Thanks for your great post on radioprotective therapies (see Radiation Protection after a Nuclear Accident).

But I'm confused. If radioidine-131 released into the atmosphere during an accident can result in a dramatic increase of thyroid cancer in children, why don't people or cats treated with I-131 for hyperthyroidism develop thyroid cancers?

My Response:

Good question. After a nuclear accident, people and animals will get exposed to varying amounts of radioiodine as I-131, as well as many other radioisotopes including cesium-137, strontium-90, and plutonium-241 (1). Some will receive a small dose to their thyroid, whereas others will get more, but it's generally not enough to destroy the thyroid — it "tickles" the thyroid and causes DNA damage, which can lead to thyroid tumors (2).  The exposure also tends to happen over a period of a few days to weeks, not all at once.

When we treat a patient (human, cat, dog) with radioiodine, we are delivering a huge, single dose of radiodine to the thyroid. This destroys the hyperfunctional adenoma/carcinoma. It tends not to be taken up by the normal, suppressed tissue. It is unclear why the remaining normal thyroid tissue doesn't develop cancer, but it appears related to the large, single dose of radioiodine administered, as opposed to chronic exposure of lower levels of radiation. It has been reported that spreading the total I-131 dose over time (from a few days to a few weeks or longer) may lower risk of thyroid cancer, probably due to the opportunity for cellular repair mechanisms to operate (3).

Infants and children have the peak risk as the result of the increased radiation sensitivity of their thyroid glands. As a result, most human patients that develop thyroid cancer after exposure to radioiodine are babies and young children (4-6), whereas adult individuals are at a lesser risk. This fact probably also contributes to why we don't see thyroid cancer developing in adult human or feline patients treated with radioiodine.

The latest study in Hiroshima and Nagasaki Atomic Bomb survivors in Japan has indicated that a biological effect from a single brief external exposure to ionizing radiation nearly 60 years in the past still occurs and can be detected (7). In childhood, once exposed even to low doses of ionizing radiation, either externally or internally, the cancer-prone cell damage within the thyroid gland can be preserved for a long time.

What Can We Do in an Nuclear Emergency?

Since children are at the highest risk to exposure to radioactive iodine, potassium iodide should be available to all children (8). Also, because of the risk to the developing fetus, pregnant women should also take potassium iodide in the event of a nuclear accident. Compared to children and the fetus, adults are at a lower risk but still would benefit from thyroid blockage with potassium iodide.
 

Iosat Tablets, one FDA approved KI preparation

Potassium iodide pills (sometimes abbreviated as KI: the K stands for potassium, the I for iodine) don’t prevent radioactive iodine from entering the body. But these pills do keep the radioiodine from accumulating in the thyroid gland. By flooding the body with non-radioactive iodine, the pills keep the gland from absorbing the radioactive iodine. Here is how the CDC fact sheet summed it up (9):

Because KI contains so much stable iodine, the thyroid gland becomes “full” and cannot absorb any more iodine—either stable or radioactive—for the next 24 hours.

ThyroShield and ThyroSafe, the 2 other FDA approved KI preparations

What Potassium Iodide Preparations Are Available?

The potassium iodide (KI) products approved by the Food and Drug Administration (FDA) include the following (10):

• Iosat Tablets (130 mg) 
• ThyroSafe Tablets (65 mg) 
• ThyroShield Solution (65 mg/ml) 

Properly packaged, potassium iodide’s shelf life is at least 5 years and possibly as long as 11 years. If you take a very old pill, it may not work but won't hurt you or do any harm.

What are the Recommended Potassium Iodide Doses?

For humans, the FDA recommends the following doses based on the patient's age:

• 0—1 months ........................................ 15 mg
• 1 months—3 years ............................30-35 mg
• 3—12 years ...........................................65 mg
• >12 years ............................................130 mg

As I discussed in my last post, the recommended dose of potassium iodide for a dog 1.4 mg/kg (11). In other words, a 20-kg dog would receive 25-30 mg, whereas a small dog or cat would receive about 5-10 mg.  The easiest way to prepare a 15-mg dose for a newborn is to dissolve a 130-mg pill in 8 oz of a clear liquid and feed the newborn 1 oz of the liquid. Similar measures could easily be used in dogs and cats.

A single dose of KI protects the thyroid gland for up to 24 hours. A one-time dose at the levels recommended by the FDA is usually all that is needed to protect the thyroid gland. In the rare instance that radioiodine is present in the environment for longer than 24 hours, continuing the dose of KI every 24 hours for a few days would be needed.

References:

1. Report of the Chernobyl Forum Expert Group. Environmental Consequences of the Chernobyl Accident and their Remediation: Twenty Years of Experience. International Atomic Energy Agency, Vienna, 2006. 
2. Awa A. Analysis of chromosome aberrations in atomic bomb survivors for dose assessment: studies at the Radiation Effects Research Foundation from 1968 to 1993. Stem Cells. 1997;15 Suppl 2:163-73.
3. Ron E, Lubin JH, Shore RE et al. Thyroid cancer after exposure to external radiation; a pooled analysis of seven studies. Radiation Research 1995;141:256-277. 
4. Jacob P, Kenigsberg Y, Zvonova I, et al. Childhood exposure due to the Chernobyl accident and thyroid cancer risk in contaminated areas of Belarus and Russia. British Journal of Cancer 1999;80:1461-1469. 
5. Ivanov VK, Gorski AI, Maksiutov MA, et al. Thyroid cancer incidence among adolescents and adults in Bryansk region of Russia following the Chernobyl accident. Health Physics 2003;84: 46-60. 
6. Cardis E, Kesminiene A, Ivanov V, et al. Risk of thyroid cancer after exposure to I-131 in childhood. Journal of the National Cancer Institute 2005;97:724-732. 
7. Imaizumi M, Usa T, Tominaga T, et al. Radiation dose-response for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki Atomic Bomb Survivors 55-58 years after radiation exposure. Journal of the American Medical Association 2006;295:1011-1022. 
8. National Research Council. Distribution and  administration of potassium iodide in the event of a nuclear incident, Washington, DC: National Academies Press, 2004.
9. Center for Disease Control and Prevention website. Potassium iodide factsheet. 
10. FDA website. Frequently asked questions on potassium iodide (KI). www.fda.gov
11. Ribela MT, Marone MM, Bartolini P. Use of radioiodine urinalysis for effective thyroid blocking in the first few hours post exposure. Health Physics 1999;76:11-16.

Źródło: endocrinevet.blogspot.com

I attended the North American Veterinary Conference (NAVC) in Orland Florida this week, where I presented a number of lectures on a variety of endocrine topics (complete list of topics on my website). 

One lecture that I had agreed to present 9 months ago was part of a Hill's seminar on diagnosis and treatment of feline hyperthyroidism. The topic that I had agreed to present (which I did present last Monday morning on January 16th), was entitled "Feline Hyperthyroidism: Risk Factors and Diagnosis." This was arranged before Hill's iodine deficient y/d diet had been released, so the intense marketing campaign that we have seen over the last 3 months had not yet begun.
 

The day before I traveled to the NAVC conference, I received an email from Hill's with the above ad, promoting the hyperthyroid seminar that I would soon be a part of — to be honest, I was shocked and rather embarrassed that I was to be a part of this y/d promotion.

Once I arrived in Orlando, the slogan, Believe The Hype was posted as a prominent banner almost everywhere that one looked. Again, I was feeling more and more uncomfortable that I was to be included as part of this "hype,"especially since I'm not convinced that this diet is even safe to use, based on the evidence.  (To see my past posts which discuss the y/d diet, click here.)

Remember that we have yet to see any referred scientific publications with the complete data that answer all of our questions. The Hill's research team certainly hasn't responded to most of my questions that I've brought up about y/d in my blogs.

Defining the Term, Hype

After thinking about "Believe The Hype" banner and discussing the matter over dinner with friends, someone asked the obvious question —What does the word hype really mean, anyway?

Well, according to the Merriam-Webster Dictionary, the word, when used as a noun as it is in the slogan, has two possible meanings:

1. deception, put-on
2. publicity; especially: promotional publicity of an extravagant or contrived kind 

And according to an online dictionary (dictionary.com), the word hype has three meanings, all similar to those found in the Merriam-Webster  source:

1. exaggerated publicity; hoopla
2. an ingenious or questionable claim, method, etc., used in advertising, promotion, or publicity to intensify the effect
3. a swindle, deception, or trick

So What Is Hill's Implying with the Believe The Hype Slogan?

At face value, is the marketing division at Hill's actually asking us to believe that the information they have provided about the y/d diet is all hype? Remember that the word is defined as exaggerated, ingenious or questionable claims, put-ons, or tricks!

Interesting thought, isn't it.

Personally, I find the slogan to be "over-hyped" — unnecessarily exaggerated to the point of overkill. Why don't they present the hard evidence, answer the real questions that we all have, and forget this foolishness?

My Bottom Line

We all need to remember that this marketing campaign for the Hill's y/d diet, as well as the marketing ads for the multitudes of products that we get bombarded with every day, is all about hype.

As veterinarians and advocates for our feline patients, our job is to dig below this exaggerated hype and find the real science (if any) behind this sensational publicity. In the case of y/d, Hill's has created much more hype than usual or really necessary (at least in my opinion).  If half of this money spent on this marketing campaign would be directed toward research on feline hyperthyroidism, we may be able to find the cure for this disease!

I know that it is tempting to get taken in with all marketing of new products, especially y/d. My goal in writing these blog posts, the way I see it, is to try to bring everyone back to earth and make the practicing veterinarian think about the possible long-term implications of feeding y/d to cats. That's what I have tried to do over the past few weeks and will continue to do as needed in the future.

Hill's y/d diet is different than all of the other commercial pet foods on the market because they are promoting y/d as a treatment for a disease — in other words, Hill's is marketing y/d more like a drug than a diet per se.  In that regard, I believe that they need to do the studies to ensure that this diet is safe, as well as effective, just as any pharmaceutical company would have to do for FDA approval.  From what I've heard, however, no further safety studies are planned simply because they are not required to do them.

But is that the "right" thing to do, just because the diet isn't regulated as a drug by the FDA? Or is it all about selling as much cat food as possible to keep the shareholders happy?

Źródło: endocrinevet.blogspot.com

Rex is an 8-year-old male Schnoodle who presented to us a month ago with owner complaints of polyuria and polydipsia (PU/PD) and polyphagia. On physical examination, his abdomen was a bit pendulous, with a body condition score of 7/9 (body weight, 8.5 kg). Marked hepatomegaly was found, which was verified by abdominal radiography. The physical examination was otherwise unremarkable, with no other signs of Cushing's syndrome (e.g., no hair loss, muscle atrophy, comedomes, calcinosis cutis).

We submitted a complete blood count, serum chemistry panel, complete urinalysis, and urine culture to the lab that day, which showed the following abnormalities:

Serum Chemistry Panel:

• Alkaline phosphatase: 1061 IU/L (reference range, 5-131)
• GGT: 18 IU/L (reference range, 1-12)
• Glucose: 649 mg/dl (reference range, 70-138)
• Triglyceride 414 mg/dL (reference range, 29-291)

Urinalysis and Culture

• Specific gravity: 1.029
• Glucosuria: 3+
• Ketones: Negative  
• Urine culture:

• negative

Based on the hyperglycemia and glycosuria we diagnosed diabetes mellitus and started Rex on NPH insulin (Humulin-N) at the dosage of 4 U BID (0.5 U/kg/injection). He responded to insulin with a moderate decrease in PU/PD, but the thirst remained excessive.

We did an serial blood glucose cure 2 weeks later. Results showed marked and persistant hyperglycemia (> 400 mg/dl) throughout the day. Based upon the glucose curve, we diagnosed insulin resistance and did a low-dose dexamethasone response test. Results of that test were positive, and indicate pituitary-dependent Cushing's disease (see below):

• Basal cortisol: 5.8 μg/dl (reference range, 1.0-5.0 μg/dl)
• 4-hr post-cortisol: 0.9 μg/dl (reference range, <1.4 μg/dl)
• 8-hr post-cortisol:  5.7 μg/dl (reference range, <1.4 μg/dl)

I'd like to start Rex on trilostane (Vetoryl, Dechra Animal Health) for the Cushing's disease and insulin resistance. Am I on the right course with this dog?

My Response:

The problem with diabetic dogs is that it's very difficult to make a diagnosis of Cushing's with certainty unless we see cutaneous changes. PU/PD, polyphagia, and high liver values all could be secondary to the diabetes. False-positive test results on a LDDST are very common in dogs with nonadrenal illness, such as diabetes (1-3).

Does he have any cutaneous signs (hair loss, etc)? His insulin dose isn't high enough to say that he has insulin resistance. I'd recommend that you continue to monitor Rex closely an slowly raise his NPH dose to see if that helps control his signs. Because it can be very difficult to be sure in these diabetic dogs, sometimes observation and monitoring is the best course.

Follow-up:

Rex's coat looks pretty normal right now. We'll try raising his insulin dose before assuming that Cushing's disease is his underlying problem. Two more questions:

1. At what insulin dose do we get concerned about resistance?
2. Could diabetes explain the pot belly and marked hepatomegaly?

My Response:

We define insulin resistance as doses greater than 2.2 U/kg/injection to control hyperglycemia (4), so we aren't even close to the doses required to diagnose resistance.

And yes, diabetic dogs can get marked hepatomegaly secondary to fat accumulation in the liver. That can lead to a mild-moderate "pot bellied" appearance.

Because it can be very difficult to make a diagnosis of Cushing's syndrome in dogs with diabetes, observation and monitoring is the best course in many of these patients. If Cushing's disease is present, it will be progressive and other signs will develop to make the diagnosis easier to confirm.

References:

1. Kaplan AJ, Peterson ME, Kemppainen RJ. Effects of disease on the results of diagnostic tests for use in detecting hyperadrenocorticism in dogs. Journal of the American Veterinary Medical Association 1995;207:445-451.
2. Kaplan A, Peterson ME. Effects of nonadrenal disease on adrenal function tests In: Bonagura JD (ed): Current Veterinary Therapy XIII. Philadelphia, WB Saunders Co., 2000; pp 362-363.
3. Melián C, M. Pérez-Alenza, D, Peterson ME. Hyperadrenocorticism in dogs, In: Ettinger SJ (ed): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Seventh Edition). Philadelphia, Saunders Elsevier, 2010; pp. 1816-1840.
4. Peterson ME. The difficult diabetic: Acromegaly, Cushing’s, and other causes of insulin resistance. North American Veterinary Conference (NAVC) Conference 2012: Small Animal & Exotics Proceedings. pp. 873-879.

Źródło: endocrinevet.blogspot.com

I have an interesting situation with a dog with polyuria and polydipsia (PU/PD) that I have not seen before, and wonder if you can offer any insight.

My patient is a 7-year old, male neutered Golden Retriever-mix weighing 69 pounds who was diagnosed as being hypothyroid and has been on L-thyroxine replacement (Soloxine) for at least 5 years. He was recently diagnosed with diabetes insipidus (DI) because of signs of severe PU/PD and low urine specific gravity. The dog was examined by a neurologist, who found no neurological deficits. On MRI examination, the dog had no abnormal findings to explain the onset of DI (i.e, no hypothalamic or pituitary lesions or masses). 

He is now on Soloxine at a dosage of 0.7 mg twice daily (there has been no change in L-T4 dose for last year). For the DI, we have him on 0.01% desmopressin, with drops administered twice daily into the conjunctival sac (1 drop in morning and 2 drops in evening).

His owner reports he has been doing great in the last 3 to 4 months since he added the desmopressin. Recently, however, we rechecked a 6-hour post-pill serum T4 concentration and found that the value was high at 5.5 μg/dl (reference range, 1-4 μg/dl).

My questions are:

1. Can this be due to an interaction of desmopressin and L-thyroxine?
2. Is this a result of correcting/properly treating his diabetes insipidus and is this common?
3. Do we need to take any special factors into consideration with dosing either drug, or just lower his Soloxine as we would in other hypothyroid dogs getting routine T4 rechecks for proper dosing?
4. Is this just a coincidence and no known correlation?

My Response:

The main sign of hyperthyroidism in dogs is PU/PD so I'm be a bit worried that the thyroid hormone supplementation is causing the signs (1-4). You could drop the dose down a bit to see if that helps the PU/PD. After a week or so on the reduced dose of L-T4, you could try stopping the desmopressin for a couple of days and see if the PU/PD returns.

I don't know of any problems with concurrent use of desmopressin and thyroid hormone. But it is somewhat unlikely that a 7-year old dog would develop DI without the presence of any obvious pituitary or CNS pathology (1,2,4).

Many dogs with undefined PU/PD will respond to desmopressin but most of those dogs do not have DI. I'm not saying that we shouldn't use the desmopressin to control the signs, but DI is very unlikely.

Follow-up Question:

Thank you for your ideas, Dr. Peterson.

Do you mean that perhaps he was being overtreated for his hypothyroidism thus making him hyperthyroid leading to the PU/PD that initially caused us to diagnose the diabetes insipidus? I'm pretty sure that his T4 was in the normal range at that time. And now when we just tested him and discovered the T4 high, he is no longer PU/PD (since being on the desmopressin).

That is interesting that even dogs who do not truly have DI will respond to desmopressin. Will desmopressin eventually stop helping though? Or would you just keep him on it as long as it controls the severe PU/PD?

My Response:

Remember that when we are doing a post-pill T4, we are only doing a single spot check. That doesn't really indicate that is happening throughout the day.

In addition, the finding of a serum T4 value within the lab's reference range does not indicate what that particular dog's individual T4 normal range actually is — in other words, some dogs may be perfectly euthyroid having a serum T4 value of 4.5 μg/dl, whereas others may be clinically hyperthyroid with a serum T4 of 3.5 μg/dl.

And yes, most dogs that respond to desmopressin do not really have DI. As long as you and the client realize that, this is a pretty safe drug and it can be used to control PU/PD for long periods (and maybe forever).

Again, I'd still try cutting back on the L-T4 dose first -- why give desmopressin if we can figure out the real cause of the PU/PD?

References:

1. Peterson ME, Nichols R: Investigation of polyuria and polydipsia, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Third Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, pp 16-25, 2004.
2. Randolph JF, Nichols R, Peterson ME: Diseases of the hypothalamus and pituitary. In: Birchard SJ, Sherding RG (eds): Manual of Small Animal Practice (Third Edition), Philadelphia, Saunders Elsevier, pp 398-408, 2006.
3. 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, pp 113-125.
4. Nichols R, Peterson ME: Investigation of polyuria and polydipsia, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Fourth Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, 2012; in press.

Źródło: endocrinevet.blogspot.com

My patient is a 6.5-year old male neutered Belgian Malinois who has a history of weight loss and intermittent vomiting of 3-weeks duration.

A CBC and serum chemistry panel were both unremarkable, with normal serum sodium and potassium values. Abdominal ultrasonography was performed, which revealed a splenic mass. A splenectomy and liver biopsy were performed, which revealed a splenic hematoma and hepatopathy, thought to be secondary to Rimadyl (1). The drug has subsequently been discontinued with no improvement.

Today we did an ACTH stimulation test to rule out Addison's disease, using a dose of 2.2 U ACTH gel administered intramuscularly. The baseline cortisol value was 2.2 μg/dl (reference range, 1-4 μg/dl) and the 2-hour post-ACTH cortisol was 3.6 μg/dl (reference range, 6-20 μg/dl).

Is this subnormal cortisol response consistent with mild Addison's disease?

My Response:

This ACTH stimulation test completely rules out spontaneous hypoadrenocorticism (Addison's disease). Most dogs with primary, secondary, or atypical hypoadrenocorticism will have a low basal cortisol concentration (< 1 μg/dl) and all will have a baseline cortisol value that is less than 2 μg/dl (2-4).

After ACTH stimulation, dogs with hypoadrenocorticism tend not to have any cortisol response to ACTH stimulation, and post-ACTH cortisol values should never be greater than 2.5-3.0 μg/dl (see Figure below)

In many dogs, the blunted cortisol response, as seen in this dog, is either due to prior administration of glucocorticoid sometime in the last few weeks. However, in this dog, the likely cause for the subnormal cortisol response is the compounded ACTH preparation that you used.

In a study performed a few years ago (5), normal dogs were tested with cosyntropin (Cortrosyn, 5 μg/kg, IV) and 4 different compounded forms of ACTH (all manufacturers recommend a dose of 2.2 U/kg, IM).  For all 5 of the ACTH stimulation tests, samples for cortisol analysis were collected before and 1 and 2 hours after ACTH injection.

After administration of the 4 forms of compounded ACTH, the time to reach peak cortisol concentrations varied, with some dogs showing the maximal cortisol value at 1 hour and others having peak cortisol concentrations at 2 hours.With 2 of the 4 products, serum cortisol concentration returned to baseline values by 2 hours in many of the dogs.

Thus, due to variability in duration of cortisol response after injection of the compounded ACTH products, the investigators recommend that we need to collect several post-ACTH samples for cortisol analysis after administration of a compounded ACTH preparation to ensure that we detect the peak cortisol response. At the minimum, we recommend collecting samples at 1 and 2 hours following injection.

Because of this variability in cortisol stimulation, I'm not a fan of using compounded ACTH preparations. I would rather use low-dose Cortrosyn (6) and collect only one post-ACTH blood sample at 1-hour and be assured that will produce the maximal cortisol response at that time.

References:

1. MacPhail CM, Lappin MR, Meyer DJ, et al. Hepatocellular toxicosis associated with administration of carprofen in 21 dogs. Journal of the American Veterinary Medical Association 1998; 212: 1895-1901.
2. Lifton SJ, King LG, Zerbe CA. Glucocorticoid deficient hypoadrenocorticism in dogs: 18 cases (1986-1995). Journal of the American Veterinary Medical Association 1996;15;209:2076-2081. 
3. Cook AK, Bond KG. Evaluation of the use of baseline cortisol concentration as a monitoring tool for dogs receiving trilostane as a treatment for hyperadrenocorticism. Journal of the American Veterinary Medical Association 2010;237:801-805.
4. Klein SC, Peterson ME. Canine hypoadrenocorticism: part II. Canadian Veterinary Journal 2010;51:179-184.
5. Kemppainen RJ, Behrend EN, Busch KA. Use of compounded adrenocorticotropic hormone (ACTH) for adrenal function testing in dogs. Journal of the American Animal Hospital Association 2005;41:368-372. 
6. Martin LG, Behrend EN, Mealey KL, et al.  Effect of low doses of cosyntropin on serum cortisol concentrations in clinically normal dogs. Journal of the American Veterinary Medical Association 2007;230:555-560.

Źródło: endocrinevet.blogspot.com

Efficacy of Protamine Zinc Recombinant Human Insulin for Controlling Hyperglycemia in Dogs with Diabetes Mellitus

Background
Treatment of diabetes mellitus in dogs requires daily insulin administration to achieve control of hyperglycemia. Commonly used insulin preparations for diabetes in dogs include recombinant human NPH insulin and purified pork source lente insulin (Vetsulin in the USA; Caninsulin elsewhere in the world) (1,2). However, the withdrawal of purified pork source lente insulin by the FDA in November 2009 has practicing veterinarians in the USA searching for an alternative insulin replacement. Recombinant human NPH insulin can be used to treat diabetes in dogs, but control of diabetes is difficult in some dogs because of NPH's short duration of action (1). Alternative insulin preparations are needed when NPH insulin is ineffective in diabetic dogs.

A recombinant human PZI preparation (rhPZI, Prozinc, Boehringer Ingelheim Vetmedica) was approved by the FDA in 2009 for managing diabetes in cats (3,4). This recent availability of this insulin may provide another viable insulin option for treating diabetic dogs.  This study evaluated the efficacy of recombinant human protamine zinc insulin (ProZinc) in dogs with diabetes mellitus (5).

Hypothesis
Protamine zinc insulin (rhPZI; ProZinc) is effective for treating diabetic dogs.

Animals
Seventeen dogs (6 newly diagnosed and 11 insulin-treated diabetics) were included in this study.

Methods
Prospective clinical trial. Dogs were treated with rhPZI for 60 days. Control of glycemia was assessed on days 7, 14, 30, and 60 by evaluation of history, physical examination, body weight, serum fructosamine concentration, and blood glucose concentrations measured before and 2, 4, 6, 8, and 10 hours after rhPZI administration. Adjustments in dosage of rhPZI were made as needed to control glycemia.

Results
Compared to pretreatment (day 1) results, protamine zinc insulin (rhPZI) administration resulted in significant decreases in both 10-hour mean blood glucose (from 457 to 299 mg/dl) and mean serum fructosamine concentrations (557 to 478 mg/dl) at day 60.

By day 60, polyuria and polydipsia had improved in 14 of the 17 dogs, body weight was stable or increased in 16 of 17, 10-hour mean blood glucose concentrations had decreased in 16 of 17, and serum fructosamine concentration had decreased in 11 of 17 dogs, compared with day 1. Hypoglycemia (<80 mg/dl) was the only consistent adverse event.

Conclusions
PZI (ProZinc insulin) is effective in diabetic dogs and can be considered as an alternative treatment in diabetic dogs that are poorly-controlled using other insulin preparations.

My Bottom Line:

PZI insulin (Prozinc, Boehringer Ingelheim Vetmedica) was effective in improving or maintaining control of the diabetic state in almost all of the diabetic dogs in this study.

However, the median PZI insulin dosage required for glycemic control in these diabetic dogs was much higher than reported for other insulin preparations in dogs with diabetes.  The final median PZI dosage needed in these dogs was 0.9 U/kg, bid (range, 0.4–1.5 U/kg/injection). These doses are much higher than that generally needed when dogs are treated with either NPH or Vetsulin/Caninsulin, where insulin dosages ranging from 0.25 to 1.0 U/kg, bid (median, 0.5 U/kg/injection) are generally effective in regulation of the diabetic state (1,2).

The higher PZI dosage requirements in the dogs of this study is likely due to the fact that PZI is a long-acting insulin. Compared with intermediate-acting insulins such as NPH or lente, longer-acting insulin preparations typically have a slower rate of absorption and lower peak blood insulin concentration (6). These properties may result in higher PZI dosage requirements to attain comparable glycemic control as compared to the shorter-acting insulin prepartions.

Based on the results of this study, use of ProZinc at a starting dose of 0.5 U/kg, bid, should be considered in diabetic dogs that are poorly controlled because of the short duration of NPH or Vetsulin/Caninsulin. Prolonged duration of PZI, however, may result in problems with hypoglycemia and induction of the Somogyi response when PZI is administered twice a day in a few diabetic dogs.

The biggest disadvantage of ProZinc for use in dogs is the relatively high cost of injecting the higher doses of insulin needed. This is especially true in larger breed dogs with doses of 30-50 U, bid, might be needed to achieve diabetic control.

References:

1. 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.
2. Fleeman LM, Rand JS, Morton JM. Pharmacokinetics and pharmacodynamics of porcine insulin zinc suspension in eight diabetic dogs. Veterinary Record 2009;164:232–237.
3. 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. J Vet Intern Med. 2009;23:787-93.
4. Norsworthy G, Lynn R, Cole C. Preliminary study of protamine zinc recombinant insulin for the treatment of diabetes mellitus in cats. Veterinary Therapeutics 2009;10:24-28.
5. Della Maggiore A, Nelson RW, Dennis J,  et al. Efficacy of protamine zinc recombinant human insulin for controlling hyperglycemia in dogs with diabetes mellitus. Journal of Veterinary Internal Medicine 2012;26: 109-115. 
6. Wallace MS, Peterson ME, Nichols CE. Absorption kinetics of regular, isophane, and protamine zinc insulin in normal cats. Domestic Animal Endocrinology 1990;7:509-515.

Źródło: endocrinevet.blogspot.com

I have a 12-year old female DSH cat with hyperthyroidism that we have been managing with the new Hill's y/d diet. The cat was eating both the canned and dry y/d, and the serum T4 fell from 7.0 μg/dl to 3.2 μg/dl after 2 months.

So everything was going along fine on y/d without any other medication. But now the cat has completely stopped eating for the last 2 days. Other than the cat's palpable thyroid tumor and low body condition score, my physical examination was normal. Repeat routine blood work did not reveal any abnormalities.

So what should we do in this situation? The owner suspects it's an issue with the taste of the y/d and thinks that she would eat her "regular" cat food.

Is there something else to do first before doing a further workup searching for a concurrent disease? If we give her another food, will she become hyperthyroid once again?

My Response:

This is one of the major disadvantages we have when relying on a extremely low iodine diet (Hill's y/d) to control a cat's hyperthyroidism.  Let's face it — Hill's y/d isn't the tastiest cat food on the market, and most cats (if not all) would prefer to eat another type of diet.

But more importantly is the fact that almost all cats, as they age, will develop episodes of partial to complete anorexia secondary to nonthyroidal illness. In these sick cats, we often first tempt them to eat with different foods (fish-flavored, etc) or use recovery-type diets before embarking on a major workup for a concurrent disease. However, feeding these cats any other food but y/d increases their iodine intake, and will result in relapse of the cat's hyperthyroid state.

How long to relapse on the y/d diet is stopped? Well, that depends on a number of factors including the following:

• The size of the hyperthyroid cat's thyroid tumor (which will continue to grow on the y/d diet).
• The magnitude of the cat's original serum T4 value (i.e., higher T4 values reflect an increase in severity of hyperthyroidism, with a larger thyroid tumor size).
• The time on the y/d diet.
• How low the cat's T4 fell on the y/d diet, which reflects how iodine depleted the cat's thyroid tumor became on the diet. In other words, if the serum T4 decreased into low-normal range of on the y/d, we would expect the cat to remain euthyroid longer than if the T4 only fell to upper limit of the reference range, as in this cat.

In any case, we know that the serum T4 will increase again, once the y/d is not fed exclusively. You must continue this iodine deficient diet for the rest of the cat's life for this diet to continue to manage the hyperthyroidism. So we would want to get them back on y/d and off the "temporary" foods as soon as possible. If they remain on a diet other than y/d for any length of time (certainly longer than 1 to 2 weeks), it's likely that they will show relapse and T4 will have to be monitored.

Remember that once they relapse, it's going to take a few weeks feeding the y/d diet exclusively for the serum T4 to again fall into the euthyroid range.

Bottom Line:

Veterinarians have to be prepared for the fact that many, if not all, senior hyperthyroid cats will develop concurrent diseases as they age, some of which will require management with a diet other than Hill''s y/d. This is one of the major downsides of using this diet management for the long-term control of cats with hyperthyroidism.

Owners must be made aware of the fact that another treatment method might be needed if the cat's disease state dictates the need for another diet plan.

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My patient is an older 17-year old male Chihuahua. His weight is normal at 6.8 pounds. He is having episodes of pain at time of defecation and appears painful in his back.

We ran routine blood work which was all completely normal. However, a screening serum total T4 concentration was low at 0.4 μg/dl (reference range, 0.38-4.0 μg/dl). I added on a free T4 concentration and that was also low at  0.3 ng/ml (0.6 to 3.7 ng/ml). 

Would you recommend starting a thyroid supplementation in this dog?

My Response:

I doubt if this dog is truely hypothyroid for a number of reasons (1-3).

• First of all, the clinical signs the dog is showing are not at all characteristic of hypothyroidism.
• Secondly, the dog has neither anemia or hypercholesterolemia, which would make a diagnosis of hypothyroidism more likely.
• Finally, would be very unusual for a 17-year old dog to develop hypothyroidism; most dogs with hypothyroidism are young to middle age adult dogs, not geriatric animals.

In this dog, it's more likely that the serum thyroid concentrations are low either because of 1) a non-thyroidal illness, or 2) administration of a drug that is causing "suppression" of the circulating thyroid values. Such thyroid-lowering drugs include the following (3-5):

• Phenobarbital
• Sulfur antibiotics
• Clomipramine (Clomicalm) 
• Aspirin and other anti-inflammatory drugs
• Glucocorticoids

The steroids involved can be oral, parenteral, or topical, applied to the eyes, ears or skin. We need to get a good drug history in these dogs not only by reviewing the record to see what has been dispensed, but also by asking the owner what they're actually doing, as they may have bags of medications at home that we know nothing about.

Of course, if you do believe that the dog has hypothyroidism, then the next step would be to verify the low serum T4 concentration, repeat the serum free T4 using an equilibrium dialysis technique if possible, and to measure a serum cTSH concentration (2,3). If the total and free T4 remain low and the cTSH value is high, then treatment would be indicated.

The most accurate way to make a diagnosis (or rule out) a diagnosis of hypothyroidism is by use of thyroid scintigraphy (6,7). Although not widely used or available as a diagnostic test for dogs with suspected hypothyroidism, the diagnosis of hypothyroidism is easily made by the lack of finding any visible cervial thyroid tissue with thyroid imaging (see Figure below).

Thyroid Image (Scintigraphy) in a Boston Terrier with Hypothyroidism. Notice the uptake of the radioactive tracer by the salivary glands, but the complete lack of uptake by the thyroid gland.  The normal location for the 2 thyroid lobes is indicated by yellow ovals.

Thyroid imaging typically reveals decreased or even absent radionuclide uptake in dogs with hypothyroidism (thyroid gland is not visible on the scan). In contrast, dogs that have falsely low serum thyroid hormone concentrations secondary to illness or drug therapy have a normal thyroid image. In one study of comparing thyroid imaging to other diagnostic tests for hypothyroidism in dogs, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness when thyroid scintigraphy was employed (6).   Of all of the current thyroid imaging techniques (CT, ultrasound), nuclear imaging is considered to be the best test for dogs with suspected hypothyroidism.

References:

1. Chastain CB. Canine pseudohypothyroidism and covert hypothyroidism. Problems in Veterinary Medicine 1990;2:693-716.  
2. Mooney, CT. Canine hypothyroidism: A review of aetiology and diagnosis. New Zealand Veterinary Journal 2011;59:105-114.
3. Peterson ME, Melián C, Nichols R. Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and thyrotropin concentrations for diagnosis of hypothyroidism in dogs. Journal of the American Veterinary Medical Association 1997;211:1396-1402. 
4. Kantrowitz LB, Peterson ME, Trepanier LA, et al. Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in epileptic dogs treated with anticonvulsants. Journal of the American Veterinary Medical Association 1999;214:1804-1808. 
5. Williamson NL, Frank LA, Hnilica KA. Effects of short-term trimethoprim-sulfamethoxazole administration on thyroid function in dogs. Journal of the American Veterinary Medical Association 2002;221:802-806. 
6. Diaz Espineira MM, Mol JA, Peeters ME, et al. Assessment of thyroid function in dogs with low plasma thyroxine concentration. J Vet Intern Med 2007;21:25-32. http://www.ncbi.nlm.nih.gov/pubmed/17338146
7. Taeymans O, Peremans K, Saunders JH. Thyroid imaging in the dog: current status and future directions.J Vet Intern Med 2007;21:673-684. http://www.ncbi.nlm.nih.gov/pubmed/17708386

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Is it safe to eat canned foods? 

That’s a question worth asking after a recent study in human volunteers found a huge spike in urinary levels of the chemical bisphenol A – commonly known as BPA – in a group of volunteers who ate canned vegetable soup for several days. BPA, which has been linked to a variety of health disorders, is used in the lining of many food and beverage cans.

The results suggest BPA is being absorbed by the canned food and then ingested by consumers.

The study, published recently in the Journal of American Medical Association (1), represents one of the first attempts to measure BPA urine levels soon after the consumption of canned foods.

Title of Study (Research Letter)
Canned Soup Consumption and Urinary Bisphenol A: A Randomized Crossover Trial. Journal of the American Medical Association 2011;306:2218-2220.

Study Protocol
The experiment involved 75 participants. Half of them were asked to eat a 12-ounce bowl of canned vegetable soup at lunch for five consecutive days. After a two-day break, they consumed the same-sized serving of fresh vegetable soup for five lunches in a row. The other volunteers did the experiment in the reverse order – starting with five days of fresh soup, followed by five lunches of canned soup.

Five kinds of canned vegetarian Progresso soups (including tomato and minestrone) were used in the study, as well as five similar homemade soups. Participants were not aware of whether they were consuming canned or fresh soup during any given period.

Urine samples were collected on several occasions, usually a few hours after the noon-time meal.

Study Results
About 25% of urine samples from the homemade soup periods contained no detectable bisphenol A, all study participants were found to have bisphenol A in their urine after consuming canned soup for 5 days.

The analysis revealed that when participants ate the canned Progresso soup, their urinary BPA concentrations rose to levels 12-times higher than when they dined on fresh soup.

Study Discussion
The results of this study (1) suggest that the endocrine disruptor BPA is being absorbed by the canned food and then ingested by consumers. Because BPA is used in the liners of most canned foods and beverages it can be hard to avoid.

Although the team investigated only canned vegetable soup, the researchers suspect they would find similar results with other canned food and possibly canned beverages (e.g., soda) as well.

Scientists have warned that BPA could interfere with numerous biological processes because its structure resembles the hormone estrogen. It has been shown to interfere with reproductive development in animals and it has been linked to cardiovascular disease, diabetes, thyroid disease, and obesity in humans. Aside from cans, it’s also used to make some hard, clear plastics, dentistry composites and sealants, and some cash register receipts.

This study has reported that consuming canned soup increases urinary bisphenol A (BPA) excretion to levels that would be considered potentially very harmful to health if they were sustained.

My Comments

Bisphenol A (BPA) is a key building block of the epoxy resins commonly used for lining metal cans.  This thin epoxy coating on the interior surface of almost all metal food cans helps prevent corrosion of the can and makes it possible for food products to maintain their quality and taste, while extending shelf life (2-4).

Exposure to the endocrine disruptor BPA is thought to occur primarily through ingestion (2). BPA is a chemical of concern because it is an endocrine disruptor and has been associated with various adverse health effects, including thyroid disorders (5-7). It is well established that residual BPA monomer migrates into can contents during processing and storage (9,10), and evidence of BPA contamination of canned foods for human use has been widely reported (3,10).  Similarly, in two studies which measured the levels of BPA in pet foods, most dog and cat foods were found to contain measurable levels of BPA (10,11).  In one of the studies, investigators confirmed that the BPA had originated from the can coating, which had leached into the food (11).

Does BPA Ingestion Contribute to Feline Hyperthyroidism?

One large study of control and hyperthyroid cats demonstrated an association between hyperthyroidism and cats fed food from “pop-top” cans (12). Results of that study suggested that overall consumption of pop-top canned food at various times throughout a cat's life was associated with greater risk of developing hyperthyroidism. In female cats, increased risk was associated with consumption of food packaged in pop-top cans or in combinations of pop-top and non-pop-top cans. In male cats, increased risk was associated with consumption of food packaged in pop-top cans alone. Although these investigators suggested that only the lids of the pop-top cans are lined with the BPA-containing epoxy resins, it appears that most cans (even those that require a can opener to open them) are coated with BPA (10,11). Nevertheless, it appears that feeding canned cat food may pose a greater risk than feeding food from pouches or sachets.

Blood or tissue levels of BPA have not yet been measured in cats, but life long, continuous daily exposure to even the relatively low doses of this chemical found in commercial canned cat foods would likely result in potentially harmful effects (13).

In one of the major proposed actions, BPA acts as a thyroid hormone receptor antagonist, which might work at the pituitary level to increase circulating TSH concentrations (14-16). This could lead to thyroid hyperplasia, goiter formation, and hyperthyroidism in susceptible cats (17).

References

1. Carwile JL, Ye X, Zhou X, Calafat AN, Michels KB. Canned soup consumption and urinary bisphenol A: a randomized crossover trial.  JAMA 2011;306:2218-2220. 
2. Tsai WT. Human health risk on environmental exposure to Bisphenol-A: a review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2006;24:225-255.
3. Noonan GO, Ackerman LK, Begley TH. Concentration of bisphenol A in highly consumed canned foods on the U.S. market. J Agric Food Chem 2011;59:7178-7185.
4. Vandenberg LN, Maffini MV, Sonnenschein C, et al. Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev 2009;30:75-95
5. Boas M, Main KM, Feldt-Rasmussen U. Environmental chemicals and thyroid function: an update. Curr Opin Endocrinol Diabetes Obes 2009;16:385-391.
6. Patrick L. Thyroid disruption: mechanism and clinical implications in human health. Altern Med Rev 2009;14:326-346.
7. Meeker JD, Ferguson KK. Relationship between urinary phthalate and bisphenol A concentrations and serum thyroid measures in U.S. adults and adolescents from the National Health and Nutrition Examination Survey (NHANES) 2007-2008. Environ Health Perspect 2011;119:1396-1402.
8. Goodson A, Robin H, Summerfield W, et al. Migration of bisphenol A from can coatings--effects of damage, storage conditions and heating. Food Addit Contam 2004;21:1015-1026.
9. Cabado AG, Aldea S, Porro C, et al. Migration of BADGE (bisphenol A diglycidyl-ether) and BFDGE (bisphenol F diglycidyl-ether) in canned seafood. Food Chem Toxicol 2008;46:1674-1680.
10. Schecter A, Malik N, Haffner D, et al. Bisphenol A (BPA) in U.S. food. Environ Sci Technol. 2010;44:9425-9430.
11. Kang JH, Kondo F. Determination of bisphenol A in canned pet foods. Res Vet Sci 2002;73: 177-182.
12. Edinboro CH, Scott-Moncrieff JC, Janovitz E, et al. Epidemiologic study of relationships between consumption of commercial canned food and risk of hyperthyroidism in cats. J Am Vet Med Assoc 2004;224:879-886. 
13. Welshons WV, Nagel SC, vom Saal FS. Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology 2006;147(6 Suppl):S56-69.
14. Moriyama K, Tagami T, Akamizu T, et al. Thyroid hormone action is disrupted by bisphenol A as an antagonist. J Clin Endocrinol Metab 2002;87:5185–5190.
15. Kitamura S, Jinno N, Ohta S, et al. Thyroid hormonal activity of the flame retardants tetrabromobisphenol A and tetrachlorobisphenol A. Biochem Biophys Res Commun 2002;293:554–559.
16. Zoeller RT, Bansal R, Parris C. Bisphenol-A, an environmental contaminant that acts as a thyroid hormone receptor antagonist in vitro, increases serum thyroxine, and alters RC3/neurogranin expression in the developing rat brain. Endocrinology 2005;146:607-612.
17. Peterson ME: Feline hyperthyroidism – Risk factors and diagnosis. North American Veterinary Conference (NAVC) Conference 2012: Small Animal & Exotics Proceedings. pp. 865-872, 2012.

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What is the difference between calcitriol and vitamin D3? They both appear to be 1,25-hydroxycholecalciferol.

How about vitamin D2? It that form active at all in dogs and cats with renal failure?

My Response:

Vitamin D is a fat-soluble vitamin that exists in various forms (1). The chemical structure of vitamin D was established in the early 1930's. The main forms are vitamin D2 (ergocalciferol), found in plants, yeasts and fungi and vitamin D3 (cholecalciferol) of animal origin. Vitamin D2 and D3 are not biologically active; rather, they must be modified in the body to have any effect.

Vitamin D2 or D3 must then be first hydroxylated in the liver and then in the kidneys to become active. At this point, as biologically active 1,25-OH-cholecalciferol (also called calcitriol), this form of vitamin D can exert its endocrine effects (1).

By the early 1970's, it had become clear that calcitriol was the active form of vitamin D. It is over 1,000 times as potent as Vitamin D2 and D3 in binding to the vitamin D receptor.

The sun
Vitamin D has long been considered an essential dietary ingredient, but in several species, including humans, sheep, cattle, horses, and pigs, vitamin D3 can be formed in the skin from a cholesterol metabolite (7-dehydrocholesterol) after exposure to natural sun light.

In dogs and cats, however, this skin production of vitamin D3 does not occur (2), so they are dependent entirely on a dietary source of vitamin D.

Food
Large amounts of vitamin D are not found in adequate amounts in most foods. It’s found in fish, cod liver oil, mushrooms, liver and eggs – but usually not in substantial amounts (except in cod liver oil). Thus, getting enough vitamin D naturally from whole foods is difficult.

Both vitamin D2 and D3 have been commercially synthesized and both forms seem to be effective at maintaining blood levels of vitamin D in the body.

Use of vitamin D in renal disease
In severe renal failure, the kidneys cannot produce adequate amounts of the biologically active vitamin D, and this commonly leads to abnormalities of calcium and phosphorus metabolism (3). Oral administration of active calcitriol to animals with chronic kidney disease helps compensate for the reduced production of the active hormone (4).

It is critical to understand that administration of vitamin D2 and D3 will not work to raise active vitamin D concentrations in these animals with renal disease. Active calcitriol must be used as the form of vitamin D to treat these animals (4).

References

1. Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 2006;92:4-8.
2. How KL, Hazewinkel HA, Mol JA. Dietary vitamin D dependence of cat and dog due to inadequate cutaneous synthesis of vitamin D. Gen Comp Endocrinol. 1994;96:12-18.
3. Gerber B, Hässig M, Reusch CE. Serum concentrations of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol in clinically normal dogs and dogs with acute and chronic renal failure. Am J Vet Res. 2003;64:1161-1166.
4. Hostutler RA, DiBartola SP, Chew DJ, et al. Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure. J Vet Intern Med. 2006;20:1307-1313.

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