This condition may be more common than you think, so evaluate all dogs with increased calcium concentrations.
A middle-aged or older dog presenting with hypercalcemia could have one of several underlying health conditions, including primary hyperparathyroidism (PHP).
In addition to PHP, hypercalcemia could be caused by malignancy (e.g., lymphosarcoma, apocrine gland adenocarcinoma of the anal sac, thymoma), Addison's disease, vitamin D toxicosis, renal disease or skeletal lesions. Or the finding could be a spurious laboratory error. Hypercalcemia of malignancy, Addison's disease and renal failure seem to be the most common causes of hypercalcemia in dogs.
Recent studies, however, have shown that up to one-third of dogs with PHP may be asymptomatic, and their calcium concentrations may be only mildly increased. Therefore, PHP may actually be more common among middle-aged and older dogs than previously thought.
Most dogs have four parathyroid glands, though the actual number of glands can vary. The parathyroid glands are located either external to the thyroid capsule or within the capsule. Parathyroid glands may be ectopic (i.e., located in an abnormal position because of their development). The thymus develops alongside the internal parathyroid glands, and islets of parathyroid tissue may break off and continue descending into the mediastinum with the thymus, resulting in additional and ectopic parathyroid glands. Parathyroid glands normally are small, ranging in size from 2 to 4 mm; they may be difficult to detect or can easily be mistaken for a thyroid cyst or nodule.
The parathyroid glands generate, store and secrete parathyroid hormone (PTH). PTH is made autonomously and stored within the gland's cells. PTH is secreted in response to decreased extracellular calcium concentrations. Special calcium-sensing receptors reside within the chief cells of the parathyroid glands that send signals to either increase or decrease PTH synthesis and release. PTH acts directly on the kidneys to increase calcium reabsorption, phosphorus excretion and biosynthesis of calcitriol. Calcitriol and PTH act synergistically to increase calcium and phosphate release from bones. Calcitriol also will increase calcium reabsorption in the intestines.
A dog with primary hyperparathyroidism may have signs classified as the following:
Urinary signs seem to be the most common, with up to 50 percent of patients having urinary tract infections or bladder stones. Renal insufficiency or failure may be correlated with the total calcium concentration and prolonged hypercalcemia.
In dogs with PHP, hypercalcemia may be noted incidentally on routine geriatric blood work. Since the true incidence of PHP can be underestimated, it's a good idea to evaluate any dog with a slightly increased calcium concentration. A standard workup for such dogs includes a full physical examination with thorough lymph node evaluation and a rectal examination to assess the anal sacs. If a full serum chemistry profile, complete blood count, and urinalysis have not already been performed, these tests should be ordered and the results assessed.
Next, evaluate the ionized calcium concentration, as this is the most accurate way of assessing a patient's true calcium status. Laboratory orders for PTH and PTH-related protein tests usually can be submitted at the same time to help keep costs down and prevent the owner from having to bring the patient back to the hospital several times.
Given the high incidence of urinary tract infections, a urine culture also should be considered as dictated by the clinical signs; ordering an abdominal radiograph to assess for bladder stones would be prudent.
Finally, a three-view thoracic radiographic examination can be useful to assess cardiothoracic structures. And ultrasonography can detect the parathyroid nodule preoperatively, but this is user-dependant because of the small size of the parathyroid glands.
An increased ionized calcium concentration with a concurrent normal or increased PTH concentration is consistent with a diagnosis of PHP. A common misconception is that the PTH concentration must be above the reference range; this is not true. In fact, the PTH concentration can be in the middle of the reference range. Because increased calcium provides a negative feedback loop to the parathyroid glands, a dog with hypercalcemia should have a very low PTH concentration. Therefore, a dog with a normal PTH concentration and hypercalcemia actually has an inappropriate PTH concentration.
Once PHP has been diagnosed, recommend to the client that treatment be given to prevent the effects of prolonged hypercalcemia. The most common and effective treatment method is surgical excision of the hyperfunctional parathyroid nodule or nodules (Photo 1). The surgical cure rate is 95 percent if all hyperfunctional tissue is removed. Success, of course, depends on the surgeon's experience level.
Photo 1: An intraoperative view of a thyroid gland with an enlarged parathyroid nodule. (Photo courtesy of: Dr. Kathleen Ham)
A less-invasive treatment is glandular ablation. An ultrasound probe is used to detect the enlarged gland or glands, and heat is used to ablate the tissue. The cure rate is about 90 percent, but the patient may require multiple treatments.
A common owner misconception is that their pets are too old for anesthesia and surgical treatment. If the surgery is being performed by an experienced surgeon, the anesthetic time and risks are low, and the success rate is high.
PHP may be more common than originally described, and all dogs with any increase in calcium concentration should be fully evaluated. An ionized calcium concentration is the most reliable determinant of a dog's calcium status. Understand that dogs with PHP may have a normal PTH concentration. Treatment is highly effective and should be strongly recommended in all patients, even older dogs.
Dr. Ham is an ACVS board-certified veterinary surgeon. She is an assistant professor at The Ohio State University in the Department of Veterinary Clinical Sciences. In 2009, she received an award from the ACVS for her clinical research in dogs with primary hyperparathyroidism.