Predicting Which Dogs will Develop Hypocalcemia after Parathyroidectomy for Primary Hyperparathyroidism

Evaluation of preoperative serum concentrations of ionized calcium and parathyroid hormone as predictors of hypocalcemia following parathyroidectomy in dogs with primary hyperparathyroidism: 17 cases (2001-2009)

Melissa Arbaugh, Daniel Smeak, and Eric Monnet

Journal of the American Veterinary Medical Association  2012;24:233-236

In dogs, primary hyperparathyroidism causes hypercalemia through the excessive secretion of parathyroid hormone (PTH), usually by an adenoma affecting one of the parathyroid glands (1-6). Such autonomous hypersecretion of PTH by the parathyroid tumor may lead to disuse atrophy of the remaining parathyroid glands (7).

Removal or ablation of the affected parathyroid tumor(s) is the treatment of choice for dogs with primary hyperparathyroid (1-6,8). Following surgery, these dogs may develop transient hypocalcemia while the suppressed parathyroid glands regain appropriate function. If hypocalcemia occurs, it generally does so within the first 7 days following surgery, and affected dogs often require extensive hospitalization and monitoring of serum ionized calcium concentrations (1-6,8).

It has been suggested that hyperparathyroid dogs with more severe hypercalcemia (total serum calcium concentrations > 14 mg/dL) should be started on supplementation with oral calcium and vitamin D prior to surgery (4,5). These dogs with more severe hypercalcemia may be at a greater risk for developing iatrogenic hypocalcemia after parathyroidectomy, since it is likely that their severe hypercalcemia would result in atrophy of the remaining parathyroid glands. These recommendations, however, are not based on clinical studies. If it turns out that theses dog did not actually require the calcium and vitamin D supplementation to prevent clinical hypocalcemia, then these supplements become unnecessary treatments that may delay recovery of the suppressed parathyroid glands to normal function.

Currently, there are no published predictors to indicate which hyperparathyroid dogs will become hypocalcemic and require calcium supplementation following parathyroidectomy. The purpose of the study reported by Arbaugh, et al (9) was to evaluate predictors of postoperative hypocalcemia in dogs following parathyroidectomy. They hypothesized that both the absolute preoperative calcium concentrations and its rate of decrease would aid in predicting clinical hypocalcemia.

Objective—To determine whether preoperative serum ionized calcium (iCa) or parathyroid hormone (PTH) concentrations help predict postoperative hypocalcemia following parathyroidectomy in dogs with primary hyperparathyroidism.

Design—Retrospective case series.

Animals— 17 dogs with primary hyperparathyroidism treated with parathyroidectomy.

Procedures—Medical records were evaluated from years 2001 to 2009. Data evaluated included age, breed, sex, clinical signs, diagnostic tests performed, preoperative and postoperative iCa concentrations, preoperative PTH concentrations, and whether calcium supplementation was provided following surgery. Two groups were identified on the basis of whether dogs became hypocalcemic (iCa < 1.2 mmol/L) following parathyroidectomy.

Results—12 dogs developed hypocalcemia after surgery. Preoperative (within 24 hours before surgery) iCa concentrations for the hypocalcemic group (mean ± SD, 1.82 ± 0.22 mmol/L) and the nonhypocalcemic group (1.83 ± 0.29 mmol/L) were not significantly different.

Calcium concentrations decreased in a linear fashion during the 24 hours following parathyroidectomy, and the slopes of the decrease over that time were not significantly different between the 2 groups of dogs. Preoperative PTH concentrations were not significantly different between the hypocalcemic and nonhypocalcemic groups.

Conclusions and Clinical Relevance —Preoperative iCa and PTH concentrations were not predictive of postoperative hypocalcemia in dogs undergoing parathyroidectomy for primary hyperparathyroidism. Future studies to evaluate whether calcium supplementation should be provided on an individual basis with perhaps more emphasis on clinical signs than iCa concentrations after surgery may be warranted.

My Bottom Line

Can preoperative calcium or PTH predict postoperative hypocalcemia?
The results of the this study by Arbaugh (9) indicate that preoperative serum concentrations of iCa or PTH concentrations are not reliable predictors of postoperative hypocalcemia in dogs undergoing parathyroidectomy for primary hyperparathyroidism.

These results agree with studies reported in human patients with  primary hyperparathyroidism, in which no difference could be detected in the preoperative serum values for calcium or PTH and the development of postoperative hypocalcemia (10). In addition, in a recent study by Milovancev and Schmiedt (11) of 62 dogs that had parathyroidectomy for primary hyperparathyroidism, these investigators arrived at the same conclusion. No correlation existed between preoperative serum total and ionized calcium concentrations and the development of postoperative hypocalcemia in these 62 dogs (11).

The hypothesis that dogs with higher preoperative serum concentrations of calcium would have more severe postoperative hypocalcemia versus dogs with lower preoperative serum concentrations of calcium would appear on the surface to be a logical one.  However, since this hypothesis is not supported by any these research studies (9-11), it must, therefore, be seriously questioned.

How often does postoperative hypocalcemia develop?
In the present study by Arbaugh (9), only 4 (24%) of the 17 dogs developed postoperative hypocalcemia, but none of the dogs developed clinical signs of hypocalcemia, even those with low iCa concentrations. Similarly, in the recent study reported by Milovancev and Schmiedt (11), approximately one-third of their 62 dogs became hypocalcemic following parathyroidectomy, but only a quarter of those dogs developed associated clinical signs. Of all 62 dogs in that study, less than 10% developed clinical hypocalcemia and required treatment with calcium and vitamin D (11).

When does postoperative hypocalcemia require treatment?
Overall, these two studies indicate an important fact about the need for treatment— that is, although postoperative hypocalcemia is a common complication in dogs after surgical parathyroidectomy, associated life-threatening clinical signs (e.g., tetany, seizures) are very uncommon (9,11).

These findings suggest that dogs treated with parathyroidectomy should be supplemented with calcium and vitamin D only when they have clinical signs of hypocalcemia, rather than started on these medications prophylactically or based solely on the postoperative iCa concentration.

References:

1. Berger B, Feldman EC. Primary hyperparathyroidism in dogs: 21 cases (1976-1986). J Am Vet Med Assoc 1987;191:350-356. 
2. Bonczynski J. Primary hyperparathyroidism in dogs and cats. Clin Tech Small Anim Pract 2007;22:70-74. 
3. Feldman EC, Hoar B, Pollard R, et al. Pretreatment clinical and laboratory findings in dogs with primary hyperparathyroidism: 210 cases (1987-2004). J Am Vet Med Assoc 2005;227:756-761.  
4. Gear RN, Neiger R, Skelly BJ, et al. Primary hyperparathyroidism in 29 dogs: diagnosis, treatment, outcome and associated renal failure. J Small Anim Pract 2005;46:10-16. 
5. Feldman EC, Nelson RW. Hypercalcemia and primary hyperparathyroidism. Canine and Feline Endocrinology and Reproduction. 3rd ed. St. Louis: Saunders Elsevier, 2004;660–715.
6. Skelly BJ. Hyperparathyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;43-55.
7. Thiele J, Kärner J, Fischer R. Ultrastructural morphometry on human parathyroid tissue. Morphological and functional implications. J Submicrosc Cytol Pathol. 1988;20:491-500. 
8. Rasor L, Pollard R, Feldman EC. Retrospective evaluation of three treatment methods for primary hyperparathyroidism in dogs. J Am Anim Hosp Assoc 2007;43:70-77. 
9. Arbaugh M, Smeak D, Monnet E. Evaluation of preoperative serum concentrations of ionized calcium and parathyroid hormone as predictors of hypocalcemia following parathyroidectomy in dogs with primary hyperparathyroidism: 17 cases (2001-2009). J Am Vet Med Assoc 2012;241:233-236. 
10. Strickland PL, Recabaren J. Are preoperative serum calcium, parathyroid hormone, and adenoma weight predictive of postoperative hypocalcemia? Am Surg 2002;68:1080-1082. 
11. Milovancev M, Schmiedt CW. Preoperative factors associated with postoperative hypocalcemia in dogs with primary hyperparathyroidism that underwent parathyroidectomy: 62 cases (2004-2009). J Am Vet Med Assoc 2013;242:507-515. 

Vetsulin Insulin Updated and Approved For Release in USA

Merck Animal Health just announced that Vetsulin (porcine insulin zinc suspension) will again be available for distribution in the USA this week (1). This is welcome news, especially for dogs with diabetes mellitus that are not well regulated with other available insulin preparations, such as human recombinant NPH. Most authorities consider Vetsulin, known as Caninsulin outside the USA (2), to be the initial insulin of choice for treatment of dogs with diabetes mellitus (3-6). It can also be used to successfully manage cats with diabetes (7,8), but we have many other good options for treatment of feline diabetes.

As you may know, Vetsulin has had its share of problems in the last few years, which lead to the FDA having it withdrawn from the US market. All of these manufacturing issues have been resolved, and the FDA has re-approved the drug for release.

How is the "new" Vetsulin different than the original insulin product?

According to the company, the updated Vetsulin product has the same characteristics as the original insulin preparation, and the action in diabetic patients is expected to be the same as before. There have been no changes in the safety profile of Vetsulin for use in either dogs or cats.

The only difference in the Vetsulin itself is a slight change in the listed proportion of the short-acting amorphous fraction and long-acting crystalline fraction. The short-acting amorphous fraction is now listed as 35% (it was 30%), whereas the long-acting crystalline fraction is now reported as 65% (it was 70%).

Vetsulin will now be available only in 10-ml vials. The 2-5 ml vial formulation of Vetsulin has been discontinued.

Two important differences in the updated Vetsulin Package Insert: (9)

1. Prior to use, vials of Vetsulin should be shaken thoroughly (manually) until a homogeneous, uniformly, milky suspension is obtained. Foam on the surface of the suspension formed during shaking should be allowed to disperse before the product is used.
2. Vetsulin contents should be used within 42 days after the vial is first punctured.  

For the first new vials of Vetsulin that are released, the initial product dating will be only 12 months from the manufactured date. The company expects that Vetsulin will eventually have a 24-month shelf-life.

Additional information can be found on the Veterinary Home Page under the Product Update section (10). Also, see the package insert for full information regarding contraindications, warnings, and precautions (9).

Bottom line:

It's great to have Vetsulin, an FDA-approved insulin for use in both dogs and cats, back on the market. The company has done a great deal of work showing that Vetsulin is stable and effective, and they have made a few minor but good improvements in this insulin preparation.

Vigorous manual shaking of the Vetsulin? How will that impact accurate dosing?
We have all been taught that vigorous shaking will interfere with accurate dosing because of air bubbles that form when the insulin bottle is shaken (5,11). When the dose is drawn up, the insulin suspension may come out into the syringe together with lots of air bubbles.  In addition, we tend to worry that too vigorous shaking may damage the insulin protein structure itself. For these reasons, we generally instruct owners to gently roll the insulin vial than to vigorously shake it!

According to the company, the instructions are now to give the Vetsulin bottle a vigorous shake on initial use; then let it settle for a few minutes to let the bubbles rise before drawing up the dose. Upon subsequent insulin dosing, the bottle should only need a quick shake (less vigorous) to resuspend the insulin prior to drawing up the insulin dose.

Why this difference in vigorous shaking vs. rolling? I don't know, but I suspect it has something to do with the way the study was designed and input from the FDA. In any case, Merck Animal Health actually has done the studies to prove that this vigorous manual shaking does not interfere with the measured insulin concentration in the product (10).

Why was the proportion in the short-and long-acting insulin fractions changed? 
According to the company, the proportions of the short-acting amorphous fraction and long-acting crystalline fraction have not actually changed, as compared to the original Vetsulin product. Instead, the new stated ratio (65% long-acting and 35% short-acting insulin) represents a more accurate reflection of the actual composition of both the original and updated Vetsulin product (10).

Nevertheless, on a clinical basis, such a small change in the short- vs. the long-acting insulin fractions would not be expected to make any difference in the animal's glycemic control, even if the composition of the product did change slightly.

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

Must Vetsulin really be discarded after only 42 days? 
The Vetsulin product insert (9) clearly states that the product should be used within "42 days of first vial puncture."

Has the efficacy really been determined to decrease after 42 days?  The answer to that is no — it's almost certain that the potency of this preparation will extend many days (or even weeks) longer than this 42 days.  However, because Merck Animal Health only did the FDA studies for a period of 42 days, that's what they have been required to put on the package insert. But remember, in addition to efficacy, we must also worry about bacterial contamination secondary to repeated puncture of the insulin vial (11).

Why such a short expiration date? 
Again, for the first new vials of Vetsulin that are released, the initial product dating will be only 12 months from the manufactured date. This is not because the updated Vetsulin is unstable, but the FDA requires ongoing studies of the insulin's duration. The company expects that Vetsulin will eventually have a 24-month shelf-life (10).

Since we do not have to worry about Vetsulin disappearing again, at least anytime soon, I wouldn't recommend purchasing too many insulin vials now, since the initial "expiration" date will be only a few months.

References:

1. Vetsulin website. www.vetsulin.com
2. Caninsulin website. www.caninsulin.com
3. Monroe WE, Laxton D, Fallin EA, et al. Efficacy and safety of a purified porcine insulin zinc suspension for managing diabetes mellitus in dogs. J Vet Intern Med 2005;19:675-682. 
4. Fleeman LM, Rand JS, Morton JM. Pharmacokinetics and pharmacodynamics of porcine insulin zinc suspension in eight diabetic dogs. Vet Rec 2009;164:232-237. 
5. Nelson RW. Canine diabetes mellitus In: Ettinger SJ,Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. Seventh Edition ed. St. Louis: Saunders Elsevier, 2010;1449-1474.
6. Davison LJ. Canine diabetes mellitus In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;116-132.
7. Michiels L, Reusch CE, Boari A, et al. Treatment of 46 cats with porcine lente insulin—a prospective, multicentre study. J Feline Med Surg 2008;10:439-451. 
8. Martin GJ, Rand JS. Control of diabetes mellitus in cats with porcine insulin zinc suspension. Vet Rec 2007;161:88-94. 
9. Vetsulin Package Insert. www.vetsulin.com/PDF/Vetsulin-Package-Insert.pdf
10. Vetsulin website: Veterinary Product Updates. www.vetsulin.com/vet/Product_Update.aspx
11. American Diabetes Association. Insulin administration. Diabetes Care 2001;24:1984-1987. 

Intraoperative Parathyroid Hormone Monitoring in Dogs with Hyperparathyroidism

Intraoperative Parathyroid Hormone Concentration to Confirm Removal of Hypersecretory Parathyroid Tissue and Time to Postoperative Normocalcaemia in Nine Dogs with Primary Hyperparathyroidism

K.J. Graham, M. Wilkinson, J. Culvenor, N.K. Dhand, and R.K. Churcher

Australian Veterinary Journal 2012;90:203-209.

Primary hyperparathyroidism is a relatively uncommon disease in dogs but must always be considered as a differential cause of hypercalcemia, particularly in an older, relatively asymptomatic dog with no evidence for malignancy (1-5). In primary hyperparathyroidism, parathyroid gland function is autonomous and nonresponsive to inhibition.  In approximately 90% of dogs, single parathyroid adenomas are responsible, but two adenomas, hyperplastic nodules or, rarely, carcinomas have been reported (2,6)

In human patients suffering from primary hyperparathyroidism, intraoperative parathyroid hormone (PTH) measurement is a highly sensitive and specific tool for determining successful removal of autonomously functioning parathyroid tissue (7-10). In this procedure, PTH is measured just prior to parathyroidectomy and at least 10 minutes after parathyroid tumor removal.  Since PTH has a plasma half life of less than 5 minutes (11), removal of a parathyroid tumor leads to a rapid fall in circulating PTH concentrations within minutes. The criterion for a positive test result varies between studies, but is generally accepted that > 50% decrease in PTH values indicates successful parathyroid tumor removal (7-10). A recent prospective veterinary study of 12 dogs demonstrated a greater than 50% reduction in parathyroidectomy PTH in all dogs, confirming correct removal of the hypersecretory gland (12).

The aims of this study by Graham et al (13) were to determine if serum PTH concentrations would decrease after successful parathyroidectomy and whether manipulation or dissection of the target gland would cause a transient increase in PTH, given its rapid half-life.

Objective of Study — To determine whether the intraoperative parathyroid hormone concentration (PTH) during parathyroidectomy can be used to indicate a cure in dogs with primary hyperparathyroidism. A secondary objective was to determine the time taken for the postoperative serum calcium concentration to normalize.

Design — Retrospective study (2005–2010) from a private referral hospital in Sydney, New South Wales, Australia.

Procedure — Nine client-owned dogs underwent surgical parathyroidectomy for naturally occurring primary hyperparathyroidism. The first PTH sample was taken immediately after induction of anesthesia and prior to manipulation of parathyroid tissue.  A second sample was collected as the abnormal parathyroid gland was being manipulated or excised in 6 dogs. A final PTH sample was taken 20–30 minutes after completion of parathyroidectomy in all dogs.

The concentration of ionized calcium (iCa) was measured at various time points postoperatively until it normalized, then stabilized or decreased below reference ranges. Statistical analysis compared the mean pre-, intra- and post-parathyroidectomy PTH concentration and the average rate of decline of iCa concentration postoperative.

Assays—Blood for PTH measurement was collected from the jugular vein and placed into plain tubes on ice for 30 minutes, centrifuged at 2500g and the serum transferred to a plain tube for storage at 4°C until assay. The serum specimens were assayed for PTH within 2 hours of collection, and results were available by the afternoon of surgery.

Intact serum PTH was assayed using an in-house, quick chemiluminescent enzyme immunometric assay, which is a modification of the Immulite PTH assay (Immulite Turbo: Siemens Medical Solutions Diagnostics).

Results – Serum PTH concentrations fell significantly when measured before and shortly after parathyroidectomy from mean pre-PTH value of 168.51 pg/mL to mean post-parathyroidectomy value of 29.20 pg/mL (Fig. 1). Intraoperative manipulation of the parathyroid tumor resulted in a significant increase in the mean PTH value to 279.78 pg/mL (Fig. 1). The average rate of decline of iCa concentration to within the reference range (1.12-1.40 mmol/L) occurred after 24 hours postoperatively.

Figure 1: Mean PTH concentration before surgery, at time of manipulation of the parathyroid tumor, and 20 min after parathyroidectomy.

Conclusions – Intraoperative measurements of PTH can be used clinically to determine cure of primary hyperparathyroidism. Parathyroid hormone increases significantly during parathyroid gland manipulation. Plasma iCa concentration returns to within the reference range on average 24 hours after successful parathyroidectomy. Not all dogs require vitamin D or calcium supplementation postoperatively.

My Bottom Line:

In this study (13), the investigators were able to document that use of intraoperative PTH in dogs undergoing parathyroidectomy for primary hyperparathyroidism can be a very powerful technique to determine successful surgical removal of the parathyroid tumor and predict outcome. Following parathyroid tumor removal, serum PTH fell dramatically when remeasured at 20-30 minutes postoperatively (see Figure 1). This agrees with another study performed in dogs in which serum PTH fell by >50% when rechecked 30-45 minutes after excision of the diseased parathyroid gland (12).

The finding that PTH concentrations can rise dramatically after manipulation of the abnormal parathyroid tissue highlights the importance of waiting at least 20 minutes to collect the final PTH sample after adenoma removal. This interval ensures that circulating PTH has had enough time to fall to it nadir level before collection.  If collected too soon, the PTH may still be too high, leading one to believe that the surgery was not successful.

Is intraoperative PTH testing practical?
The cost and availability of PTH assays is a major limiting factor for use of intra-operative PTH testing in dogs. Very few veterinary practices, even large speciality hospitals, will have access for the dedicated lab equipment needed to perform these assays. A nearby human facility was used in this case series reported by Graham (13), whereas the only other veterinary case series (12) performed quick parathyroid testing with a in-house, dedicated machine.

And that brings up the biggest down-side to this method —is it feasible to have the results of PTH testing back during the surgical procedure so that we know that all of the involved parathyroid tissue has been removed hyperfunctioning gland prior to closing?  If the PTH samples must be sent out to an outside lab for analysis, that typically will take a few days to receive the PTH results. Such a delay overrides or negates almost all of the advantages of this diagnostic technique.

Remember, as shown in this present study (13), we can judge the success of the operation on the basis of serial serum ionized calcium concentrations, which normalize by 24 hours after successful surgery. We do not need a serum PTH measurement to tell us that operation for hyperparathyroidism has been successful, at least not in most dogs with this disease.

References:

1. Berger B, Feldman EC. Primary hyperparathyroidism in dogs: 21 cases (1976-1986). J Am Vet Med Assoc 1987;191:350-356. 
2. Feldman EC, Hoar B, Pollard R, et al. Pretreatment clinical and laboratory findings in dogs with primary hyperparathyroidism: 210 cases (1987-2004). J Am Vet Med Assoc 2005;227:756-761. 
3. Gear RN, Neiger R, Skelly BJ, et al. Primary hyperparathyroidism in 29 dogs: diagnosis, treatment, outcome and associated renal failure. J Small Anim Pract 2005;46:10-16.  
4. Skelly BJ. Hyperparathyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;43-55.
5. Jores K, Kessler M. Primary hyperparathyroidism in the dog. Diagnosis, therapy and postoperative management in 19 dogs. Tierarztliche Praxis Ausgabe K, Kleintiere/Heimtiere 2011;39:389-396.
6. Sawyer ES, Northrup NC, Schmiedt CW, et al. Outcome of 19 dogs with parathyroid carcinoma after surgical excision. Vet Comp Oncol 2012;10:57-64. 
7. Irvin GL, 3rd, Solorzano CC, Carneiro DM. Quick intraoperative parathyroid hormone assay: surgical adjunct to allow limited parathyroidectomy, improve success rate, and predict outcome. World J Surg 2004;28:1287-1292. 
8. Sharma J, Milas M, Berber E, et al. Value of intraoperative parathyroid hormone monitoring. Ann Surg Oncol 2008;15:493-498. 
9. Richards ML, Thompson GB, Farley DR, et al. An optimal algorithm for intraoperative parathyroid hormone monitoring. Arch Surg 2011;146:280-285. 
10. Carneiro-Pla D. Contemporary and practical uses of intraoperative parathyroid hormone monitoring. Endocr Pract 2011;17 Suppl 1:44-53. 
11. Bieglmayer C, Prager G, Niederle B. Kinetic analyses of parathyroid hormone clearance as measured by three rapid immunoassays during parathyroidectomy. Clin Chem 2002;48:1731-1738.
12. 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. Vet Surg 2009;38:122-132.  
13. Graham KJ, Wilkinson M, Culvenor J, et al. Intraoperative parathyroid hormone concentration to confirm removal of hypersecretory parathyroid tissue and time to postoperative normocalcaemia in nine dogs with primary hyperparathyroidism. Aust Vet J 2012;90:203-209. 

Top Endocrine Publications of 2012: Canine & Feline Parathyroid & Calcium Disorders

In my third compilation of the canine and feline endocrine publications of 2012, I’m moving on to disorders of the parathyroid gland, including the clinical problems of hypercalcemia and hypocalcemia.

Listed below are 22 research papers written in 2012 that deal with a variety of topics and issues related to calcium, parathyroid or vitamin D metabolism.

These range from iatrogenic hypoparathyroidism following parathyroid or thyroid surgery (1,20,21) to dietary hypocalcemia in growing dogs (2,14); from paraneoplastic hypercalcemia (3) to puerperal tetany (eclampsia) and hypocalcemia associated with whelping (6); and from dietary and animal-related factors associated with urinary calcium and calcium oxalate stones (7,8) to circulating PTH concentrations in cats with secondary hyperparathyroidism due to renal disease (9).

Other papers discuss the use of intraoperative PTH measurements during parathyroidectomy to help predict cure in dogs with primary hyperparathyroidism (10) to characterization of a mutation that causes vitamin D-dependent rickets in cats (11); from a study of hypovitaminosis D in dogs with endotoxemia (12) to the effect of prednisolone therapy on calcium and vitamin D metabolism in dogs (16,17); from studies of the outcome of dogs with thyroid or parathyroid carcinoma treated with surgical excision (20,21) to an evaluation of calcium and phosphate homeostasis in hyperthyroid cats with chronic kidney disease.

References:

1. Arbaugh M, Smeak D, Monnet E. Evaluation of preoperative serum concentrations of ionized calcium and parathyroid hormone as predictors of hypocalcemia following parathyroidectomy in dogs with primary hyperparathyroidism: 17 cases (2001-2009). J Am Vet Med Assoc 2012;241:233-236. 
2. Becker N, Kienzle E, Dobenecker B. Calcium deficiency: a problem in growing and adult dogs: two case reports. Tierarztl Prax Ausg K Kleintiere Heimtiere 2012;40:135-139. 
3. Bergman PJ. Paraneoplastic hypercalcemia. Top Companion Anim Med 2012;27:156-158. 
4. Brockley LK, Heading KL, Jardine JE, et al. Polyostotic lymphoma with multiple pathological fractures in a six-month-old cat. J Feline Med Surg 2012;14:285-291. 
5. Corbee RJ, Tryfonidou MA, Meij BP, et al. Vitamin D status before and after hypophysectomy in dogs with pituitary-dependent hypercortisolism. Domest Anim Endocrinol 2012;42:43-49. 
6. Davidson AP. Reproductive causes of hypocalcemia. Top Companion Anim Med 2012;27:165-166. 
7. Dijcker JC, Hagen-Plantinga EA, Everts H, et al. Dietary and animal-related factors associated with the rate of urinary oxalate and calcium excretion in dogs and cats. Vet Rec 2012;171:46. 
8. Dijcker JC, Kummeling A, Hagen-Plantinga EA, et al. Urinary oxalate and calcium excretion by dogs and cats diagnosed with calcium oxalate urolithiasis. Vet Rec 2012;171:646. 
9. Finch NC, Syme HM, Elliott J. Parathyroid hormone concentration in geriatric cats with various degrees of renal function. J Am Vet Med Assoc 2012;241:1326-1335. 
10. Graham KJ, Wilkinson M, Culvenor J, et al. Intraoperative parathyroid hormone concentration to confirm removal of hypersecretory parathyroid tissue and time to postoperative normocalcaemia in nine dogs with primary hyperparathyroidism. Aust Vet J 2012;90:203-209. 
11. Grahn RA, Ellis MR, Grahn JC, et al. A novel CYP27B1 mutation causes a feline vitamin D-dependent rickets type IA. J Feline Med Surg 2012;14:587-590. 
12. Holowaychuk MK, Birkenheuer AJ, Li J, et al. Hypocalcemia and hypovitaminosis D in dogs with induced endotoxemia. J Vet Intern Med 2012;26:244-251. 
13. Hong HH, Chou TA, Yang JC, et al. The potential effects of cholecalciferol on bone regeneration in dogs. Clin Oral Implants Res 2012;23:1187-1192. 
14. Hutchinson D, Freeman LM, McCarthy R, et al. Seizures and severe nutrient deficiencies in a puppy fed a homemade diet. J Am Vet Med Assoc 2012;241:477-483. 
15. Kovalik M, Mellanby RJ, Evans H, et al. Ciclosporin therapy is associated with minimal changes in calcium metabolism in dogs with atopic dermatitis. Vet Dermatol 2012;23:481-491. 
16. Kovalik M, Thoday KL, Berry J, et al. Prednisolone therapy for atopic dermatitis is less effective in dogs with lower pretreatment serum 25-hydroxyvitamin D concentrations. Vet Dermatol 2012;23:125-130, e127-128.
17. Kovalik M, Thoday KL, Evans H, et al. Short-term prednisolone therapy has minimal impact on calcium metabolism in dogs with atopic dermatitis. Vet J 2012;193:439-442. 
18. Nunamaker EA, Sherman JG. Oral administration of lanthanum dioxycarbonate does not alter bone morphology of normal cats. J Vet Pharmacol Ther 2012;35:193-197. 
19. Pineda C, Aguilera-Tejero E, Raya AI, et al. Feline parathyroid hormone: validation of hormonal assays and dynamics of secretion. Domest Anim Endocrinol 2012;42:256-264. 
20. Sawyer ES, Northrup NC, Schmiedt CW, et al. Outcome of 19 dogs with parathyroid carcinoma after surgical excision. Vet Comp Oncol 2012;10:57-64. 
21. Tuohy JL, Worley DR, Withrow SJ. Outcome following simultaneous bilateral thyroid lobectomy for treatment of thyroid gland carcinoma in dogs: 15 cases (1994-2010). J Am Vet Med Assoc 2012;241:95-103. 
22. Williams TL, Elliott J, Syme HM. Calcium and phosphate homeostasis in hyperthyroid cats - associations with development of azotaemia and survival time. J Small Anim Pract 2012;53:561-571.