Understanding Pseudohypoparathyroidism: Symptoms and Treatment

Written by Medicover Team and Medically Reviewed by Dr Prashant Manohar Gaikwad , Endocrinologists

Pseudohypoparathyroidism (PHP) is a rare inherited disorder in which the body is unable to respond properly to parathyroid hormone (PTH), a hormone that regulates calcium and phosphate levels in the blood.

Although individuals with this condition typically have normal or elevated levels of PTH, the body's tissues are resistant to its effects, resulting in low blood calcium levels and high phosphate levels. This hormone resistance can lead to a variety of symptoms affecting the bones, muscles, and overall growth and development.

Pseudohypoparathyroidism is most commonly associated with mutations in the GNAS gene, which plays a key role in hormone signaling pathways. Early diagnosis and appropriate treatment are important to manage symptoms, prevent complications, and maintain healthy calcium and phosphate balance.

Genetic Factors in Pseudohypoparathyroidism:

The most common form of pseudohypoparathyroidism is PHP type 1a, which is associated with Albright's hereditary osteodystrophy (AHO). AHO is characterized by physical features such as short stature, round face, and short hand bones (brachydactyly). Mutations in the GNAS gene disrupt the normal function of PTH receptors, leading to resistance to the hormone.

Pseudohypoparathyroidism vs. Hypoparathyroidism:

While both pseudohypoparathyroidism and hypoparathyroidism result in low calcium levels and high phosphate levels, their underlying causes differ significantly. Hypoparathyroidism is caused by insufficient production of PTH, often due to damage to the parathyroid glands. In contrast, pseudohypoparathyroidism involves normal or elevated levels of PTH, with the body's tissues being unresponsive to the hormone.

What Are the Types of Pseudohypoparathyroidism?

Pseudohypoparathyroidism (PHP) is classified into several types based on the underlying genetic changes, hormone resistance, and physical features. Although all types involve resistance to parathyroid hormone (PTH), they differ in symptoms and severity.

Type 1A

Type 1A is the most common form and is caused by mutations in the GNAS gene inherited from the mother. People with this type have resistance to PTH and may also develop resistance to other hormones. They often have characteristic physical features known as Albright hereditary osteodystrophy (AHO), including short stature, a round face, shortened fingers or toes, and obesity.

Type 1B

Type 1B primarily causes resistance to PTH without the typical physical features of Albright hereditary osteodystrophy. It is usually linked to changes in the regulation of the GNAS gene rather than mutations in the gene itself.

Type 1C

Type 1C is rare and closely resembles Type 1A. People with this type have hormone resistance and the physical features of Albright hereditary osteodystrophy, but the underlying genetic changes differ from those seen in Type 1A.

Type 2

Type 2 is a rare form in which the body is resistant to PTH but does not have the physical characteristics of Albright hereditary osteodystrophy. The exact genetic cause is not fully understood, and the hormone signaling pathway differs from that of Type 1.

Pseudopseudohypoparathyroidism (PPHP)

Pseudopseudohypoparathyroidism is related to mutations in the GNAS gene inherited from the father. Individuals have the physical features of Albright hereditary osteodystrophy but do not develop resistance to parathyroid hormone, so calcium and phosphate levels usually remain normal.

What Are the Symptoms of Pseudohypoparathyroidism?

The symptoms of pseudohypoparathyroidism can vary widely depending on the severity of the condition and the specific type of PHP. Common symptoms include:

What Causes Pseudohypoparathyroidism?

Pseudohypoparathyroidism is a rare genetic disorder caused by changes in genes involved in the body's response to parathyroid hormone (PTH). Although the body produces enough PTH, the kidneys and bones do not respond to it properly. As a result, calcium levels become low, phosphate levels rise, and the body produces even more PTH in an attempt to restore balance.

Genetic Mutations

The most common cause of pseudohypoparathyroidism is a mutation or alteration in the GNAS gene. This gene helps produce proteins that allow cells to respond to hormones such as PTH. When the gene does not function correctly, the body's tissues become resistant to the effects of PTH.

Inherited Genetic Changes

Many cases are inherited from a parent, although some occur due to new (sporadic) genetic changes. The type and severity of the condition often depend on whether the altered gene is inherited from the mother or the father because of a process called genomic imprinting.

Hormone Resistance

The underlying problem in pseudohypoparathyroidism is resistance to parathyroid hormone rather than a lack of the hormone itself. In some types of the condition, the body may also become resistant to other hormones, including thyroid-stimulating hormone (TSH), gonadotropins, and growth hormone-releasing hormone (GHRH).

Epigenetic Changes

Some forms, particularly pseudohypoparathyroidism type 1B, result from epigenetic changes that affect how the GNAS gene is regulated instead of changes in the gene's DNA sequence. These changes can interfere with normal hormone signaling.

Sporadic Cases

Not all people with pseudohypoparathyroidism have a family history of the disorder. In some individuals, the genetic or epigenetic changes occur spontaneously during early development.

When Should You See a Doctor for Pseudohypoparathyroidism?

If you experience persistent or worsening symptoms of pseudohypoparathyroidism, consult an endocrinologist. Early evaluation can help identify calcium and phosphate imbalances, prevent complications, and improve treatment outcomes. Prompt medical attention is important when symptoms begin affecting daily activities or overall health.

You should see a doctor if you have:

Get medical help immediately if:

These could be signs of a serious complication like pseudohypoparathyroidism, which needs urgent care.

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How is Pseudohypoparathyroidism Diagnosed?

Diagnosing pseudohypoparathyroidism requires a comprehensive clinical evaluation, including a detailed medical history, physical examination, and laboratory tests. Critical diagnostic steps include:

What Are the Treatment Options for Pseudohypoparathyroidism?

The treatment of pseudohypoparathyroidism focuses on managing symptoms and preventing complications. Key treatment strategies include:

Calcium and Vitamin D Supplementation:

Calcium and active forms of vitamin D (such as calcitriol) are commonly prescribed to maintain normal calcium levels and prevent hypocalcemia. Regular monitoring of blood calcium and phosphate levels is essential to adjust dosages and avoid complications.

Phosphate Binders:

Phosphate binders may be used to reduce phosphate absorption in the gut and manage hyperphosphatemia. These medications help prevent calcifications in soft tissues and organs.

Hormone Replacement Therapy:

In some cases, hormone replacement therapy with recombinant human PTH may be considered to improve calcium and phosphate balance. However, the efficacy of this treatment in pseudohypoparathyroidism is still under investigation, and it is not widely used.

Managing Associated Conditions:

Individuals with AHO may require additional treatments for associated conditions, such as obesity, cognitive impairment, and dental abnormalities. Multidisciplinary care involving endocrinologists, geneticists, dentists, and other specialists is often necessary to provide comprehensive management.

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What Are the Complications of Pseudohypoparathyroidism?

Long-term management of pseudohypoparathyroidism is crucial to prevent complications and improve quality of life. Potential long-term effects include: