Hypoparathyroidism of various causes is recognized primarily in dogs and is characterized by insufficient parathyroid hormone (PTH) secretion by the parathyroid glands. PTH deficiency results in an inability to respond adequately to hypocalcemia. Chronic hypocalcemia results in increased neuromuscular excitability and restlessness. Treatment consists of initial correction of hypocalcemia and long-term stabilization of the calcium balance through dietary adjustments and vitamin D supplementation.
In hypoparathyroidism, either subnormal amounts of parathyroid hormone (PTH) are secreted, or the secreted hormone is unable to interact normally with target cells. Hypoparathyroidism has been recognized primarily in dogs, particularly in smaller breeds such as Miniature Schnauzers; however, other breeds can be affected.
Various pathogenic mechanisms can result in inadequate PTH secretion. The parathyroid glands could be damaged or inadvertently removed during thyroid surgery. After damage to the glands or their vascular supply, adequate functional parenchyma often regenerates, and clinical signs subsequently disappear.
Idiopathic hypoparathyroidism in adult dogs usually is the result of diffuse lymphocytic parathyroiditis that causes extensive degeneration of chief cells and replacement by fibrous connective tissue. Other possible causes of hypoparathyroidism include neoplastic destruction of the parathyroids or atrophy of the parathyroids associated with chronic hypercalcemia.
Agenesis of the parathyroids is a rare cause of congenital hypoparathyroidism in pups. Certain cases of idiopathic hypoparathyroidism in animals (including in humans) with histologically normal parathyroids could be due to lack of the specific enzyme in chief cells that converts the pro-PTH molecule into the biologically active PTH that is secreted by the gland. In other cases, an immune-mediated mechanism might be involved, because a similar destruction of secretory parenchyma and lymphocytic infiltration has been produced experimentally in dogs by repeated injections of parathyroid tissue emulsions.
Pseudohypoparathyroidism is a variant of hypoparathyroidism that occurs in humans; however, it is uncertain whether it occurs in animals. Target cells in kidney and bone are unable to respond to normal or increased amounts of PTH, and severe hypocalcemia develops, even though the parathyroid glands are hyperplastic.
A state of dietary pseudohypoparathyroidism is recognized in late-pregnant dairy cows that are fed an alkalinizing diet. Dry cow diets with an excessively high cation content resulting in a high dietary cation-anion difference induce mild metabolic alkalosis, which hampers the responsiveness of target tissues to PTH. The result is an increased risk of hypocalcemia at the onset of lactation, when the fresh cow experiences a sudden increase in calcium loss through the mammary gland while the body's sensitivity to PTH is impaired.
Clinical Findings and Lesions of Hypoparathyroidism in Dogs
The functional disturbances and clinical signs of hypoparathyroidism are primarily the result of increased neuromuscular excitability and tetany. Bone resorption is decreased because of the lack of parathyroid hormone, and blood calcium levels diminish progressively (to 4–6 mg/dL). Affected dogs are restless, nervous, and ataxic, with weakness and intermittent tremors of individual muscle groups that progress to generalized tetany and seizures.
Blood phosphorus concentrations are substantially increased in dogs with hypoparathyroidism, owing to increased renal tubular reabsorption. Hyperphosphatemia triggers an upregulation of the synthesis of fibroblast growth factor 23 (FGF-23) in bone, which hampers the hydroxylation of vitamin D3 in the kidney to its active form. This decrease in vitamin D3 hydroxylation further impairs the counterregulatory response to hypocalcemia.
Calcification of microvasculature, intracerebral calcification, decreased mental function, cataracts, osteopenia, and ligamentous ossification have been associated with chronic hypoparathyroidism.
In the early stages of immune-mediated lymphocytic parathyroiditis in dogs, the gland is infiltrated with lymphocytes and plasma cells, and the remaining chief cells undergo nodular regenerative hyperplasia. Later, the parathyroid gland is replaced by lymphocytes, fibroblasts, and capillaries, with only an occasional viable chief cell.
Diagnosis of Hypoparathyroidism in Dogs
Clinical signs of persistent hypocalcemia with neuromuscular excitability
Species-specific radioimmunoassay of serum PTH concentration
Diagnosis of hypoparathyroidism is based on clinical signs of increased neuromuscular excitability, severe hypocalcemia, and often moderate hyperphosphatemia in a nonparturient animal, as well as on the patient's response to treatment. Measurement of serum parathyroid hormone concentrations should be considered to confirm the diagnosis.
Radioimmunoassays of PTH are commercially available for most companion animal species and horses.
Some of the clinical signs (eg, tetany) and laboratory results (eg, hypocalcemia) in cases of hypoparathyroidism are similar to those of puerperal hypocalcemia. However, puerperal hypocalcemia usually is accompanied by hypophosphatemia and a low-normal or subnormal blood glucose concentration because of the associated intense muscular activity.
Treatment of Hypoparathyroidism in Dogs
Calcium supplementation
Vitamin D supplementation
Decrease of dietary phosphorus
In cases of hypoparathyroidism in dogs, neuromuscular tetany should be treated initially by restoring blood calcium concentrations to near normal via IV administration of calcium gluconate. For IV treatment, a 10% calcium gluconate solution (containing 9.3 mg of calcium per milliliter) is commonly used; 0.5–1.5 mL/kg body weight is administered via slow IV drip over 10–30 minutes, until tetany resolves (1).
Because of its cardiotoxic properties, IV calcium must be administered slowly, and monitoring cardiac activity for tachycardia and arrhythmias is advisable. Fluid administration should be discontinued temporarily until cardiac arrhythmia resolves. Alternatively, 1–2 mL/kg of 10% calcium gluconate diluted 1:1 with saline solution [0.9% NaCl] can be administered subcutaneously (1). Incidents of iatrogenic calcinosis cutis after repeated subcutaneous administration of calcium salts have been reported in the human and veterinary literature.
Pearls & Pitfalls
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Long-term maintenance of blood calcium concentrations in the absence of normal PTH secretion should be attempted by feeding diets that are high in calcium and low in phosphorus and that are supplemented with calcium salts at a dose of approximately 25 mg/kg of elemental calcium every 8–12 hours (1), as well as with vitamin D3.
Various compounds are available for oral supplementation of vitamin D. Ergocalciferol is an inexpensive nonactivated form of vitamin D that is also referred to as vitamin D2. Disadvantages of this compound over calcitriol (see below) are the slow onset of action and its long half-life, which make a possible overdosage with ensuing hypercalcemia more difficult to reverse. Treatment is initiated with a loading dose of 4,000–6,000 IU/kg every 24 hours that is followed by a maintenance dose of 1,000–2,000 IU/kg, administered between once daily and once weekly (1).
Calcitriol is the activated form of vitamin D3, with faster onset of treatment effect and shorter half-life. Treatment consists of an initial dose of 0.02–0.03 mcg/kg, PO, every 24 hours for 3–4 days, followed by a maintenance dose of 0.005–0.015 mcg/kg every 24 hours (1). The dietary phosphate content should be decreased to the lowest possible level when supplementing vitamin D3; the use of oral phosphate binders should be considered in patients with marked hyperphosphatemia.
To prevent hypercalcemia and extensive soft tissue mineralization, the dosage of vitamin D should be carefully adjusted after frequent determination of the serum calcium concentration. After adjusting the dosage of vitamin D, an interval of 4–5 days should precede the next blood calcium determination. When the blood calcium concentration has returned to normal, substantially lower dosages of vitamin D are indicated for longterm maintenance. In some dogs, only dietary calcium supplementation is required for long-term stabilization.
Key Points
Hypoparathyroidism of various etiologies is recognized in most animal species but is most prevalent in dogs.
Persistent hypoparathyroidism results in sustained hypocalcemia because of the impaired regulation of calcium homeostasis.
Treatment consists of initial correction of hypocalcemia, followed by long-term support of calcium homeostasis through dietary adjustments and oral vitamin D supplementation.
For More Information
Schaefer C, Goldstein RE. Canine primary hyperparathyroidism. Compend Continuing Educ Vet. 2009;31(8):382-390.
Also see pet owner content regarding disorders associated with calcium, phosphorus, and vitamin D in dogs.
References
Henderson AK, Mahony O. Hypoparathyroidism: treatment. Compend Contin Educ Vet. 2005;27(4):280-287.
