Causes of Hypoparathyroidism

Hypoparathyroidism is a rare disease in which the parathyroid glands — four small glands in the neck — produce low levels of parathyroid hormone (PTH).

PTH has a key role in regulating and maintaining the balance of calcium and phosphorus. As such, low levels of PTH result in hypocalcemia (low levels of calcium) and high levels of phosphorus in the blood.

This imbalance can cause a wide range of symptoms, including muscle weakness, fatigue, twitching and cramping of legs, and spasms of the hands, feet, mouth, or throat.

The disorder has several causes, each of which results in a different type of hypoparathyroidism.

Acquired hypoparathyroidism

This is the most common type of hypoparathyroidism, and is usually caused by damage to, or removal of, the parathyroid glands.

These small glands can be accidentally damaged during surgery to the head or neck, particularly in patients with thyroid problems, or neck or throat cancer. In these cases, the disease may either occur shortly after surgery, or appear several months or years later. Depending on the extent of damage to the glands, acquired hypoparathyroidism could be temporary.

Damage can also occur during radiation therapy used to treat cancer, especially radiation therapy to the neck or face.

Due to magnesium’s role in modulating the function of the parathyroid glands, low levels of this mineral can also cause acquired hypoparathyroidism.

Autoimmune hypoparathyroidism

In autoimmune diseases, the immune system produces antibodies against a person’s own cells and tissues, as if they were foreign.

In the case of autoimmune hypoparathyroidism, the immune system wrongly attacks the parathyroid glands, and the damage affects PTH production.

Autoimmune hypoparathyroidism can exist as part of an inherited condition called autoimmune polyendocrine syndrome type 1 (APS1), which frequently begins in childhood or adolescence and affects several organs. However, not all patients with APS1 develop hypoparathyroidism.

Mutations in an immune regulator gene (AIRE) were found to be related to a recessive form of APS1, which means that two copies of the mutated gene, one from each parent, must be present for the disease to develop.

Congenital hypoparathyroidism

Hypoparathyroidism can also be a congenital disease, meaning that babies are born without parathyroid glands, or the glands exist but are not able to produce PTH. As such, the symptoms usually start during the first few months of life.

Congenital hypoparathyroidism may be temporary or permanent. Temporary hypoparathyroidism can occur, for example, in infants whose mothers have excessive levels of calcium in the blood due to hyperparathyroidism (too much PTH), which prevents PTH production in the fetus. As a result, blood calcium levels will be unusually low in a newborn.

Temporary hypoparathyroidism may also be seen in premature infants whose mothers have diabetes. People with diabetes have high levels of glucose (sugar) in the blood, and lose a greater amount of magnesium through urine excretion.

Familial isolated hypoparathyroidism

This disease type is caused by genetic mutations in one of several genes, and these are inherited, meaning they are passed from parents to children. It occurs in the absence of other endocrine (hormone-related) diseases or developmental problems.

Mutations in the calcium-sensing receptor (CASR) gene is one such example. CASR contains information to produce the CaSR protein that stimulates the release of PTH in response to low calcium levels. People with mutations in the CASR gene have poor PTH production, because the faulty calcium sensor will wrongly consider calcium levels to be high in the blood, leading to excessive excretion of this mineral in the urine.

Mutations in the GNA11 gene are also related with familial isolated hypoparathyroidism. This gene contains the information to produce part of a protein known to work with the CaSR protein. 

Another form of familial isolated hypoparathyroidism is caused by mutations in the GMC2 gene, which encodes a protein that has a key role in the development of parathyroid glands. People with these mutations may have extremely low PTH activity.

X-linked recessive hypoparathyroidism, which affects males almost exclusively, is caused by mutations in a gene located in the X chromosome. The gene is key in the development of the parathyroid glands.

Idiopathic hypoparathyroidism

This form of the disease refers to insufficient PTH production due to unknown cause, meaning that it is not acquired, inherited or secondary to other disease.

Idiopathic hypoparathyroidism is very rare, occurring in approximately 0.02% of all patients.


In contrast to hypoparathyroidism, people with pseudohypoparathyroidism have normal levels of PTH but the body is unable to respond to this hormone due to genetic mutations.

One of those mutations is in the GNAS1 gene, which normally works to stimulate an enzyme called adenylate cyclase that controls the production of several hormones. A mutation in GNAS1 gene is most often inherited from the mother.

Lack of response to PTH leads to low levels of calcium and high levels of phosphorus in the blood.


Last updated: April 13, 2021


Hypoparathyroidism News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.