Hypoparathyroidism is caused by insufficient or inactive parathyroid hormone secretion or, to put it simply, low PTH. There are a number of conditions in which this happens and they all have different causes.
These conditions fall into two main types of hypoparathyroidism:
1) Iatrogenic hypoparathyroidism
The most common form of hypoparathyroidism is caused by the surgical removal of, or damage to, the parathyroid glands. It is usually called post surgical or post operative hypoparathyroidism (PoSH).
(Iatrogenic means ’caused by treatment’.)
2) Idiopathic hypoparathyroidism
The more rare forms of Hypoparathyroidism are grouped together under the heading Idiopathic hypoparathyroidism. This group of rare conditions may be either congenital (occurring in the womb ) or acquired in childhood or later in life as an inherited and/or autoimmune condition. The term ‘idiopathic’ is also used to denote a form of hypopara of unknown cause.
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 extremely 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.
b) Radiation or drug treatment
Hypopara can be caused by treatment for thyroid and other cancers eg radioactive iodine thyroid ablation or external beam radiation to neck or use of chemotherapy drugs. It can also occur from cancer of the parathyroid glands, HIV and AIDS.
c) Hungry bone syndrome
This is a temporary situation which can sometimes develop after a parathyroidectomy for primary hyperparathyroidism. In this case, the body has been used to high levels of calcium which 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 hypoparathyroid. 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.
The term Idiopathic hypoparathyroidism is used to describe a number of very rare conditions which may be autoimmune, congenital or genetically inherited have no defined cause (such a surgery).
a) Congenital hypoparathyroidism
Congenital hypoparathyroidism is a permanent condition where the the development of the parathyroid glands are affected at or before birth. It can be acquired during development of the foetus or it may 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.
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.
- development of the gland in the womb as in DiGeorge Syndrome
- the calcium-sensing receptor gene
- the PTH gene
- PTH action as in
Albrights’ Hereditary Osteodystophy, Pseudohypoparathyroidism (PHP) and Pseudopseudohypoparathyroidism (PPHP). These forms are very rare.They appear to have hypoparathyroidism, but they do not; thus the name pseudo-hypoparathyroid.
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.
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 hypopara, the body’s 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 of autosomal dominance.
Transient or temporary hypopara with no family history may develop in the womb so the baby is born with symptoms of low calcium at birth or develops low calcium during the newborn period.
This 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 more prolonged.
- a delay in the PTH surge that happens normally at birth. This can sometimes occur in both normal weight and premature very low weight babies.
- a diabetic mother has a low level of magnesium
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
HIV or AIDS
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.