Causes and Risk Factors of Pediatric Growth Hormone Deficiency

Pediatric growth hormone deficiency is a rare childhood condition where the pituitary gland produces an insufficient amount of growth hormone. When the pituitary gland or hypothalamus, which helps regulate the pituitary gland, is malformed or damaged, a growth hormone deficiency can occur. Growth hormone stimulates the growth of bones and other tissues. A low level of this hormone can cause slowed growth in children.

Pediatric growth hormone deficiency can be present at birth or develop later on in childhood. Causes of pediatric growth hormone deficiency can be congenital, acquired, or idiopathic.

Common Causes

The causes of pediatric growth hormone deficiency are typically classified as congenital (present at birth), acquired (develops during or after birth), or idiopathic (unknown cause). These causes lead to the damage to or a malformation of the pituitary gland or hypothalamus in the brain.

Congenital

A congenital cause of pediatric growth hormone deficiency stems from a genetic mutation or structural abnormality. Congenital growth hormone deficiency can occur if there are mutations in genes for factors that are important in pituitary gland development, or in receptors and factors (including growth hormone) along the growth hormone pathway.

Structural abnormalities of the pituitary gland or hypothalamus may also be present at birth and usually cause symptoms such as a cleft palate or cleft lip.

Acquired

An acquired cause of pediatric growth hormone generally involves damaging the pituitary gland or hypothalamus. Once the gland is damaged, it cannot function properly and may stop producing or secreting growth hormone.

Possible acquired causes include:

• Brain tumor in the hypothalamus or pituitary gland
• Infection
• Head trauma
• Radiation therapy for cancer, if the treatment field includes the hypothalamus and pituitary
• Diseases that infiltrate the hypothalamus or its connection to the pituitary gland, such as histiocytosis (an abnormal increase in the number of immune cells known as histiocytes)
• Autoimmune condition, such as lymphocytic hypophysitis

Idiopathic

When the cause of growth hormone deficiency is unknown, it's considered idiopathic. This is most often the case.

Genetics

Pediatric growth hormone deficiency can occur due to a genetic condition caused by a mutation in one or more of a child’s genes. Our genes are made up of DNA, and when part of the DNA is damaged or missing, a genetic condition can occur. A genetic cause is typically found in about 11% of pediatric growth hormone deficiency cases.

Types of growth hormone deficiencies caused by genetic abnormalities include:

• Growth hormone deficiency type IA is an autosomal recessive condition with a total absence of growth hormones. Newborns with type IA are born with a short length and usually diagnosed right away. This is the most severe type of genetic growth hormone deficiency. It is caused by a mutation in the GH1 gene.
• Growth hormone deficiency type IB is less severe than type IA because individuals are able to produce a small amount of growth hormone. This is also an autosomal recessive condition. Most children with this type respond to treatment with injections of human growth hormone. Type IB is caused by a mutation in the GH1 or GHRHR gene.
• Growth hormone deficiency type II is also characterized by the production of a low level of growth hormone. It appears with similar symptoms as type IB, but is different because it is autosomal dominant. Most children with this type are diagnosed in mid-childhood. Like type IA, type II is caused by a mutation in the GH1 gene.
• Growth hormone deficiency type III is an X-linked condition that is usually evident in early to mid-childhood. This type of growth hormone deficiency also causes a compromised immune system because B cell production is also affected. Children with this type of deficiency are more prone to infection. Type III is caused by a mutation in the BTK gene.

Trauma or Infection

Any trauma or infection that affects the pituitary gland can lead to pediatric growth hormone deficiency. Trauma to the brain can occur before or after birth. A deficiency of growth hormone is the most common pituitary hormone deficit following a traumatic brain injury.

In addition to head trauma, certain infections may lead to pediatric growth hormone deficiency. When an infection targets a child’s central nervous system, the brain is affected and the pituitary gland can be damaged. For example, it’s estimated that 20% of children who recover from meningitis experience pituitary dysfunction for several years after the infection.

Infections that can infiltrate the hypothalamus or its connection to the pituitary gland include:

• Meningitis
• Toxoplasmosis

Risk Factors

Unlike many other chronic health conditions, the risk factors for pediatric growth hormone deficiency are not related to lifestyle. Factors like diet, exercise, and adherence to medical advice do not affect the risk of developing growth hormone deficiency.

Childhood Cancer 

Survivors of childhood cancer are at high risk of having short stature in adulthood. Studies estimate that 10% to 20% of cancer survivors experience impaired growth.

A cancer diagnosis puts children at higher risk for pediatric growth hormone deficiency because of the side effects of treatment. High-dose radiation is known to cause hypopituitarism, where the pituitary gland is lacking in multiple pituitary hormones. Radiation of the spine can also impede growth and lead to short stature in adulthood.

When a child’s cancer affects the brain, the disease itself could lead to growth hormone deficiency as well. Brain tumors such as craniopharyngioma affect the function of the pituitary gland and can lead to hypopituitarism.

Cleft Palate 

Physical defects of the head and skull can lead to a malformed pituitary gland or hypothalamus. When this occurs, the gland cannot make enough growth hormone and deficiency occurs. Midline defects like cleft lip or cleft palate could indicate that there is also an abnormality in the pituitary gland.

A Word From Verywell

We realize that having a child diagnosed with a chronic condition is scary for any parent, especially if the cause is unknown. Many parents wonder if they have done something to cause the condition in their child. It is important to know that even when the cause of pediatric growth hormone deficiency is unknown, it’s not related to any action or lifestyle practice by you. Your pediatrician and pediatric endocrinologist will work closely with you to determine the cause of your child’s hormone deficiency and address any complications. Regardless of what the cause is, you can implement effective treatment and management of the condition itself once it is diagnosed.