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Causes of Hypopara

What causes hypoparathyroidism?

Hypoparathyroidism is caused by a group of conditions in which low calcium and high phosphate levels occur as a result of insufficient or inactive parathyroid hormone secretion.

These conditions fall into two main types of hypoparathyroidism:

1) Iatrogenic  hypoparathyroidism

Most commonly, Hypoparathyroidism is acquired by the surgical removal of, or damage to, the parathyroid glands . Iatrogenic means 'caused by treatment'.

2) Idiopathic hypoparathyroidism

Hypoparathyroidism without a defined cause (such as surgery) is called Idiopathic hypoparathyroidism. This is the name of a group of rare conditions which may be either congenital (occurring in the womb ) or acquired in childhood or later in life as an inherited and /or autoimmune condition.


1) Iatrogenic hypoparathyroidism

a) Post Surgical

This is the most common cause of hypoparathyroidism in adulthood although it is still a rare condition. Permanent hypoparathyroidism occurs in around 7-10% of all neck operations. The British Association of Endocrine & Thyroid Surgeons (BAETS) say that about 30% of those who have thyroid operations will experience temporary symptoms of low calcium and may require treatment. If treatment is still ongoing after 6 months it is known as 'late hypocalcaemia' or hypoparathyroidism and may be permanent, requiring lifelong medication. Late hypocalcaemia after total thyroidectomy is the commonest reported complication. The overall incidence is about 9%.*

Hypoparathyroidism can occur following any surgery to the neck (thyroid, parathyroid, laryngeal or oesophogeal) where the parathyroids have been accidentally or intentionally removed or damaged and have lost their blood supply. For example, during surgery on the thyroid gland, the parathyroid glands may be accidentally damaged or removed. The parathyroid glands may also be intentionally removed if cancerous (although this is rare) or as treatment for hyperparathyroidism when parathyroid glands are overactive.

Post surgical hypoparathyroidism may be a temporary situation - if there is sufficient undamaged parathyroid tissue left or when the remaining tissue is no longer suppressed, the parathyroid glands will recover, usually within 6 months to a year. If parathyroid hormone levels remain above 18ng/L then there is a good chance that patients will eventually be able to come off their medication. If this is not the case, permanent hypoparathyroidism results.

Women more commonly require thyroid or parathyroid surgery and the average age for diagnosis of both thyroid disease and parathyroid disease is in the fifth decade, but both conditions can occur from childhood onwards.

b) Radiation or drug treatment

This can also occur from cancer of the parathyroid glands, HIV AIDS, or following treatment for thyroid and other cancers eg radioactive iodine thyroid ablation or external beam radiation to neck or use of chemotherapy drugs.

c) Hungry bone syndrome

This develops after a parathyroidectomy for hyperparathyroidism where the body has been used to high levels of  calcium, whihc has been taken from the bones into the blood. When the parathyroid gland or glands are removed, the PTH level in the blood drops suddenly and the patient becomes temporarily hypothyroid. The bone, which has been starved of calcium, now grabs it back and blood calcium level falls suddenly. This requires postoperative treatment with calcium for up to several days until the hypoparathyroid state resolves, and calcium levels are stabilised.


2) Idiopathic hypoparathyroidism

Deficient PTH secretion without a defined cause (e.g. surgical injury) is termed Idiopathic hypoparathyroidism. It includes a number of very rare conditions which may be congenital or genetically inherited and may have an autoimmune cause.

a) Congenital hypoparathyroidism

Permanent conditions which affect the development of the parathyroid glands in the womb may also be inherited. People with this condition are born without parathyroid tissue, as in DiGeorge Syndrome

b) Inherited genetic hypoparathyroidism

Other conditions may be passed on through your genes by your family and may occur in childhood or later in life. Genes that function abnormally cause genetic disorders. Since genes are passed on from one generation to the next, genetic disorders often run in families.

The basic patterns of inheritance are: autosomal dominant, autosomal recessive, and X-linked inheritance.

These inherited forms of hypoparathyroidism arise from faulty genes that affect the proper functioning of parathyroid hormone in the body in a number of ways.

Pseudohypoparathyroidism (PHP)
There are several types of pseudohypoparathyroidism: 1a, 1b, 1c and 2.

In this condition , the glands produce parathyroid hormone but the body is resistant to it. So although there are normal to high levels of PTH, the body cannot respond normally to it causing low calcium levels. Phosphate levels may be normal or high. People with PHP are usually short, with shortened bones in their feet and hands. They may also have diabetes and an underactive thyroid gland.

Type Ia is inherited in an autosomal dominant manner. That means only one parent needs to pass you the defective gene in order for you to develop the condition. The condition causes short stature, round face, and short hand bones, as in Albright hereditary osteodystrophy. Type Ib also involves resistance to PTH but only in the kidneys. It is less understood than type Ia and has no skeletal abnormalities. In type 1c the protein shows normal activity.

Type 2 pseudohypoparathyroidism also involves low blood calcium and high blood phosphate levels, but none of the physical characteristics seen in 1a. Type 2 has not yet been genetically characterized.

Pseudopseudohypoparathyroidism (PPHP)
Patients with this condition have all the features of Pseudohyporathyroidism (PPHP) but normal calcium and phosphate levels. Levels may fluctuate.

c) Autoimmune Hypoparathyroidism

In an autoimmune problem, the bodies autoantibodies attack normal cells instead of infections. In autoimmune hypoparathyrodism, the autoantibodies attack the cells of the parathyroid glands. It  may exist alone or in sporadic or familial forms of hypoparathyroidism.

Autoimmune conditions may be isolated or part of a polyglandular syndrome such as  Autoimmune polyglandular syndrome type 1 (APS-1). This usually consists of skin infections, hypoparathyroidism and primary adrenal problems (developing in that order ). Also known as APECED. This version is inherited ( autosomal recessive) and it usually occurs in children aged 3-5 years or in early adolescence, but it always occurs by the age of 25.

Autoimmune polyglandular syndrome type 2 (APS-2). This version presents in adulthood and also appears as part of a syndrome . It may Addison's Disease (adrenal insufficiency) in combination with type 1 diabetes mellitus and thyroid disease, eg Hashimoto's thyroiditis and/or Graves Disease. 75% of cases occur in women and it is not linked to any one gene.

Isolated idiopathic hypoparathyroidism also have a possible autoimmune cause and may be inherited.

d) Genetic syndromes

Hypoparathyroidism sometimes occurs as part of a developmental genetic syndrome or group of conditions. In HDR or Barakat syndrome there is hypoparathyroidism, deafness and renal dysplasia  caused by a mutation of the GATA3 gene. Inheritance is probably autosomal dominance.


Other Causes

Transient hypoparathyroidism

Transient or temporary conditions with no family history may develop  in the womb and  cause hypoprathyroidism with symptoms of low calcium at birth or in the newborn period. These can occur when

  • the mother's own overactive parathyroid glands have produced too much calcium, causing the baby's parathyroid glands to be temporarily suppressed. This version may be prolonged.

  • a delay in the PTH surge that happens at birth. This can sometimes occur in normal weight and also premature very low weight babies.

  • low levels of magnesium in diabetic mothers which also causes low calcium.

Impaired PTH secretion


Magnesium is needed to make parathyroid hormone. When magnesium levels are too low, calcium levels fall as well. A deficiency may be caused by poor diet, severe burns, alcohol abuse or malabsorption.

Neonatal suppression due to maternal hypercalcaemia.

Alcoholism or alcohol withdrawal


Infiltration of glands

This is rare but can occur with heavy metal deposits in the blood (eg iron and copper) as in Wilson's Disease; metastatic tumours; Riedel's thyroiditis.

* BAETS 4th National Audit

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