly, thyroid carcinoma. No one has ever documented  shrinkage of the thyroid tumor or significant lowering of the serum T4 value after these alternative medications.

Herbs and homeopathic drugs are vastly powerful entities. Holistic practitioners may tell you that some of these therapies work well. However, this is based on an improvement in the cat’s clinical signs alone. It is not based on dramatic lowering or normalization of the cat’s serum T4 value or a reduction in thyroid tumor size. To my knowledge, no cases have ever been published in a referred journal that document that these therapies cure or even result in significant improvement in cats with hyperthyroidism.

References
  1. Behrend EN. Medical therapy of feline hyperthyroidism. Compendium on Continuing Education for the Practicing Veterinarian 1999;21:235-237.
  2. Mooney CT, Thoday KL. CVT Update: Medical treatment of hyperthyroidism in cats. In: Bonagura JD, ed. Kirk’s Current Veterinary Therapy XIII. Philadelphia: Saunders, 2000:333–337.
  3. Mooney CT, Peterson ME. Feline hyperthyroidism. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association; 2012:92-110. 
  4. Baral R, Peterson ME. Thyroid gland disorders. In: Little, S.E. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders 2012;571-592. 
  5. Henik RA, Stepien RL, Wenholz LJ, et al. Efficacy of atenolol as a single antihypertensive agent in hyperthyroid cats. Journal of Feline Medicine and Surgery 2008;10:577-582.
  6. Wolff J, Chaikoff IL, Goldberg RC, et al. The temporary nature of the inhibitory action of excess iodine on organic iodine synthesis in the normal thyroid. Endocrinology 1949;45:505-513. 
  7. Foster DJ, Thoday KL. Use of propranolol and potassium iodate in the presurgical management of hyperthyroid cats. Journal of Small Animal Practice 1999;40:307-315.
  8. Braga M, Cooper DS. Clinical review 129: Oral cholecystographic agents and the thyroid. Journal of Clinical Endocrinology and Metabolism 2001;86:1853-1860. 
  9. Murray LA, Peterson ME. Ipodate treatment of hyperthyroidism in cats. Journal of the American Veterinary Medical Association 1997;211:63-67.
  10. Gallagher AE, Panciera DL. Effects and safety of iopanoic acid in cats administered levothyroxine. Journal of Feline Medicine and Surgery 2009;11:69-75.
  11. Benvenga S, Ruggeri RM, Russo A, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. Journal of Clinical Endocrinology and Metabolism 2001;86:3579-3594.
  12. Benvenga S, Amato A, Calvani M, et al. Effects of carnitine on thyroid hormone action. Annals of the New York Academy of Sciences 2004;1033:158-167.
  13. Dobias P. Homeopathic treatment of feline hyperthyroidism. World Congress WSAVA/ FECAVA/CSAVA 2006;124-126.
  14. Chapman SF. Homeopathic and integrative treatment for feline hyperthyroidism—four cases (2006-2010). Homeopathy 2011;100:270-274. 

13 comments:

jennyk said...

When you use L-carnitine by itself or as an adjunct, what form do you use? According to the Office of Dietary Supplements, the terms carnitine, L-carnitine and acetyl-L-carnitine are often used interchangeably to refer to the same basic compound. Supplements for humans often contain a mixture of forms (one uses 3 forms, with 230mg per capsule in total but only 117mg of that is 'plain' L-carnitine). Would you avoid supplements which contained other forms? Would you take other forms into account when assessing dosage?

Dr. Mark E. Peterson said...

I'm well aware that there are different forms of L-carnitine, but a comparison these different compounds have not been evaluated in hyperthyroidism (not cats or humans to my knowledge). At this time, I would recommend just plain L-carnitine, since it is the least expensive form.

I dose this drug based on the response of the cat (lowering of the heart rate, etc) so there isn't an exact dosage for hyperthyroid cats.

This drug is generally used either as an adjunct to other treatments or as a short-term treatment to stabilize the cats in preparation for surgery or radioiodine. However, in some cats with milder disease, L-carnitine by itself may be enough to control signs of the disease, at least for a few weeks to months.

jennyk said...

Thank you for your prompt response, Dr Peterson! We have a hyperthyroid cat who gets facial skin lesions on methimazole or carbimazole. Radioiodine is not an option as she is 19 and has late Stage 2 CKD, so clinics here in the UK will not even consider her. She had a unilateral thyroidectomy in February but her test results show she is still somewhat hyperthyroid. At the moment she is asymptomatic, but at some point she will probably need treatment, so I am trying to learn as much as I can about possible options.

I forgot to thank you in my first post for the invaluable information on your two blogs. They have been immensely helpful to me since our cat's hyperthyroid diagnosis.

jennyk said...

Hello again, Dr Peterson!

The cat I mentioned above is now symptomatic so, with her vet's agreement, we are going to try L-carnitine, possibly alongside a very low dose of methimazole.

I was intending to mix the L-carnitine with her wet food, but the package labelling says to give without other proteins, at least half an hour before a meal. Other sources (for humans) give conflicting informaton, some saying taking with a meal increases bioavailability and others disagreeing.

When you use it as adjunct therapy for your patients, do you advise them to give it with meals or separately, or do you find it doesn't matter as long as it is consistent?

Dr. Mark E. Peterson said...

I haven't done any studies of L-carnitine absorption but most of the cats we've treated had the supplement put directly into the cat food.

Maybe it would have been better absorbed if not given with food, but it did appear to help — most cats improved clinically.

jennyk said...

Thank you!

jennyk said...

I hope you don't mind me commenting with another question. I'm wondering how quickly you usually see an improvement in symptoms when giving l-carnitine. We have been giving it for just over 2 weeks now and there has been no noticeable improvement yet. We will be talking with her vet next week about increasing the dose (currently about 165mg a day), but would you expect to see some response within 2-3 weeks or does it take longer?

Dr. Mark E. Peterson said...

I wouldn't expect a huge improvement in clinical signs on L-carnitine alone, especially at the low dose that you are giving. This agent helps to mitigate hyperthyroid symptoms but I'd be very surprised if all signs resolved. Remember that the thyroid values will not generally change with L-carnitine. I would monitor body weight and heart rate as indicators of the drug's effectiveness.

What is your goal? If it's to use the drug long-term, I'd go up to 250-500 mg per day.

jennyk said...

If l-carnitine alone could control her symptoms, that would be ideal. If not, we can try adding a very small amount of methimazole, hoping that will not be enough to trigger her facial sores. She was asymptomatic with a T4 of 4.98 (case-specific range 1.6 to 2.5) and an FT4 of 3.9 (c-s tange 0.5 to 2.5), so she wouldn't necessarily need enough MMI to get her T4 into 'normal' range to control her symptoms. If l-carnitine can help even a little I'll be pleased.

We started by splitting one 500mg capsule over 3 days (2 batches of blended food) to see how she reacted. She's had a little diarrhoea but not much, and not necessarily due to the l-carnitine, so if her vet agrees we will increase to 250mg a day and see what happens.

Thanks again!

Dr. Mark E. Peterson said...

Adding in a small daily dose of methimazole would probably be a good idea. Some of these cats will develop the facial reaction to the drug, even with tiny doses. Let's hope that doesn't redevelop.

joel said...

My experience has been that using L-carnitine by itself is ineffective. However, when combined with a low dose of methimazole, it seems to be quite effective in terms of relieving obvious symptoms of feline hyperthyroidism. I have been using 100mg of L-carnitine twice daily combined with 2.5mg methimazole transdermal cream once daily. This cat is quite intolerant of methimazole, so a low dose is all that is possible.

Dr. Mark E. Peterson said...

I agree that L-carnitine is not always effective, especially at lower doses. I generally start cats on a daily dose of 250 mg but some cats do much better on 500 mg per day or even more.

But your approach makes sense, especially if your cat tolerates the concurrent methimazole treatment. Not all cats do.

Dr. Mark E. Peterson said...

L-carnitine is not a long-term solution for most cats and 200 mg per day will not do very much, if anything, to help the hyperthyroidism. If methimazole cannot be used, I'd recommend either thyroidectomy or radioiodine.