Changing Brand of NPH Insulin May Disrupt Diabetic Control

Treating dogs and cats with diabetes can be challenging but this article— Changing insulin brands may disrupt diabetics— published on the Veterinary Information News Service points out another issue to complicate treatment of this common disease (1).

In dogs, we commonly use human NPH insulin, which is an intermediate-acting insulin preparation (2,3). This insulin does not work well in cats, and I do not recommend using it for initial treatment of feline diabetes.

Two brands of NPH insulin are on the market: Humulin N, made by Eli Lilly and Co. and Novolin N, made by Novo Nordisk Inc. (2-4). Although both contain NPH insulin, Humulin and Novolin are made using different ingredients and manufacturing techniques, so they are not exactly the same. A number of owners and veterinarians around the country have reported in recent months cases of dogs whose insulin brands were switched developing out-of-control blood glucose levels, a potentially life-threatening condition that can be expensive to remedy.

Most diabetic cats are treated with either insulin glargine (Lantus) or PZI insulin (ProZinc), both long-acting insulin preparations (5-7). Only one brand of these insulin preparations exists, so this will not ever be a problem.

References:

1. Lau E. Changing insulin brands may disrupt diabetes. The VIN News Service, February 5, 2013.
2. Peterson ME. Blog Post, Insights to Veterinary Endocrinology. Insulin Choice for the Diabetic Dog and Cat: Which is Best? h 
3. Palm CA, Boston RC, Refsal KR, et al. An investigation of the action of Neutral Protamine Hagedorn human analogue insulin in dogs with naturally occurring diabetes mellitus. Journal of Veterinary Internal Medicine 2009;23:50-55. 
4. American Diabetes Association. Insulin administration. Diabetes Care. 2004;27 (Suppl 1):S106-9. 
5. Gilor C, Graves TK. Synthetic insulin analogs and their use in dogs and cats. Veterinary Clinics of North America: Small Animal Practice 2010; 40:297-307. 
6. Nelson RW, Henley K, Cole C, et al. Field safety and efficacy of protamine zinc recombinant human insulin for treatment of diabetes mellitus in cats. Journal of Veterinary Internal Medicine 2009;23:787–793. 
7. Norsworthy GD, Lynn R, Cole C. Preliminary study of protamine zinc recombinant insulin for treatment of diabetes mellitus in cats. Veterinary Therapeutics 2009;10:24–28. 

NYSVMS Veterinary News Interviews Dr. Peterson About His Endocrine Textbook

Should Hill's y/d Diet Ever Be Used to Manage Cats with Hyperthyroidism?

Hyperthyroid cat with an allergic reaction (facial pruitus) secondary to methimazole

We are unlikely enough to have not one... but two cats with hyperthyroidism. One has responded well to treatment with methimazole, with normalization of the serum T4 value, while the other cat had a severe allergic reaction (facial pruitus) so we had to stop the medication. Because of her age and how ravaged she was by the allergic reaction, we didn't want to do radiation or surgery.

My veterinarians suggested that we could try Hills' y/d diet, since no other good options were available. Since we had no other options available, we felt that we had nothing to lose.  Luckily, our cat will eat the diet. Slowly, she has improved and is doing fairly well.

Who knows if this food will be good for her long term (I take your comments seriously about what cats truly need in their diet), but she's almost 16-years old and has enjoyed a good life. Considering our situation, trying the diet was worth a shot, and it has lowered the serum T4 value to normal.

Now I'm feeling guilty — should I continue the y/d or should I rethink my decision not to use the radioiodine?

My Response:

I consider the feeding of Hill's y/d diet to be a fourth-line of treatment for hyperthyroidism; I'd recommend this treatment only if none of the 3 other options (i.e., radioiodine, surgical thyroidectomy, or methimazole) can be used (1-3).

If a hyperthyroid cat will eat this ultra-low iodine food (and not eat anything else), the y/d certainly will lower the serum thyroid hormone concentrations (4). Remember that iodine is an essential nutrient and is needed to make thyroid hormone; with this diet, we are inducing an iodine deficient state so the cat's thyroid tumor will not be able to continue to produce large amounts of thyroid hormone on this diet (5).

However, like methimazole, feeding an ultra-low iodine diet can not cure the primary cause of hyperthyroidism (ie, the thyroid tumor). The thyroid tumor, which is almost always benign at time of diagnosis) will continue to grow with time (5,6). In some cats, this benign tumor can also transform to a more malignant carcinoma after a few months to years. So whenever possible,  I believe it's always better to remove the thyroid tumor with surgery or ablate it with radioiodine —in that way, we are curing rather than prolonging the disease and not allowing the thyroid tumor to continue to grow.

Now, if you consider 16 year's of age too old for definite treatment, then y/d can certainly be fed. For a geriatric cat, I don't consider 15 or 16 years of age too old for definitive treatment unless other concurrent problems are present that are known to shorten their lives. Remember that old age itself isn't a disease, and I see many senior cats that are still doing well at 18 to 20 years of age.

The main advantage of the methimazole over the y/d is that we can control what the cat is fed (remember that cats managed with y/d can ONLY eat that diet).  The best diet for a hyperthyroid cat or any senior cat for that matter is one that is lower in carbohydrates (<15% of calories) and higher in protein (>35-40% of calories) (7).  Senior cats don't absorb protein as well as younger cats and will develop weight loss and muscle wasting as they age (8-11). Other than exercise (and good luck with getting most cats to enter a weight lifting regime), the best way we know to maintain muscle mass is to feed a higher protein diet.

When we look at the dietary composition of Hill's y/d, it's way too high in carbs (>23% of calories), and much too low in protein (<28% of calories). In addition, the protein that's contained in the dry y/d is all plant protein, which isn't as good as animal protein is for cats — when was the last time you heard of a feral cat that was a vegetarian?

Obviously, in your cat, we can never use methimazole again because of the severe allergic reaction that occurred.  So, should you continue the y/d for your cat?  That's a decision that you will have to make— remember that any treatment, including the y/d, is better than no treatment at all.

But I like to treat the whole animal, however, and that involves more than just giving pills, feeding an iodine-deficient diet, or even giving an injection of radioiodine. For me, that involves proper geriatric nutrition, supplements in some cats, and finally, environmental stimulation to help enrich their lives (1-3, 7).

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. 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. 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.
5. 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.
6. 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.
7. Peterson ME. Nutritional management of endocrine disease in cats. Proceedings of the Royal Canin Feline Medicine Symposium 2013; 23-28 2013;23-28.
8. Teshima E, Brunetto MA, Vasconcellos RS, et al. Nutrient digestibility, but not mineral absorption, is age-dependent in cats. J Anim Physiol Anim Nutr (Berl) 2010;94:e251-258. 
9. Sparkes AH. Feeding old cats--an update on new nutritional therapies. Top Companion Anim Med 2011;26:37-42. 
10. Perez-Camargo G. Feline decline in key physiological reserves implications for mortality. Proceedings of the Nestlé Purina Companion Animal Nutrition Summit: Focus on Gerontology 2010;6-13. 
11. Freeman LM. Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats. J Vet Intern Med 2012;26:3-17.

My Related Posts on Hill's y/d Diet (Insights into Veterinary Endocrinology Blog)

Treating Dogs with Hyperthyroidism and Thyroid Carcinoma

I have a 12 year-old, spayed, female, Chocolate Lab named "Coco" who was diagnosed with hyperthyroidism. Coco has lost 2.5 pounds of weight over the last 6 months but otherwise she was asymptomatic.

Coco's routine laboratory workup was unremarkable but her serum thyroid hormone panel was diagnostic for hyperthyroidism.  The panel showed high serum concentrations of T4 (4.3 μg/dl; reference range, 1-4 μg/dl), T3 (209 ng/dl; reference range, 50-150 ng/dl) and free T4 (52 pmol/L; reference range, 10-50 pmol/L), and low serum concentrations of TSH (<0.03 ng/ml; reference range, 0-0.6 ng/ml).

Chest radiographs were performed but no tumor metastasis was detected. My veterinarian palpated a small (grape-sized), freely movable right thyroid mass on Coco and performed a unilateral thyroidectomy last week to remove the tumor. The pathology report states the following:

• The tumor was completely surrounded by a fibrous capsule
• No capsular or vascular invasion
• A few mitotic figures (7 mitotic figures seen with 10 high-powered fields)
• Diagnosis ”thyroid follicular tumor, probably adenoma but carcinoma cannot be excluded” 

Do you have any information that you can share (or guide me to) regarding thyroid tumors and hyperthyroidism in dogs? I can find a lot of information about cats (you seem to be THE expert in feline hyperthyroidism), but I can not find very much information about treatment of hyperthyroid dogs. I'd love to come and see you, but I live in Western Pennsylvania and it would be a very long drive.

Other than this, my Coco has always been in excellent condition/health.

My Response:

Most dogs with naturally occurring hyperthyroidism will have a thyroid tumor, and most of these overactive thyroid tumors will be malignant (thyroid carcinomas). Very few dogs with hyperthyroidism have benign thyroid tumors, but it looks like your dog may be one of the lucky ones.  Based on the small tumor size and noninvasive nature, the thyroid tumor is likely to be either benign in the early stages of malignancy. The fact that the chest x-ray did not detect any cancer metastasis is a good sign.

Additional treatments that could be considered include the use of radioactive iodine (I-131), chemotherapy, and/or local radiotherapy of the cervical tumor bed. Based on the fact that she was hyperthyroid, radioiodine would be my first choice of treatment since any residue tumor tissue should "take up" the injected I-131 very well. However, radioiodine facilities for dogs are limited, and, to my knowledge, no one in the State of Pennsylvania offers radioiodine treatments for dogs; the closest place that I know of is Michigan State University.

In your dog, however, further treatment may not be necessary. By surgically removing the thyroid tumor, it's very possible that Coco has been cured. I'd certainly follow-up with another serum thyroid hormone panel in 2-4 weeks to ensure that her values have all returned to normal range.  Additional thyroid testing should be done quarterly. If hyperthyroidism persists or recurs, that likely indicates local recurrence of the thyroid tumor tissue or tumor metastasis.

Likewise, I would continue to monitor Coco's chest x-rays at least quarterly, again looking for tumor metastasis. If pulmonary nodules are ever detected, that could indicate thyroid metastasis and additional therapy would certainly be needed. Hopefully, Coco will be one of the lucky dogs, and her thyroid tumor has been cured.

Suggested Reading:

1. Panciera DL, Peterson ME, Birchard, SJ: Diseases of the thyroid gland. In: Birchard SJ, Sherding RG (eds): Manual of Small Animal Practice (Third Edition), Philadelphia, Saunders Elsevier, 2006;327-342.
2. Peterson ME: Hyperthyroidism and thyroid tumor in dogs. In: Melian C, Perez Alenza MD, Peterson ME, Diaz M, Kooistra H (eds): Manual de Endocrinología en Pequeños Animales (Manual of Small Animal Endocrinology). Multimedica, Barcelona, Spain, 2008;113-125.
3. Mooney CT. Canine hyperthyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;86-91.

My Related Posts on Hyperthyroidism in Dogs:

• Thyroid Tumors and Hyperthyroidism in Dogs  
• Canine Hyperthyroidism and the Heart 
• Dietary Hyperthyroidism in Dogs  

Interpreting the ACTH Stimulation Test in Dogs with Suspected Addison's Disease

I am hoping you may be able to offer me some insight/information about testing for hypoadrenocorticism (Addison's disease) in dogs.

I have a 3-year old male neutered German Shorthaired Pointer. Since April, Luke has been steadily losing weight despite no changes in his diet. He has also seemed "off" (slightly lethargic, just not himself) and had slight changes in gait from time to time. He then would seem better and back to his normal self.

In November, he began having chronic diarrhea and losing weight at a much more rapid pace. He has now last 20 pounds, going down from 85 to 65 lbs. He has had an ultrasound, exocrine pancreatic insufficiency test, full tick panel, fecal tests, serum thyroid tests, and complete blood count and serum chemistry panel. No clinically significant abnormalities have been detected in any these tests.

He had no response to treatment with Panacur, Proviable, or Flagyl. He responded to high-dose prednisone, but then when we tapered the dose, his clinical signs returned. He was off prednisone for 3 days before doing the first ACTH stimulation test, which came back out of range:

• Basal cortisol: 1.2 μg/dl (Reference range, 1.0-6.5 μg/dl)
• ACTH-stimulated cortisol:  3.6 μg/dl (Reference range, 6.5-18.0 μg/dl)

We waited 3 weeks to do the second ACTH stimulation test which came in within the normal range. These results were as follows:

• Basal cortisol: 1.3 μg/dl  
• ACTH-stimulated cortisol:  9.5 μg/dl  

Based on this information, is it possible he has Addison's disease? Or is the fact that his stimulated cortisol value came back within the normal range on the second test just an indication that the prednisone was affecting the results in the first ACTH stimulation test?

I have been doing a lot of research on this because he seems to have many symptoms that match up with Addison's disease. Some things I've read have said that it is possible in atypical Addison's disease to have varying test results. Other things have disagreed. This is why I am trying to contact someone who specializes in this field. In your experience, is this something you have encountered?

I really appreciate any insight you may be able to give me. Thank you for your time.

My Response:

Causes of Hypoadrenocorticism in Dogs
In dogs, as in man, hypoadrenocorticism can be classified into primary and secondary subtypes (1-6). With primary hypoadrenocorticism, the primary disease process is in the adrenal glands themselves. In secondary hypoadrenocorticism, the problem lies in the pituitary gland where ACTH is secreted; with secondary forms of the disease, the cortisol secretion goes down because of too little ACTH secretion from the pituitary gland.

The most common cause of secondary hypoadrenocorticism is iatrogenic (induced inadvertently by the veterinarian) resulting from overly rapid discontinuation of long-term and/or high-dose glucocorticoid therapy. Very rare spontaneous or natural causes in the dog include pituitary or hypothalamic lesions (e.g., large destructive pituitary tumors) or idiopathic isolated ACTH deficiency.

In addition to primary Addison's disease or hypoadrenocorticism  (the failure of the adrenal glands to produce both glucocorticoid and mineralocorticoid hormones), and secondary (which is the failure of the pituitary gland to secrete ACTH, a hormone which stimulates the adrenal glands), a third type of hypoadrenocorticism has been described — "atypical" Addison's disease (7-9). This is a confusing term, which I believe can and should not be avoided because it really does not describe a definitive diagnosis.

Almost all of these dogs diagnosed with atypical Addison's can be classified into primary or secondary forms of the disease with proper diagnostic testing (10-11). In addition to ACTH stimulation testing, this may include  determination of circulating ACTH concentrations (the pituitary hormone). In some dogs, repeating the ACTH stimulation test and measuring the basal and ACTH-stimulated concentrations of aldosterone, a mineralocorticoid hormone is helpful.  Properly classifying the dogs into primary and secondary subtypes helps us better predict the needs for long-term treatment.

In  this dog, there is no reason to go any further because the last ACTH stimulation test completely rules out all forms of Addison's disease — primary, secondary, and atypical hypoadrenocorticism (see below).

ACTH Stimulation Testing
In normal dogs, administration of a dose of ACTH generally produces a rise in serum cortisol to values greater than 6 μg/dl. In contrast, dogs with hypoadrenocorticism (typical or atypical Addison's disease) have an absent or blunted response to ACTH administration. Basal and post-ACTH serum cortisol concentrations are less than 1 μg/dl in over 75% of dogs and less than 2 μg/dl in virtually all dogs with primary hypoadrenocorticism (1-6).

Although the post-ACTH serum cortisol concentration may be as high as 2 to 3 μg/dl in a few dogs with naturally occurring secondary hypoadrenocorticism (due to pituitary ACTH deficiency), the great majority of these dogs also have ACTH-stimulated cortisol concentrations of less than 2 μg/dl.

When borderline results occur (post ACTH cortisol concentrations between 2 and 6 μg/dl), the first thing that one must consider is the recent use of glucocorticoids, which would act through the negative-feedback effect to suppress circulating ACTH and cause temporary and mild atrophy of the adrenal cortical cells that secrete cortisol. That is likely what happened in your dog.

My Bottom Line

So in your dog, the first ACTH stimulation test is borderline for Addison's, but the cortisol response is high enough to make it unlikely. Remember that the dose given for Addison's disease would only be between 2.5-5 mg per day (around 0.1 mg/kg/day), so anything higher than that dose would suppress pituitary ACTH secretion and could lead to blunting of the cortisol response.

In accord with that, his second ACTH stimulation test done 3 weeks later is completely normal, totally excluding Addison's disease.

It's time to look for another disease. Consider an abdominal ultrasound or endoscopy next to better define your dog's gastrointestinal disease.

References:

1. Church DB. Canine hypoadrenocorticism. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. 3rd ed. Quedgeley, Gloucester: British Small Animal Veterinary Assoc, 2004; 172-180.
2. Feldman EC, Nelson RW. Hypoadrenocorticism (Addison’s disease). In: Canine and Feline Endocrinology and Reproduction, 3rd ed. Philadelphia: Saunders, 2004; 394-439.  
3. Kintzer PP, Peterson ME. Primary and secondary canine hypoadrenocorticism. Veterinary Clinics of North American Small Animal Practice 1997;27:349-357. 
4. Peterson ME, Kintzer PP, Kass PH. Pretreatment clinical and laboratory findings in dogs with hypoadrenocorticism: 225 cases (1979-1993). Journal of the American Veterinary Medical Association 1996; 208: 85-91.
5. Klein SC, Peterson ME. Canine hypoadrenocorticism: part I. Canadian Veterinary Journal 2010;51:63-69.
6. Klein SC, Peterson ME. Canine hypoadrenocorticism: part II. Canadian Veterinary Journal 2010;5:179-184.
7. Bartges JW, Nielson DL. Reversible megaesophagus associated with atypical primary hypoadrenocorticism in a dog. Journal of the American Veterinary Medical Association 1992; 201: 889-891.
8. Lifton SJ, King LG, Zerbe CA. Glucocorticoid deficient hypoadrenocorticism in dogs: 18 cases (1986-1995).  Journal of the American Veterinary Medical Association1996;209:2076-2081. 
9. Sadek D, Schaer M. Atypical Addison’s disease in the dog: A retrospective survey of 14 cases. J Am Anim Hosp Assoc 1996;32:159-163. 
10. Mueller C, Boretti FS, Wenger M, et al. Investigation on the aldosterone concentration before and after ACTH application in 44 dogs with hypoadrenocorticism. Kleintierpraxis 2007;52:216-224.
11. Insights into Veterinary Endocrinology Blog. Atypical Addison's Disease in Dogs with Gastrointestinal Signs. April 14, 2011.

Favorable review of Dr. Peterson's BSAVA Manual of Canine and Feline Endocrinology

Dr. Peterson's BSAVA Manual of Canine and Feline Endocrinology was favorably reviewed in the December 15 issue of the Journal of the American Veterinary Medical Association.

January is National Thyroid Awareness Month

"If your thyroid isn't working properly, neither are you."

January is Thyroid Awareness Month, which is sponsored by the American Association of Clinical Endocrinologists (AACE).  We must remember that thyroid disease commonly affects people, as well as our cats and dogs. The AACE also estimates that approximately 30 million Americans may be affected by thyroid disorders (hypothyroidism, hyperthyroidism, and thyroid cancer) — with half of these cases currently undiagnosed.

In humans, the thyroid gland is a small, butterfly-shaped gland found immediately below the Adam’s apple. This gland produces hormones that influence every organ, tissue and cell in your body. If thyroid disease is left untreated, there are serious consequences including elevated cholesterol levels, heart disease, infertility, muscle weakness, and osteoporosis.

Testing for thyroid disease is easy, although not routinely included in an annual physical blood work. However, the diagnosis of thyroid disease can sometimes be challenging. Patients often present with vague, general clinical manifestations that may not be obvious to either the doctor or patient. Understanding the facts about thyroid disease and its symptoms is the best defense in diagnosing and treating thyroid disease.

What Are The Symptoms Of Thyroid Disease In Humans?

The following are some of the symptoms of various thyroid conditions and diseases.

Hypothyroidism
The symptoms of hypothyroidism (i.e., an underactive thyroid) tend to mirror the slowing down of physical processes that result from insufficient thyroid hormone. Common symptoms include fatigue, weight gain, constipation, fuzzy thinking, low blood pressure, fluid retention, depression, body pain, slow reflexes, and much more.

Hyperthyroidism
The symptoms of hyperthyroidism (i.e., an overactive thyroid) tend to reflect the rapid metabolism that results from an oversupply of thyroid hormone. Common symptoms include anxiety, insomnia, rapid weight loss, diarrhea, high heart rate, high blood pressure, eye sensitivity or bulging, and vision disturbances.

Thyroid Nodules or Goiter
Symptoms of goiter — an enlarged thyroid gland— include a swollen, tender or tight feeling in the neck or throat, hoarseness or coughing, and difficulty swallowing or breathing. Sometimes, the goiter is visible to yourself or others.

Some thyroid nodules cause no symptoms, while others may cause difficulty swallowing, a feeling of fullness, pain or pressure in the neck, a hoarse voice, or neck tenderness. Some nodules trigger hyperthyroid-like symptoms such as palpitations, insomnia, weight loss, anxiety, and tremors. Nodules can also trigger hypothyroidism, and symptoms might include weight gain, fatigue, and depression.

Thyroid Cancer
Although many patients are asymptomatic at first, possible symptoms of thyroid cancer include a lump in the neck, voice changes, difficulty breathing or swallowing, or lymph node swelling.

Thyroiditis
Symptoms of thyroiditis typically include pain and tenderness in the thyroid area, neck and throat, difficulty sleeping. Thyroiditis may also trigger traditional hypothyroid or hyperthyroid symptoms. 

Where To Get More Information?

For more information on thyroid disease and/or to find a medical expert in thyroid conditions, please visit the American Association of Clinical Endocrinologists website. The AACE’s Thyroid Awareness website also features articles, videos and FAQ on thyroid conditions.

For a detailed description of various thyroid disorders in human patients, including hypothyroidism and Hashimoto’s thyroiditis, hyperthyroidism and Graves’ disease, multinodular goiter, thyroid nodules and thyroid cancer, I'd strongly recommend that you visit the Thyroid Disease Manager Website.

Thyroid Disease Manager offers an up-to-date analysis of all aspects of human thyroid disease and thyroid physiology. It provides physicians, researchers, and patients from around the world with an authoritative, current, complete, objective, free, and down-loadable source on the thyroid and its diseases.

Useful Links:

• American Association of Clinical Endocrinologists (AACE) website — https://www.aace.com/
• AACE's Thyroid Awareness website — www.thyroidawareness.com
• Thyroid Disease Manager website —www.thyroidmanager.org