Q & A: Addison's Disease in a Puppy

Maxine is a 6-month-old female Puggle (a small breed of dog created by mating a pug and beagle) that presented with a 2-day history of lethargy, anorexia, and vomiting. My physical examination revealed extreme dehydration, depression, and a uremic smell to the breath.

Results of CBC and serum chemistry analysis revealed a high urea nitrogen (110 mg/dl) with a normal creatinine concentration(1.9 mg/dl), as well as hyperphosphatemia (14.0 mg/dl). The urine specific gravity was 1.020 with an inactive sediment. Serum electrolyte changes included moderate hypercalcemia (calcium = 13.3 mg/dl), mild hyponatremia (sodium = 134 mEq/L), marked hyperkalemia (potassium = 8.8 mEq/L), and a low Na:K ratio (15.9).

I submitted a resting cortisol concentration to the lab and started the dog on intravenous 0.9% NaCl, ampicillin, and famotidine. By the next morning, the dog was eating well and was much brighter. Repeat chemistry panel showed resolution of the azotemia (BUN = 30 mg/dl and creatinine = 0.9 mg/dl). However, hyperkalemia (potassium = 7.0 mEq/L), hyponatremia (sodium = 135 mEq/L), and low Na:K ratio (19.2) persisted. The resting cortisol concentration was very low at 0.2 μg/dl.

The dog continued to do well and was eating well with no vomiting on continued fluid therapy. However, 12 hours after stopping the IV fluids, the dog again became anorexic, depressed, and hypothermic.

Is this puppy an Addisonian? Do I have to do an ACTH stimulation test to confirm the diagnosis or is that resting cortisol low enough to diagnose Addison's disease? Should I start her on Percorten-V and prednisone?

The owner is limited financially. What's the cheapest way to treat her?

My Response:

I would strongly recommend that you perform an ACTH stimulation test ASAP to confirm Addison's disease, given that it's a lifelong disease that is quite expensive to control and treat. There are other conditions that could produce hyponatremia and hyperkalemia and mimic true Addison's disease (e.g., whipworms causing pseudo-Addison's)(1). Although this dog probably does have Addison's disease based on the clinical signs and low basal cortisol concentration (2), I've seen other dogs that appeared to be Addisonian that turned out not to be when the ACTH stimulation test was done.

The hypercalemia is also consistent with Addison's disease and develops in 25% of dogs in adrenal crisis (3). If the ACTH stimulation test confirms Addison's disease, the serum calcium should normalize within a day or two of glucocorticoid and mineralocorticoid replacement. If not, a workup for hypercalcemia should also be considered.

Addison's disease, not matter what drugs given, is an expensive disease to treat. Although desoxycorticosterone pivalate (Percorten-V) is the most effective mineralocorticoid replacement in most dogs, fludrocortisone acetate (Florinef) also works well in most cases. If you have use generic fludrocortisone prepared by a compounding pharmacy, the drug generally costs much less to maintain an Addison's dog that does Percorten-V.

References:

1. Graves TK, Schall WD, Refsal K, et al. Basal and ACTH-stimulated plasma aldosterone concentrations are normal or increased in dogs with trichuriasis-associated pseudohypoadrenocorticism. Journal of Veterinary Internal Medicine 1994;8:287-289.
2. Lennon EM, Boyle TE, Hutchins RG, et al. Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005). Journal of the American Veterinary Medical Association 2007;231:413-416.
3. Peterson ME, Feinman JM. Hypercalcemia associated with hypoadrenocorticism in sixteen dogs. Journal of the American Veterinary Medical Association 1982;181:802-804.

Final Diagnosis and Outcome:

An ACTH stimulation test confirmed hypoadrenocorticism, based on an undetectable basal cortisol (less than 0.1 μg/dl) with no response to ACTH stimulation (post-ACTH cortisol - 0.2 μg/dl). Maxine has had an excellent clinical response to treatment with generic fludrocortisone (20 μg/kg)and low daily doses of prednisone (0.1 mg/kg). All of the serum electrolytes imbalances, including the hypercalcemia, hyperkalemia, and hyponatremia were completely resolved at the dog's initial 2-week recheck.

Q & A: Trouble Converting Cortisol Units

Cortisol

I am having the hardest time converting units for cortisol measurement. Can you help me with this conversion?

If the laboratory is reported the cortisol results in ng/ml, how do I convert to μg/dl? For example, if the lab has reported a cortisol measurement of 28.2 ng/ml, is that result equal to 2.82 μg/dl?

My Response:

Your conversion is correct. If you are interested, the  mathematical formula for future conversions is as follows:

• 28.2 ng/ml x 1 µg/1000 ng x 100 ml/1 dl = 2.82 µg/dl

There are many online sites that can help us do these conversions. Here's a web site that I have found helpful.

Personally, I had more difficulty in remembering how to convert traditional endocrine units commonly used in the UA to Standard International (SI) or molar units that some laboratories use to report hormone results. The calculator offered by Veterinary Information Network (VIN) is by far the best I've found (click here to use their calculator).

Top Endocrine Publications of 2010: The Canine Adrenal Gland

In my sixth compilation of the canine and feline endocrine publications of 2010, I’m moving on to disorders of the canine adrenal gland.

Listed below are 31 research papers written in 2010 that deal with a variety of adrenal gland issues of clinical importance in dogs.

These range from the investigations of hypoadrenocorticism (1, 14-16, 19, 29) to typical (3, 5, 8-10, 13, 17, 20, 24, 26, 30) and atypical (4, 6) hyperadrenocorticism; from diagnostic tests for Cushing's syndrome (17, 30) to studies of ultrasonography for evaluation  and differentiation of adrenal disease (5, 28);  and from trilostane (3,8, 9, 24) to studies of the efficacy of transsphenoidal surgery as treatment for Cushing's disease (13.

In addition, other studies include the investigation of urine and plasma catecholamines in diagnoses of canine pheochromocytoma (7, 11, 18,  23) to a review of canine chemodectoma (22); and from  studies of the endocrine hypertension (19, 25) to reports on the risks of human estrogen sprays to pets through contact with treated skin (28).

References:

1. Adissu HA, Hamel-Jolette A, Foster RA. Lymphocytic adenohypophysitis and adrenalitis in a dog with adrenal and thyroid atrophy. Veterinary Pathology 2010;47:1082-1085.
2. Adissu HA, Hayes G, Wood GA, et al. Cardiac myxosarcoma with adrenal adenoma and pituitary hyperplasia resembling Carney complex in a dog. Veterinary Pathology 2010;47:354-357.
3. Arteaga A, Dhand NK, McCann T, et al. Monitoring the response of canine hyperadrenocorticism to trilostane treatment by assessment of acute phase protein concentrations. The Journal of Small Animal Practice 2010;51:204-209.
4. Behrend EN, Kennis R. Atypical Cushing's syndrome in dogs: arguments for and against. The Veterinary Clinics of North America: Small Animal Practice 2010;40:285-296.
5. Benchekroun G, de Fornel-Thibaud P, Rodriguez Pineiro MI, et al. Ultrasonography criteria for differentiating ACTH dependency from ACTH independency in 47 dogs with hyperadrenocorticism and equivocal adrenal asymmetry. Journal of Veterinary Internal Medicine 2010;24:1077-1085.
6. Bromel C, Feldman EC, Davidson AP, et al. Serum 17-alpha-hydroxyprogesterone concentrations during the reproductive cycle in healthy dogs and dogs with hyperadrenocorticism. Journal of the American Veterinary Medical Association 2010;236:1208-1214.
7. Cameron KN, Monroe WE, Panciera DL, et al. The effects of illness on urinary catecholamines and their metabolites in dogs. Journal of Veterinary Internal Medicine 2010;24:1329-1336.
8. 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.
9. Galac S, Buijtels JJ, Mol JA, et al. Effects of trilostane on the pituitary-adrenocortical and renin-aldosterone axis in dogs with pituitary-dependent hypercortisolism. Veterinary Journal 2010;183:75-80.
10. Galac S, Kool MM, Naan EC, et al. Expression of the ACTH receptor, steroidogenic acute regulatory protein, and steroidogenic enzymes in canine cortisol-secreting adrenocortical tumors. Domestic Animal Endocrinology 2010;39:259-267.
11. Gostelow R, Syme H. Plasma metadrenalines in canine phaeochromocytoma. The Veterinary Record 2010;166:538.
12. Hanson JM, Mol JA, Meij BP. Expression of leukemia inhibitory factor and leukemia inhibitory factor receptor in the canine pituitary gland and corticotrope adenomas. Domestic Animal Endocrinology 2010;38:260-271.
13. Hara Y, Teshima T, Taoda T, et al. Efficacy of transsphenoidal surgery on endocrinological status and serum chemistry parameters in dogs with Cushing's disease. The Journal of Veterinary Medical Science 2010;72:397-404.
14. Hughes AM, Jokinen P, Bannasch DL, et al. Association of a dog leukocyte antigen class II haplotype with hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers. Tissue Antigens 2010;75:684-690.
15. Klein SC, Peterson ME. Canine hypoadrenocorticism: part I. The Canadian Veterinary Journal 2010;51:63-69.
16. Klein SC, Peterson ME. Canine hypoadrenocorticism: part II. The Canadian Veterinary Journal 2010;51:179-184.
17. Kooistra HS, Galac S. Recent advances in the diagnosis of Cushing's syndrome in dogs. The Veterinary Clinics of North America: Small Animal Practice 2010;40:259-267.
18. Kook PH, Grest P, Quante S, et al. Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a phaeochromocytoma. The Veterinary Record 2010;166:169-174.
19. Kook PH, Grest P, Raute-Kreinsen U, et al. Addison's disease due to bilateral adrenal malignancy in a dog. The Journal of Small Animal Practice 2010;51:333-336.
20. Lien YH, Hsiang TY, Huang HP. Associations among systemic blood pressure, microalbuminuria and albuminuria in dogs affected with pituitary- and adrenal-dependent hyperadrenocorticism. Acta Veterinaria Scandinavica 2010;52:61.
21. Mori N, Lee P, Muranaka S, et al. Predisposition for primary hyperlipidemia in Miniature Schnauzers and Shetland sheepdogs as compared to other canine breeds. Research in Veterinary Science 2010;88:394-399.
22. Noszczyk-Nowak A, Nowak M, Paslawska U, et al. Cases with manifestation of chemodectoma diagnosed in dogs in Department of Internal Diseases with Horses, Dogs and Cats Clinic, Veterinary Medicine Faculty, University of Environmental and Life Sciences, Wroclaw, Poland. Acta Veterinaria Scandinavica 2010;52:35.
23. Quante S, Boretti FS, Kook PH, et al. Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs. Journal of Veterinary Internal Medicine 2010;24:1093-1097.
24. Ramsey IK. Trilostane in dogs. The Veterinary clinics of North America Small Animal Practice 2010;40:269-283.
25. Reusch CE, Schellenberg S, Wenger M. Endocrine hypertension in small animals. The Veterinary Clinics of North America: Small Animal Practice 2010;40:335-352.
26. Trapani F, Del Basso De Caro ML, Insabato L, et al. Type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog. Folia histochemica et Cytobiologica 2010;48:403-406.
27. van Rijn SJ, Grinwis GC, Penning LC, et al. Expression of Ki-67, PCNA, and p27kip1 in canine pituitary corticotroph adenomas. Domestic Animal Endocrinology 2010;38:244-252.
28. Voelker R. Estrogen spray poses risks to children, pets through contact with treated skin. Journal of the American Medical Association 2010;304:953.
29. Wenger M, Mueller C, Kook PH, et al. Ultrasonographic evaluation of adrenal glands in dogs with primary hypoadrenocorticism or mimicking diseases. The Veterinary Record 2010;167:207-210.
30. Zeugswetter F, Bydzovsky N, Kampner D, et al. Tailored reference limits for urine corticoid:creatinine ratio in dogs to answer distinct clinical questions. The Veterinary Record 2010;167:997-1001.
31. Zimmerman KL, Panciera DL, Panciera RJ, et al. Hyperphosphatasemia and concurrent adrenal gland dysfunction in apparently healthy Scottish Terriers. Journal of the American Veterinary Medical Association 2010;237:178-186.

Q & A: Renal Disease in a Newly Diagnosed Hyperthyroid Cat

I have a 14-year-old, male DSH cat that I diagnosed recently with hyperthyroidism (serum T4 value = 10.9 μg/dl; reference range, 0.8-4.0 μg/dl). However, this cat has a 5-year history of clinical signs consistent with hyperthyroidism. The cat used to weigh 8.0 kg and now is only 2.6 kg!

The cat is now showing all of the classical clinical features of hyperthyroidism, including weight loss despite an increased appetite, vomiting, diarrhea, and polyuria with polydipsia. On physical examination, he has a very large left thyroid lobe, a heart murmur, and severe hypertension.

Serum chemistry analysis revealed a high urea nitrogen (62 mg/dl) with a normal creatinine (1.5 mg/dl). The urine specific gravity is 1.020.

I'm worried about concurrent renal disease in this cat. I've had poor luck treating severe, long-standing hyperthyroid cats like this one. Some of the other cats with concurrent hyperthyroidism and kidney disease that I've cared for in the past developed renal failure weeks after treating with low dose methimazole. Despite stopping the drug and starting fluid therapy, I couldn't reverse the renal azotemia in some of those cats.

So, do you have a suggestion for handling hyperthyroid cats like this?

Thank you very much.

My Response:

First of all, it is certainly clear that this cat as chronic kidney disease (CKD). The serum urea nitrogen concentration is about twice the upper limit of the reference range.

Although the serum creatinine is normal, it's very likely that the creatinine value would be quite high if the cat didn't have muscle wasting associated with the hyperthyroidism. (Remember, creatinine is made in muscle tissue.) In addition, cats with moderate to severe hyperthyroidism will develop an increased renal blood flow and glomerular filtration rate (GFR), which could lower the circulating levels of both urea nitrogen and creatinine (1,2).

Although it is difficult to classify the stage of CKD in this cat, I'd predict that he probably has Stage 3 CKD (see this link for more more information on IRIS staging of renal disease in cats). Based on the length of time he probably has been hyperthyroid, he could even be in Stage 4 CKD.

So how would I handle this cat? First of all, I would control all of the possible contributing factors before you do too much to treat the hyperthyroidism. For instance, I would definitely start amlodipine to control the cat's hypertension (2,3). I would also culture the cat's urine and treat any urinary tract infection that may be present. I'd check a urine protein:creatinine ratio to evaluate for proteinuria, which may need to be treated with an ACE inhibitor. Finally, I'd start the cat on a renal diet to find a food that he will eat; diet is the mainstay of management of CKD in cats with renal disease.

Once we get those treatments underway, then you can start low-dose methimazole treatment (1.25 mg once a day, initially). Because this will lower the the renal blood flow and GFR to where the values should be (right now they are artificially high, even for a normal cat), it is the azotemia will worsen. You may want to start the cat on subcutaneous fluids (100 ml per day or so, depending on cardiac status) to help maintain hydration and increase renal blood flow. I would check the serum urea nitrogen and creatinine every 3 to 5 days during the initial treatment, and make dose adjustments as needed.

If the azotemia worsens dramatically on methimazole, you might NOT be able to treat the cat's hyperthyroidism. Remember, however, that the hyperthyroid state is likely contributing to this cat's kidney disease through the development of systemic and glomerular hypertension (4,5). In addition, this cat will soon die because of the hyperthyroidism if we don't try to get it under control.

The Bottom Line: Because control of the hyperthyroidism will reverse the glomerular hypertension and slow down progression of renal disease, I believe that we should try to treat all hyperthyroid cats with renal disease. In those cats with severe underlying renal disease whose azotemia dramatically worsens after methimazole, continued treatment of the hyperthyroidism might not be possible. In those cats, however, the long-term prognosis is very poor to grave.

References: 

1. Langston CE, Reine NJ. Hyperthyroidism and the kidney. Clinical Techniques in Small Animal Practice 2006;21:17-21.
2. Syme HM. Cardiovascular and renal manifestations of hyperthyroidism. Veterinary Clinics of North America: Small Animal Practice 2007;37:723-743.
3. Stepien RL. Feline systemic hypertension: Diagnosis and management. Journal of Feline Medicine and Surgery 2011;13:35-43.
4. van Hoek I, Meyer E, Duchateau L, et al. Retinol-binding protein in serum and urine of hyperthyroid cats before and after treatment with radioiodine. Journal of Veterinary Internal Medicine 2009;23:1031-1037.
5. van Hoek I, Lefebvre HP, Peremans K, et al. Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine. Domestic Animal Endocrinology 2009;36:45-56.

Q & A: High Serum ALT Values in a Cat with a Normal T4

I have a quick question about liver function tests in hyperthyroid cats. Is there a serum thyroid concentration at which you begin to believe elevations in the serum alanine aminotransferase (ALT) activity may be due to subtle (occult) feline hyperthyroidism?

I have a cat with mildly high ALT activity with a serum T4 value of 3.8 μg/dl (reference range, 0.8-4.0 μg/dl). Thanks!

My Response:

As you know, mild to marked increases in the serum activities of many liver enzymes, including alanine aminotransferase (ALT) and alkaline phosphatase (ALP) are the most common and striking biochemical abnormalities of feline hyperthyroidism (1,2). These liver enzymes changes and T4 concentrations are related, with liver enzyme abnormalities being more common in cats with severe hyperthyroidism. That said high liver enzymes can be an early indicator of hyperthyroidism in cats. Although how thyroid hormone excess stimulates the high ALT and ALP activity is not completely understood, it is clear that these high liver enzymes return to normal upon successful treatment of hyperthyroidism (3).

If a cat with a high ALT also has mild weight loss, a good appetite, and a serum T4 in the upper half of the reference range (or higher), I would certainly consider hyperthyroidism as a differential diagnosis.

How do we best diagnose early hyperthyroidism when the serum T4 concentrations are normal?  Your options would be to follow the serum concentrations of total T4 and free T4 at monthly intervals for awhile to see if they increase into the hyperthyroid range (4). Or you could do a T3 suppression test or do a thyroid scan (if available) if you and the owner are in a hurry to make a diagnosis of mild hyperthyroidism.

Of course, as you are monitoring the serum T4 concentration, you also want to follow the serum ALT values. An abdominal ultrasound to look at the liver is never a bad idea either, especially if the liver function tests continue to rise but the serum thyroid function tests remain normal.

References:

1. Thoday KL, Mooney CT. Historical, clinical and laboratory features of 126 hyperthyroid cats. Veterinary Record 1992;1:257-64.
2. Broussard JD, Peterson ME, Fox PR. Changes in clinical and laboratory findings in cats with hyperthyroidism from 1983 to 1993. Journal of the American Veterinary Medical Association 1995;206:302-5.
3. Berent AC, Drobatz KJ, Ziemer L, Johnson VS, Ward CR. Liver function in cats with hyperthyroidism before and after 131-I therapy. Journal of Veterinary Internal Medicine 2007;2:1217-23.
4. Peterson ME. Diagnostic tests for hyperthyroidism in cats. Clinical Techniques in Small Animal Practice 2006;21: 2-9.

Q & A: Hypothyroidism in a Cat Treated with Radioiodine (I-131)

I have a question about Mischief, a 13-year-old female spayed DSH cat, who was treated 3 years ago for hyperthyroidism with radioiodine (I-131).

At her first recheck 1-month after treatment, her serum T4 concentration was low-normal at 1.0 μg/dl (reference range, 0.5-4.5 μg/dl). In the months and years since that time, the serum T4 values have continued to be slightly low. On her annual exam a year ago, the T4 was low at 0.4 μg/dl.

This year she had gained a great deal of weight (she now weighs 7 kg) and has a body condition score of 4/5. The owners have noticed increasing more dandruff and shedding, and they were worried that she was becoming hypothyroid. I rechecked her serum T4 concentration, which was still low at 0.4 μg/dl.

I know that cat can develop iatrogenic hypothyroid after radioiodine treatment. To help rule out hypothyroidism, I had the lab measure a serum TSH on the same sample (since there isn’t a feline TSH assay, the lab used the canine-specific TSH assay). The cTSH level was 8.29, which seems very high, at least based on the reference range limits for cTSH in dogs (0.05 - 0.42 ng/ml).

My plan is to start l-thyroxine supplementation and monitor signs. However, I have two questions:

1. I don't have reference values for feline TSH, so I was hoping for some confirmation that this cat’s TSH value is indeed high.
2. What dose of L-T4 should I use?

My Response:

It's very uncommon for hypothyroidism to develop clinically this long after treatment with radioiodine. Generally, the serum T4 values in cats with iatrogenic hypothyroidism are already low by 1 month after I-131 treatment and stay low thereafter. And most of these hypothyroid cats become quite symptomatic by 3 to 6 months, not 3 years (1-3).

That said, the cTSH value in this cat is high and that would be consistent with primary hypothyroidism (3,4).  A good reference range has not been established for  serum cTSH in cats, but I like to see the values rise above 1.0 ng/ml before I say it's definitely elevated.

Before you start treatment, I would definitely do all that you can to rule out nonthyroidal illness, inasmuch as this is a well-known reason for low serum T4 values in cats (5, 6).

Although the canine TSH assay appears to work fairly well in some cats with apparent hypothyroidism (4), sometimes the results just don't make a whole lot of sense. For example, I've had a couple cats now on replacement doses of L-T4 as high as 0.3-0.4 mg per day that failed to normalize their cTSH level, despite serum T4 values that were in the high-normal to slightly high range.

By definition, a high circulating T4 should suppress the TSH level to non-detectable levels. So what's going on here? We still don't know, but it may be the assay. Hopefully, the development of a feline TSH assay will solve these issues.

We also don't know how nonthyroidal illness affects the cTSH levels but we do certainly know that any illness will lower the total T4 into the subnormal range. So this cat could be suffering from any number of other diseases, such as renal, liver, or GI disease (4,5).

Have you done a routine blood and urine testing (eg, CBC, serum chemistry panel, and urinalysis)? If not, I'd certainly do that, together with a free T4, before you start L-T4 supplementation. Many hypothyroid cats will develop mild anemia and hypercholesterolemia, similar to what we see in dogs that are hypothyroid (1-3).

If you do decide to supplement, start with a dose of 0.1 mg once daily or divided. It's quite safe to increase to 0.1 mg BID, if needed. I know that this sounds high, but remember that a cat is NOT a dog!

There is much to learn about thyroid hormone supplementation in cats. I give the medication on an empty stomach if possible, based on the fact that the absorption of L-T4 is better in both humans and dogs when given this way. I follow post-pill T4 values (4-6 hours) and cTSH levels, but again, no one knows when the best time is to recheck these cats.

References:

1. Peterson ME: Feline hypothyroidism, In: Kirk RW (ed): Current Veterinary Therapy X. Philadelphia, WB Saunders Co., pp 1000-1001, 1989
2. Greco DS. Diagnosis of congenital and adult-onset hypothyroidism in cats. Clin Tech Small Anim Pract 2006;21:40-44.
3. Daminet S. Feline hypothyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Small Animal Endocrinology. 4th ed. Shurdington, Cheltenham: British Small Animal Veterinary Association, 2010.
4. Wakeling J. Use of thyroid stimulating hormone (TSH) in cats. Can Vet J 2010;51:33-34.
5. Peterson ME, Gamble, DA: Effect of nonthyroidal disease on serum thyroxine concentrations in cats: 494 cases (1988). Journal of the American Veterinary Medical Association 197:1203-1208, 1990
6. Peterson ME, Melián C, Nichols CE: Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. J Am Vet Med Assoc 218: 529-536, 2001

More information:

I just came across a recent study which studied the absorptive kinetics of L-thyroxine in young, healthy cats (La Traon, et al, 2009). In that abstact reported at the ECVIM meeting in 2009, normal cats were given a single oral dose of L-T4 (Leventa solution, Merke Animal Health, 1 mg/ml) as a single dose (0.1 mg per cat) after an overnight fast, with food withheld for an additional 8 hours after the L-T4 administration.

The L-T4 was rapidly absorbed in these cats, reaching a mean peak concentration of around 5 μg/dl at 2-4 hours after administration. The L-T4 was also rapidly cleared in these cats, with an apparent serum half-life of 5.5 hours. This is shorter than the half -life reported for healthy dogs after administration of the same liquid formulation. Despite the short half-life, serum T4 value at 24 hours post-pill were generally higher than pre-pill concentrations, suggesting that once daily supplementation may be adequate in cats.

Although this study of the L-T4 absorption in normal cats helps us, we aren't treating clinically normal cats with a single oral dose after an overnight fast — rather, we are chronically treating hypothyroid cats that are generally older, sometimes with other concurrent diseases.  So we still don't really yet know the best dose or timing for post-pill T4 testing in cats with hypothyroidism.

Reference:

1. Le Traon G, Burgaud S, Horspool L. Pharmacokinetics of L-thyroxine after oral administration to healthy cats. Proceedings of the 19th ECVIM-CA Congress (European College of  Veterinary Internal Medicine - Companion Animals). p. 269, 2009.

Top Endocrine Publications of 2010: The Feline Thyroid Gland

In my fifth compilation of the canine and feline endocrine publications of 2010, I’m moving on to disorders of the feline thyroid gland.

Listed below are 18 research papers written in 2010 that deal with a variety of thyroid gland topics of issues of clinical importance in cats.

These range from the investigations of thyroid ultrasonography (1) to thyroid scintigraphy for hyper- or hypothyroidism (2,6,12); from studies of iodine metabolism in the normal and hyperthyroid cat (4,15) to investigation of G protein activation in the pathogenesis of feline hyperthyroidism (13); from thyroid carcinoma (5) to studies of the use of serum T4 and TSH measurements in the diagnosis and monitoring of thyroid disease (10,14,11,16-18); and from reports of spontaneous feline hypothyroidism (2,7) to investigations of the effect of hypothyroidism on renal function in cats (8,16-18).

References:

1. Barberet V, Baeumlin Y, Taeymans O, et al. Pre- and posttreatment ultrasonography of the thyroid gland in hyperthyroid cats. Veterinary Radiology & Ultrasound 2010;51:324-330.
2. Blois SL, Abrams-Ogg AC, Mitchell C, et al. Use of thyroid scintigraphy and pituitary immunohistochemistry in the diagnosis of spontaneous hypothyroidism in a mature cat. Journal of Feline Medicine and Surgery 2010;12:156-160.
3. Blois SL, Dickie EL, Kruth SA, et al. Multiple endocrine diseases in cats: 15 cases (1997-2008). Journal of Feline Medicine and Surgery 2010;12:637-642.
4. Edinboro CH, Scott-Moncrieff JC, Glickman LT. Feline hyperthyroidism: potential relationship with iodine supplement requirements of commercial cat foods. Journal of Feline Medicine and Surgery 2010;12:672-679.
5. Knowles S, Uhl EW, Blas-Machado U, et al. Intrapericardial ectopic thyroid carcinoma in a cat. Journal of Veterinary Diagnostic Investigation 2010;22:1010-1013.
6. Lee WR, Pease AP, Berry CR. The effects of iohexol administration on technetium thyroid scintigraphy in normal cats. Veterinary Radiology & Ultrasound 2010;51:182-185.
7. Quante S, Fracassi F, Gorgas D, et al. Congenital hypothyroidism in a kitten resulting in decreased IGF-I concentration and abnormal liver function tests. Journal of Feline Medicine and Surgery 2010;12:487-490.
8. van Hoek IM, Vandermeulen E, Peremans K, et al. Thyroid stimulation with recombinant human thyrotropin in healthy cats, cats with non-thyroidal illness and in cats with low serum thyroxin and azotaemia after treatment of hyperthyroidism. Journal of Feline Medicine and Surgery 2010;12:117-121.
9. Vandermeulen E, De Sadeleer C, Piepsz A, et al. Determination of optimal sampling times for a two blood sample clearance method using (51)Cr-EDTA in cats. Journal of Feline Medicine and Surgery 2010;12:577-583.
10. Vieira AB, Castro MCN, Freire IMA, et al. Measurement of serum total thyroxine by chemiluminescence method in clinically healthy cats. Brazilian Journal of Veterinary Research and Animal Science 2010; 47:224-230.
11. Wakeling J. Use of thyroid stimulating hormone (TSH) in cats. The Canadian Veterinary Journal 2010;51:33-34.
12. Wallack S, Metcalf M, Skidmore A, et al. Calculation and usage of the thyroid to background ratio on the pertechnetate thyroid scan. Veterinary Radiology & Ultrasound 2010;51:554-560.
13. Ward CR, Windham WR, Dise D. Evaluation of activation of G proteins in response to thyroid stimulating hormone in thyroid gland cells from euthyroid and hyperthyroid cats. American Journal of Veterinary Research 2010;71:643-648.
14. Wasser SK, Azkarate JC, Booth RK, et al. Non-invasive measurement of thyroid hormone in feces of a diverse array of avian and mammalian species. General and Comparative Endocrinology 2010;168:1-7.
15. Wedekind KJ, Blumer ME, Huntington CE, et al. The feline iodine requirement is lower than the 2006 NRC recommended allowance. Journal of Animal Physiology and Animal Nutrition 2010;94:527-539.
16. Williams TL, Elliott J, Syme HM. Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. Journal of Veterinary Internal Medicine 2010;24:1086-1092.
17. Williams TL, Peak KJ, Brodbelt D, et al. Survival and the development of azotemia after treatment of hyperthyroid cats. Journal of Veterinary Internal Medicine 2010;24:863-869.
18. Williams TL, Elliott J, Syme HM. Iatrogenic hypothyroidism (IH) contributes to the development of azotemia in hyperthyroid cats. Journal of Veterinary Internal Medicine 2010;24:684.

Q & A: Hypothyroid Dog on T4 Treatment with Persistent High TSH Value

This patient is a 6-year-old, female spayed dachshound, first diagnosed as being hypothyroid almost a year ago At that time, the main owner complains included obesity (body weight, 10.1 kg) and lethargy. My physical examination findings included moderate alopecia of the ventral chest and abdomen, with some hyperpigmentation. The body condition score was 4 out of 5.

Result of my complete blood count and serum chemistry panel were normal except for mild hypercholesterolemia (302 mg/dl; reference range < 250 mg/dl). My thyroid panel result were as follows:

• Total T4: 0.5 μg/dl (reference range, 1.0-4.0 μg/dl)
• Free T4: 5 pmol/L  (reference range, 10-40 pmol/L)
• cTSH: 3.2 mg/ml  (reference range, 0.01-0.6 ng/mll)

Based upon these results, the dog was diagnosed with primary hypothyroidism. She was initially treated with levothyroxine (L-T4) at the dose of 100 μg twice daily.  Two months later, her recheck thyroid and cTSH values were the following:

• Total T4 (before treatment): 2.5 μgdl 
• Total T4 (4 hrs after treatment): 4.9 μg/dl
• cTSH: 2.5 ng/ml

Based on these results, I continued the same dosage of L-T4 and rechecked 3 months later:

• Total T4 (before treatment): 2.0 μgdl 
• Total T4 (4 hrs after treatment): 4.1 μg/dl
• cTSH: 2.8 ng/ml

Because the cTSH value remained high, I raised the dosage up to 150 μg twice daily, and rechecked again 4 months later:

• Total T4 (before treatment): 2.6 μgdl 
• Total T4 (4 hrs after treatment): 5.5 μg/dl
• cTSH: 1.9 ng/ml

During the treatment the dog clinically seems to be doing well. The hair coat has regrown and the dog has lost a pound — still  a bit overweight but better.   So, I have a dog on a daily dose of L-T4 that may be  slightly too high dose based on my post-pill T4 values, but the dose still it seems to be deficient based on the high cTSH values.

Do you have an explanation? How I should proceed with this dog's treatment?

My Response:

All of the reasons why L-T4 supplementation would not lower serum TSH concentration generally all  come down to a single issue — we have failed to adequately raise circulating T4 (and T3) values. If circulating thyroid hormone levels stay too low, we will not see the negative-feedback, suppressive effect on pituitary TSH secretion, and serum TSH values may remain high.

So what could lead to subnormal post-pill T4 levels? These are the most common reasons:

• failure of the owner to actually administer the L-T4 supplementation
• failure of a thyroxine preparation to be potent (some generic L-T4 preparations)
• presence of a non-thyroidal illness suppressing the serum T4 to low values
• presence of thyroid-lowering drugs (e.g., steroids, phenobarbatol, sulfa drugs) suppressing circulating T4 and T3 concentrations

But the idea that the serum TSH concentration remains high despite a post-pill T4 that is too high doesn't fit with any of my above explanations.

The first thing I would recommend is to verify the high canine TSH concentrations by submitting a sample to another laboratory. I would expect the result to be similar, especially since we have multiple cTSH values that are all very high.

When I see dogs with persistently high cTSH values on LT4 supplementation, another explanation that we should consider (based on studies in human patients) is the phenomenon termed the "reset thyrostat" (1,2).

• In human patients, this condition of "reset thyrostat" reflects an initial transient unresponsiveness of the hypothalamic-pituitary axis (hypertrophied thyrotrophs) to thyroid hormone replacement). 
• The higher the initial serum TSH concentrations, the more likely one is to observe persistent elevations in TSH concentrations despite adequate L-T4 replacement. 
• Once appropriate thyroid hormone replacement therapy is given, however, the thyrostat typically (but not always) resets to normal within a few months.
• Most of the human patients in which the "reset thyrostat" phenomenon has been reported were either clinically normal, obese, or had a long history of hypothyroidism.
• Some researchers have even reported that euthyroid but obese individuals maintain normal serum T4 values but have higher levels of TSH, again suggesting that they may have reset their "central thyrostat."

As all of you know, there have been no reports of reset thyrostat in dogs or cats (at least to my knowledge) but I think we must consider it in a dog like this. Maybe his obesity is playing a role in the increased TSH secretion, like that reported in the obese human patients (2). If that's the problem, the solution would be not to worry about it!   

Unfortunately, it's clear we still have much to learn about both the canine and feline thyroid gland physiology and regulation of their pituitary-thyroid axis, especially in states of hyper- and hypothyroidism.  

References:

1. Kabadi UM, Cech R. Normal thyroxine and elevated thyrotropin concentrations: evolving hypothyroidism or persistent euthyroidism with reset thyrostat. Journal of Endocrinological Investigation 1997;20:319-326.
2. Michalaki MA, Vagenakis AG, Leonardou AS, et al. Thyroid function in humans with morbid obesity. Thyroid 2006;16:73-78.

Q & A: Monitoring Hypothyroid Dogs With T4 and T3 Autoantibodies

This patient is a 9-year-old, F/S, mixed-breed dog that I recently diagnosed with hypothyroidism based on clinical signs of obesity, lethargy, and seborrhea. Results of a CBC and serum chemistry panel were relatively normal, except for mild hypercholesterolemia. 

A thyroid panel was send to the laboratory, with the following results:  

• T4: 6.5 μg/dl (0.8-4.0 μg/dl)
• T3: 320 ng/dl (45-150 ng/dl)
• Free T4 by ED: 6 pmol/L (10-50 pmol/L)
• TSH: 0.92 ng/ml (0.03-0.32 ng/ml)
• T4 autoantibody: 24% (0-20%)
• T3 autoantibody: 20% (0-10%)
• Thyroglobulin autoantibody (TgAA): 100% (0-25%)

I'm confused? What does this mean? Does she have hyper- or hypothyroidism? Why is the serum concentrations of both T4 and T3 high with a low free T4?

My Response:

The positive thyroglobulin autoantibody titer is diagnostic for lymphocytic thyroiditis. The presence of T4 and T3 autoantibodies in this dog is also consistent with thyroiditis.

The presence of clinical sign, taken together with the low serum free T4 value and high serum cTSH concentration, is consistent with primary hypothyroidism. It's likely that both the total T4 and T3 values are falsely high due to interference of the autoantibodies in the assays.

I'd recommend starting this dog on thyroid hormone replacement and evaluating the clinical response. 

Follow-up:

Thanks for your advice. The dog weighs 50 kg, so I started her on levo-thyroxine at a dose of 0.8 mg BID. 

After 4 weeks, the owner reported an increase in the dog's energy, improvement in her skin and hair coat, and a 2-kg loss in body weight. I rechecked the serum T4 and TSH concentrations on a blood sample collected about 6 hours after the morning pill. Results are as follows: 

• T4 8.6 μg/dl (0.8-4.0 μg/dl)
• TSH: 0.03 ng/ml (0.03-0.32 ng/ml)

Since her total T4 was high even before starting thyroid supplementation, what should I do now? The dog is showing clinical improvement and not acting hyperthyroid. Should I just decrease her dose a bit, or cut it in half?

My Response:

The dog definitely has T4 and T3 autoantibodies. In these dogs, you can not use post-pill total T4 values to monitor thyroid hormone supplementation because the reported numbers are meaningless (the autoantibodies interfere with the T4 and T3 determinations).  

The only thyroid tests that can be accurately monitored in a dog with T4 and T3 autoantibodies is cTSH and free T4 by ED. The fact that the dog's serum TSH value has fallen so dramatically from 0.92 to 0.03 ng/ml suggests that the replacement dose is at least adequate and may be more than enough. You certainly could monitor his free T4 values, but the ideal post-pill time for free T4 monitoring has not been determined.

What I'd recommend at this point is to adjust the L-T4 dosage based upon clinical signs and serum chemistry results. Has the high serum cholesterol

normalized after treatment? If the dose is adequate, the hypercholesterolemia should resolve. 

If the dog is being overdosed with L-T4, signs of hyperthyroidism will develop. These may include tachycardia, excitability, excessive weight loss, and polyuria.

You current dose is quite high, so I would decrease the dose. Cutting in half may be fine, but I'd probably go down to 0.5-0.6 BID for now and then reevaluate in a month.

Follow-Up:

If I understand you correctly, I should only monitor clinical signs and not depend on thyroid blood work for dose adjustments for this dog?

The Bottom Line:

Yes, you are going to have to be a clinician and use your history and physical examinations to monitor this dog. 

I'd recommend that you do routine blood work (complete blood count, serum chemistry panel, and complete urinalysis) at least once a year.  At 9-years of age, you would do that even if he wasn't on the thyroid medication.

Top Endocrine Publications of 2010: The Canine Thyroid Gland

In my fourth compilation of the canine and feline endocrine publications of 2010, I’m moving on to disorders of the canine thyroid gland.

Listed below are 17 research papers written in 2010 that deal with a variety of thyroid gland topics and issues of clinical importance.

These range from the immune-mediated secondary hypothyroidism (1) to investigations of the CNS and peripheral nervous system in canine hypothyroidism (10,13); from iatrogenic hyperthyroidism (6) to thyroid cancer (5,12,17); from diagnostic tests for hypothyroidism (8,11,14,15) to investigations of effect of recombinant human TSH on the uptake of radioactive iodine by the thyroid gland (3,4); and from studies of the effect of topical glucocorticoids on serum thyroid concentrations (7) to studies of the genetics of hypothyroidism (16).

References:

1. Adissu HA, Hamel-Jolette A, Foster RA. Lymphocytic adenohypophysitis and adrenalitis in a dog with adrenal and thyroid atrophy. Veterinary Pathology 2010;47:1082-1085.
2. Ajitkumar G, Sreekumaran T, Praseeda R, et al. Comparative efficacy of bromocriptine, cabergoline and thyroxine in inducing oestrus in bitches. Veterinary Research Communications 2010;34:65-69.
3. Campos M, Peremans K, Duchateau L, et al. Effect of recombinant human TSH on the uptake of radioactive iodine (123-I) by the thyroid gland in healthy beagles. Domestic Animal Endocrinology 2010;39:215-221
4. Campos M, Saunders JH, Duchateau L, et al. Short-term effect of recombinant human thyroid-stimulating hormone on thyroid volume and echogenicity in healthy beagles. Veterinary Radiology & Ultrasound 2010;51:331-334.
5. Di Palma S, Lombard C, Kappeler A, et al. Intracardiac ectopic thyroid adenoma in a dog. The Veterinary Record 2010;167:709-710.
6. Fine DM, Tobias AH, Bonagura JD. Cardiovascular manifestations of iatrogenic hyperthyroidism in two dogs. Journal of Veterinary Cardiology 2010;12:141-146.
7. Gottschalk J, Einspanier A, Ungemach FR, et al. Influence of topical dexamethasone applications on insulin, glucose, thyroid hormone and cortisol levels in dogs. Research in Veterinary Science 2010.
8. Liles SR, Linder KE, Cain B, et al. Ultrasonography of histologically normal parathyroid glands and thyroid lobules in normocalcemic dogs. Veterinary Radiology & Ultrasound 2010;51:447-452.
9. Mazaki-Tovi M, Feuermann Y, Segev G, et al. Increased serum leptin and insulin concentrations in canine hypothyroidism. Veterinary Journal 2010;183:109-114.
10. Pancotto T, Rossmeisl JH, Jr., Panciera DL, et al. Blood-brain-barrier disruption in chronic canine hypothyroidism. Veterinary Clinical Pathology 2010;39:485-493.
11. Piechotta M, Arndt M, Hoppen HO. Autoantibodies against thyroid hormones and their influence on thyroxine determination with chemiluminescence immunoassay in dogs. Journal of Veterinary Science 2010;11:191-196.
12. Rebhun RB, Thamm DH. Multiple distinct malignancies in dogs: 53 cases. Journal of the American Animal Hospital Association 2010;46:20-30.
13. Rossmeisl JH, Jr. Resistance of the peripheral nervous system to the effects of chronic canine hypothyroidism. Journal of Veterinary Internal Medicine 2010;24:875-881.
14. Shiel RE, Sist M, Nachreiner RF, et al. Assessment of criteria used by veterinary practitioners to diagnose hypothyroidism in sighthounds and investigation of serum thyroid hormone concentrations in healthy Salukis. Journal of the American Veterinary Medical Association 2010;236:302-308.
15. Wasser SK, Azkarate JC, Booth RK, et al. Non-invasive measurement of thyroid hormone in feces of a diverse array of avian and mammalian species. General and Comparative Endocrinology 2010;168:1-7.
16. Wilbe M, Sundberg K, Hansen IR, et al. Increased genetic risk or protection for canine autoimmune lymphocytic thyroiditis in Giant Schnauzers depends on DLA class II genotype. Tissue Antigens 2010;75:712-719.
17. Wucherer KL, Wilke V. Thyroid cancer in dogs: an update based on 638 cases (1995-2005). Journal of the American Animal Hospital Association 2010;46:249-254.

Q & A: Unexplained Hypercalcemia in a Middle-Aged Boxer Dog

My patient is an 8-year-old F/S Boxer, F/S, 8.5 years, 58.2 lb. The owners main presenting complaint was excessive thirst and urination, poor appetite, and occasional urinary accidents.

My physical examination was noncontributory. Results of a complete blood count and serum chemistry panel were normal except for hypercalcemia (14.6 mg/dl) with a high-normal phosphorus (4.9 mg/dl). The urine specific gravity was 1.008. Results of a urine culture was negative.

An abdominal ultrasound revealed an irregularly shaped left kidney with 2-3 mm calculi in renal pelvis. No other abnormalities in abdomen noted.

I repeated the serum total and ionized calcium which confirmed hypercalcemia. The total calcium was 14.9 mg/dl with a high ionized calicum of 3.72 mmol/L (normal, 2.2-3 mmmol/L). A serum PTH concentration was low at 0.4 pmol/L (reference range, 0.5-5.8 pmol/L).

Based on the high calcium with low serum PTH values, I'm worried about hypercalcemia of malignancy. I'm not sure where the cancer could be hiding, but the only place that I haven't looked is in the chest. Your thoughts?

My Response:
The thorax would certainly be a good place to look for un underlying malignancy. Did the peripheral lymph nodes all palpate normally? Did you check the anal glands for tumors?

You might also want to run a serum parathyroid hormone-related protein (PTHrp) level to help diagnose or exclude hypercalcemia of malignancy (1). If the PTHrP is positive, it's strongly suggestive for malignancy but it cannot tell you what the cancer is located.

If the dog does not have any lymphadenopathy or anal gland tumors, then you might want to do the following to help rule out lymphosarcoma:

• take chest radiographs, looking for a mediastinal mass
• aspirate multiple peripheral lymph nodes, even if not enlarged
• aspirate liver and spleen while doing an ultrasound exam, even if they're not grossly abnormal
• do a bone marrow aspirate

Follow-up and Diagnosis:
I repeated the physical examine and found that the dog had lost 2 more pounds. The dog's lymph nodes all palpated normally and no anal gland tumors were found. The chest films were normal, with no masses found.

I referred the dog to an oncologist who did fine needle aspirate and PCR testing on an slightly enlarged prescapular lymph nodes. This was diagnostic for lymphoma and PCR indicated primarily B cell lymphoma (with a T cell component).

The dog was also started on prednisone, which normalized the serum calcium concentration within 2 days. We also started on a 20-week course of a COAP chemotherapy protocol (2) with includes the following agents: cyclophosphamide (Cytoxan), vincristine (Oncovin), cytosine arabinoside (Cytosar-U), and prednisone.

Outcome:
This dog had the 20 weeks of chemotherapy and the lymphoma remained in remission. The serum total and ionized calcium concentrations continue to be normal when rechecked at the 20-week recheck.

References:

1. Kubota A, Kano R, Mizuno T, et al. Parathyroid hormone-related protein (PTHrP) produced by dog lymphoma cells. Journal of Veterinary Medical Science 2002: 64:835-837.
2. Rebhun RB, Kent MS, Borrofka SA, et al. CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma. Veterinary Comparative Oncology 2011: 9: 38-44.

Q & A: Hypercalcemia with Normal Serum PTH Value in an Older Poodle

This patient is a 10-year-old male castrated Poodle who presented for partial anorexia and weight loss. About a month ago, the owners brought the dog to another veterinarian for a routine dentistry. A serum chemistry panel at that time revealed hypercalcemia (14.9 mg/dl; reference range, 8.9-11.4 mg/dl) with hypophosphatemia (1.3 mg/dl).

On my physical examination, the dog was relatively alert and active. His rectal exam was normal with no masses palpated in the anal sacs. There was no lymphadenopathy or organomegaly.

I repeated the serum total calcium, which confirmed severe hypercalcemia (15.5 mg/dl). The serum ionized calcium (iCa) value was also very high at 2.15 mmol/L (reference range, 1.24-1.43 mmol/L). The serum parathyroid hormone (PTH) concentration was mid-normal 8.6 pmol/L (reference range, 3-17 pmol/L). Serum concentrations of parathyroid hormone-related polypeptide (PTH-rp) were undetectable.

An abdominal ultrasound was performed and was considered normal. Ultrasound examination of the cervical neck, however, revealed a 3.2-x-4-mm mass on the right cranial parathyroid gland. The mass was hypoechoic compared with the surrounding thyroid tissue. The remaining three parathyroid glands were markedly smaller and appeared to be normal. 

I am considering referring this dog to a board-certified surgeon for neck exploratory for presumed parathyroid gland neoplasia. But, my concern is this: if the serum PTH value is so normal, is this more likely related to a non-parathyroid gland neoplasia? Or something causing a high circulating Vitamin D (calcitriol)? 

I don't deal with a lot of these more complicated endocrine cases. So I need your help!

My Response:

Although the serum PTH concentration is technically "normal," it is inappropriately elevated given that the dog has such profound hypercalcemia (1). If the parathyroid glands were functioning normally, the high circulating calcium concentration would totally suppress PTH secretion and the serum PTH value would fall to low to undetectable values (See figure below).

Diagnostic of calcium disorders by
 PTH and iCa Values

So, the finding of a mid-normal serum PTH concentration together with severe hypercalcemia is diagnostic for primary hyperparathyroidism. It addition, the cervical ultrasound examination also supports the diagnosis of a parathyroid tumor (2).

As far as the parathyroidectomy is concerned, the actual surgery is not a huge challenge, albeit it always helps to have someone operate who had experience with the technique. The bigger worry is the preoperative and postoperative management of the patient with primary hyperparathyroidism.

This dog's severe hypercalcemia can have implications for renal and cardiac problems in the intraoperative period. Prior to surgery, you should monitor serum chemistries for azotemia and an ECG for rate or conduction abnormalities. I would also strongly consider 12 to 24 hours of intensive saline diuresis to try and lower the calcium as much as possible.

The severity of hypercalcemia in this dog also makes her much more prone to iatrogenic hypoparathyroidism and hypocalcemia after removal of the parathyroid gland tumor (3,4). The other glands are likely suppressed at this time, and that suppressed function can persist for weeks after surgery. Post-op hypocalcemia can be severe and quickly life-threatening, so you monitor the dog and promptly treat the hypoparathyroidism if it does develop. We generally recommend hospitalization for at least 3 to 5 days after surgery at a 24-hour facility where serum calcium values can be checked at least twice daily, and where treatment with a parenteral calcium infusion can be administered if needed.

I don't generally start calcitriol treatment preoperatively. But this dog's hypercalcemia is so severe that I would have the calcitriol on-hand, just in case it is needed to help in the treatment of hypoparathyroidism.

Bottom line: If you are not familiar with this disease and its management, you just need to explain this to your client and tell them that the best chance for successful treatment would be at a practice that offers the surgical and critical care expertise and 24-hour staffing that a dog like this requires.

Outcome:
At surgery, dog had large, solitary right parathyroid mass successfully removed. Histologic examination of the mass was consistent with a completely excised parathyroid adenoma.

On the first postoperative day, the dog's total calcium concentration fell to 5.1 mg/dl, so a calcium gluconate infusion was instituted. The dog was also started on oral  calcium and calcitriol. By day 4, the total calcium concentration stabilized at 6.4 mg/dl without the IV calcium drip, and the dog was discharged from the hospital. The oral calcium and calcitriol were continued at home, with a plan to slowly taper over the next few weeks to months as the remaining parathyroid glands start to regain normal function.

Discussion:
Naturally occurring primary hyperparathyroidism is not common in dogs (1,5,6). It occurs when abnormal autonomously functioning parathyroid chief cells produce excessive PTH, most often because of a solitary adenoma.  Of dogs with primary hyperparathyroidism, benign adenomatous transformation of one parathyroid gland occurs in about 90% of cases, malignant transformation in 5%, and adenomatous hyperplasia in the remaining 5% (1,2).

Surgical removal of the affected parathyroid gland(s), as was done in this case, is the gold standard of therapy. The most common postoperative complication is hypocalcemia because autonomous PTH secretion form the parathyroid tumor causes atrophy of the remaining parathyroid glands.

References:

1. Feldman EC, Nelson RW. Hypercalcemia and primary hyperparathyroidism. In: Canine and Feline Endocrinology and Reproduction. 3rd ed. St. Louis: Elsevier Science, 2003:661-715. 
2. Wisner ER, Penninck D, Biller DS, et al. High-resolution parathyroid sonography. Veterinary Radiology and Ultrasound. 1997;38:462-466.
3. Peterson ME. Treatment of canine and feline hypoparathyroidism. Journal of the American Veterinary Medical Association 1982; 181; 1434-1436
4. Chew D, Nagode L. Treatment of hypoparathyroidism. In: Bonagura JD, ed. Kirk's Current Veterinary Therapy XIII: Small Animal Practice. Philadelphia: WB Saunders, 2000;340-345.
5. Gear RN, Neiger R, Skelly B, Herrtage ME. Primary hyperparathyroidism in 29 dogs: Diagnosis, treatment, outcome and associated renal failure. Journal of Small Animal Practice 2005;46:10-16.
6. Feldman EC, Hoar B, Pollard R, Nelson RW. Pretreatment clinical and laboratory findings in dogs with primary hyperparathyroidism: 210 cases (1987-2004). Journal of the American Veterinary Medical Association 2005;227;756-761.

Top Endocrine Publications of 2010: Canine and Feline Parathyroid and Calcium Disorders

In my third compilation of the canine and feline endocrine publications of 2010, I’m moving on to disorders of the parathyroid gland, including the clinical problems of hypercalcemia and hypocalcemia.

Listed below are 18 research papers written in 2010 that deal with a variety of topics and issues related to calcium, parathyroid or vitamin D metabolism.

These range from the nutritional secondary hyperparathyroidism (2, 10) to calcium and phosphorus homeostasis in chronic kidney disease (1, 13) and in the whelping bitch (9); from studies of the feline calcium-sensing receptor (6) to investigations of feline tooth resorptive lesions and vitamin D3 status (7); and from studies of ionized calcium assays (15) to rapid parathyroid hormone assays (8).

Other papers discuss clinical issue ranging from primary hyperparathyroidism (14) to hypercalcemia of malignancy (5, 12, 16, 17); and from the hypercalcemia associated with Heterobilharzia and Leishmaniasis infections (3,4) to treatment of idiopathic hypercalcemia in cats with oral alendronate (18).

References:

1. Cortadellas O, Fernandez del Palacio MJ, Talavera J, et al. Calcium and phosphorus homeostasis in dogs with spontaneous chronic kidney disease at different stages of severity. Journal of Veterinary Internal Medicine 2010;24:73-79.
2. Dimopoulou M, Kirpensteijn J, Nielsen DH, et al. Nutritional secondary hyperparathyroidism in two cats: evaluation of bone mineral density with dual-energy X-ray absorptiometry and computed tomography. Veterinary and Comparative Orthopaedics and Traumatology 2010;23:56-61.
3. Fabrick C, Bugbee A, Fosgate G. Clinical features and outcome of Heterobilharzia americana infection in dogs. Journal of Veterinary Internal Medicine 2010;24:140-144.
4. Freeman KS, Miller MD, Breitschwerdt EB, et al. Leishmaniasis in a dog native to Colorado. Journal of the American Veterinary Medical Association 2010;237:1288-1291.
5. Gajanayake I, Priestnall SL, Benigni L, et al. Paraneoplastic hypercalcemia in a dog with benign renal angiomyxoma. Journal of Veterinary Diagnostic Investigation 2010;22:775-780.
6. Gal A, Ridge TK, Graves TK. Cloning and sequencing of the calcium-sensing receptor from the feline parathyroid gland. Domestic Animal Endocrinology 2010;38:57-61.
7. Girard N, Servet E, Hennet P, et al. Tooth resorption and vitamin D3 status in cats fed premium dry diets. Journal of Veterinary Dentistry 2010;27:142-147.
8. Ham K, Greenfield CL, Barger A, et al. Validation of a rapid parathyroid hormone assay and intraoperative measurement of parathyroid hormone in dogs with benign naturally occurring primary hyperparathyroidism. Veterinary Surgery 2009;38:122-132.
9. Hollinshead FK, Hanlon DW, Gilbert RO, et al. Calcium, parathyroid hormone, oxytocin and pH profiles in the whelping bitch. Theriogenology 2010;73:1276-1283.
10. Krook L, Whalen JP. Nutritional secondary hyperparathyroidism in the animal kingdom: report of two cases. Clinical Imaging 2010;34:458-461.
11. Liles SR, Linder KE, Cain B, et al. Ultrasonography of histologically normal parathyroid glands and thyroid lobules in normocalcemic dogs. Veterinary Radiology & Ultrasound 2010;51:447-452.
12. Neihaus SA, Winter JE, Goring RL, et al. Primary clitoral adenocarcinoma with secondary hypercalcemia of malignancy in a dog. Journal of the American Animal Hospital Association 2010;46:193-196.
13. Pusoonthornthum R, Pusoonthornthum P, Krishnamra N. Calcium-phosphorus homeostasis and changes in parathyroid hormone secretion in cats with various stages of spontaneous chronic renal failure. Comparative Clinical Pathology 2010;19:287-293.
14. Sakals SA, Gillick MS, Kerr ME, et al. Diagnosing the etiology of hypercalcemia in a dog: a case of primary hyperparathyroidism. Veterinary Pathology 2010;47:579-581.
15. Schenck PA, Chew DJ. Prediction of serum ionized calcium concentration by serum total calcium measurement in cats. Canadian Journal of Veterinary Research 2010;74:209-213.
16. Schoen K, Block G, Newell SM, et al. Hypercalcemia of malignancy in a cat with bronchogenic adenocarcinoma. Journal of the American Animal Hospital Association 2010;46:265-267.
17. Seelig DM, Perry JA, Avery AC, et al. Monoclonal gammopathy without hyperglobulinemia in 2 dogs with IgA secretory neoplasms. Veterinary Clinical Pathology 2010;39:447-453.
18. Whitney JL, Barrs VR, Wilkinson MR, et al. Use of bisphosphonates to treat severe idiopathic hypercalcaemia in a young Ragdoll cat. Journal of Feline Medicine and Surgery 2011;13:129-134.