Thursday, August 1, 2019

Introducing My New Textbook: Feline Endocrinology - The First Book Fully Dedicated to Endocrine Disorders of the Cat



Over the last year, I have been hard at work editing and writing chapters for this book, the first one written exclusively about Feline Endocrinology.

Our primary goal for this book is to provide veterinarians, veterinary students, and others interested in cats with a concise and complete information resource on the pathophysiology, clinical signs, differential diagnosis, diagnosis, and treatment of endocrine disorders in cats.

If you are a veterinarian that sees cats with endocrine disorders, I highly recommend that you get this book. I have included everything I know about cats in this book!

Take a look at the video below, where we (the 3 editors) talk about the development of this valuable reference.



Click here to watch


The book is divided into 6 sections, including:
  • Hypothalamus and pituitary
  • Thyroid gland
  • Calcium and parathyroid glands
  • Adrenal glands
  • Endocrine pancreas
  • Blood pressure, body condition and nutrition

Moving forward, I will be blogging a series of posts about the 6 sections of this book, including the topics, authors, and even a few videos (included in the chapter) where applicable. 



From the publisher:
Developed by 50 of the most renowned feline experts from 13 countries around the world, this unique and practical book of feline endocrinology is a most valuable tool for small animal veterinarians who want to deepen their understanding on the pathophysiology, clinical signs, diagnosis, treatment, and prognosis of every endocrine condition recognized in cats. Rather than have the authors treating cats as small dogs, a cat-only text will allow fully focused description of conditions in this one species. 

Allowing these experts in feline endocrinology space to fully teach us what they have learned about cats will result in a superior resource composed of text, figures, boxes, tables, algorithms, and videos (presented on an electronic version of the text).

Wednesday, July 31, 2019

PBS Article Covers Our Paper About Organophosphate Esters (OPEs), Housecats and Hyperthyroidism


In addition to covering our recently published paper, this PBS article also mentioned my article in NY Times Magazine.

From the PBS post:

In the study, published July 10 in Environmental Science & Technology, researchers outline a connection between hyperthyroidism in indoor cats to organophosphate esters (OPEs), which have since supplanted PBDEs.
As manufacturers voluntarily phased out PBDEs because of health concerns in both pets and humans, OPEs were substituted in a range of household products to meet fire safety regulations.
Some research has pointed to OPEs as potential hormone disruptors. And if OPEs are making their way into house cats, those chemicals might be affecting humans, too.

Wednesday, July 24, 2019

Dr. Peterson Wins Award for Paper: Spontaneous primary hypothyroidism in 7 adult cats

One of Dr. Peterson's recently published papers won an award, presented by Oxford Laboratories, for "excellence in the advancement of knowledge concerning small animal endocrinology."

The paper,  Spontaneous primary hypothyroidism in 7 adult cats, is available in full as a download at this link.

We've cross-posted this paper on Medium here.

Given the paucity of data regarding adult‐onset feline hypothyroidism, we sought to describe the history, clinical features (including presence or absence of goiter), diagnostic testing, treatment, and long‐term outcome of 7 adult cats with spontaneous primary hypothyroidism. For these cats, we used the serum concentrations of T4, free T4 (fT4), and thyroid stimulating hormone (TSH), and results of thyroid scintigraphy to aid in both the diagnosis and long‐term monitoring of thyroid hormone replacement treatment.



Wednesday, July 17, 2019

New Chemicals in Environment (Organophosphate Esters) Linked to Hyperthyroidism in Cats


Dr. Peterson was involved in a recent study which linked the use of flame retardants and other common household compounds to hyperthyroidism in cats.
This study, published in Environmental Science & Technology, used silicone pet tags to monitor feline exposure to various chemicals and compounds found throughout the home. These silicone tags were attached to a standard cat collar (see photo above), and most owners reported that wearing the silicone tags didn't bother their cat at all.
The concern, in general, is that cats are being exposed to OPEs inside the home. OPEs (organophosphate esters) are one type of flame retardant, a chemical alternative to PDBEs. PDBEs began appearing as flame retardants in the 1970s and have been associated with hyperthyroidism in cats in a number of studies, as well as being harmful to humans. PDBEs were phased out beginning in 2004, and OPEs were substituted by manufacturers as an alternative flame retardant. 
This study is the first time we've taken a hard look at OPEs and how they affect cats.


From one of the press releases: "In the mid-1970s, manufacturers began to put polybrominated diphenyl ethers (PBDEs) into textiles, polyurethane foam, plastics, and electronics. But in 2004, U.S. manufacturers started voluntarily phasing out these flame retardants amidst environmental and health concerns. Alternatives including organophosphate esters (OPEs), such as tris(1,3-dichloroisopropyl) phosphate (TDCIPP), were added instead, but recent research suggests these flame retardants, like PBDEs, can act as endocrine disruptors. Prior research suggested a link between PBDE levels and feline hyperthyroidism, but so far OPEs have not been examined in this context."
A direct quote from this study: "To our knowledge, this is the first study to investigate bioavailable household OPE exposures between hyperthyroid and non-hyperthyroid cats."
Conclusion: Higher concentrations of harmful compounds were found on the tags of cats in homes with air fresher use (versus no air freshener use), as well as modern residences build after 2005 (versus pre-1989), and on the tags of cats who spend more time on upholstered furniture. 
More directly, harmful compounds were found in higher concentration on the tags of hyperthyroid cats, versus on the tags of non-hyperthyroid cats, indicating a higher level of exposure to the compounds (such as OPEs) in the environments of the cats who have become hyperthyroid.

Friday, June 22, 2018

Dr. Peterson Receives the 2018 Robert W. Kirk Award for Professional Excellence from ACVIM


Dr. Mark E. Peterson has been awarded the Robert W. Kirk Award for Professional Excellence by the American College of Veterinary Internal Medicine (ACVIM).

This award is presented annually to an ACVIM Diplomate with an outstanding career in veterinary medicine, including national and international recognition for contributions and services in activities such as clinical medical practice, instruction, research and/or public service.

The ACVIM writes: “(Dr. Peterson) pioneered clinical work to identify canine hyperadrenocorticism and feline hyperthyroidism - now the most common endocrine disease of that species.

Dr. Peterson was also the first person to use radioiodine to treat feline hyperthyroidism, now the preferred therapy. Dr. Peterson’s dedication to the feline hyperthyroidism makes him a truly distinguished contributor to the field of veterinary medicine and to the ACVIM.”


Dr. John Randolph presented the award to Dr. Peterson, and his presentation included a few quotes from fellow veterinarians:

“He is an important role model for private practice internists. He has shown …that it is possible to do research, teach, and publish while being in private practice and continuing to see a high volume of patients.”

Another colleague: “Dr. Peterson has not defined his work by merely cataloguing disease syndromes in review papers or book chapters. Rather, he frequently challenges long-held unproven presumptions through thoughtful hypothesis-driven evidence-based outcome studies that include significant case numbers.”

“His impact on veterinary medicine through his keen clinical observations and seminal research publications is astonishing especially considering that most of his work has been completed in clinical practice settings."


“While his contributions to veterinary medicine make him a very special veterinarian, his personal attributes make him an exceptional human being. He is one of the most cheerful and exciting people I have ever met. His humbleness as well as his ability to believe in everyone’s potential has been an example to me.” 


Dr. Peterson is humbled to be honored with the Robert W. Kirk Award and will continue his research to further the knowledge of feline and canine endocrine disorders. To learn more about Dr. Peterson's current research studies, click here.

Tuesday, September 12, 2017

The Mystery of the Wasting House Cat: Watch the Lecture Online

IDEXX has very kindly made the video recording of my August 25th Fellows Presentation available online. 

The Mystery of the Wasting House Cat was a lecture I presented on their Portland, Maine campus. 

Watch it here (90 minute lecture).

Tuesday, July 11, 2017

Dr. Peterson Recognized for Contribution to Feline Medicine


Mark Peterson has been awarded the International Society of Feline Medicine (ISFM) and Hill’s Pet Nutrition Award for Outstanding Contributions to the Advancement of Feline Medicine.

Dr Peterson is well known for his clinical work, research and teaching in veterinary endocrinology – and, for more than 35 years, has focused most of his research on advancing understanding of endocrine disorders in dogs and cats.

He has a special interest in hyperthyroidism and diabetes mellitus in cats, and was the first vet to document hyperthyroidism in cats (in 1979) and the first to treat hyperthyroid cats with radioiodine (in 1980).

Dr Peterson was also the first person to document acromegaly, hypoparathyroidism, insulinoma and Addison’s disease in cats.

Dr Peterson has published more than 500 journal articles, book chapters and research abstracts, and has received several other distinguished awards during his career.


ISFM veterinary director Andy Sparkes said: “Very few people can claim to have had anything like the impact Mark Peterson has had in the field of veterinary science and feline medicine.

“We are absolutely thrilled to be able to give Mark the ISFM/Hill’s Award for Outstanding Contributions to the Advancement of Feline Medicine. There can be no more worthy recipient, and Mark’s numerous contributions to our knowledge and understanding of feline endocrinology have impacted the health of cats all over the world.”
article courtesy of Vet Times

Click below to watch Dr. Peterson receiving the award:


Monday, August 3, 2015

Hypothyroidism in Cats—How is it Diagnosed and Treated?


Earlier this year, Dr. Mark Peterson participated in an Endocrinology course organized by the American College of Veterinary Internal Medicine (ACVIM). An overview of his lecture on feline hypothyroidism was summarized by Dr. Jennifer Garcia and published in the July 2015 issue of Veterinary Medicine. To access this article online, click here.

Hypothyroidism in cats—how is it diagnosed and treated? 
More cats may be affected by this disease than you think, and even cats with subclinical or mild forms may benefit from thyroid replacement therapy. In his presentation at the American College of Veterinary Internal Medicine (ACVIM) Small Animal Internal Medicine Endocrinology Course “Feline hypothyroidism: Current aspects on prevalence, diagnosis, and treatment,” Mark E. Peterson, DVM, DACVIM, noted that the number of cats with this disorder may be higher than we think and that many of these cats may benefit from therapy. Peterson explained that most cases of hypothyroidism in cats are iatrogenic in nature—after iodine-131 therapy, antithyroid drug therapy or thyroidectomy. Congenital and adult-onset forms of the disease occur but are considered rare.

As clinicians, we need to be more aware of this disease since even cats with subclinical or mild forms may benefit from thyroid replacement therapy. Peterson pointed out that up to 20% to 50% of cats with hypothyroidism may have azotemia, which will improve with treatment of the hypothyroidism. Diagnosing hypothyroidism in cats could be challenging, as even cats that are ultimately diagnosed with this disorder may initially have a thyroxine (T4) concentration in the low end of the reference range. The same can be true of a free T4 concentration, even if performed by using equilibrium dialysis.

Patient evaluation and monitoring
For patients in which hypothyroidism is suspected, either based on clinical signs or history (e.g. post iodine-131 therapy), Peterson recommends evaluating the T4 concentration in conjunction with a thyroid-stimulating hormone (TSH) concentration. While the only commercially available TSH assay is canine-specific, the assay cross-reacts with feline TSH as well. As in dogs, finding a low or low-normal T4 concentration in conjunction with an elevated TSH concentration is supportive of a diagnosis of hypothyroidism in cats.

Three months after iodine-131 therapy or antithyroid drug therapy is initiated or a thyroidectomy is performed, Peterson recommends monitoring T4 concentrations for up to six months. This should be considered sooner in cats that develop evidence of renal disease. He suggests that a post-treatment T4 concentration should be in the mid-normal range. Cats with values lower than this should have a measurement of their TSH concentration, but Peterson says some cats will experience an increase in their TSH concentration prior to a decrease in their T4 concentration.

Treatment recommendations 
So which cats should be treated with thyroid hormone therapy? Peterson suggests that cats that have supportive clinical signs—lethargy and weight gain—and low T4 or high TSH concentrations should be treated. Cats that have no clinical signs but have supportive laboratory test results and azotemia should also be treated.

For cats that require thyroid hormone supplementation, Peterson recommends a starting dose of levothyroxine 0.075 mg orally twice a day. This is higher than what is commonly used in dogs because cats metabolize the hormone much more quickly and don’t absorb it as well as dogs. Administration on an empty stomach is recommended. To monitor cats that are receiving replacement therapy, Peterson recommends a four-hour post-pill T4 concentration with a therapeutic goal in the mid-normal range.

Friday, July 31, 2015

Diagnosing Feline Hyperthyroidism: Not Always as Simple as One Might Believe


Earlier this year, Dr. Mark Peterson participated in an Endocrinology course organized by the American College of Veterinary Internal Medicine (ACVIM). An overview of his lecture on "Diagnosing feline hyperthyroidism" was summarized by Dr. Jennifer Garcia and published in the July 2015 issue of Veterinary Medicine. To access this article online, click here.

Diagnosing feline hyperthyroidism: It's not always as simple as it seems

Don't rely too heavily on T4 concentrations since cats can have a false elevation.

In his presentation, “Diagnosis of hyperthyroidism: A critical evaluation of our current available tests,” Mark Peterson, DVM, DACVIM, discussed some of the pitfalls in relying too heavily on thyroid (thyroxine, or T4) testing alone. While a total T4 concentration will be enough to make an accurate diagnosis of hyperthyroidism in more than 90% of cases, he warned to always pay attention to the clinical signs and physical examination findings. There are cats that can have a false elevation in their T4 concentration, so supportive clinical signs as well as a palpable thyroid nodule will help rule in or rule out the diagnosis.

When it comes to successfully palpating for evidence of a thyroid nodule, Peterson detailed a few of his favorite techniques:
  • Stand behind the cat with the cat facing away from you—the cat feels less stressed if it can’t see you. Peterson also puts the cat in a basket with a towel so the cat feels more secure and is less squirmy. Use your thumb and index finger to gently run the length of the trachea from the larynx to the thoracic inlet.
  • Alternatively, with the cat in the same position, turn its head to the left and palpate. Repeat with the cat’s head turned in the other direction.
Examine the cat from behind, with the cat facing the owner.

For patients in which a thyroid nodule can be palpated but there are no clinical signs and there is no elevation in T4 concentration, he recommends monitoring signs at home and rechecking the level in six to 12 months.

Peterson also noted that there are different cut-off values from laboratory to laboratory. This means that a T4 concentration that is normal at one laboratory, may actually be elevated at another. This serves as another reminder of the importance of the physical examination and clinical signs when trying to diagnose hyperthyroidism.

Monday, June 15, 2015

When To Start Thyroid Hormone Replacement in Cats Treated with Radioiodine (I-131)


I have a question about thyroid hormone supplementation for iatrogenic hypothyroidism, especially in cats treated with radioiodine (I-131). More specifically, how long after radioactive iodine therapy do you wait before recommending supplementing hypothyroid cats with thyroxine?

I work as a small animal internist at a referral hospital where we treat hyperthyroid cats with radioiodine. After treatment, we routinely run serum T4 and free T4 concentrations and full blood work 30 and 90 days after the cat is discharged. I have found that about 20% of these cats are biochemically hypothyroid (low total or free T4 values) at the 30-day recheck, but many of these cats will revert to normal by the 90-day recheck. The other internist at my practice supplements these cats with L-thyroxine at the first recheck if the serum T4 and free T4 values are low. She does this even if they are not azotemic, with the rationale being that the studies show that hypothyroid cats develop worsening azotemia, which can affect their survival (1).

I am not sure if this is the best approach since I have heard that the residual thyroid follicles may take a few months to regain full function after being suppressed by the over-active thyroid tissue for so long. However, I just want to do what's best (don't we all!)

Thank you so much. I enjoy reading your website and attending your lectures at conferences.

My Response:

First of all, I don't find that free T4 determinations are all that helpful in the diagnosis of feline hypothyroidism (2-4). Many cats treated with radioiodine with maintain low-normal values for both total and free T4 but develop high serum TSH concentrations, a situation commonly referred to as subclinical hypothyroidism in human patients. The problem with our cats, however, is that although most of these cats do remain nonclinical for hypothyroidism, many will develop azotemia that will progressively worsen without treatment with thyroid hormone replacement.

So what I do is as follows: at 30-days post-treatment, I monitor serum concentrations of T4, free T4, and TSH, along with a serum chemistry panel to follow kidney values. If T4 or free T4 values fall into the lower third of the reference range (below 1.5-2.0 µg/dl; reference interval ≈1-4 µg/dl) and TSH rises (above 0.5-0.6 ng/dl; reference range, 0.03-0.03 ng/ml), then the cat is mildly hypothyroid. Some of these cats will recover enough thyroid function to end up as euthyroid, but most remain mildly hypothyroid at both 3 and 6 months, at least based on the finding of high TSH concentrations.

In these cats with mild or subclinical hypothyroidism, I don't like to treat with levothyroxine (LT4) at this time unless evidence of chronic kidney disease (CKD) has developed, with serum creatinine values rising from normal to greater than 2.0 mg/dl. However, this definitely indicates the need for LT4 replacement in order to help maintain renal perfusion and stabilize the serum creatinine concentrations (3-5).

If we decide not to treat (which is generally the case unless new azotemia has developed), then we monitor again with the same thyroid and renal profiles at 3- and 6 months. Again, if T4 falls into the low-normal range (less than 1.5-2.0 µg/dl) and TSH is clearly high (above 0.5-0.6 ng/dl), I would definitely supplement if new or worsening azotemia is detected. If no azotemia is present, I generally continue to monitor and don't supplement with LT4 unless azotemia does develop.

Now, if the serum T4 is below normal and the TSH is clearly high at 3 or 6 months (or later), then the cat has overt hypothyroidism (no longer subclinical) and I would definitely supplement with L-T4 (2-4). Many of these cats are still not very symptomatic, but that may simply be a matter of time. If left untreated for 1 to 2 years, most of those cats will develop classical signs of hypothyroidism (eg, lethargy, hair loss, etc).

So in your case, I would add-in serum TSH to your monitoring protocol. If your owners find that too expensive, then I would replace the free T4 measurement with TSH determination, which is more more helpful in monitoring for cats treated with radioiodine.

References:
  1. Williams TL, Peak KJ, Brodbelt D, et al. Survival and the development of azotemia after treatment of hyperthyroid cats. J Vet Intern Med 2010;24:863-869. 
  2. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism. Compend Contin Educ Vet 2013;35:E4.  
  3. Peterson ME. Diagnosis and management of iatrogenic hypothyroidism In: Little SE, ed. August's Consultations in Feline Internal Medicine: Elsevier, 2014;in press.
  4. Peterson ME, Guterl JN.Subclinical iatrogenic hypothyroidism in the cat: Clinical, laboratory, and thyroid scintigraphic findings in 35 cases. J Vet Intern Med 2015;29:448-449.
  5. Williams TL, Elliott J, Syme HM. Effect on renal function of restoration of euthyroidism in hyperthyroid cats with iatrogenic hypothyroidism. J Vet Intern Med 2014;28:1251-1255.

Monday, May 11, 2015

Top Endocrine Publications of 2014: The Feline Thyroid Gland


In my fourth compilation of the canine and feline endocrine publications of 2014, I’m moving on to disorders of the feline thyroid gland. Listed below are 32 papers that deal with a variety of thyroid gland topics of issues of clinical importance in cats.

These range from from a survey of owners' perceptions and experiences after using radioiodine to treat their hyperthyroid cats (1) to the results of an online survey to determine owner experiences and opinions on the management of their cats using oral anti-thyroid medications (14); from case reports of methimazole or carbimazole-induced toxicity in cats with hyperthyroidism (3,5,19) to a number of publications involving various issues of medical treatment with methimazole (2,4,7,14,15,20); from a study of the concurrent diseases detected in hyperthyroid cats undergoing assessment for radioiodine treatment (25) to concurrent diseases and conditions in cats with renal infarcts (including hyperthyroidism (12); and finally, from studies investigating the efficacy of an iodine-restricted diet for management of cats with hyperthyroidism (9,30) to other forms of dietary management for this endocrine disease (19,24).

Finally, 2 investigations add further data concerning chronic renal disease in hyperthyroid cats (31,32), as well as the fact that iatrogenic hypothyroidism contributes to azotemia in these cats (31). A number of 2014 publications deal with the rising prevalence and/or etiopathogenesis of hyperthyroidism in cats (6,16,17,21,22,23,29). Unfortunately, further studies are needed to better define the cause(s) of this perplexing disease (download my review paper for more discussion) (23).

References:
  1. Boland LA, Murray JK, Bovens CP, et al. A survey of owners' perceptions and experiences of radioiodine treatment of feline hyperthyroidism in the UK. J Feline Med Surg 2014;16:663-670. 
  2. Boretti FS, Sieber-Ruckstuhl NS, Schafer S, et al. Transdermal application of methimazole in hyperthyroid cats: a long-term follow-up study. J Feline Med Surg 2014;16:453-459. 
  3. Bowlt K, Cattin I, Stewart J. Carbimazole-associated hypersensitivity vasculitis in a cat. J Small Anim Pract 2014;55:643-647. 
  4. Bruyette D. Methimazole management of feline hyperthyroidism. Today's Veterinary Practice 2014;July/August:38-41.
  5. Castro Lopez J, Lloret A, Ravera I, et al. Pyogranulomatous mural folliculitis in a cat treated with methimazole. J Feline Med Surg 2014;16:527-531. 
  6. Chow K, Beatty JA, Barrs VR, et al. PBDEs and feline hyperthyroidism. Vet Rec 2014;175:433-434. 
  7. Daminet S, Kooistra HS, Fracassi F, et al. Best practice for the pharmacological management of hyperthyroid cats with antithyroid drugs. J Small Anim Pract 2014;55:4-13. 
  8. Daniel GB, Neelis DA. Thyroid scintigraphy in veterinary medicine. Semin Nucl Med 2014;44:24-34. 
  9. Fritsch DA, Allen TA, Dodd DE, et al. A restricted iodine food reduces circulating thyroxine concentrations in cats with hyperthyroidism. Intern J Appl Res Vet Med 2014;12:24-32. 
  10. Fryers A, Elwood C. Hypokalaemia in a hyperthyroid domestic shorthair cat with adrenal hyperplasia. J Feline Med Surg 2014;16:853-857. 
  11. Galgano M, Spalla I, Callegari C, et al. Primary hypothyroidism and thyroid goiter in an adult cat. J Vet Intern Med 2014;28:682-686. 
  12. Hickey MC, Jandrey K, Farrell KS, et al. Concurrent diseases and conditions in cats with renal infarcts. J Vet Intern Med 2014;28:319-323. 
  13. Higgs P, Costa M, Freke A, et al. Measurement of thyroxine and cortisol in canine and feline blood samples using two immunoassay analysers. J Small Anim Pract 2014;55:153–159. http://onlinelibrary.wiley.com/doi/10.1111/jsap.12181/abstract
  14. Higgs P, Murray JK, Hibbert A. Medical management and monitoring of the hyperthyroid cat: a survey of UK general practitioners. J Feline Med Surg 2014;16:788-795. 
  15. Hill K, Gieseg M, Bridges J, et al. The pharmacokinetics of methimazole in a novel lipophilic formulation administered transdermally to healthy cats. N Z Vet J 2014;62:208-213. 
  16. Hill KE, Shaw IC. Does exposure to thyroxine-mimics cause feline thyroid hyperplasia? Vet Rec 2014;175:228-229. 
  17. Kooistra HS. Feline hyperthyroidism: a common disorder with unknown pathogenesis. Vet Rec 2014;175:456-457. 
  18. Kujawa A, Olias P, Bottcher A, et al. Thyroid transcription factor-1 is a specific marker of benign but not malignant feline lung tumours. J Comp Pathol 2014;151:19-24. 
  19. Laflamme D, Gunn-Moore D. Nutrition of aging cats. Vet Clin North Am Small Anim Pract 2014;44:761-774, vi. 
  20. Mardell EJ. Diagnosis and management of feline hyperthyroidism. In Practice 2014;35:162-170.
  21. McLean JL, Lobetti RG, Schoeman JP. Worldwide prevalence and risk factors for feline hyperthyroidism: A review. J S Afr Vet Assoc 2014;85:1097. 
  22. O'Neill DG, Church DB, McGreevy PD, et al. Prevalence of disorders recorded in cats attending primary-care veterinary practices in England. Vet J 2014;202:286-291. 
  23. Peterson ME. Feline hyperthyroidism: an animal model for toxic nodular goiter. J Endocrinol 2014;223:T97-T114. 
  24. Peterson ME, Eirmann L. Dietary management of feline endocrine disease. Vet Clin North Am Small Anim Pract2014;44:775-788. 
  25. Puig J, Cattin I, Seth M. Concurrent diseases in hyperthyroid cats undergoing assessment prior to radioiodine treatment. J Feline Med Surg 2014. 
  26. Rasmussen SH, Andersen HH, Kjelgaard-Hansen M. Combined assessment of serum free and total T4 in a general clinical setting seemingly has limited potential in improving diagnostic accuracy of thyroid dysfunction in dogs and cats (Letter). Vet Clin Pathol 2014;43:1-3. 
  27. Sangster JK, Panciera DL, Abbott JA, et al. Cardiac biomarkers in hyperthyroid cats. J Vet Intern Med 2014;28:465-472. 
  28. Schober KE, Kent AM, Aeffner F. Tachycardia-induced cardiomyopathy in a cat. Schweiz Arch Tierheilkd 2014;156:133-139. 
  29. Stephens MJ, Neill DG, Church DB, et al. Feline hyperthyroidism reported in primary-care veterinary practices in England: prevalence, associated factors and spatial distribution. Vet Rec 2014;175:458. 
  30. van der Kooij M, Becvarova I, Meyer HP, et al. Effects of an iodine-restricted food on client-owned cats with hyperthyroidism. J Feline Med Surg 2014;16:491-498. 
  31. Williams TL, Elliott J, Syme HM. Effect on renal function of restoration of euthyroidism in hyperthyroid cats with iatrogenic hypothyroidism. J Vet Intern Med 2014;28:1251-1255. 
  32. Williams TL, Elliott J, Syme HM. Association between urinary vascular endothelial growth factor excretion and chronic kidney disease in hyperthyroid cats. Res Vet Sci 2014;96:436-441. 

Friday, May 1, 2015

Can Thyroid Function be Monitored in Hypothyroid Dogs Treated with Steroids?


Some of my hypothyroid dogs also intermittently receive corticosteroids at anti-inflammatory doses to treat flare-ups of allergic dermatitis. Does the corticosteroid therapy affect thyroid hormone concentrations and interfere with testing—either for the initial diagnosis or for therapeutic monitoring purposes?

Are thyroxine supplementation dosage adjustments needed during corticosteroid therapy?

My Response:

Glucocorticoids are known to affect serum thyroid hormone concentrations in dogs (1-4). Dogs receiving anti-inflammatory or immunosuppressive doses of prednisone or prednisolone can have altered thyroid function test results, especially if they have been receiving the corticosteroids for more than 2 weeks. In general, I would prefer to see dogs off of all forms of corticosteroids for at least 4-to 6-weeks before trying to evaluate thyroid function.

In dogs receiving thyroid hormone supplementation that subsequently begin to receive corticosteroid therapy, we generally do not perform laboratory tests to evaluate thyroid function until the corticosteroids have been removed. However, one paper in 2011 by O'Neill et al did study the effect of short-term anti-inflammatory doses of prednisone in dogs with naturally occurring hypothyroidism (5).

In that report, 8 dogs with spontaneous hypothyroidism already being treated with levothyroxine (L-T4) were given prednisone (1 mg/kg orally) daily for 7 days and then on alternate days for 14 days (5). Serum total thyroxine (T4), free T4, and thyroid-stimulating hormone (TSH) concentrations were measured on days 7, 21, and 28 and compared with baseline data. Results showed that total T4 concentrations were significantly decreased after 7 days of an anti-inflammatory dose of prednisone, but T4 values were not significantly altered from baseline on days 21 or 28 while on every other day dosing. Free T4 and TSH concentrations were not significantly altered from baseline at any point during the study.

My Bottom Line

Based on the results of the O'Neill study (5) administration of prednisone at a dosage of 1 mg/kg given orally once daily for 7 days decreased total T4 concentrations, while free T4 concentrations were unchanged. This suggests that free T4 concentrations may be less affected by daily prednisone administration. Anti-inflammatory doses of prednisone, when administered every other day, did not interfere with thyroid hormone monitoring.

These results also agree with two previous studies, which showed that anti-inflammatory prednisone did not affect serum total T4 concentrations in thyroid-supplemented, thyroidectomized dogs (3,6).

So, at least with short-term administration of a single daily anti-inflammatory dose of prednisone, thyroid function may be evaluated by looking at free T4 or TSH concentrations. However, these results cannot be generalized to dogs taking prednisone for longer periods or at higher immunosuppressive doses (2-4 mg/kg/day).

References

  1. Woltz HH, Thompson FN, Kemppainen RJ, et al. Effect of prednisone on thyroid gland morphology and plasma thyroxine and triiodothyronine concentrations in the dog. Am J Vet Res 1983;44:2000-2003. 
  2. Torres SM, McKeever PJ, Johnston SD. Effect of oral administration of prednisolone on thyroid function in dogs. Am J Vet Res 1991;52:416-421. 
  3. Moore GE, Ferguson DC, Hoenig M. Effects of oral administration of anti-inflammatory doses of prednisone on thyroid hormone response to thyrotropin-releasing hormone and thyrotropin in clinically normal dogs. Am J Vet Res 1993;54:130-135. 
  4. Daminet S, Paradis M, Refsal KR, et al. Short-term influence of prednisone and phenobarbital on thyroid function in euthyroid dogs. Can Vet J 1999;40:411-415. 
  5. O'Neill SH, Frank LA, Reynolds LM. Effect of an anti-inflammatory dose of prednisone on thyroid hormone monitoring in hypothyroid dogs. Vet Dermatol 2011;22:202-205.
  6. Kaptein EM, Moore GE, Ferguson DC et al. Effects of prednisone on thyroxine and 3,5,3’-triiodothyronine metabolism in normal dogs. Endocrinology 1992;130:1669–1679.

Wednesday, April 22, 2015

Methimazole Treatment of Canine Hyperthyroidism


My patient is a 13-year old spayed female Golden retriever that presented with history of progressive polydispia, polyuria, panting, and weight loss despite a good appetite. On my physical examination, I palpated a freely-movable right cervical mass (2-3 inch in diameter) in the area of the thyroid gland. I aspirated the mass, and the results of thyroid cytology were consistent with carcinoma of thyroid origin.

Chest radiographs were clear, with no metastasis detected. Routine blood testing (CBC and serum chemistry panel) was normal except for a slightly high serum alkaline phosphatase (281 U/L; reference interval, 20-120 IU/L).

Results of a serum thyroid panel showed a high total T4 concentration (6.5 µg/dl; normal, 1-4 µg/dl), a high free T4 by dialysis (75 pmol/L; normal, 10-50 pmol/L), and suppressed cTSH value (less than 0.03 ng/ml).

I advised a thyroid biopsy and thyroidectomy, but owner is reluctant to do because of the expense and dog’s older age. If this dog is hyperthyroid, what is the treatment of choice? Do I have any medical options to control the signs? Can I use methimazole to lower the high serum T4 and free T4 values?

My Response:

I agree that this dog likely has a hyperfunctioning thyroid tumor, based on the clinical features, high T4 and free T4, suppressed TSH concentration, and results of the thyroid cytology (1-4). As in cats (5), high serum alkaline phosphatase activity is also seen in some dogs with hyperthyroidism, so that finding too goes along with the diagnosis.

Most dogs with hyperfunctioning thyroid tumors have thyroid carcinoma. In general, these thyroid carcinomas are quite malignant in dogs and pulmonary metastasis in not uncommon (1-4).

Methimazole can be used to control the hyperthyroidism but this will not stop tumor growth, local invasion, or metastasis. Radioiodine, surgery followed by chemotherapy, or local external radiation are all options (1-4). In this dog, radioiodine might be ideal because the tumor would likely concentrate the injected radioiodine very nicely; it may result in cure, even if we have undetected metastasis (6).

If methimazole is used, I'd start with 5 mg twice daily, in a dog of this size. You should adjust the dose as needed, monitoring serum T4 concentrations as you would in a hyperthyroid cat. Again, without definitive treatment, this dog’s thyroid tumor will likely metastasize and eventually lead to the dog's death.

References:
  1. Rijnberk A. Hyperthyroidism in the dog and its treatment with radioactive iodide. Tijdschr Diergeneeskd 1966;91:789-794.
  2. Rijnberk A, der Kinderen PJ. Toxic thyroid carcinoma in the dog. Acta Endocrinological 1969;Supplement 138:177.
  3. Peterson ME, Kintzer PP, Hurley JR, et al. Radioactive iodine treatment of a functional thyroid carcinoma producing hyperthyroidism in a dog. J Vet Intern Med 1989;3:20-25. 
  4. Peterson ME. Hyperthyroidism and thyroid tumors in dogs In: Melian C, Perez Alenza MD, Peterson ME, et al., eds. Manual de Endocrinología en Pequeños Animales (Manual of Small Animal Endocrinology). Barcelona, Spain: Multimedica, 2008;113-125.
  5. Berent AC, Drobatz KJ, Ziemer L, et al. Liver function incats with hyperthyroidism before and after 131I therapy. J Vet Intern Med 2007;21:1217-1223. 
  6. Turrel JM, McEntee MC, Burke BP, et al. Sodium iodide I 131 treatment of dogs with nonresectable thyroid tumors: 39cases (1990-2003). J Am Vet Med Assoc 2006;229:542-548. 

Friday, April 17, 2015

Hypothyroidism Associated with Acromegaly and Insulin-resistant Diabetes Mellitus in a Samoyed



PAPER REVIEW

Hypothyroidism Associated with Acromegaly and Insulin-resistant Diabetes Mellitus in a Samoyed

by T. Johnstone, E. Terzo, and C. Mooney

Background
Although both hypothyroidism and diabetes mellitus are common disorders of dogs, it is relatively uncommon for a dog to develop both diseases concurrently. Insulin-resistant diabetes has been reported in a few dogs with underlying hypothyroidism (1-3), but the mechanisms underlying the insulin resistance is not clear. However, hypothyroidism may lead to alteration of other hormones that influence glucose metabolism, and previous studies of hypothyroid dogs have documented excessive production of growth hormone (GH), a known insulin antagonist (4,5). In one study, Beagles with radioiodine-induced hypothyroidism were reported to have a progressive elevation in serum GH concentrations (a known insulin antagonist), but none of those dogs developed overt diabetes (6).

The purpose of this case report by Johnstone et al. (7) is to describe a dog diagnosed with naturally occurring hypothyroidism that also had concurrent signs of acromegaly and diabetes. In this dog, the insulin resistance and associated diabetic state was reversed with appropriate L-thyroxine supplementation.

Case Report
A 4-year-old male entire Samoyed presented with an 8-month history of pedal hyperkeratosis and shifting lameness, which had been unresponsive to zinc supplementation, antibiotics, and glucocorticoid therapy. The dog also exhibited exercise intolerance of 12-months duration. Recently, polydipsia and polyuria were also noted.

Marked interdental spacing
On physical examination, obesity, poor coat condition, widened spaces between the teeth, and mild respiratory stridor were noted (see Figure).

Initial laboratory test results confirmed marked hyperglycemia, consistent with diabetes mellitus. Serum concentrations of total thyroxine (T4), free T4 by equilibrium dialysis, and free triiodothyronine (T3) were below the reference limits, and canine thyroid-stimulating hormone (cTSH) levels was above the reference limits, diagnostic for primary hypothyroidism.

Before treatment for diabetes and hypothyroidism was initiated, further tests were performed to investigate a potential link between these two conditions. An upper airway examination revealed mild soft tissue hypertrophy but normal laryngeal function. The pretreatment serum insulin concentration was above the reference limits, suggesting endogenous insulin resistance. A baseline serum IGF-1 concentration was within reference limits. However, basal serum GH concentrations were markedly elevated, and a further paradoxical increase in GH concentration was noted after administration of thyrotropin-releasing hormone (TRH). CT imaging of the pituitary suggested slight enlargement of the gland but no pituitary tumor was evident.

Overall, the high serum GH concentrations, together with the clinical features (e.g., widened interdental spaces, and mild respiratory stridor), was considered diagnostic for acromegaly.

Treatment was initiated using both insulin (Caninsulin, 20 IU every 12 h) and thyroid supplementation (levothyroxine, L-T4, 0.02 mg/kg every 24 h). Over the next few weeks, the exogenous insulin requirements started to decrease, and all exogenous insulin was discontinued 155 days later. The dog remained euglycemic 2 years after diagnosis, with continued daily supplementation of L-T4 alone.

My Bottom Line:

In this dog, diabetes mellitus was thought to be a secondary consequence of insulin resistance, as demonstrated by the high pretreatment serum insulin concentration. Insulin-resistant diabetes mellitus has been previously described in a few dogs with naturally occurring hypothyroidism (1-3), but the pathogenesis for the concurrent development of the two diseases is not totally understood.

It has been reported, however, that primary hypothyroidism can lead to with functional and morphological changes of the pituitary gland (4-6). Most notably, transdifferentiation of pituitary TSH-producing cells to cells producing both TSH and GH has been documented (6), which can result in increased GH production and secretion in these dogs. The high basal GH concentration and the paradoxical increase of GH after stimulation with TRH in this dog (7) confirmed that hypothyroidism-induced acromegaly and secondary diabetes was likely.

Although the true prevalence of hypothyroidism-induced acromegaly in dogs is not known, our clinical experience suggests that hypothyroidism is rarely associated with acromegaly. However, it is likely that acromegaly goes under-diagnosed in some hypothyroid dogs since many of the clinical signs of both disorders are similar. Furthermore, pituitary transdifferentiation of TSH to GH hypersecretion would be expected to take a long time to develop, and therefore, hypothyroidism-induced acromegaly may only become significant when hypothyroidism remains undiagnosed or untreated for several months to years (6).

In this dog, the fact that the diabetic state resolved during treatment with L-T4 suggests that the pituitary GH overproduction resolved as euthyroidism was achieved. Unfortunately, repeat TRH stimulation testing or serum GH measurements were not repeated after resolution of the diabetic state, so we can not say for certain that the acromegalic state truly resolved. Further studies certainly are needed to investigate hypothyroidism-induced GH production, but this interesting case certainly does add some insight to what may be going on in these dogs.

References:
  1. Blois SL, Dickie E, Kruth SA, et al. Multiple endocrine diseases in dogs: 35 cases (1996-2009). J Am Vet Med Assoc 2011;238:1616-1621. 
  2. Ford SL, Nelson RW, Feldman EC, et al. Insulin resistance in three dogs with hypothyroidism and diabetes mellitus. J Am Vet Med Assoc 1993;202:1478-1480. 
  3. Hess RS, Saunders HM, Van Winkle TJ, et al. Concurrent disorders in dogs with diabetes mellitus: 221 cases (1993-1998). J Am Vet Med Assoc 2000;217:1166-1173. 
  4. Lee WM, Diaz-Espineira M, Mol JA, et al. Primary hypothyroidism in dogs is associated with elevated GH release. J Endocrinol 2001;168:59-66. 
  5. Diaz-Espineira MM, Galac S, Mol JA, et al. Thyrotropin-releasing hormone-induced growth hormone secretion in dogs with primary hypothyroidism. Domest Anim Endocrinol 2008;34:176-181. 
  6. Diaz-Espineira MM, Mol JA, van den Ingh TS, et al. Functional and morphological changes in the adenohypophysis of dogs with induced primary hypothyroidism: loss of TSH hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with transdifferentiation. Domest Anim Endocrinol 2008;35:98-111. 
  7. Johnstone T, Terzo E, Mooney CT. Hypothyroidism associated with acromegaly and insulin-resistant diabetes mellitus in a Samoyed. Aust Vet J 2014;92:437-442.