What's the Expected Time for Signs of Feline Hyperthyroidism to Resolve after Treatment?

My 16-year old cat was recently treated with radioiodine (I-131) for his severe hyperthyroidism. How long after radioiodine treatment will the thyroid values normalize and the symptoms of the hyperactive thyroid begin to resolve so he feels better? 

My cat lost about half of his body weight, much of it in muscle mass. Will his wasted muscles ever return to normal? If so, when can I expect to see improvement?

My Response: 

You have asked two good questions, which, on the surface seem simple enough to answer. The answers to "how long for clinical signs to resolve" however, depend on a number of factors. I'll do my best to explain why it's not possible for me to give you the definitive answers you want.

How long does it take for serum thyroid hormone levels to normalize after I-131?
Depending on the dosing protocol used, about 90% of cats will have serum thyroid hormone concentrations (e.g., T4 and T3) within reference range limits by 30 days after I-131 treatment. Most of the remaining cats will show a nice drop in T4 and T3 levels when rechecked in a month, but it will take longer to for their thyroid hormone concentrations to completely normalize.

In general, the full extent of the radioiodine treatment will be evident by 3 months after treatment, although a few cats continue to show even more (minor) improvement when rechecked at 4 to 6 months.

As the thyroid values normalize, the clinical signs we see also gradually resolve. Some signs, such as nervousness or rapid heart rate, generally resolve fairly quickly, whereas other signs, such as marked weight loss and muscle wasting, obviously take much longer.

How fast do we want the serum thyroid values to fall after radioiodine treatment?
My goal in treating hyperthyroid cats with radioiodine is to gradually normalize the high serum thyroid hormone concentrations— not lower the values too quickly. I'd rather that the thyroid values fall slowly over the first month after treatment, allowing the rest of the body to gradually get used to being euthyroid once again. This is especially true in cats with concurrent kidney disease, when a drastic fall in thyroid values can aggravate the serum kidney values and can even lead to severe renal failure.

To achieve this gradual fall in the high serum thyroid hormone levels, I administer the smallest dose necessary to cure the hyperthyroidism. By giving individualized, lower doses of radioiodine, we can also reduce the incidence of post-treatment hypothyroidism (underactive thyroid condition) in these cats.

How often does the radioiodine fail to cure the hyperthyroidism?
About 5% of cats that I treat will remain slightly hyperthyroid at the 3-month follow-up period. Many treatment facilities will claim a higher rate of cure (98-100%) than I do, which is made possible by administering higher doses of radioiodine to their cats. In addition to decreasing the incidence of persistent hyperthyroidism, the use of higher radioiodine doses will also hasten the rate of decline in the serum thyroid hormone concentrations.

So why not use this high-dose I-131 protocol instead of my lower-dose approach? Simple — the downside of administering higher radioiodine doses is that this method will lead to a higher rate of iatrogenic hypothyroidism as both the thyroid tumor, as well as most normal thyroid tissue, are irradiated and destroyed (1,2). As I've previously discussed (see my post, Estimating the Radioiodine Dose to Administer to Cats with Hyperthyroidism), more that 30% of cats will become hypothyroid using the standard high-dose treatment protocol, but this incidence could in fact be much higher, possibly up to 75%.

Diagnosing iatrogenic hypothyroidism
To monitor for iatrogenic hypothyroidism, we routinely run a serum thyroid panel (i.e., total T4, T3, free T4, and TSH) at 1 and 3 months after treatment (2,3). Most facilities recommend monitoring just the total T4 concentration, but this is not adequate for monitoring since many hypothyroid cats will maintain a low-normal total T4 value, despite being hypothyroid.  Based on our studies, it's becoming increasing clear that feline hypothyroidism can only be diagnosed by finding low to low-normal T4 and T3 values in conjunction with high TSH values.

Restoring lost body weight and muscle mass
Once euthyroidism is reestablished, most cats will gain weight within a few weeks (certainly by 2-3 months). If marked muscle wasting has occurred, it may not be possible to completely regain the lost muscle. Remember that it will help to feed a diet that's higher in protein (40-50% of calories), higher in fat (40-50% of calories), and relatively low in carbs (less than 15% of calories) (4). For more information, check out my post on The Best Diet to Feed Hyperthyroid Cats.

References:

1. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2014.
2. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism. Compend Contin Educ Vet 2013;35:E4. 
3. Peterson ME. Diagnosis and management of iatrogenic hypothyroidism In: Little SE, ed. August's Consultations in Feline Internal Medicine: Elsevier, 2014;in press.
4. Peterson ME. Nutritional management of endocrine disease in cats. Proceedings of the Royal Canin Feline Medicine Symposium 2013;23-28.

Related Blog Posts:

• Peterson ME. How Does Radioiodine Really Work to Treat Hyperthyroidism? Insights into Veterinary Endocrinology blog.  July 12, 2012.
• Peterson MEL Estimating the Radioiodine Dose to Administer to Cats with Hyperthyroidism. Animal Endocrine Clinic blog. April 30, 2013.
• Peterson ME. Success Rates for Radioiodine Treatment in Hyperthyroid Cats. Animal Endocrine Clinic blog. May 24, 2013.
• Peterson ME. The Best Diet to Feed Hyperthyroid Cats. Insights into Veterinary Endocrinology blog. September 13, 2011

Combining Rapid and Long-Acting Insulin Analogs for Dogs with Diabetes

I am the owner of Coco, a 6-year old male Poodle who has been diagnosed with diabetes mellitus. I noticed the symptoms myself, as I too am a Type 1 diabetic (I was diagnosed 42 years ago at the age of 7 years). 

My dog's blood sugar was slightly more than 400 mg/dl when I brought him in for testing. That’s terribly high. I am a man with deep concern about this disease, and I personally keep myself in very good control (my A1-C tests are always in the 6’s). And thus, I am interested in having excellent control of my dogs health too. 

I’ve been directed by my veterinarian to give ”Coco” 2 daily injections of long-acting type insulin (I give him glargine (Lantus) since that’s what I use for my diabetes). So I started him 5 units of Lantus twice a day but still found him to be drinking far too much water and still having high sugar levels. So, I then added in small amounts of insulin lispro (Humalog) to better control his sugar. I’ve not yet taken him back in for spot checking of his blood, but I do notice the Humalog is helping decrease his water drinking and urinating at normal levels. So now, I give him 2 shots at breakfast and 2 at dinner—5 units of Humalog and 10 units of Lantus twice per day. And I watch him closely but find he is doing well. I see no signs of low blood sugar. 

Do you find my plan a good one? Am I overreacting by giving him Humalog in addition to the Lantus? I’m not a doctor, but I think a blood sugar curve should be between 70-150 mg/dl to keep him healthy, just like in human diabetic patients. Is this correct? Is there something better I can do? 

Finally, is there a simpler way to give the injections? I use a small needled Pen for his injections between his shoulders in a pinch of skin. Is there a needle-free ”Jet” type injection system that would be better than the needles? 

Thank you very much for any help advice you can share. 

My Response: 

Although insulin glargine (Lantus) can be used to treat diabetic dogs (1-3), it doesn't always work well as the sole insulin preparation, as you have discovered in your dog. Therefore, I don't usually start with glargine in dogs, but I use either NPH (Humulin) or lente (Vetsulin) insulins, which give us a higher success rate (4,5).

Your approach to combining a long-acting insulin analog (glargine; Lantus) with a rapid-acting analog (lispro; Humalog) is certainly an acceptable one. Insulin lispro has been proven to be effective in dogs (6) and combing Lantus with Humalog  has been recommended as an option by some investigators (1). If you use Lantus and Humalog yourself, this may be a good option for you. The rapid-acting Hunalog insulin will lower the blood sugar rise that occurs after meals, whereas the longer-acting Lantus will act as a background insulin to maintain glucose levels between meals.

You mention that you would like keep your dog's blood sugar well-controlled. That is a good idea, especially if you want to prevent the formation of diabetic cataracts, which are common in dogs with diabetes (7,8). However, to do that, the use of "spot checks" of his blood glucose concentration will not be enough. You are going to have to do periodic blood glucose curves, either done at home or in the hospital (9-11). 

Finally, our current options for insulin injections are either use of an insulin needle and syringe or an insulin pen, such as the Lantus SoloStar pen (12).Use of needle-free, jet injector for insulin delivery has been reported (13,14). However, to my knowledge, such jet injectors are not yet available commercially, and they certainly have not been tested in diabetic dogs.

References:

1. Mori A, Sako T, Lee P, et al. Comparison of time-action profiles of insulin glargine and NPH insulin in normal and diabetic dogs. Vet Res Commun 2008; 32:563-573. 
2. Fracassi F, Boretti FS, Sieber-Ruckstuhl NS, et al. Use of insulin glargine in dogs with diabetes mellitus. Vet Rec 2012;170(2):52.
3. Peterson ME. Treating diabetic dogs with insulin glargine. Blog post. May 3, 2012.
4. Palm CA, Boston RC, Refsal KR, et al. An investigation of the action of neutral protamine Hagedorn human analogue insulin in dogs with naturally occurring diabetes mellitus. J Vet Intern Med 2009;23:50–55. 
5. Monroe WE, Laxton D, Fallin EA, et al. Efficacy and safety of a purified porcine insulin zinc suspension for managing diabetes mellitus in dogs. J Vet Intern Med 2005;19:675-82.
6. Sears KW, Drobatz KJ, Hess RS. Use of lispro insulin for treatment of diabetic ketoacidosis in dogs. J Vet Emerg Crit Care (San Antonio) 2012;22:211-218. 
7. Beam S, Correa MT, Davidson MG. A retrospective-cohort study on the development of cataracts in dogs with diabetes mellitus: 200 cases. Vet Ophthalmol 1999;2:169-172. 
8. Wilkie DA, Gemensky-Metzler AJ, Colitz CM, et al. Canine cataracts, diabetes mellitus and spontaneous lens capsule rupture: a retrospective study of 18 dogs. Vet Ophthalmol 2006;9:328-334. 
9. Wiedmeyer CE, DeClue AE. Glucose monitoring in diabetic dogs and cats: adapting new technology for home and hospital care. Clin Lab Med 2011;31:41-50. 
10. Cook AK. Monitoring methods for dogs and cats with diabetes mellitus. J Diabetes Sci Technol 2012;6:491-495.
11. Davison LJ. Canine diabetes mellitus In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;116-132.
12. Association AD. Insulin administration. Diabetes Care 2001;24:1984-1987. 
13. Engwerda EE, Abbink EJ, Tack CJ, et al. Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology. Diabetes Care 2011;34:1804-1808. 
14. Engwerda EE, Tack CJ, de Galan BE. Needle-free jet injection of rapid-acting insulin improves early postprandial glucose control in patients with diabetes. Diabetes Care 2013;36:3436-3441. 

What's the Human Risk Associated with Handling of Thyroid Medications?

Maybe I am missing something here, but I have a question about the human risk associated with handling thyroid medications. Why do you state that owners should be careful when handling and cutting methimazole tablets (Tapazole of Felimazole) because of the human safety concerns (1,2), when I can find no mention that we should use any precautions when handling or cutting L-thyroxine (L-T4) tablets?  I've heard that we should wear gloves when handling methimazole tablets or applying methimazole transdermally to the cat's ear, but no one has ever mentioned the need for gloves with L-T4 tablets.

So why is handling L-thyroxine any less of a concern than handling methimazole? Do they not both have the same potential to affect human thyroid levels? If handling methimazole can lower a human's thyroid levels, why wouldn't handling an L-thyroxine preparation potentially lead to hyperthyroidism?

My Response: 

Methimazole and L-thyroxine are totally different drugs, with different patterns of absorption and metabolism. Methimazole is a potent antithyroid drug whereas L-thyroxine is a synthetic form of natural thyroid hormone.

Methimazole
As you state, we must be careful when cutting methimazole tablets or applying transdermal methimazole since either form of methimazole could potentially be absorbed via human skin (1,2). Methimazole is a human teratogen (i.e., the drug may cause birth defects) and crosses the placenta concentrating in the fetal thyroid gland. Besides being a safety issue in pregnant women or women who may become pregnant, the drug should not be handled by lactating women because methimazole is transferred in breast milk at a high rate.

The same precautions pertain regardless of what methimazole product is used, i.e., the veterinary brand-name Felimazole preparation or a human brand-name or generic product. The methimazole tablets should not be cut with our bare hands. We want to wash our hands after administering the medication to minimize skin and oral contamination; repeated and chronic exposure could pose a risk.

L-Thyroxine
As compared to methimazole, L-thyroxine is not absorbed well from the skin. Results of two studies found that the hormone is not absorbed into the systemic circulation to have an effect on all tissues of the body (3,4). In support of that, of the few dogs that I have evaluated on transdermal L-T4, none have responded to the transdermal replacement therapy with a rise in serum T4 concentrations (5). I know that some compounded pharmacies will sell transdermal preparations of L-T4 but I do not believe that they actually work. Ask for some actual data and you will get none!

So go ahead and cut all the L-T4 pills that you want. It will not get absorbed unless you ingest the hormone supplement so you should still wash your hands to remove any residual L-T4 residue from your hands.

References:

1. Peterson ME. Methimazole-Handling Precautions for Cat Owners. Blog post, Animal Endocrine Clinic, September 2, 2012.
2. Felimazole-Coated Tablets. Product insert. Available at: www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Felimazole.pdf 
3. Padula C, Pappani A, Santi P. In vitro permeation of levothyroxine across the skin. Int J Pharm 2008 12;349:161-165. 
4. Padula C, Nicoli S, Santi P. Innovative formulations for the delivery of levothyroxine to the skin. Int J Pharm 2009;372:12-16.
5. Peterson ME. Alternative Dosage Forms of L-Thyroxine for Hypothyroid Dogs. Blog post, Insights into Veterinary Endocrinology, March 28, 2012.