Hypoparathyroidism

1 What is Hypoparathyroidism?

Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone.

This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary muscle contraction), and several other symptoms.

The condition can be inherited, but it is also encountered after thyroid or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes.

The diagnosis is made with blood tests, and other investigations such as genetic testing depending on the results.

The treatment of hypoparathyroidism is limited by the fact that there is no artificial form of the hormone that can be administered as replacement; calcium replacement or vitamin D can ameliorate the symptoms but can increase the risk of kidney stones and chronic kidney disease.

2 Symptoms

Some of the most common symptoms of hypoparathyroidism are:

Clinical findings depend on the level of

  • calcium,
  • duration,
  • acid base disorder,
  • and age at onset of disease.

Nueromuscular irritability is seen, such as tetany, laryngospasm, cramping, seizures, and impaired memory function.

Chvostek sign may be positive (percussion of the facial nerve in front of the ear, which elicits a contraction of facial muscles and upper lip).

Trousseau sign may be positive (inflation of blood pressure cuff on the arm to a pressure higher than the patient’s systolic pressure for 3 min elicits flexion of metacarpophalangeal joints and extension of interphalangeal joints).

Ocular findings such as cataract and soft tissue calcifications may occur.

Cardiovascular system involvement manifests as QT prolongation, refractory CHF and or hypotension.

Hypocalcemia frequently results in circumoral tingling as well as tingling of hands and feet.

Hyperventilation worsens symptoms of hypocalcemia because alkalosis decreases free calcium levels.

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3 Causes

The most common cause of hypoparathyroidism is iatrogenic following anterior neck surgery. Hypoparathyroidism may be transient, congenital/genetically inherited or acquired. 

Transient hypoparathyroidism in the neonatal period

Healthy term neonates undergo a reduction in serum calcium levels by 24-48 hours of age. Some neonates, especially high-risk (eg, infants of mothers with diabetes, preterm infants and infants with perinatal asphyxia), may develop hypocalcaemia.

Early-onset hypocalcaemia presents within 72 hours and requires treatment with calcium supplementation for at least 72 hours. Late-onset hypocalcaemia usually presents after seven days and requires longer-term therapy.

  • Prematurity at birth: very low birth weight infants may not have a normal PTH surge postnatally, thus resulting in hypocalcaemia.
  • Infants of mothers with diabetes: hypomagnesaemia due to maternal magnesuria impairs PTH release and action.
  • Delay in PTH surge postnatally: this can occur in otherwise healthy neonates.
  • Maternal hyperparathyroidism: this results in hypercalcaemia which can cause prolonged PTH suppression in the neonate.

Congenital or genetically inherited hypoparathyroidism

Defects in parathyroid gland development:

  • DiGeorge's syndrome: there is abnormal development of the parathyroid glands from the third and fourth pharyngeal pouches. The thymus gland, aortic arch and parts of the lips and ears also develop from these pouches.There is hypoparathyroidism, T-cell immune deficiency, abnormal facies such as cleft palate, and cardiac anomalies.
  • Defects in the PTH gene.

Defects in the calcium-sensing receptor gene:

  • Presents as hypocalcaemia, inappropriately normal levels of PTH and raised phosphate levels.
  • This is not true hypoparathyroidism but its presentation mimics it.
  • Can present from birth to adulthood.
  • Defects in PTH action (pseudohypoparathyroidism): this occurs when the somatic features of pseudohypoparathyroidism are present in patients with normal serum calcium and phosphate levels. PTH is either normal or raised. The patient may fluctuate between hypocalcaemia and normocalcaemia and may develop cataracts:
      • A rare inherited disorder where there is failure of target cells to respond to PTH, i.e. there is PTH resistance.
      • PTH levels are not low but are appropriate for the degree of hypocalcaemia.

There is an association with:

  • Somatic anomalies.
  • Short stature.
  • Round face.
  • Short neck.
  • Shortening of the metacarpals and metatarsals.
  • Hypothyroidism.
  • Diabetes mellitus.
  • Gonadal dysgenesis.

As part of an autoimmune process:

  • Autoimmune polyglandular syndrome type 1 (APS-1): autosomal recessive inheritance. Features include hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneous candidiasis. Also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Presents in childhood.

Autoimmune polyglandular syndrome type 2 (APS-2): features include adrenal insufficiency, insulin-dependent diabetes mellitus and thyroid disease. Presents in adulthood. Autosomal dominant inheritance.

Isolated hypoparathyroidism with a possible autoimmune cause can also be inherited.

Genetic syndromes, including:

  • Hypoparathyroidism, deafness and renal (HDR) dysplasia syndrome.
  • Hypoparathyroidism, retardation and dysmorphism (HRD) syndrome.

Acquired hypoparathyroidism

Neck surgery (thyroid, parathyroid, laryngeal or oesophageal surgery) is the most common cause and includes:

  • Accidental damage to, or accidental removal of, the parathyroid glands. Most likely during thyroid surgery. May be transient or permanent. Surgeon-dependent.
  • Removal of parathyroid glands because of potential malignancy.

After surgery for hyperparathyroidism. Transient hypoparathyroidism may occur whilst the body returns to a normal response to PTH.

Radiation or drugs

  • Neck or chest irradiation during radiotherapy treatment.
  • Radioactive iodine treatment for hyperthyroidism: a rare side-effect.
  • Chemotherapeutic/cytotoxic agents.
  • Alcohol.
  • Infiltration of the parathyroid glands:
  • Destruction of the parathyroid glands due to iron deposition can occur in haemochromatosis or multiple blood transfusions.
  • Destruction of the parathyroid glands due to copper deposition can occur in Wilson's disease.
  • Infiltration of the parathyroid glands by malignant metastases.

Magnesium deficiency, which can occur in:

  • Chronic alcoholism.
  • Burns.
  • Hereditary renal or intestinal hypomagnesaemia.
  • Magnesium excess - e.g., when magnesium is used for the treatment of preterm labor or pre-eclampsia.
  • Autoimmune process: sporadic forms of APS-1 can occur as described above.
  • Isolated idiopathic hypoparathyroidism:
  • PTH deficiency is present but no other associated endocrine or developmental disorders.
  • Usually sporadic but can be familial.
  • May possibly be a form of autoimmune hypoparathyroidism.

Pseudohypoparathyroidism

Pseudohypoparathyroidism includes a heterogeneous group of rare metabolic disorders that include characteristic morphological features and end-organ resistance to the action of PTH. Plasma concentrations of PTH are elevated and reflect the failure of target tissues to respond appropriately to the biological actions of PTH.

Pseudopseudohypoparathyroidism

This is very rare and occurs when there is no endocrine abnormality but the morphological features are otherwise the same as for pseudohypoparathyroidism.

4 Making a Diagnosis

Making a diagnosis of hypoparathyroidism is done by performing several tests.

  • Blood tests (to exclude other causes of hypocalcaemia)
  • Calcium, phosphate, PTH and alkaline phosphatase

Typical blood test results in hypoparathyroidism

  • Low serum calcium.
  • High serum phosphate.
  • Low PTH.
  • Normal alkaline phosphatase.

Typical blood test results in pseudohypoparathyroidism

  • Low serum calcium.
  • High or normal PTH.
  • Serum magnesium: may be low.
  • U&Es: to exclude chronic kidney disease.
  • 25-hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3: to exclude vitamin D deficiency as a cause of hypocalcaemia. 25-hydroxyvitamin D3 is normal in hypoparathyroidism and pseudohypoparathyroidism but 1,25-dihydroxyvitamin D3 is low because PTH is not available for its activation

Additional blood tests

If an autoimmune process is suspected, look for co-inciding thyroid and adrenal insufficiency:

  • Thyroid-stimulating hormone (TSH), thyroxine and thyroid autoantibodies.
  • Adrenocorticotrophic hormone (ACTH) and adrenal antibodies.
  • Urine tests: 24-hour urinary calcium is usually low.
  • Other possible investigations:
  • ECG: prolonged QT interval which may progress to ventricular fibrillation or heart block.
  • Echocardiogram: cardiac abnormalities (in DiGeorge's syndrome).
  • Renal ultrasound: looking for renal calculi.
  • Hand radiography: looking for shortened metacarpals.
  • Brain MRI scan: basal ganglia calcification (sign of a long-standing hypocalcaemic state).
  • Genetic studies: as appropriate.

5 Treatment

Several treatment methods are used for hypoparathyroidism.

Acute treatment

If severe hypocalcaemia symptoms are present, such as tetany, urgent IV calcium should be given.

Dietary advice

A diet rich in dairy products containing calcium and vitamin D is recommended.

Calcium and vitamin D3

The basis of treatment is with calcium and vitamin D.

The doses are tailored to the individual's needs and regular monitoring is needed.

In some people, once adequate doses of vitamin D are achieved, they can absorb all the calcium that they need through the diet. However, in others, calcium levels remain permanently unstable and maintenance doses of calcium and vitamin D will need to be regularly monitored and adjusted.

Treatment is lifelong.

There is no restriction on activities but patients should wear a bracelet to identify themselves as suffering from hypoparathyroidism.
PTH

As yet, PTH is not commercially available to treat hypoparathyroidism.

However, recombinant PTH is used for the treatment of postmenopausal osteoporosis.

PTH replacement improves serum calcium and lowers serum phosphate. It has been shown to lower urinary calcium loss.

Careful monitoring of vitamin D, phosphorous, and calcium is necessary during acute and long-term therapy.

Parathyroid autotransplantation and allotransplantation

If a patient has a thyroidectomy, one of the parathyroids can be 'autotransplanted' into either the neck or the forearm to give a continuing supply of PTH.

Allotransplantation of cultivated parathyroid tissue is also a possibility.

  • Pregnancy,
  • diuretics,
  • antacids,
  • anticonvulsants,
  • intercurrent illness,
  • ammonium chloride
  • and acetazolamide

may alter the requirements for vitamin D.

Close monitoring of calcium levels is needed.

6 Prevention

The best way to prevent hypoparathyroidism due to mishap of surgical resection would be to avoid injury to the parathyroids.

This can be done by meticulous surgical dissection. The problem is very much less likely when an experienced surgeon is performing the operation.

The temporary problem of hypoparathyroidism with distressing hypocalcaemia may be prevented by temporary pre-emptive treatment with calcium and/or calcitriol for a period when temporary hypocalcaemia is a distinct risk.

7 Alternative and Homeopathic Remedies

Several alternative and homeopathic remedies exist for hypoparathyroidism.

Nutrition

The following supplements have been used clinically for the purposes indicated and, therefore, may be valuable adjuncts in the treatment of hypoparathyroidism:

  • Calcium if dietary intake is not adequate
  • Magnesium aids in the absorption of calcium; plus, often low levels of magnesium are present in the case of hypoparathyroidism
  • Boron enhances the absorption of calcium
  • Vitamin K, produced by bacteria in the intestines or obtained through the diet (e.g. dark leafy greens) is important for the uptake of calcium by cells throughout the body

Foods rich in calcium include:

  • Almonds
  • Legumes
  • Dark leafy greens
  • Blackstrap molasses
  • Oats
  • Sardines
  • Tahini
  • Prunes
  • Apricots
  • Sea vegetables

Calcium and vitamin D are thought to be best absorbed in an acidic environment; lemon juice, for example, may be added to greens to facilitate calcium absorption. Other dietary recommendations made by some naturopaths to help maintain healthy calcium levels are as follows:

Limit carbonated beverages, as they are high in phosphates and may reduce calcium absorption; dairy may diminish calcium absorption for similar reasons.
Avoid caffeine (such as in coffee, black tea, colas, and chocolate); it can lead to calcium loss through the urine.

Herbs

Herbs rich in minerals, such as the following, have been used in traditional remedies to support normal bone growth:

  • Horsetail (Equisetum avense)
  • Oat straw (Avena sativa)

Homeopathy

Homeopaths may use the following remedies to treat problems related to calcium levels:

  • Calcarea carbonica (calcium carbonate)
  • Calcarea phosphorica (calcium phosphate)

8 Risks and Complications

There are several complications associated with hypoparathyroidism.

Reversible complications including those that would improve with calcium treatment:

  • Heart arrhythmias, heart failure
  • Fainting
  • Malformation of teeth
  • Tetany-prolonged and painful cramping spasms/twitches in muscles, hands, face, throat, arms. Throat spasms may lead to critical breathing impairment that may require emergency help.
  • Convulsions with loss of consciousness
  • Paraesthesias-strange, tingling sensations such as pins and needles throughout fingers, tongue, lips and feet
  • Impaired kidney function

Irreversible complications which will not improve with calcium and Vitamin D administration include:

  • Cataract
  • Slow mental development and mental retardation in children
  • Calcium deposits in brain
  • Stunted growth
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