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.