Celebrate the Seventh Annual World Thyroid Day

It's not just cats and dogs that develop thyroid disease. Approximately 750 million people worldwide are affected by thyroid disorders, and the Seventh Annual World Thyroid Day, being held this weekend, has 5 major goals, say the organizations who support it. These include the American Thyroid Association (ATA), the European Thyroid Association, the Asia Oceania Thyroid Association, and the Latin American Thyroid Society.

The thyroid gland produces hormones that regulate the body's metabolism and influence every cell, tissue, and organ in the body, they point out. Hypothyroidism is characterized by symptoms of fatigue, depression, and forgetfulness, while hyperthyroidism is associated with irritability, nervousness, and muscle weakness.

The aims of World Thyroid Day are the following:

• Increase awareness of thyroid health. 
• Promote understanding of advances made in treating thyroid diseases. 
• Emphasize the prevalence of thyroid diseases. 
• Focus on the urgent need for education and prevention programs.
• Expand awareness of new treatment modalities.

The thyroid gland, butterfly-shaped and located in the middle of the lower neck, produces hormones that influence every cell, tissue and organ in the body. The thyroid hormones regulate the body's metabolism—the rate at which the body produces energy from nutrients and oxygen—and affects critical body functions, such as energy level and heart rate.

The thyroid also plays a critical role during pregnancy, the thyroid societies explain. Consequently, the ATA recommends that pregnant women at high risk for thyroid disease should have their thyroid function tested early in their pregnancy. Another important issue is thyroid cancer, which is rapidly increasing, according to the ATA, which says there were 44,670 new cases of thyroid cancer recorded in 2010 in the United States.

But when thyroid cancer is identified and treated early, "the majority of patients can be completely cured," the American Thyroid Association stresses. The organization also notes that it is important to distinguish thyroid cancer from benign thyroid nodules, which are common in the population.

Patient education on human thyroid conditions can be found on the ATA website at http://www.thyroid.org/patient-thyroid-information/.

Insect Repellent, Antiviral Drug Detected in Jerky Pet Treats for Dogs

Chicken jerky treats consumed by dogs that became sick over the past few month have now been found to be tainted by the insect repellent N,N-diethyl-meta-toluamide, better known as DEET, as well as the antiviral drug amantadine.

This is according to a veterinary pathologist leading an independent probe of the ongoing pet treat mystery.  For more information, click this link to read the article by the Veterinary Information Network News Service.

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. 

What's the Best Insulin for Treating Dogs with Diabetes Mellitus?

I am writing you regarding my 11-year old male Weimaraner, Duke. He has always been in good health but over this past week he has had 2 ”accidents” where he has urinated in the bed. He has also been drinking a lot more water than usual and urinating more too.

I  took him to the vet because I had a feeling he might be diabetic. My veterinarian confirmed that it was indeed diabetes mellitus and started him on 10 units of NPH, once after breakfast and once after dinner.  He has improved since starting the insulin, but remains quite thirsty and continues to urinate excessively.

Now I know that this will not give very good control alone because NPH is only a long-acting insulin. I am a Type 1 diabetic, diagnosed when I was 12 years old, so I have quite a bit of experience dealing with this disease. I want my poor puppy to be as controlled as possible so he does not feel like I do when my sugars are out of control— lethargic, nausea, headaches, unquenchable thirst, urinating all the time, and just plain crappy! Not to mention the stress this puts on the on the rest of the body.

If dogs are anything like people, I believe that Duke needs an insulin mixture that will bring his blood glucose down to normal and keep it leveled out. I have been giving him the rapid-acting insulin analog Humalog (insulin lispro) along with the NPH and that seems to be working really well, with marked improvement in his thirst and urination.  The only problem is that he needs 4-6 injections of Humalog each day. I was hoping you have had experience with something that would give him the same control as Humalog but with less injections daily.

In the past, I have used short-acting Regular insulin (before Humalog was invented) but I do not remember how the dosing went. I do have much better control with the Humalog but I am also on an insulin pump, so NPH insulin is no longer necessary.

Any help you can give to allow my dog Duke better control long term without so many injections would be greatly appreciated.

My Response:

In dogs, veterinarians commonly start with an intermediate-acting insulin (NPH or Vetsulin) twice a day (1,2). In some dogs, I find it necessary to add a short-acting insulin to the longer-acting insulin preparation, but many dogs can achieve adequate glucose control without giving more than 2 injections per day.

Insulin of choice for canine diabetics
In my opinion, the insulin of choice for most dogs is Vetsulin (porcine insulin zinc suspension; Merck Animal Health) (3). The main advantage of Vetsulin (known as Caninsulin outside the USA (4), is that it is actually composed of both short- and long-acting insulin components (see Figure below, showing the duel peaks of activity) (5,6). So giving Vetsulin is like administrating NPH together with a second, short-acting insulin preparation, like you are doing now.  However, Vetsulin works better than NPH for most dogs because it has a longer duration of action than NPH.

Timing of meals and insulin injection
The short-acting amorphous fraction of the Vetsulin, which composes 35% of the insulin activity, acts like regular insulin or Humulog, mainly to control the rise in blood glucose after each meal (6).  To help prevent severe rises in glucose after meals, however, it is also important to give the insulin before meals, instead of after the food is ingested, as you are doing now. This protocol will allow the short-acting insulin to be absorbed into the blood stream and ready to act to lower the blood sugar as soon as the food is absorbed from the gastrointestinal tract (7).

The only time I don't do this insulin-feeding protocol is in dogs that don't always eat their meal well; but even in those dogs, I never wait long after the meal is finished to give the insulin. Instead, I always give the insulin injection as soon as possible, once the dog has eaten a sufficient amount of food.

Vetsulin (porcine insulin zinc suspension), with it's 2 peaks of insulin activity

References:

1. Nelson RW. Canine diabetes mellitus In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. Seventh Edition ed. St. Louis: Saunders Elsevier, 2010;1449-1474.
2. 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.
3. Vetsulin website. www.vetsulin.com 
4. Caninsulin website. www.caninsulin.com
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;19:675-682.
6. Fleeman LM, Rand JS, Morton JM. Pharmacokinetics and pharmacodynamics of porcine insulin zinc suspension in eight diabetic dogs. Vet Rec 2009;164:232-237.
7. Cobry E, McFann K, Messer L, et al. Timing of meal insulin boluses to achieve optimal postprandial glycemic control in patients with type 1 diabetes. Diabetes Technol Ther 2010;12:173-177. 

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.