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Types & Causes of HypoPARAthyroidism

There are over 25 different types of hypoPARAthyroidism. Each type can be classified as either surgical or non-surgical.

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Non-Surgical HypoPARAthyroidism

Genetic HypoPARAthyroidism

Symptoms of genetic hypoPARA present in the first few years of life, absent surgical causes. There is often a family history of the condition. Genetic hypoPARA may be part of a syndrome involving other organs or tissues, such as:

Gene Mutations and Disorders

Currently there are 26 identified hypoPARAthyroidism gene mutations:

ACADM, AIRE, ATP1A1, CASR, CHD7, CLDN16, CLDN19, CNNM2, DHCR7, EGF, FAM111A, FXYD2, GATA3, GCM2, GNA11, HADHA, HADHB, KCNA1, NEBL, PTH, SEMA3E, SLC12A3, SOX3, TBCE, TBX1, TRPM6

Genetic forms of hypoPARAthyroidism include disorders of parathyroid gland formation, parathyroid hormone secretion, and parathyroid gland damage (Mannstadt et al. 2022). Disorders of parathyroid gland formation can be inherited in an autosomal dominant (TBX1, NEBL, SEMAE3, CHD7, GATA3, FAM111A, GCM2), autosomal recessive (TBCE, HADHA, HADHB, ACADM, DHCR7, GCM2), or X-linked manner (SOX3). Disorders of parathyroid hormone secretion can be inherited in an autosomal dominant (CASR, GNA11, PTH, FXYD2, CNNM2, ATP1A1, KCNA1) or autosomal recessive manner (PTH, TRPM6, CLDN16, EGF, CLDN19, CNNM2, SLC12A3). Disorders consisting of parathyroid gland damage can be inherited in an autosomal dominant or autosomal recessive manner.

Calcilytix (a Bridgebio company) offers free genetic testing and counseling for non-surgical hypoPARAthyroidism patients. It must be ordered by a physician.

Learn More About Calcilytix

More Resources About Genetic Hypoparathyroidism

An idiopathic infographic highlighting the PTH secretion, gland destruction, and gland development.

Idiopathic HypoPARAthyroidism

Idiopathic HypoPARAthyroidism means hypoPARAthyroidism where the cause is unknown. A lot of times the cause is unknown because doctors don’t think genetic testing is necessary because treatment won’t change or is too costly.

If you have been diagnosed with Idiopathic hypoPARAthyroidism discuss genetic testing with your doctor. Let them know there is an option for free testing. Also talk to them about the fact that there are treatment options in the works specifically for genetic patients. Encalaret is in clinical trials for ADH1 and ADH2.

No Cost Genetic Testing

Learn More About Encalaret

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PseudohypoPARAthyroidism and PseudopseudohypoPARAthyroidism

PseudohypoPARAthyroidism is characterized by an inability of the body to respond to parathyroid hormone (PTH). This is termed resistance to PTH. This condition is associated with low serum levels of calcium and high serum levels of phosphorus but unlike other forms of hypoPARAthyroidism the PTH level is high rather than low.

There are several different types of pseudohypoPARAthyroidism: types 1A and 1B, type 1B, and type 2.

Type 1A and Type 1C

PseudohypoPARAthyroidism type 1A and type 1C are associated with resistance to multiple hormones in addition to PTH, including TSH resistance with mild hypothyroidism, resistance to LH and FSH with pubertal and reproductive problems, and GHRH with decreased secretion of growth hormone that contributes to poor growth and short stature. In addition, pseudohypoPARAthyroidism is associated with other features, termed Albright hereditary osteodystrophy (AHO), that include short fingers and toes and development of bone fragments under the skin and sometimes in the muscles. AHO is also associated with mild to moderate developmental delays.

Type 1B

Patients with pseudohypoPARAthyroidism type 1B have a more limited condition with PTH resistance as the primary manifestation. A few patients may also have mild shortening of a few fingers and very modest hypothyroidism. These patients have imprinting defects that affect methylation of the GNAS gene, which reduces expression of the GNAS gene, and usually do not have genetic defects.

Type 2

The type 2 form of pseudohypoPARAthyroidism is limited to PTH resistance with low serum calcium levels and elevated serum phosphate levels, and usually occurs in patients with severe vitamin D deficiency. This form of pseudohypoPARAthyroidism is reversible with vitamin D replacement.

PseudopseudohypoPARAthyroidism

PseudopseudohypoPARAthyroidism is related to type 1A and type 1B, but patients have only AHO and respond normally to their hormones. These patients have normal serum levels of calcium, phosphate and PTH without the resistance to PTH and other hormones. Patients with these disorders usually have mutations in the GNAS gene, but inheritance follows an unusual pattern. If the GNAS mutation occurs on the gene inherited from the mother, the child will have pseudohypoPARAthyroidism but if the GNAS mutation occurs on the gene copy inherited from the father the child will have PseudopseudohypoPARAthyroidism.

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Treatment

Goals of treatment are to achieve normal serum calcium and phosphate levels while avoiding increased urinary calcium levels. Treatment consists of oral calcium supplements plus active forms of vitamin D such as calcitriol. PTH levels should be monitored and maintained at levels near or slightly above the upper limits of normal.
* With treatment consisting of oral calcium and activated forms of vitamin D (e.g., calcitriol)

References

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Surgical HypoPARAthyroidism

Surgical hypoPARAthyroidism is acquired after neck surgery. Neck surgery could be because a patient had Thyroid Cancer (ThyCA), hyperparathyroidism, parathyroid adenoma(s) or Graves disease. Each of these diseases that the patient had before acquiring hypoPARA brings with it unique challenges and comorbidities that change how the patient may respond to treatment.

Unlike genetic patients who may have perfectly normal thyroid function most of these patients do not.

Warnings for Treatment of Surgical HypoPARA

  • Don’t take your Synthroid (Levothyroxine) at the same time as your calcium medication. This can interfere with absorption.
  • Some patients still have partial parathyroid function after surgery. This may affect how much medication you need. Also, hypoPARA may not be permanent in surgical patients.

 

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Pediatric Hypoparathyroidism

Pediatric hypoPARAthyroidism is the same disease as in adults at the basic level in the fact that it means the patient has both low calcium levels and low or no PTH levels at the same time. However, unlike adults with hypoPARA, the majority of children with the disease are non surgical. Rarely would it be the result of a neck surgery although it could be the result of a neck injury.

Symptoms of Pediatric HypoPARA

HypoPARAthyroidism in children usually first presents with seizures. Other symptoms children tend to experience are:

  • Dry brittle hair and nails
  • Tingling in the toes, fingers and lips
  • Abdominal pain
  • Muscle pain
  • Teeth don’t grow in on time or at all
  • Constipation

You may notice that some of these symptoms are different from the adult ones. Your child may experience some of the adult symptoms as well.

Resources for Pediatric HypoPARA

It is very important to seek care with an experienced endocrinologist early on in treatment to help protect their kidneys. Typically with most diseases genetic testing for a rare disease like this is expensive so doctors are hesitant to order it. Thanks to one of our industry partners we have a no-cost genetic test to offer for those that need it. It also comes with genetic counseling. For more information, visit Calcilytix online. 

Visit the Calcilytix Website

Talk to your doctor and let them know that there are treatments in the works that may be specific to genetic patients. For more support there is also a parent support group on Facebook.

Visit the Parent Support Group

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