Besides calcium, there are several other substances that influence PTH secretion. High levels of magnesium may also inhibit PTH secretion. For instance, the high levels of magnesium sulfate administered to patients in premature labor cause a reduction in PTH levels. Conversely, low levels of magnesium can stimulate PTH secretion although prolonged depletion of magnesium can paralyze PTH secretion. Catecholamines, such as epinephrine and norepinephrine, also stimulate PTH secretion. As serum calcium decreases acutely, PTH secretion may rise up to five times the normal secretion rate. If the hypocalcemia is chronic, PTH secretion may approach 50 times the basal rate. A rising serum calcium will suppress PTH secretion.
Besides controlling how much PTH is secreted by the parathyroid glands, calcium regulates the amount of PTH produced or synthesized by the parathyroid glands. This is important because the stores of PTH contained in the gland normally must remain sufficient to maintain maximal rates of secretion for no more than one and a half hours. PTH synthesis is also regulated by vitamin D. High levels of vitamin D inhibit PTH synthesis. This is one of the ways in which PTH and vitamin D work together to regulate calcium levels. This synchronicity is relied on in the treatment of parathyroid gland disorders. Vitamin D derivatives can be used to prevent secondary hyperparathyroidism in dialysis patients with renal osteodystrophy, a type of mineral imbalance and bone deterioration caused by impaired kidney function.
In both hypoparathyroidism and pseduodhypoparathyroidism, plasma calcium levels are usually < 7.0 mg/dl while plasma calcium levels are usually > 6.2 mg/dl. The degree of phosphorus elevation is less marked in pseudohypoparathyroidism and in adults with hypoparathyroidism. The plasma PTH is low or undetectable in hypoparathyroidism, although the PTH level may be elevated in pseudohypoparathyroidism.
Despite the body’s tendency towards homeostasis, certain systems can go awry. In hypoparathyroidism, the parathyroid glands fail to secrete sufficient parathyroid hormone for the body’s needs. In a similar condition, pseudohypoparathyroidism, levels of parathyroid hormone are adequate, but the body’s cells fail to respond to it.
The most common cause of hypoparathyroidism is surgery, usually thyroid gland surgery (either total or partial thyroidectomy). One of more of the parathyroid glands may also be diseased, excreting excess parathyroid hormone and causing symptoms of hyperparathyroidism. In hyperparathyroidism, the parathyroid gland or glands may need to be surgically removed. Because of their close proximity to the lobes of the thyroid gland, the parathyroid glands may be damaged, as mentioned, during thyroid surgery. The parathyroid and thyroid glands share the same blood supply. On occasion, surgical intervention interferes with this blood supply, causing transient or sporadic symptoms of hypoparathyroidism, which persist for several weeks after surgery. Once the blood vessels in this area recover, parathyroid function may be restored.
Ionizing radiation (I 131) used to destroy thyroid cells in patients with thyroid cancer or hyperthyroid disorders may also damage the parathyroid glands. In one study, researchers observed a 58 % incidence of diminished parathyroid reserve among 53 patients given high doses of I 131.[i][i] Hypoparathyroidism typically develops within 4 to 18 months after treatment with radioiodine.
In familial or autoimmune (idiopathic) hypoparathyroidism, autoantibodies to parathyroid cells develop in genetically susceptible individuals. These autoantibodies damage parathyroid cells and interfere with the production and release of parathyroid hormone. The age at onset of idiopathic hypoparathyroidism is usually 2-10 years, and there is a preponderance of female cases. Circulating parathyroid antibodies are common with up to one-third of patients having antibodies that recognize the parathyroid calcium sensor.
Idiopathic hypoparathyroidism may also occur in combination with other autoimmune endocrine disorders in a condition known as autoimmune polyglandular syndrome, type 1. In this condition, patients usually develop candidiasis and yeast infections at a very early age followed by hypoparathyroidism between ages 5-9. This is followed by the development of adrenal insufficiency or Addison’s disease.
Resistance to PTH or pseudohypoparathyroidism can result from renal insufficiency due to aberrations in mineral balance. It can also be caused by medications that block osteoclastic bone resorption, including plicamycin, calcitonin, gallium nitrate, oral phosphates and bisphosphonates.[ii][ii]
Hypoparathyroidism has also been associated with sepsis (infection). Furthermore, progressive systemic sclerosis may cause fibrosis of the parathyroid glands causing clinical symptoms of hypoparathyroidism.