World Diabetes Day: November 14 2014

Today, November 14th, is World Diabetes Day

World Diabetes Day is the primary global awareness campaign of the diabetes mellitus world and is held on November 14 of each year (1). It was introduced in 1991 by the International Diabetes Federation and the World Health Organization in response to the alarming rise of human diabetes around the world.

World Diabetes Day is a campaign that features a new theme chosen by the International Diabetes Federation each year to address issues facing the global diabetes community. This year's campaign theme is "Healthy Living and Diabetes"(1).

While the campaigns last the whole year, the day itself marks the birthday of Frederick Banting who, along with Charles Best, first conceived the idea which led to the discovery of insulin in 1922 (2). You can also find out more about Frederick Banting in Wouter de Herder's review Heroes in Endocrinology: Nobel Prizes (3).

Charles H. Best and Frederick G. Banting (on right) with one of the diabetic dogs used in their studies of insulin

In the past few years, diabetes rates among our pets in the U.S. have increased roughly 33% among dogs and 16% among the nation's cat population, per a national analysis of pet health (4). This emphasizes the importance of this disorder in our cats and dogs as well as human patients with diabetes. To successfully manage diabetes in animals, one must understand the disease and monitor and provide daily treatments to the cat or dog with diabetes. Treatment involves a combination of weight loss (if obese), diet, and insulin injections generally twice daily.

References 

1. World Diabetes Day – Official website.
2. Frederick Grant Banting (1891-1941), codiscoverer of insulin. Journal of the American Medical Association 1966;198:660-661. 
3. de Herder WW. Heroes in endocrinology: Nobel Prizes. Endocr Connect. 2014;3:R94-R104. doi: 10.1530/EC-14-0070. 
4. Washburn L. Human health risks on the rise in animals. The Record. April 20, 2011. 

Dr. Peterson Interviewed in the Journal of Feline Medicine and Surgery

Dr. Peterson was interviewed for the September issue of the Journal of Feline Medicine and Surgery.

The interview provides some interesting insights into Dr. Peterson's career, his own cats, and his aspirations and goals as he continues his research.

Click here to download and read the full interview.

Dr. Peterson Interviewed for Dog Fancy Article About Insulin Pen for Dogs

Dr. Peterson was interviewed for the September 2014 issue of Dog Fancy (pictured above). Merck Animal Health has just received approval from the FDA to sell their VetPen product, the first insulin injection pen available for diabetic dogs and cats, and Dr. Peterson weighed in on the benefits of such an easy-to-use device.

Insulin Injection Pen (VetPen): More Questions (and Answers) about this New Diabetic Product

Since the FDA approved the use of a new insulin injection pen (VetPen) made by Merck Animal Health last week (1,2), I've received a number of questions from both veterinarians and owners of diabetic pets. Listed below are some of the most common questions with my responses.

Do we buy a single VetPen and use it forever? Or does the VetPen have to be replaced after a month or two?

The VetPen has been tested for at least 3,000 actuations (i.e., how many times the insulin release button is pressed and released). Therefore, a single VetPen is likely to last a lifetime for the majority of dogs and cats treated with diabetes.

How are the pens and cartridges sold? 
The reusable VetPen is supplied in a Starter Kit which contains everything you need to get started (see below). This included everything except the Vetsulin cartridges, which are supplied separately in cartons of ten, 2.7-mL cartridges.

The VetPen itself is available in 2 sizes. For greater accuracy at low doses, the first option (blue cap) has a maximum total dose of 8 units, allowing for dosing increments of 0.5 unit per injection. If higher insulin doses are being administered, the second VetPen option (tan cap) has a maximum total dose of 16 IU per injection, with dosing increments of 1 unit.

What is in each VetPen Starter Kit?
Each Starter Kit contains either an 8-unit or 16-unit VetPen with an instruction leaflet.

The kit also contains a box of 28-g, ultra-thin needles that feature a silicone coating to help minimize injection discomfort, as well as a needle remover that helps to remove used needles, while minimizing the risk of accidental needle stick injury. There is also a travel pouch to hold all of the components.

The kit also contains two adaptors to assist those with dexterity issues. The dose selector adaptor may be used to provide a better grip when selecting a dose. The release button extension may be used to provide a better grip when giving injections.

Are the VetPens an accurate way for insulin dosing?
The VetPen is ideal for cats and small dogs on low doses of insulin, in which dosing accuracy can be a concern (3,4). A recent study comparing the precision and accuracy of the VetPen to U40 syringes demonstrated that even when doses were drawn up by trained laboratory technicians, syringes were found to deliver at least 20% to 25% more insulin than needed for a 1-unit dose (5).

In contrast, VetPen enables doses to be delivered with accuracy and precision down to 0.5 units. In large dogs, dosing accuracy is generally not a problem.

Do the pens and cartridge need to be refrigerated? Other handling precautions?
The VetPen cartridges should be refrigerated (not frozen) and protected from light before opening.

VetPen does not need to be refrigerated after a cartridge has been started (4), although it probably is best to do so. The loaded VetPen can be stored on its side in the refrigerator.

VetPen should always be stored or carried with the needle removed and the cap on. To clean the device, wipe with a damp cloth. Do not immerse in water.

Are the VetPens expensive? How would the costs of the VetPen compare to those associated with the standard insulin vial/syringe method?

The cost of treatment will depend upon the size of the diabetic pet. For smaller dogs and cats, the price of the VetPen with the Vetsulin cartridges and needles will be similar to the cost of the standard 10-mL Vetsulin vial and U-40 insulin syringes.   For larger dogs, the standard way of administering Vetsulin (via an insulin syringe) would generally be a more economical way to provide insulin treatment.

Bottom Line:

These insulin pen devices are an alternative to the traditional insulin vial-and-syringe method and offer many advantages. In human diabetic patients, insulin pens have also been found to be less painful than the vial-and-syringe method and are often associated with greater patient preference and social acceptability (6-11).  Similar preliminary findings have been documented in dogs and cats (12,13). As a result, this method of insulin delivery may ultimately help to improve glycemic control and should be considered as an alternative insulin delivery method.

Insulin pens are designed to deliver a fixed insulin dose while insulin syringes rely on the ability of the user to accurately draw up the required insulin dose. One recent study reported that for low doses (below 8 units), the VetPens were more precise and accurate than the insulin syringes (5). In particular, insulin syringes tend to over-deliver, compared to the insulin pen, for very low doses (1 unit). For higher doses (16 units), both devices were comparable (5).

Similar findings have been reported in human pediatric patients, in which very low doses of insulin must be administered. One older study looked at the reliability of using U100 syringes for accurately administering low doses of insulin in the hospital by pediatric nurses. In that study, attempts to administer doses of 0.5 U or 1.0 U of U-100 insulin resulted in overdosage of 95% and 66%, respectively (14). Based on this study, it's no wonder that small diabetic dogs or cats are often a challenge to regulate when small insulin doses are needed.

References: 

1. FDA website. FDA Approves First Insulin Product for Use with Automatic Injection Pen in Cats and Dogs.
2. Press release. Merck Animal Health Receives FDA Approval of VetPen  
3. Merck Caninsulin website. Caninsulin® VetPen® helps make pet diabetes management easier 
4. Pet Diabetes website. What you need to know about the Caninsulin VetPen. 
5. Burgaud S, Riant S, Piau N. Comparative laboratory evaluation of dose delivery using a veterinary insulin pen. Proceedings World Congress ASAVA/FECAVA/BSAVA 2012;567.
6. Molife C, Lee LJ, Shi L, et al. Assessment of patient-reported outcomes of insulin pen devices versus conventional vial and syringe. Diabetes Technol Ther 2009;11:529-538. 
7. Pearson TL. Practical aspects of insulin pen devices. J Diabetes Sci Technol 2010;4:522-531. 
8. Wright BM, Bellone JM, McCoy EK. A review of insulin pen devices and use in the elderly diabetic population. Clin Med Insights Endocrinol Diabetes 2010;3:53-63. 
9. Cuddihy RM, Borgman SK. Considerations for diabetes: treatment with insulin pen devices. Am J Ther 2013;20:694-702. 
10. Davis EM, Foral PA, Dull RB, et al. Review of insulin therapy and pen use in hospitalized patients. Hosp Pharm 2013;48:396-405. 
11. McCoy EK, Wright BM. A review of insulin pen devices. Postgrad Med 2010;122:81-88. 
12. Burgaud S, Guillot R, Harnois-Milon G. Clinical evaluation of a veterinary insulin pen in diabetic cats. Proceedings World Congress ASAVA/FECAVA/BSAVA 2012;499.
13. Burgaud S, Guillot R, Harnois-Milon G. Clinical evaluation of a veterinary insulin pen in diabetic dogs. Proceedings World Congress ASAVA/FECAVA/BSAVA 2012;568.
14. Casella SJ, Mongilio MK, Plotnick LP, et al. Accuracy and precision of low-dose insulin administration. Pediatrics 1993;91:1155-1157. 

FDA Approves First Insulin Automatic Injection Pen for Diabetic Dogs and Cats

VetPen, for use with Vetsulin (in USA) and Caninsulin (outside USA)

The U.S. Food and Drug Administration (FDA) has approved the first insulin injection pen (VetPen, Merck Animal Health) for diabetic cats and dogs, the agency announced today, March 19, 2014 (1).

2 Sizes of VetPens

The VetPen may now be used to administer Vetsulin insulin cartridges, also made by Merck Animal Health. The refillable VetPen automatically measures the prescribed insulin dose and provides the owners of diabetic dogs and cats with an additional option for insulin delivery.

There are two sizes of refillable VetPens. One (tan cap) dispenses insulin doses from 1-16 units per dose in full unit increments. The other (blue cap) dispenses 0.5-8 unit doses in full or half unit increments. Both pens use 2.7 ml insulin cartridges which hold a total of 108 units (IU) of U-40 Vetsulin (or Caninsulin).

Vetsulin is an FDA-approved insulin for use in dogs and cats (2). This insulin is identical to Caninsulin, the brand name of the insulin sold in Europe (3).

Merck said the VetPen is easier to dose and administer and is more accurate than traditional delivery systems, such as syringes and vials (4). “For years, insulin pens have made managing diabetes more convenient for human diabetics,” the company said. “Merck Animal Health has now brought the same technology to veterinary medicine.”

An informational website (2) provides tools for both veterinarians and pet owners to make managing pet diabetes easier. More online information about the VetPen can also be found on the Caninsulin website (5); the Pet Diabetes website has an informational brochure that can be downloaded (6).

Administering insulin to a cat with the VetPen

For questions on how to obtain Vetsulin or the VetPen, please contact Merck Animal Health Customer Service at 800-521-5767.

References: 

1. FDA website. FDA Approves First Insulin Product for Use with Automatic Injection Pen in Cats and Dogs.
2. Merck Vetsulin website. www.vetsulin.com
3. Merck Caninsulin website. www.caninsulin.com
4. Press release. Merck Animal Health Receives FDA Approval of VetPen  
5. Merck Caninsulin website. Caninsulin® VetPen® helps make pet diabetes management easier 
6. Pet Diabetes website. What you need to know about the Caninsulin VetPen. 

U-40 Insulin Syringes Recalled

Med-Vet International Issues Recall of 1/2-cc U-40 Insulin Syringes Due to Mismarked Syringe Barrels (1).  

On February 14, 2014 , Med-Vet International initiated a voluntary nationwide recall of 140 boxes of 1/2-cc U-40 insulin syringes (1). The syringes are incorrectly labeled as 40 units per 1/2-cc syringe, whereas they should be marked with only 20 units per 1/2 cc. Obviously, this could potentially result in a lower-than-prescribed dose of insulin being administered, and lead to relapse of signs of diabetes, as well as development of ketoacidosis.

Consumers who have these insulin syringes should quarantine all products subject to recall. In addition, if you, as the veterinarian, may have sold these syringes, please inform the clients at once about this product recall so they can change to another insulin syringe.

The following 1/2-cc U-40 insulin syringes have been recalled:

• 140 boxes of 1/2-cc insulin syringe U-40 with 29g x 1/2” needle. Lot Number: 20120610
• The product can be identified by Item number: MV1/2CCINS-40 or 1/2CCINS-40 by Oasis.

Med-Vet International is arranging for return of all recalled 1/2-cc U-40 insulin syringes. Consumers with questions may contact the company via telephone at (800) 544-7521 or via e-mail at customerservice@shopmedvet.com.

References:

1. FDA website (www.fda.gov). Med-Vet International Issues Nationwide Recall of Veterinary 1/2cc U-40 Insulin Syringes Due to Mismarked Syringe Barrels

How to Manage Hyperthyroid Cats that Become Resistant to Methimazole

I have a 19-year old female DSH cat who was diagnosed with hyperthyroidism 5 years ago. I chose not to do the radioactive treatment because that treatment required her being away for several days. I didn't want to do surgery to remove the thyroid gland because she was very weak at the time of the initial diagnosis. 

Therefore, I have been treating her with methimazole over all these years. Initially, her daily dosage was 5 mg (divided twice daily). Over the years, it has become necessary to increase this first up to 10 mg/day, then to 15 mg (daily doses divided into 2-3 doses per day). This 15-mg dosage was effective at controlling her hyperthyroidism for a short time, but now her serum thyroid value is high again. Because of the persistent hyperthyroidism, many of her clinical signs have returned. She has lost weight, despite the fact that her appetite has increased.  I have just increased the methimazole dose up to 10 mg twice a day (20 mg/day) but this still does not appear to be helping.  Now I am worried about the effects of the medicine on her kidneys.

Do cats just become accustomed to the methimazole and always need an increasing amount?  How high can we go with the dosage of the methimazole?  

Thank you. 

My Response: 

This scenario that you are describing isn't that uncommon in cats treated with methimazole on a long-term basis. All hyperthyroid cats, as you may know, have one or more thyroid adenomas (benign thyroid tumors), which will continue to grow larger with time (1-7).

Thyroid scans of hyperthyroid cats, illustrating that all of these cats will have a thyroid tumor that will continue to grow larger over time. In some cats, these tumors will become very large or huge, which can lead to "resistance" to methimazole.

How methimazole works to control hyperthyroidism
Methimazole and other antithyroid drugs work by being taken up by the thyroid tumor where the drugs inhibit thyroid hormone production and secretion (1-4,7). Therefore, most hyperthyroid cats will require higher dosages of methimazole to inhibit thyroid hormone secretion as their goiters become larger and the thyroid tumor volume increases.

The methimazole does not change the tumor pathology and cannot stop the tumor from growing (5,6).  In some of these cats, the thyroid adenoma also may transform into a thyroid carcinoma as the disease progresses (6,8). Again, methimazole does nothing to the tumor pathology and cannot stop this from happening.

Why methimazole may become ineffective with time
In answer to one of your questions, hyperthyroid cats do not just become accustomed to the methimazole and need an increasing amount. There is a good explanation for the dose increases and why the drug will fail to work in some cats, especially in those treated chronically.

After use of medical treatment for a number of months to years, many hyperthyroid cats will have fairly large palpable goiters (thyroid enlargement). Because of the large goiter size, these cats can be difficult to regulate and make euthyroid, even when very high daily doses of oral or transdermal methimazole are administered (7). The reason for this is simple— with time, we just can't give a dose of methimazole that is high enough to block thyroid secretion from all of the thyroid tumor cells. In other words, the cat just has too much thyroid tumor tissue and thyroid oversecretion can no longer be adequately suppressed by the methimazole.

How high can we go with the methimazole dose in this cat?
So, what do you do?  The dose of methimazole needed to control hyperthyroid cats is based on what it takes to lower the serum T4 concentration into the reference range, so there is not an upper limit to what methimazole dosage can be used. I've gone as high as 30 mg per day in some cats, although the incidence of side effects tends to be higher as you raise the dose (7). So in your cat, I would continue to raise the dose up to 25 mg and then 30 mg/day, as needed. If this fails to completely control the hyperthyroidism, addition of other drugs such as beta-adrenergic blockers (e.g., atenolol) and/or L-carnitine could also be considered (9, 10).

If your cat was younger, I would strongly recommend definitive therapy (i.e., surgery or radioiodine) in order to remove or destroy the thyroid tumor(s). However, at 19-years of age, that may no longer be feasible, depending on your cat's overall clinical condition.

My Bottom Line:
The underlying cause of hyperthyroidism in all affected cats is a hyperfunctional thyroid tumor. Unless surgically removed or irradiated with radioiodine, these thyroid tumors will tend to grow larger with time, as the disease progressed. If methimazole is used as initial treatment, the drug may eventually become ineffective, even when higher dosages of the drug are used.

Overall, I believe that we should be curing the thyroid tumor in the hyperthyroid cat with definitive treatments, not just controlling the hyperthyroid state for the rest of the cat's life with methimazole. In most hyperthyroid cats, especially those that are young to middle-aged, the use of surgical thyroidectomy or radioiodine are, therefore, the treatments of choice. I do not generally recommend using methimazole on a long-term basis, unless we don't believe that the cat will live for another couple of years. Both surgery and radioiodine can be more difficult in cats with large goiters and severe hyperthyroidism, so early definitive therapy is always best.

References:

1. Peterson ME. Hyperthyroid diseases In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. Fourth ed. Philadelphia: WB Saunders Co, 1995;1466-1487.
2. Baral R, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012;571-592.
3. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT, Peterson ME, eds. Manual of Canine and Feline Endocrinology Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;199-203.
4. Peterson ME. Hyperthyroidism in cats In: Rand JS, Behrend E, Gunn-Moore D, et al., eds. Clinical Endocrinology of Companion Animals. Ames, Iowa Wiley-Blackwell, 2013;295-310.
5. Gerber H, Peter H, Ferguson DC, et al. Etiopathology of feline toxic nodular goiter. Vet Clin North Am Small Anim Pract 1994;24:541-565.  
6. Peterson M. Hyperthyroidism in cats: What's causing this epidemic of thyroid disease and can we prevent it? J Feline Med Surg 2012;14:804-818. 
7. Peterson ME. Treatment of severe, unresponsive, or recurrent hyperthyroidism in cats. Proceedings of the 2011 ACVIM Forum; 2011 June 15–19; Denver, CO. American College of Veterinary Internal Medicine, pp 104–106.
8. Peterson ME, Broome MR. Hyperthyroid cats on long-term medical treatment show a progressive increase in the prevalence of large thyroid tumors, intrathoracic thyroid masses, and suspected thyroid carcinoma. J Vet Intern Med 2012;26:1523.
9. Peterson ME. Alternative medical treatments for hyperthyroid cats. Conference Proceedings North American Veterinary Conference (NAVC) Conference 2012: Small Animal & Exotics Proceedings 2012;852-858.
10. Peterson ME. Alternative Medical Treatments for Hyperthyroid Cats. Animal Endocrine Clinic blog, September 13, 2012.

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

A Tribute to a Special Patient, "The Colonel"

The Colonel after his radioiodine treatment

The Colonel was one of our favorite hyperthyroid patients at the Animal Endocrine Clinic. We first met him over two years ago, when he was referred to us for severe and uncontrolled hyperthyroidism.
His thyroid tumor was huge and resistant to treatment, necessitating a large dose of radioiodine to cure him. 

The Colonel ended up staying with us for a long time after treatment since the owner has small children in the house, but none of us minded; we all loved having this wonderful cat at our practice! He had a super personality and enjoyed each day with a zest for life.  

He later when on to develop hypothyroidism, which we successfully managed with daily thyroid hormone replacement therapy. Unfortunately, he later went on to develop cancer of he urinary bladder, which lead to urinary obstruction and worsening of his kidney failure.

The Colonel's owner wrote this tribute in memory of him. This cat poem puts into words, so beautifully, what we all feel when we lose one of our best friends.  I wanted to share it with all of you so you can get a sense of how special this cat really was to all of us. 

However, I must warn you — you will likely cry as you read this touching epitaph, as we do everytime we reread it. 

We all loved this cat.  He truly will be missed.

Dr. Mark Peterson and Staff at the Animal Endocrine Clinic

Watching the gerbils during his long boarding period at the hospital

GONE 

by Beverly Cole 

I don't have to close the bedroom doors, no longer worried your nails will wreak havoc on the rugs.

I am cleaning up the last kernel of your Lord forsaken litter, a battle that I waged for years, that I have finally won. A pyrrhic victory.

I am picking off fur from my sweater without my usual grumbling. The fur will appear less and less now, the couch clean, no tufts of orange and white randomly floating through the air.

There's no more food to order for you. No more subcutaneous fluids to stave off kidney failure. No more thyroid medication. No heartburn relief pills.

We fought for you as hard as you fought for yourself. No, you fought even harder. You loved your life with a passion experienced by few, as simple and serene as it was.

I am taking your fleece blanket out of the dryer. Your urine stains now replaced by my salty tears.

You were just a cat. A 4-year-old flunky mouser who wound up at a shelter. At your best—16 pounds of pomp and circumstance and brilliance and at your worst — a shrunken shell of what was, desperately clinging to life despite the pain.

I haven't told the kids yet, just saying you're at the doctor when they asked me where you are. The little one calls to you in her small voice, then says "maybe he's in his room and you forgot," she says. No, dearest, I haven't forgotten where he is. When I close my eyes, I see you on the cold steel table, now lifeless, yet still filled with your impenetrable dignity although your eyes are now sunken and still.

I am packing up your brush, the same brush we bought when we started together, 13 years ago. When I groomed you the first time, you meowed and yawned at the same time, rolling onto your back, bored and happy, then gently nipped my hand to remind me who was in charge, a devilish glint in your eyes. When I brushed you this last time, you barely moved your head, so I stopped, not wanting to cause you more pain.

Your fur wasn't always urine soaked. Your smell wasn't always unbearable. That was only recently, after the cancer in your bladder had obstructed your ability to urinate, after the kidney failure had taken over. Before that you were impeccable. Meticulously grooming until your fur shone.

I still hear your cry—strong and plaintive, demanding, not the crusty, faltering mew you have been able to muster recently.

It is hard to be in this house without you. My stomach feels void when I realize that the small crackle I hear is not your footsteps coming upstairs to say goodnight to the kids. I stop myself when I enter the house, almost hearing my voice greet you hello, as I have for the last 13 years. You're not here to answer or come over. You'll never be here again.

I see a ghost of you on the couch waiting for me to sit down at night. I am trying to decide what's more devastating—reliving your death every moment I re-realize you're not here, or knowing that I will get used to your absence.

You were just a cat. You were mine. And I miss you so. My dear, dear friend.

You were my best friend, many times my sole ally, and you trusted me with your life. I hope it was a good one.

The Colonel (1997-2013)

Can Methimazole Cause Anemia in Hyperthyroid Cats?

I am very concerned about my 14-year old male DSH cat. He was diagnosed in the spring with hyperthyroidism and has been treated with oral methimazole (Tapazole). 

 After the first 6 months of treatment, I brought him back to my vet because I was concerned about how skinny he was (very little weight gain on the medication). The vet tested him and increased the Tapazole dosage. He said not to be concerned unless he continued to lose weight.

Now, 2 months later, my cat's weight has held steady on the increased dose of methimazole, but he still remained so skinny that I brought him back for another recheck— even though he wasn't losing weight. It turned out he has developed anemia, so severe that he needed a blood transfusion. He had a bone marrow biopsy, which was consistent with a regenerative anemia. Now my vet wants to just wait and redo his CBC to see how he is in another week.

Because we aren't sure if the methimazole caused the anemia, he isn't putting him back on it right now. He recommended trying Hill's y/d. I tried it (just one can), but my cat isn't keen on it (won't eat it), and he is skinnier than ever now so I don't have the luxury of giving it a chance — I don't want to risk him starving to death!

Now that he's been off the methimazole for about a month. I am really worried about him because he's lost even more weight.

My questions include the following:

1. Can a cat with anemia or recovering from anemia still be a candidate for radioiodine treatment?
2. Can a severely underweight cat be treated for radioiodine treatment? He's only 5 pounds now!
3. If my cat has been off of the methimazole for a month, how much time do we have to get him treated again for his hyperthyroidism? Do we need to restart the methimazole before we do the radioiodine treatment? I'm worried he'll die before I can get it properly addressed. 
4. If I do go for the radioiodine treatment, will he have to wait for a period of time to be treated, since he's eaten a bit of y/d?

Thank you so much!

My Response:

Sorry to hear that your cat isn't doing well. Although rare, antithyroid drugs, including methimazole, can produce hematologic abnormalities, including hemolytic anemia in cats (1-5).  If the drug is responsible for the anemia in your cat, it should never be restarted because that would be life-threatening.

Even if we forget about the anemia for a moment, it is certainly clear that methimazole has not been an effective treatment in your cat. Feeding a low-iodine diet (y/d) might help if he would eat it (many cats won't) but that too is less likely to be successful in cats with severe, chronic, or advanced hyperthyroidism.

Treatment with radioiodine would probably the best treatment, but we would need to be certain that the anemia is resolving before moving forward with this treatment. Anemia is a sign, not a diagnosis in itself. If the methimazole isn't causing it, we need to figure out what is responsible, since that is a sign of serious disease. The good news is that if it is regenerative, that suggests that the bone marrow will be able to respond once the insulting factor (e.g., methimazole) has been removed. Nonregenerative, aplastic anemia is a rare but very serious complication of methimazole treatment in man (5,6), which has only been reported in 1 cat (7); let's hope that this is not the case in your cat.

If the anemia resolves and doesn't recur now that your cat is off the methimazole, I would strongly consider the radioiodine treatment. To do that treatment, we do NOT need to pretreat a cat with methimazole; in fact, we like to have owners stop the drug 1-2 weeks prior to I-131 treatment. Feeding a small amount of y/d will not interfere with the treatment. And finally, severely underweight cats with hyperthyroidism certainly can be treated with radioiodine. Since it's likely that your cat's thyroid tumor may be larger than the average hyperthyroid cat, a larger dose of radioiodine might be needed.

References:

1. Peterson ME, Hurvitz AI, Leib MS, et al. Propylthiouracil-associated hemolytic anemia, thrombocytopenia, and antinuclear antibodies in cats with hyperthyroidism. J Am Vet Med Assoc 1984;184:806-808. 
2. Peterson ME, Kintzer PP, Hurvitz AI. Methimazole treatment of 262 cats with hyperthyroidism. J Vet Intern Med 1988;2:150-157. 
3. Baral R, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012;571-592.
4. Peterson ME. Hyperthyroid diseases In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. Fourth ed. Philadelphia: WB Saunders Co, 1995;1466-1487.
5. Yamamoto A, Katayama Y, Tomiyama K, et al. Methimazole-induced aplastic anemia caused by hypocellular bone marrow with plasmacytosis. Thyroid 2004;14:231-235. 
6. Edell SL, Bartuska DG. Aplastic anemia secondary to methimazole-case report and review of hematologic side effects. J Am Med Womens Assoc 1975;30:412-413. 
7. Weiss DJ. Aplastic anemia in cats - clinicopathological features and associated disease conditions 1996-2004. J Feline Med Surg 2006;8:203-206. 
8. 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 (in press).

Using a Low-Iodine Diet (y/d) in Hyperthyroid Cats Allowed Outdoors

Is feeding the low-iodine diet (Hill's y/d) an appropriate or reasonable choice for a hyperthyroid cat that is allowed outside and hunts? 

Will the diet work to control the hyperthyroid state if the cat eats small prey?

My Response: 

No, Hill's y/d would not work to lower the high serum T4 and T3 in a cat in this situation.

All species (cattle, pigs, chickens, birds, mice and other rodents) all contain iodine in their muscle tissue (1,2). Iodine may be ingested in the diet as a supplement, but it's also present in soil, which ends up in the plants ruminants and other animals may eat (3,4). Remember that iodine is an essential nutrient and is needed by all animals (including humans!).

This cat, by eating birds and rodents (not eating an iodine deficient diet, of course), would ingest too much iodine for the y/d to be effective. To lower T4 secretion, the diet has to be very, very low in iodine.

References:

1. Hemken RW. Factors that influence the iodine content of milk and meat: a review. Journal of Animal Science 1979;48:981-985.  
2. Downer JV, Hemken RW, Fox JD, et al. Effect of dietary iodine on tissue iodine content in the bovine. Journal of Animal Science 1981;52:413-417. 
3. Whitehead DC. Studies on iodine in British soils. Journal of Soil Science 1973;24:260-270.  
4. Fuge R, Johnson CC. The geochemistry of iodine — a review. Environmental Geochemistry and Health 1986;8:31-54.

Difficult Swallowing in Cats with Hyperthyroidism

We have a 13-year old male cat named Balki with hyperthyroidism and moderate renal disease. He has a history of diabetes, but that has been in remission for the latter for several months.

Balki's main problem at the moment is trouble eating. My veterinarian just puts it down to the renal disease. However, it seems he wants to eat, but has difficulty swallowing. It has progressively gotten worse, to the point where he is now barely eating.

He also has had several episodes of reverse sneezing. When trying to eat, he extends his neck and gulps, then turns away from the food being offered. He also sometimes drools, and often spits out the food. He has most difficulty with dry food.

Can you give any advice on what might be causing this, and what tests he might need to find out, and how to help him to be able to eat?

My Response:

The typical hyperthyroid cat eats well (usually an increased appetite). These cats almost never develop anorexia, and difficulty swallowing (dysphagia) never occurs as a direct result of hyperthyroidism (1-4).

Most cats with moderate to severe renal disease will develop a decreased appetite as a result of their uremia, but they don't show signs of dysphagia (5). Most likely, your cat has disease either in the caudal pharygeal (throat) region or esophagus that is causing some obstruction to the food eaten (6-10). With the history of reverse sneezing, I'd say the problem is most likely in the caudal pharynx.

I'd recommend starting with a good oral examination (under sedation) to look for a lesion or mass in the pharygeal area. If nothing is seen, then endoscopy may be needed. Radiography or other imaging (e.g., CT scan) may also be required to help define the extent of your cat's disease (9-11).

Could thyroid tumors ever grow large enough to compress the esophagus and produce signs of dysphagia? That would be extremely unlikely, since even cats with large thyroid carcinomas almost always continue to eat well and don't have any problems swallowing.  However, I have had two cats in my career that had thyroid carcinoma which invaded the esophagus, leading to signs of esophagitis and esophageal obstruction. In any case, the chance of that being the problem in your cat would be about 1 in a million; again, that would best be diagnosed with endoscopy and CT imaging.

References:

1. Baral R, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012;571-592.
2. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT, Peterson ME, eds. Manual of Canine and Feline Endocrinology Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;199-203.
3. Peterson ME. Hyperthyroidism in cats In: Rand JS, Behrend E, Gunn-Moore D, et al., eds. Clinical Endocrinology of Companion Animals. Ames, Iowa Wiley-Blackwell, 2013;295-310.
4. Peterson ME. Top 10 signs of hyperthyroidism in cats. Animal Endocrine Clinic blog post. March 21, 2011.
5. DiBartola SP, Rutgers HC, Zack PM, et al. Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984). J Am Vet Med Assoc 1987;190:1196-1202. 
6. Watrous BJ. Clinical presentation and diagnosis of dysphagia. Vet Clin North Am Small Anim Pract 1983;13:437-459.  
7. Vos JH, van der Gaag I. Canine and feline oral-pharyngeal tumours. Zentralbl Veterinarmed A 1987;34:420-427.
8. Mattson A. Pharyngeal disorders. Vet Clin North Am Small Anim Pract 1994;24:825-854. 
9. Gengler W. Gagging. In: Ettinger SJ, Feldman EC, eds.The Textbook of Veterinary Internal Medicine. St Louis, Mo, USA: Saunders Elsevier; 2010:189–191.  
10. Jergens AE. Diseases of the esophagus. In: Ettinger SJ, Feldman EC, eds. The Textbook of Veterinary Internal Medicine. St Louis, Mo, USA: Saunders Elsevier; 2010:1487–1499. 
11.  Pollard RE. Imaging evaluation of dogs and cats with dysphagia. ISRN Vet Sci 2012;2012:238505. 

Can a Special Diet be Formulated to Treat Hyperthyroidism in Cats?

I have a 13-year old female DSH cat that has recently been diagnosed with hyperthyroidism. Unfortunately found out that she is severely allergic to methimazole (severe vomiting and anorexia), so I cannot treat her with medication (even though I've read this medicine can cause other health issues).

My next option was to feed her the Hill's y/d diet, but she absolutely refuses to eat that food. I then began an online search to see if I could make my own low-sodium cat food that would mimic the Hill's diet. My online research brought me to your blogs about hyperthyroidism and diet.

After reading many of your blogs, I found where you say that a high protein/low carb diet is beneficial to the hyperthyroid cat (http://endocrinevet.blogspot.com/2011/09/best-diet-to-feed-hyperthyroid-cats.html), but it doesn't address sodium content.

Do you believe a diet referenced in your blog would be a life-long treatment for a cat with hyperthyroidism? Or should I pay a veterinary nutritionist to compose a diet for my cat with an iodine level at or below 0.32 ppm (www.2ndchance.info/lowIodine.htm), which Hill's y/d diet allows? I recently called the nutritionists at UC Davis about such a diet, but was told that they have never made a diet for hyperthyroidism in cats.

I've also read that too low of sodium in a cat's diet will cause the thyroid to once again over-produce hormones to compensate. To say the least, I'm confused. I'm at a crossroad wondering if I should try a diet or go ahead and have the I-131 treatment done for my cat. 

Thank you so much for your opinion and response.

My Response:

High protein, low-carbohydrate diet for hyperthyroid cats
First of all, my recommendation to feed hyperthyroid cats a diet higher in protein and lower in carbohydrates is based on what we know about the secondary complications of hyperthyroidism.

Hyperthyroidism is a hypermetabolic, catabolic state. Therefore, in hyperthyroidism, the body may be forced to use it's own muscle tissue to supply increased energy it needs. Because of these increased protein needs of the hyperthyroid cats, loss of lean body mass and muscle wasting is common. By adding more protein to the diet, this will help preserve or restore lost muscle mass, but feeding a high protein diet, by itself, will do nothing to lower thyroid hormone secretion or correct hyperthyroidism.

My recommendation for feeding hyperthyroid cats a low-carb diet is based on the fact that hyperthyroid cats commonly develop a form of prediabetes. Feeding a lower carb diet will help prevent the onset of overt diabetes in these cats. Even if this was not true, cats have absolutely no dietary requirement for carbohydrate and cats in the wild would normally ingest only 1-2% of their daily calories in the form of carbs (1).  But again, limiting the amount of carbohydrates in a hyperthyroid cat's diet would do nothing to treat the hyperthyroid condition.

Overall, a diet higher in protein and lower in carbs, is actually a more "natural" diet for cats (1,2). But this natural diet fed to hyperthyroid cats must be combined with another treatment directed specially at the thyroid gland (e.g., antithyroid drugs, surgical thyroidectomy, or radioiodine).

Salt and the thyroid
In cats, both sodium and chloride (i.e., salt) are required in relatively small amounts in the diet. Nutritional requirements for dietary salt in cats are available from regulation associations or scientific councils, mostly based on studies establishing sodium requirements in cats (3,4). Salt restriction has been historically advocated for cats in some disease states (mainly cardiovascular and kidney diseases) (5,6). No study has confirmed the benefit of such dietary intervention in cats.

However, feeding a cat a low sodium (or salt) diet will not do anything to lower thyroid hormone secretion from the thyroid gland. In other words, we have no evidence at all that a low salt diet can be used as a treatment for hyperthyroidism. Now, because iodine is commonly added to salt as a treatment for iodine deficiency (7,8), using a lower salt diet could lower iodine levels very slightly.

Iodine and the thyroid
The y/d diet made by Hill's (named, Prescription Diet y/d Feline –Thyroid Health) is an iodine deficient diet (9-11). Unlike sodium or chloride, iodine is one of the essential building blocks needed for thyroid hormone synthesis.

The main thyroid hormones secreted by the feline thyroid include thyroxine (T4) and triiodothyronine (T3).  If we look at the thyroxine molecule, it contains four atoms of iodine per molecule, and that's how the common abbreviation "T4" was derived. Triiodothyronine contains one less iodine atom, thus the common abbreviation "T3." Therefore, it's the number of iodine atoms in each of these thyroid hormones that determines the "number" in T4 or T3.

The basis for using a severely restricted iodine diet to treat hyperthyroid cats is that iodine is an essential component of both T4 and T3. With severe dietary iodine deficiency, the thyroid cannot produce adequate amounts of thyroid hormone (8,9).

Hill's y/d is clearly an iodine deficient diet, containing levels of approximately 0.2 mg/kg (0.2 ppm) on a dry matter basis, well below the minimum daily requirement for adult cats (0.46 mg/kg or 0.46 ppm) of food (9-11).  Our current data does indicate that feeding y/d, a diet severely restricted to overtly deficient in iodine, will result in normalization of T4 levels in most hyperthyroid cats. Since iodine is an essential nutrient and has other functions other than making T4 and T3 (12), the long-term effects of such iodine deficiency in cats remains unclear.

Can a low-iodine home-made diet be formulated?

I am well aware of the claim by some, including Dr. Hines, that it is possible to make your own low-iodine diet. However, if this were true, then why would we ever feed the Hill's y/d diet, which is very unnatural? 

You can certainly talk to a veterinary nutritionist about making an iodine-deficient diet for your cat (13). Unfortunately, it is just not that easy to formulate such a diet, and I do not know of anyone who has made one. That's especially true if we want to feed a higher protein, lower-carbohydrate diet (iodine is present is most meat, since iodine is a required nutrient in all animals, including cattle, chickens, and pigs). And remember, cats are meant to eat a low-carb, high-protein diet!

My Bottom Line:

At 13-years of age (a middle-aged senior cat), I would consider a definitive form of treatment of the hyperthyroidism to be ideal. I'd talk to your veterinarian about the possibility of the use of radioiodine or surgical thyroidectomy. Once your cat is cured, then we can concentrate on the use of nutrition to help restore any lost muscle mass and to improve glucose metabolism.

References:

1. Eisert R. Hypercarnivory and the brain: protein requirements of cats reconsidered. J Comp Physiol B 2011;181:1-17.
2. Zoran DL. The carnivore connection to nutrition in cats. Journal of the American Veterinary Medical Association 2002;221:1559-1567.
3. AAFCO (Association of American Feed Control Officials). Official Publication, 2007. 
4. NRC (National Research Council). Minerals. In: Nutrient Requirements of Dogs and Cats. Washington DC, The National Academy Press, 2006:145-192. 
5. Xu H, Laflamme DP, Long GL. Effects of dietary sodium chloride on health parameters in mature cats. J Feline Med Surg 2009;11:435-441. 
6. Reynolds B. Dietary salt and cats: evidence-based approach. Proceedings of the 21st ECVIM-CA Congress, 2011.
7. Zimmermann MB. Iodine deficiency. Endocr Rev 2009;30:376-408. 
8. Zimmermann MB, Andersson M. Assessment of iodine nutrition in populations: past, present, and future. Nutr Rev 2012;70:553-570.  
9. Melendez LM, Yamka RM, Forrester SD, et al. Titration of dietary iodine for reducing serum thyroxine concentrations in newly diagnosed hyperthyroid cats [abstract]. J Vet Intern Med 2011 2011;25:683. 
10. Melendez LM, Yamka RM, Forrester SD, et al. Titration of dietary iodine for maintaining serum thyroxine concentrations in hyperthyroid cats [abstract]. J Vet Intern Med 2011;25:683. 
11. Yu S, Wedekind KJ, Burris PA, et al. Controlled level of dietary iodine normalizes serum total thyroxine in cats with naturally occurring hyperthyroidism [abstract]. J Vet Intern Med 2011;25:683-684. 
12. Patrick L. Iodine: deficiency and therapeutic considerations. Altern Med Rev 2008;13:116-127. 
13. Fascetti AJ, Delaney SJ. Nutritional management of endocrine disease In: Fascetti AJ, Delaney SJ, eds. Applied Veterinary Clinical Nutrition. Chickester, West Sussex: Wiley-Blackwell, 2012;289-300.

Methimazole-induced Overgrooming in Cats

Methimazole-induced facial excoriation in a hyperthyroid cat

I have a 13-year old male DSH cat with hyperthyroidism. He's being treated with methimazole but I can't seem to really get an answer from my vet (or my online searching) as to a side effect I think he is having related to the methimazole treatment. 

Have you seen cats excessively groom and/or fur pull as a side effect of the drug? I've read where that shows up as a side effect of hyperthyroidism, but not the medicine. 

My cat only started doing this (fur pulling mostly) once he was put on 7.5mg/day of methimazole. It's so excessive that three weeks ago, I decided to stop the meds and switch him to Hill's Y/D food. That was a mistake as he lost way too much muscle weight and began to look emaciated. Plus, he had a horrible squeaking noise in his intestines! (I did gradually transition the food over a week, but the GI sounds still persisted).

I now have him back on his normal diet of Orijen Cat food (dry) and Blue Spa Turkey (wet). Anyway, he is 3 days back on the methimazole, eating well and regaining weight. But of course, on the second day of restarting the meds, he started fur pulling again.

I'm at a loss.... wondering if you have run across this ever and have any advice? Thank you so much for your time.

My Response:

This certainly sounds like your cat is having an allergic skin reaction to the methimazole. We don't see this very often in cats or humans treated with methimazole, but drug-induced cutaneous reactions can develop in association with almost any drug in the susceptible patient (1-3).

In cats, we see this most frequently around the head and neck area, and these self-induced excoriations will commonly become quite severe (see photo of cat above) (4). In these cases, we generally are forced to stop the drug and use another form of therapy.

In your cat, the fact that the "fur pulling" resolved after stopping the drug and now has recurred once you have restarted the drug is diagnostic for a cutaneous drug allergy. In this case, it doesn't sound life threatening, but if he were my cat, I would treat him with either radioiodine or surgery and get him off this drug —the pruritis must be making him very uncomfortable.

References: 

1. Svensson CK, Cowen EW, Gaspari AA. Cutaneous drug reactions. Pharmacological Reviews 2001;53:357-379. 
2. Khan DA. Cutaneous drug reactions. Journal of Allergy and Clinical Immunology 2012;130:1225-1225 e1226.  
3. Otsuka F, Noh JY, Chino T, et al. Hepatotoxicity and cutaneous reactions after antithyroid drug administration. Clinical Endocrinology 2012;77:310-315. 
4. Peterson ME, Kintzer PP, Hurvitz AI. Methimazole treatment of 262 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 1988;2:150-157. 

Diagnosing Naturally Occurring Hypothyroidism in Cats

I have a 5-year-old female DSH cat that has recently been diagnosed with hypothyroidism.  This diagnosis was based on a low serum T4 value that was detected during a pre-anesthetic workup for a preventative dental procedure. She had been looking unthrifty and "off" to me at home for a while, but has had no other signs of illness. Her appetite remains normal with no signs of vomiting or diarrhea.

We sent out a complete serum thyroid panel two weeks after the initial low T4 value and the results were as follows:

• Total T4: 0.3 µg/dL (reference range, 0.8-4.7 µg/dL)
• Free T4 - 0.35 ng/dL (reference range, 0.7-2.6 ng/dL)
• Total T3: <35 ng/dL (52-182 ng/dL)
• TSH 0.01 ng/ml (reference range, 0.05-0.42 ng/ml)

How would you interpret this panel?  Should we treat her as being hypothyroid? She has never been hyperthyroid and has never been treated with methimazole or radioiodine.

Is there value in trying to use one of the herbal remedies  for thyroid support (e.g., Thytrophin PMG) or should we just start her on thyroid hormone? If you think we should use thyroid hormone, which product is best to use (L-T4, L-T3, or a combination)?

My Response:

Based on your cat's serum thyroid panel, the results are not supportive of primary hypothyroidism. As the thyroid gland fails in hypothyroidism, the pituitary would respond by increasing the secretion of thyroid stimulating hormone (TSH) (1-4). In your cat, all of the serum thyroid hormone values (T4, T3, and free T4) are very low. However, the serum TSH level remains well within the reference range limits, not high as would be expected with primary hypothyroidism.

Again, the result of this thyroid panel goes against a diagnosis of primary hypothyroidism. Spontaneous hypothyroidism (i.e., not secondary to treatment of hyperthyroidism) is extremely rare in the adult cat, with only a few cases reported (4,5), so I'm not surprised that the serum TSH value is normal in your cat.

The most likely explanation for these serum thyroid results is that your cat is likely suffering from another illness. It's well known that any nonthyroidal disease can act to lower circulating T4 and T3 concentrations in cats (6-10); thyroid hormone replacement in those cats would unlikely be of any benefit.

I'm assuming that you did routine blood work (CBC, serum chemistry panel, urinalysis) in addition to the T4 for the pre-dental panel. Were there any abnormalities on this blood-work or urine?  If not, a chest radiography or abdominal ultrasound may be indicated as the next step to search for the underlying problem. Once we determine what's wrong with your cat and treat the primary problem, the serum thyroid values will likely normalize.

In any case, supplementation with thyroid hormone or any one of the herbal remedies are unlikely to be of any use and have the potential to do harm (11,12), depending on the underlying cause of your cats problems.  If your cat was indeed hypothyroid (which she isn't!), we generally use twice daily L-T4 replacement, but some cats do appear to respond better to combination L-T4/L-T3 therapy.

References:

1. Baral R, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012;571-592.
2. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: Hypothyroidism. Compend Contin Educ Vet 2013;35:E1-E6. 
3. Greco DS. Diagnosis of congenital and adult-onset hypothyroidism in cats. Clin Tech Small Anim Pract 2006;21:40-44. 
4. Daminet S. Feline hypothyroidism In: Mooney CT, Peterson ME, eds. Manual of Canine and Feline Endocrinology Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;1-5.
5. Rand JS, Levine J, Best SJ, et al. Spontaneous adult-onset hypothyroidism in a cat. J Vet Intern Med 1993;7:272-276. 
6. Peterson ME, Melian C, Nichols R. Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. J Am Vet Med Assoc 2001;218:529-536. 
7. Peterson ME, Gamble DA. Effect of nonthyroidal illness on serum thyroxine concentrations in cats: 494 cases (1988). J Am Vet Med Assoc 1990;197:1203-1208. 
8. Mooney CT, Little CJ, Macrae AW. Effect of illness not associated with the thyroid gland on serum total and free thyroxine concentrations in cats. J Am Vet Med Assoc 1996;208:2004-2008. 
9. McLoughlin MA, DiBartola SP, Birchard SJ, et al. Influence of systemic nonthyroidal illness on serum concentrations of thyroxine in hyperthyroid cats. J Am Anim Hosp Assoc 1993;29:227-234. 
10. Mooney CT. The effects of nonthyroidal factors on tests of thyroid function. Australian College of Veterinary Scientists, Science Week 2010;28-30.  
11. Bello G, Paliani G, Annetta MG, et al. Treating nonthyroidal illness syndrome in the critically ill patient: still a matter of controversy.  Curr Drug Targets 2009;10:778-787. 
12. Adler SM, Wartofsky L. The nonthyroidal illness syndrome. Endocrinol Metab Clin North Am 2007;36:657-672, vi.

Is a High Serum T4 or Free T4 Level Always Diagnostic for Hyperthyroidism in Cats?

Thyroid scan (scintigraphy) in a cat suspected of hyperthyroidism. Both thyroid lobes are of normal size and shape. Uptake of the radionuclide by the thyroid is also normal, with a thyroid/salivary ratio of 0.8 (normal <1.5). This is a normal study and rules out hyperthyroidism.
Scintiscan provided by Dr. Michael Broome, Advanced Veterinary Medical Imaging 

I've read on your blog "we almost never see false-positive results with the total T4 test." Since you say "almost," I'm wondering what, if anything, might cause a false-positive result? 

I have a 16-year old, male domestic long hair cat who currently has a total T4 value of 6.0 µg/dl (reference range, 0.8-4.0 µg/dl) after being off of methimazole for 5 weeks. He has a long history of chronic diarrhea associated with inflammatory bowel disease (IBD). 

About a year ago, we suspected hyperthyroidism based on a high-normal total T4 with a high free T4 concentration. He had thyroid scintigraphy at that time to confirm hyperthyroidism and help with his radioiodine dose calculation (we wanted to ensure that he wasn't overdosed — I don't want to end up with a hypothyroid cat!). Surprisingly, the results of this thyroid scintigraphy were negative (see his thyroid scintiscan above), though he was getting iodine supplements at the time. 

About 6 months ago, his serum T4 was a bit higher (and his free T4 remained high) so we started treatment with methimazole. He was on methimazole for about 6 months, which did lower his T4, but the drug seemed to significantly worsen his chronic diarrhea, and he didn't gain any weight.  My veterinarian has never been able to palpate an enlarged thyroid tumor in my cat.

I am interested in I-131 treatment, but would like to be as certain as possible he is hyperthyroid before making arrangements. Could there be any other explanation for high total and free T4 concentrations Do you see false-positive results?

His primary veterinarian and his internist both say they know of no other explanation for high total T4 concentration other than hyperthyroidism. But when I read "almost never" on your blog, that seems to imply it's possible (though unlikely) to get a false-positive test result.  Since I know that you are the expert on feline hyperthyroidism, I thought I would try asking for your advice. I don't want to pursue radioiodine treatment if he isn't truly hyperthyroid. 

My Response:

In older cats that develop clinical signs of hyperthyroidism, confirming a diagnosis of thyroid disease is usually straightforward (1-3). However, the potential for false-negative and false-positive results exists with all thyroid function tests (4,5) — especially in the context of routine screening of asymptomatic cats or cats sick with nonthyroidal disease (such as the IBD in your cat). This can lead to clinical dilemmas and misdiagnosis.

To avoid unnecessary treatment and potentially adverse effects in a euthyroid cat (i.e., normal thyroid status), thyroid function test results must always be interpreted in the light of the cat’s history, clinical signs, and other laboratory findings.

Palpating the thyroid nodule 
All cats with hyperthyroidism have a thyroid nodule (goiter) affecting one or both thyroid lobes, since in all cases there is underlying thyroid pathology leading to the disease (e.g., thyroid adenomatous hyperplasia, adenoma or carcinoma) (6).

Because all hyperthyroid cats must have at least one (if not two and sometimes more) thyroid nodules in order to develop the disease, the finding of a thyroid nodule, either by cervical palpation or by imaging (e.g., thyroid scintigraphy – see later), plays a crucial role in diagnosis in these cats (1-5).

If the veterinarian cannot palpate a thyroid nodule in the cat suspected of having hyperthyroidism, diagnosis becomes much more difficult to confirm, especially in cats with mild or borderline disease or in cats with concurrent illness.

Measuring the total T4 concentration 
A high circulating total T4 concentration is the biochemical hallmark of hyperthyroidism and is extremely specific for its diagnosis (1–5).

False-positive results (i.e., a high T4 in a cat without hyperthyroidism) are relatively rare but are being seen with increasing frequency, especially with the automated T4 immunoassays and in-house testing kits. In agreement with that statement, we recently reported that 1–2% of all cats diagnosed as hyperthyroid based on the finding of a high serum T4 concentration turn out to be euthyroid based on results of thyroid scintigraphy (4,5).

Therefore, if a high serum T4 value is found in a cat that lacks clinical signs of hyperthyroidism, especially if no thyroid nodule is palpated or when concurrent disease is present, one should never hesitate to repeat the serum T4 test using a different technique. In these cases, T4 measured by radioimmunoassay (RIA) or chemiluminescence (Immulite) is preferred (4,5). Alternatively, additional thyroid function testing (complete thyroid profile, thyroid scintigraphy) may also be recommended (4,5,7-10).

Measuring the free T4 concentration 
Many veterinarians believe that determination of a serum free T4 concentration is more reliable than measuring total T4 alone, since free T4 values are more consistently elevated in hyperthyroid cats than are total T4 concentrations (3,11). Although free T4 is a more sensitive diagnostic test than total T4 for diagnosing hyperthyroidism, the test specificity for free T4 is poor, with up to 20% of sick (and some clinically normal) euthyroid cats having false-positive free T4 results (3,11-13).

Caution is, therefore, advised in using serum measurements of free T4 as the sole diagnostic test for hyperthyroidism. As always, it is important to combine these thyroid test results with the cat’s clinical features and the presence of a palpable thyroid nodule to make the correct diagnosis.

More important, however, is the situation in cats that maintain reference interval serum T4 values and are diagnosed as hyperthyroid on the basis of a high serum free T4 concentration. Up to 30% of these cats presenting with a mid- to high–normal total T4 value, together with high free T4 concentrations by dialysis, will turn out to be euthyroid based on results of thyroid scintigraphy (4,13).

It is unclear how much additional useful information is truly gained by the use of free T4 assays over the use of total T4 estimations alone. Many veterinarians mistakenly believe that the finding of high free T4 in a cat is completely diagnostic for hyperthyroidism, especially when total T4 is within the middle to upper half of the reference interval. However, since up to a third of these cats may turn out to be euthyroid (4,13), it is clear that the free T4 test can never be considered a "gold standard" diagnostic test for thyroid disease in cats.

Use of free T4 testing can lead to more confusion than clarity in some hyperthyroid cats; certainly, reliance on free T4 results risks misdiagnosis of hyperthyroidism in many euthyroid cats, especially those with non- thyroidal illness.

Careful monitoring may be best diagnostic approach
So what is the next step if we find a high serum T4 in an asymptomatic cat in which no goiter is palpable? The first steps should always be to repeat the cervical palpation looking for a thyroid nodule and to verify the high T4 concentration. Again, the veterinarian should never hesitate to repeat the serum T4 test using a different technique, with RIA or CEIA preferred in such cats. Again, if we have any doubt about the diagnosis, thyroid scintigraphy should be considered (1,2,4,5).

In many of these asymptomatic cats in which the diagnosis is unclear (e.g., borderline or only slightly high T4 concentration, no obvious thyroid nodule), the best approach is to use close observation rather than start any treatment (4,5). With this cautious approach, one should recheck the cat at 2- to 3-month intervals, and at each visit monitoring the cat’s body weight, carefully re-palpating for a thyroid nodule, and repeating the serum T4 concentration doing a complete serum thyroid panel (T4, free T4, T3 and TSH) (4,5). If the cat is truly hyperthyroid, the thyroid tumor will continue to grow, the serum T4 will eventually rise into the hyperthyroid range, and the cat will lose weight.

My Bottom Line: 

But what's up with your cat? Is he really hyperthyroid? Well, the finding of a T4 value of 6.0 µg/dl is certainly consistent with hyperthyroidism, but I'm bothered by a number of issues with the case.

First of all, his thyroid scan done a year ago was completely normal. Of course, a thyroid tumor could have developed during this period, but the clinical signs a year ago appear to be similar to those your cat is showing at this time.

Secondly, medical treatment made the diarrhea worse, not better. If hyperthyroidism was responsible for your cat's gastrointestinal signs (the main problem), lowering the serum thyroid values should have helped, not made the situation worse.

Thirdly, remember that all cats (as well as all humans) likely have their own individual "reference range," so it's possible that a T4 value slightly outside of the lab's reference range could actually be normal for that individual (14,15). Could it be that your cat normally runs higher thyroid hormone levels than most other cats? Or is current high T4 simply a laboratory error?  That would certainly be the most common reason for the finding of a single "high" T4 concentration in a euthyroid cat.

Finally, you have seen a number of veterinarians (your regular veterinarian as well as internal medicine specialists). Despite multiple exams being performed by different vets, no one has been able to palpate a thyroid nodule.  If this was my cat, I would not rush into treatment without repeating the thyroid scan to document the presence of a hyperfunctioning thyroid tumor.

References:

1. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;92-110. 
2. Baral RM, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;571-592. 
3. Peterson ME, Melian C, Nichols R. Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. J Am Vet Med Assoc 2001;218:529-536. 
4. Peterson ME. Diagnostic testing for hyperthyroidism in cats: more than just T4. J Fel Med Surg 2013;15:765-777. 
5. Peterson ME. Diagnostic testing for feline thyroid disease: Hyperthyroidism. Compend Contin Educ Vet 2013:in press.
6. Gerber H, Peter H, Ferguson DC, et al. Etiopathology of feline toxic nodular goiter. Vet Clin North Am Small Anim Pract 1994;24:541-565. 
7. Mooney CT, Thoday JL, Nicoll JJ, et al. Qualitative and quantitative thyroid imaging in feline hyperthyroidism using technetium-99m as pertechnetate.Vet Radiol Ultrasound 1992;33:313-320. 
8. Daniel GB, Sharp DS, Nieckarz JA, et al. Quantitative thyroid scintigraphy as a predictor of serum thyroxin concentration in normal and hyperthyroid cats.Vet Radiol Ultrasound 2002;43:374-382. 
9. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clin Tech Small Anim Pract 2006;21:10-16. 
10. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. J Vet Intern Med 2012;26:754.
11. Mooney CT, Little CJ, Macrae AW. Effect of illness not associated with the thyroid gland on serum total and free thyroxine concentrations in cats. J Am Vet Med Assoc 1996;208:2004-2008.
12. Wakeling J, Moore K, Elliott J, et al. Diagnosis of hyperthyroidism in cats with mild chronic kidney disease. J Small Anim Pract 2008;49:287-294. 
13. Peterson ME, Broome MR, Robertson JE. Accuracy of serum free thyroxine concentrations determined by a new veterinary chemiluminscent immunoassay in euthyroid and hyperthyroid cats. Proceedings of the 21st Annual European College of Veterinary Internal Medicine (ECVIM-CA) Congress; 2011.
14. Andersen S, Bruun NH, Pedersen KM, et al. Biologic variation is important for interpretation of thyroid function tests. Thyroid 2003;13:1069-1078. 
15. Andersen S, Pedersen KM, Bruun NH, et al. Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab 2002;87:1068-1072.