Hypoparathyroidism

Too Little Parathyroid Hormone Production

Hypoparathyroidism is the combination of symptoms due to inadequate parathyroid hormone production.  This is a very rare condition, and most commonly occurs because of damage to or removal of parathyroid glands at the time of parathyroid or thyroid surgery.   

Normal location of 4 parathyroid glandsHypoparathyroidism is the state of decreased secretion or activity of parathyroid hormone (PTH).  This leads to decreased blood levels of calcium (hypocalcemia) and increased levels of blood phosphorus (hyperphosphatemia).

Hypoparathyroidism Symptoms

Symptoms can range from quite mild (tingling in the hands, fingers, and around the mouth) to more severe forms of muscle cramps.  The most severe symptoms are tetany (severe muscle cramping of the entire body) and convulsions (this is very rare).

Parathyroid gland insufficiency is quite rare, but it can occur in several well-defined ways.  The most common cause of hypoparathyroidism is the loss of active parathyroid tissue following thyroid or parathyroid surgery.  More rare is a defect present at birth (congenital), where a person is born without parathyroid glands.  Occasionally, the specific cause of hypoparathyroidism cannot be determined.

Two Types of Hypoparathyroidism

  • Deficient parathyroid hormone secretion
  • Inability of the kidneys and bones to respond to PTH

Deficient Parathyroid Hormone Secretion

This type of hypoparathyroidism is the easiest to understand.  A patient afflicted with this condition simply has too little (or a complete absence of) parathyroid tissue; therefore, inadequate PTH is produced.

There are 2 major causes of this problem:

Cause #1:  Hypoparathyroidism Following Thyroid or Parathyroid Surgery

The first (and by far most common) cause of inadequate parathyroid hormone production is the accidental removal of parathyroid glands during thyroid surgery. Although the vast majority of thyroid operations are not associated with hypoparathyroidism, this complication can occur in about 1% to 3% of cases following a total thyroidectomy (the removal of the entire thyroid).1

Because of the close relationship that the thyroid and parathyroid have to one another (including sharing the same blood supply), the parathyroid glands can be injured or removed accidentally when the much larger thyroid is removed.  This is a well known but uncommon complication of thyroid surgery and is one of the primary dangers of thyroid surgery. 

A number of research studies have shown that surgeons with little experience in thyroid surgery are much more likely to accidentally remove the parathyroid glands2,3.  These studies have shown that surgeons performing more than 100 thyroid operations per year are much less likely to have these complications. This is why most endocrinologists will explain to their patients that they should find the most experienced thyroid surgeon available.

Many patients who have a very successful thyroid operation can have a transient inadequate secretion of PTH for several days following surgery on the thyroid, so the diagnosis of post-surgical hypoparathyroidism cannot be made immediately following surgery. It is common for surgeons to give their thyroid patients calcium pills for a few days after surgery to prevent any symptoms from the transient lack of PTH.

The second operation associated with post-operative hypoparathyroidism is parathyroid surgery, or “parathyroidectomy.”  Parathyroid surgery is performed for patients with overactive parathyroid glands causing a disease called hyperparathyroidism.

Since hyperparathyroidism is typically caused by one or more parathyroid tumors, surgery for hyperparathyroidism is aimed at removing the parathyroid tumor(s) and leaving behind the normal parathyroid glands. We all have 4 parathyroid glands, but we can live just fine (and not have hypoparathyroidism) if we have half of one parathyroid gland that is functioning normally.

The goal of parathyroid surgery is to remove those parathyroid glands that are overproducing PTH. But occasionally, too much parathyroid tissue is removed during the operation.  Like thyroid surgery, the incidence of this complication is related to the experience of the surgeon and is why endocrinologists typically recommend surgeons with the most experience. Surgeons with little experience can have as many as 5% of their patients develop permanent hypoparathyroidism, while surgeons performing more than 100 parathyroid operations per year typically have hypoparathyroidism complications very rarely.4,5,6


Cause #2:  Idiopathic HypoparathyroidsimDeficient parathyroid hormone (PTH) secretion without a defined cause is termed idiopathic hypoparathyroidism.  This disease is rare and can be congenital or acquired later in life. 

  • Congenital Hypoparathyroidism: Patients in this category are born without parathyroid tissues.  Most patients with congenital hypoparathyroidism have no family history of the disease. Those who do may have any one of a number of congenital causes.

     
    The inherited forms tend to arise from abnormal genes that may:

    1. encode abnormal forms of PTH or its receptor
    2. prevent normal conduction of cell signals from the PTH receptor to the nucleus
    3. prevent normal gland development before birth.


    Hypoparathyroidism with onset during the first few months of life can be permanent or temporary. The cause is usually unknown if spontaneous resolution occurs.  If it does not, it will usually manifest by 24 months of age.

    Finally, if a woman with overactive parathyroid glands and high calcium levels (hyperparathyroidism) becomes pregnant, the excess calcium can enter the fetus and suppress the baby’s parathyroid gland development. These babies are at risk of being born with under-developed parathyroid glands. This is why it recommended that pregnant females with high blood calcium levels have their parathyroid operation before the middle of the second trimester of pregnancy, to decrease the chance of the child being born with poorly formed parathyroid glands.7 Usually this will not result in permanent parathyroid gland dysfunction in the child.

  • Acquired Hypoparathyroidism: The acquired form of this disease typically arises because the immune system has developed antibodies against parathyroid tissues in an attempt to reject what it sees as a foreign tissue. This disease can affect the parathyroid glands in isolation or can be part of a syndrome that involves many organs.

    An antibody that binds to the calcium sensor in the parathyroid gland has been discovered in the blood of patients with autoimmune hypoparathyroidism. It has been proposed that such binding "tricks" the parathyroid gland into believing that the blood level of ionized calcium is high. Responding to this signal, the parathyroid stops making PTH.

Hypomagnesemia: Can Cause Low Calcium Levels

The element magnesium is closely related to calcium in the body.  When magnesium levels are too low, calcium levels may also fall. Once low magnesium levels are recognized it is usually very easy to fix.  Chronic alcoholism is a frequent cause of low magnesium levels.

Resistance to Parathyroid Hormone  (Pseudo-hypoparathyroidism)

This disease is extremely rare.  Like hypoparathyroidism, this disease is characterized by hypocalcemia (too low calcium levels) and hyperphosphatemia (too high phosphorus levels), but patients with pseudo-hypoparathyroidism (or reistance to PTH) are distinguished by the fact that they produce PTH, but their bones and kidneys do not respond to it.  Even if PTH is given to them in their veins, they do not respond to it.  Even if PTH is given to them in their veins, they do not respond to it.  Therefore, these rare individuals have plenty of PTH, but their organs do not behave appropriately to it. They appear to have hypoparathyroidism,  but they do not—thus the name pseudo-hypoparathyroid.

Treatment of Hypoparathyroidism

Vitamin D and calcium supplements are the primary treatments for hypoparathyroidism, regardless of the cause.  The majority of patients need to take calcium several times per day along with high-dose vitamin D once per day. 

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References

  1. Testini M, Gurrado A, Lissidini G, Nacchiero M. Hypoparathyroidism after total thyroidectomy. Minerva Chir. 2007;62(5):409-15.
  2. Stavrakis AI, Ituarte PH, Ko CY, Yeh MW. Surgeon volume as a predictor of outcomes in inpatient and outpatient endocrine surgery. Surgery. 2007;142(6):887-99; discussion 887-99.
  3. Pieracci FM, Fahey TJ 3rd. Effect of hospital volume of thyroidectomies on outcomes following substernal thyroidectomy. World J Surg. 2008;32(5):740-6. doi: 10.1007/s00268-007-9347-1.
  4. Chen H, Zeiger M, Gordon T, Udelsman R. Parathyriodectomy in Maryland, Effects of an endocrine center. Surgery. 1996;120:948-53.
  5. Sosa JA, Powe NR, Levine MA et al. Profile of a clinical practice: Thresholds for surgery and surgical outcomes for patients with primary hyperparathyroidism: A national survey of endocrine surgeons. J Clin Endocrinol Metab. 1998;83(8):2658-65.
  6. McHenry CR. Patient volumes and complications in thyroid surgery. Br J Surgery. 2002;89(7):821-3.
  7. Norman J, Politz D, Politz L. Hyperparathryoidism during pregnancy and the effect of rising calcium on pregnancy loss: a call for earlier intervention. Clin Endocrinol (Oxf). 2009;71(1):104-9. doi: 10.1111/j.1365-2265.2008.03495.x.