Hypoparathyroidism is a condition characterized by insufficient levels of parathyroid hormone (PTH), which is produced by the parathyroid glands. These four small glands, pea-sized, are located in the neck behind the thyroid gland. They primarily regulate calcium, phosphorus, and magnesium levels in the bloodstream. When these glands are underactive, they produce too little PTH, leading to an imbalance where blood calcium levels decrease and phosphorus levels increase. This mineral imbalance can affect various bodily functions, including muscle, nerve, and bone health.
Post-Surgical Development
The most frequent cause of hypoparathyroidism is damage to or accidental removal of the parathyroid glands during neck surgery. This commonly occurs during procedures like thyroidectomy, which involves removing all or part of the thyroid gland, or during surgery for hyperparathyroidism, where one or more overactive parathyroid glands are removed. Other neck surgeries can also inadvertently affect these glands.
The parathyroid glands are small and challenging to distinguish from surrounding tissues, making them susceptible to injury during surgery. This injury can disrupt their blood supply or lead to their complete removal. While surgeons make efforts to preserve them, damage or removal occurs in approximately 8% of anterior neck surgeries. This complication can lead to temporary hypoparathyroidism, but about 25% of these cases result in permanent hypoparathyroidism.
Immune System Malfunction
Hypoparathyroidism can also result from autoimmune processes, where the body’s immune system mistakenly targets and damages the parathyroid glands. The immune system perceives the parathyroid glands as foreign invaders, leading to their destruction and reduced PTH production. This autoimmune attack can occur in isolation, affecting only the parathyroid glands, or as part of broader autoimmune syndromes.
One example is Autoimmune Polyendocrine Syndrome Type 1 (APS-1), a rare genetic disorder where the immune system attacks multiple endocrine glands, including the parathyroid glands. APS-1 is also associated with other autoimmune conditions such as chronic mucocutaneous candidiasis and pernicious anemia. These responses involve a breakdown in immune tolerance.
Inherited Predispositions
Some individuals are born with hypoparathyroidism due to inherited genetic factors that affect the development or function of the parathyroid glands. These genetic causes are rare, leading to congenital hypoparathyroidism. One example is DiGeorge syndrome, a genetic disorder caused by a microdeletion on chromosome 22q11. This syndrome can result in the absence or dysfunction of the parathyroid glands, alongside other developmental issues.
Specific gene mutations can also lead to inherited forms of hypoparathyroidism. For instance, mutations in genes such as GCM2, CASR (calcium-sensing receptor), or PTH (parathyroid hormone gene) can directly impair parathyroid gland development or PTH production. Mutations affecting the extracellular calcium-sensing receptor (CaSR) can cause autosomal dominant hypocalcemia, a condition where the body mistakenly thinks calcium levels are high, leading to reduced PTH secretion.
Other Contributing Factors
Beyond surgical complications, autoimmune conditions, and genetic predispositions, several other factors can contribute to the development of hypoparathyroidism. A severe deficiency in magnesium, for example, can impair the parathyroid glands’ ability to secrete PTH, leading to functional hypoparathyroidism. This condition is reversible once magnesium levels are restored.
Radiation therapy directed at the neck, particularly for cancers, can also damage the parathyroid glands over time. Cases have been reported following radioactive iodine 131 (131-I) treatment for thyroid disease. Infiltrative diseases, where abnormal substances accumulate and damage tissues, can affect the parathyroid glands. Conditions like hemochromatosis (iron overload) or Wilson’s disease (copper overload) can lead to the deposition of these metals within the glands, impairing their function. In some instances, the cause of hypoparathyroidism remains unknown, and these cases are termed idiopathic.