Definition

Growth hormone disorders are medical conditions where there is either a shortage or an excess of growth hormone in children, that can result in gigantism. These disorders involve irregularities in the production of growth hormone, a substance produced by the pituitary gland, which is located at the base of the brain.

When growth hormone deficiency is present, the pituitary gland does not produce enough of this crucial hormone. On the other hand, gigantism occurs when there is an overproduction of growth hormone. The pituitary gland is responsible for releasing various hormones into the bloodstream, which then travel throughout the body, influencing the function of numerous organs and tissues.

Causes

In most instances, the specific cause of growth hormone deficiency remains unidentified. The deficiency can be present from birth or result from an underlying medical condition. A significant brain injury can also interfere with the production of growth hormone. Additionally, children born with certain facial or skull abnormalities, such as a cleft lip or palate, may have lower levels of growth hormone. In rare instances, growth hormone deficiency may be part of a broader genetic syndrome.

Gigantism in children is typically linked to a benign (non-cancerous) tumor in the pituitary gland known as a pituitary adenoma, which results in excessive secretion of growth hormone. Most children with gigantism have a large tumor within the pituitary gland, often referred to as a macroadenoma, which measures 10 millimeters or more in diameter. Gigantism can also stem from an enlarged pituitary gland.

Genetic alterations are commonly found in children with gigantism, which may lead to tumor formation within the pituitary gland. The most frequent genetic changes associated with gigantism include mutations or the loss of the AIP gene.

Furthermore, gigantism can also arise as a component of several rare genetic disorders that elevate the likelihood of developing pituitary tumors. These conditions include:

• Carney complex: This genetic disorder can result in pituitary adenomas in 10-13% of affected individuals.

• McCune-Albright syndrome: This genetic disorder, which impacts the bones, skin, and endocrine system, is linked to increased growth hormone production in 20-30% of cases.

• Multiple endocrine neoplasia types 1 or 4: These conditions cause hormone-releasing glands to become overactive or form tumors.

• Neurofibromatosis: Part of a group of genetic disorders that can cause tumors to develop throughout the body, including in the pituitary gland.

• Familial isolated pituitary adenoma (FIPA): This inherited condition is marked by the presence of a benign tumor in the pituitary gland.

Risk Factor

Children are more likely to develop growth hormone deficiency if they have experienced any of the following:

• Brain injury
• Brain tumor
• Radiation therapy to the head

However, some children with growth hormone deficiency may not have any of these risk factors.

Gigantism can occur in any child who has not yet completed the closure of the growth plates in their bones, meaning they have not yet finished growing. It is more commonly observed in boys than in girls.

Symptoms

In cases of growth hormone deficiency, the first noticeable symptom often emerges in infancy, with slow growth continuing into childhood. A doctor will typically track the child’s growth on a growth chart, and children with growth hormone deficiency will show a slower or even stagnant growth curve. This deceleration in growth may not become apparent until the child reaches the age of 2 or 3 years.

As a result, the child will be significantly shorter than other children of the same age and gender. Though the child may retain normal body proportions, they might appear somewhat plumper. Additionally, their facial appearance may seem younger compared to children of the same age. Generally, children with growth hormone deficiency have typical cognitive development. However, in older children, puberty may be delayed or fail to occur entirely, depending on the underlying cause.

On the other hand, gigantism is characterized by excessive growth. Children with gigantism can experience a rapid increase in height. Aside from growing unusually tall or large for their age, the physical signs of gigantism include:

• A notably prominent forehead and jaw
• Gaps between the teeth
• Thickening of facial features
• Enlarged hands and feet with thick fingers
• Enlargement of internal organs, particularly the heart
• Increased perspiration
• Double vision
• Frequent headaches or joint pain
• Delayed puberty
• Irregular menstrual cycles
• Sleep disturbances, such as sleep apnea
• Muscle weakness

Diagnosis

A physical examination, including measuring the child's weight, height, and body proportions, can reveal signs of abnormal growth patterns, either delayed or accelerated. If the child’s growth deviates from the expected growth curve for their age, this can be a key indicator of a growth disorder.

An X-ray of the hand can help determine the child’s bone age, as bones change in size and shape during growth. These changes are visible on an X-ray and generally follow a recognizable pattern as the child ages.

The test is typically carried out after the doctor has eliminated other potential growth-related conditions. Additional tests that may be recommended include:

• A head MRI to obtain detailed images of the hypothalamus and pituitary gland in the brain.

• Tests measuring insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3), both of which are produced as a result of growth hormone activity in the body.

• Hormone level tests to assess if there are any other hormone deficiencies, as growth hormone disorders often coexist with other hormone imbalances. For example, growth hormone deficiency may occur alongside other hormonal issues such as:

  • Thyroid hormone production problems
  • Imbalances in fluid regulation in the body
  • Irregularities in male and female sex hormone production
  • Disorders related to cortisol, DHEA, and other hormones produced by the adrenal glands

Management

Growth Hormone Deficiency

For children with growth hormone deficiency, the primary form of treatment is daily growth hormone injections. This therapy is long-term, often continuing for several years. Throughout the treatment period, regular doctor visits are essential to monitor the child’s progress and ensure the therapy is effective. If needed, the doctor can adjust the hormone dose.

Possible side effects of growth hormone therapy may include:

• Headaches
• Swelling due to fluid retention in certain areas of the body
• Muscle and joint discomfort

Serious side effects are uncommon, and in most cases, the benefits outweigh the risks. Early intervention with growth hormone therapy offers the best chance for the child to reach a near-normal adult height. Typically, children can grow approximately 10 cm (4 inches) during the first year of treatment and about 7.6 cm (3 inches) in the following two years. After that, the rate of growth tends to slow down.

Gigantism

The treatment goals for gigantism include:

• Regulating growth hormone and IGF-1 levels
• Controlling the growth of pituitary tumors
• Minimizing the impact of pituitary tumors on nearby structures, such as brain tissue and the optic nerve
• Addressing or reducing the influence of excessive growth hormone on various bodily systems

In treating gigantism, doctors usually employ a combination of therapies, including surgery and radiation treatment.

Complications

If left untreated, growth hormone deficiency can lead to a number of challenges, including shorter stature and delayed onset of puberty in both boys and girls.

On the other hand, gigantism can cause several serious complications, such as:

• Movement disorders caused by muscle weakness
• Joint inflammation, including osteoarthritis
• Disorders of the peripheral nerves
• Sleep apnea
• Enlargement of the heart and problems with heart valves
• Metabolic issues, including an increased risk of developing type 2 diabetes

Prevention

Unfortunately, most growth hormone disorders in children cannot be prevented. However, it's important to monitor your child’s growth regularly during routine doctor visits. If there are any concerns about their growth pattern, it is advisable to seek an evaluation from a healthcare professional.

When to See a Doctor?

It is essential to consult a doctor if your child appears unusually short or tall compared to other children of the same age. 

Looking for more information about other diseases? Click here!