In hypoparathyroidism, either subnormal amounts of parathyroid hormone (PTH) are secreted, or the hormone secreted is unable to interact normally with target cells. It has been recognized primarily in dogs, particularly in smaller breeds such as Miniature Schnauzers, but other breeds may be affected.
Various pathogenic mechanisms can result in inadequate secretion of PTH. Parathyroid glands may 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 destruction of parathyroids by primary or metastatic neoplasms in the anterior cervical area, and atrophy of parathyroids associated with chronic hypercalcemia. The presence of numerous distemper virus particles in chief cells of the parathyroid gland may contribute to the low blood calcium in certain dogs with this disease.
Agenesis of the parathyroids is a rare cause of congenital hypoparathyroidism in pups. Certain cases of idiopathic hypoparathyroidism in animals (including people) with histologically normal parathyroids may be due to lack of the specific enzyme in chief cells that converts the pro-PTH molecule to the biologically active PTH secreted by the gland. In other cases, an immune-mediated mechanism may 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 seen in people, but it is uncertain whether it is seen in other 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 when fed an alkalinizing diet. Dry cow diets with an excessively high cation content resulting in 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 of the loss of calcium through the mammary gland while the sensitivity of the body to PTH is impaired.
The functional disturbances and clinical manifestations of hypoparathyroidism primarily are the result of increased neuromuscular excitability and tetany. Bone resorption is decreased because of the lack of PTH, and blood calcium levels diminish progressively (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 convulsions. Blood phosphorus levels are increased substantially, owing to increased renal tubular reabsorption. Hyperphosphatemia triggers an upregulation of the synthesis of fibroblast growth factor 23 in bone, which hampers the hydroxylation of vitamin D3 in the kidney to its active form. This further impairs the counter-regulatory 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, there is infiltration of the gland with lymphocytes and plasma cells and nodular regenerative hyperplasia of remaining chief cells. Later, the parathyroid gland is replaced by lymphocytes, fibroblasts, and capillaries, with only an occasional viable chief cell.
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 response to therapy. Measurement of serum PTH should be considered to confirm the diagnosis. Radioimmunoassays of PTH are commercially available for most companion animal species and horses. Some of the signs (eg, tetany) and laboratory data (eg, hypocalcemia) are similar to those of puerperal hypocalcemia. However, puerperal hypocalcemia usually is accompanied by hypophosphatemia and a low-normal or subnormal blood glucose concentration as a result of the associated intense muscular activity.
The neuromuscular tetany should be treated initially by restoring blood calcium levels to near normal by IV administration of calcium gluconate. One recommended therapeutic regimen is 10 mL of 10% calcium gluconate in 250 mL of 0.9% saline administered at 2.5 mL/kg/hour for 8–12 hours. Care must be taken not to administer the calcium too rapidly because of its cardiotoxic properties. Longterm maintenance of blood calcium levels in the absence of normal PTH secretion should be attempted by feeding diets high in calcium and low in phosphorus and that are supplemented with calcium (gluconate or lactate) and vitamin D3.
Large doses of vitamin D3 (≥25,000–50,000 U/day, depending on the weight of the dog) may be required initially to increase the blood calcium level in hypoparathyroid animals, because the lack of PTH diminishes the rate of formation of the biologically active vitamin D metabolite in the kidney. The dietary phosphate content should be reduced to the lowest possible level when supplementing vitamin D3; the use of phosphate binders administered orally 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 level. After adjusting the dosage of vitamin D, a 4- to 5-day interval should precede the next blood calcium determination. Once the blood calcium level 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 longterm stabilization.
Hypoparathyroidism of various etiologies is recognized in most animal species but is most prevalent in dogs.
Persistent hypoparathyroidism results in sustained hypocalcemia due to impaired regulation of the calcium homeostasis.
Treatment consists of initial correction of hypocalcemia followed by a longterm support of the calcium homeostasis through dietary adjustments and oral vitamin D supplementation.