Diagnosing and treating primary hypoparathyroidism in dogs and cats
In the preceding article, we discussed the pathophysiology of primary hypoparathyroidism and resulting hypocalcemia. The clinical signs of hypocalcemia are the same regardless of the underlying cause. In this article, we review the differential diagnoses in patients with hypocalcemia, the diagnostic testing to investigate clinical signs consistent with hypocalcemia, and the treatment of primary hypoparathyroidism.
The various differential diagnoses in patients with hypocalcemia can be organized based on the degree of hypocalcemia and the prevalence of the underlying disease causing hypocalcemia. An important cause for a falsely low serum calcium concentration is laboratory error or improper sample anticoagulant (addition of EDTA, which chelates calcium).1Common causes of low serum total calcium include hypoalbuminemia, renal failure, puerperal tetany, and acute pancreatitis.1,2 Less frequently, hypocalcemia occurs with ethylene glycol intoxication, administration of phosphate-containing enemas or intravenous sodium bicarbonate, soft tissue trauma, rhabdomyolysis, and primary hypoparathyroidism.1,2 Other causes of hypocalcemia include rapid intravenous administration of phosphates, dilution when calcium-free intravenous fluids are administered, intestinal malabsorption, starvation, citrated blood or plasma transfusions, hypovitaminosis D, thyroid tumors, cervical trauma or surgery, hypomagnesemia, aminoglycoside intoxication, and nutritional secondary hyperparathyroidism.1-3
Causes of hypocalcemia that have been identified in people but have not yet been clearly established in cats or dogs include pseudohypoparathyroidism (end-organ resistance to parathyroid hormone [PTH]), drug-induced hypoparathyroidism (most commonly from chemotherapeutic agents), sepsis, primary or metastatic bone tumors, hypercalcitoninism, and 131 I radiation damage.1,2,4
Primary hypoparathyroidism may be due to the absence or destruction of the parathyroid gland (as with surgical removal or immune-mediated disease, respectively). Transient hypoparathyroidism may occur with rapid correction of long-standing hypercalcemia (hypercalcemia causing temporary atrophy of the gland), as can occur with surgical removal or ablation of a parathyroid adenoma causing primary hyperparathyroidism.1,2 Thyroid surgery in both dogs and cats may result in removal or damage to the parathyroid glands. Thyroidectomy is the most common cause of hypoparathyroidism in cats.1,3 Parathyroid agenesis has been reported in a dog1 and was suspected in a cat.5
A serum chemistry profile may reveal results that are indicative of primary hypoparathyroidism. Primary hypoparathyroidism can be definitively diagnosed by measuring serum pth and ionized calcium concentrations.
In addition to ionized hypocalcemia, animals with hypoparathyroidism have relative or absolute hyperphosphatemia.1 In a case series of 37 dogs with hypoparathyroidism, the serum phosphorus concentrations were greater than the serum calcium concentrations in every case.1 Young animals normally have slightly higher phosphorus concentrations, and most laboratories include these values when establishing their reference ranges, resulting in higher reference ranges for phosphorus concentration.1,3 However, anorectic hypoparathyroid dogs may have relative phosphate depletion, which may or may not be reflected in the serum phosphorus concentration.1 The combination of hypocalcemia and hyperphosphatemia, with normal serum albumin, blood urea nitrogen, and creatinine concentrations, is indicative of primary hypoparathyroidism.1,2
Parathyroid hormone measurement
In the past 15 years, human PTH assays have been validated for use in dogs and cats.1,4,6-8 Before a validated PTH assay became available for use in animals, a histologic examination was used to confirm the diagnosis of primary hypoparathyroidism.6,9 With the advent of a reliable PTH assay, biopsy is no longer necessary to confirm hypoparathyroidism.