Wednesday, April 24, 2013

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

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, K√§rner 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. 

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