Definition

Gigantism is a rare condition where a child or adolescent has excessive levels of growth hormone (GH), resulting in abnormal height growth compared to peers. The pituitary gland, located at the base of the brain under the hypothalamus, releases eight key hormones, including GH, which plays a significant role in childhood growth. In gigantism, too much GH accelerates the growth of muscles, bones, and connective tissues, leading to an abnormal increase in height and changes in soft tissues.

During puberty, the release of sex hormones like estrogen and testosterone leads to the fusion of growth plates in the long bones. Once these plates (epiphyses) fuse, GH no longer increases height but continues to maintain bones, cartilage, organs, and metabolism. In adults, excess GH after the growth plates close results in a condition called acromegaly, where height remains the same, but bones and organs may become enlarged, and other health issues arise.

Causes

The most common cause of gigantism is a benign (noncancerous) tumor in the pituitary gland called a pituitary adenoma. This tumor releases too much GH, and children with gigantism almost always have a large tumor called a macroadenoma (10 mm or more in diameter). Another possible cause is pituitary hyperplasia, where the pituitary gland enlarges.

In many cases, gigantism is linked to a genetic mutation, such as a mutation or deletion of the AIP gene, found in 29% of individuals with gigantism. Gigantism can also occur as part of several rare genetic disorders that increase the likelihood of pituitary tumors, including:

• Carney complex: A genetic condition that affects skin pigmentation and causes benign tumors in the skin, heart, and endocrine system.
• McCune-Albright syndrome: A genetic disorder affecting bones, skin, and the endocrine system, resulting in skin pigmentation, bone scarring, and early puberty.
• Multiple endocrine neoplasia (MEN) type 1 or 4: A genetic condition in which one or more endocrine glands become overactive or develop tumors, including GH-secreting pituitary tumors.
• Neurofibromatosis: A genetic disorder affecting the skin and nervous system, leading to the formation of tumors, which can include GH-producing tumors.
• Familial isolated pituitary adenoma (FIPA): An inherited condition characterized by the formation of pituitary adenomas.

Risk Factors

Although gigantism is a rare condition, it can affect any child whose bone growth plates have not yet fused (which typically occurs during puberty). Gigantism tends to be more common in boys than in girls.

Symptoms

The signs and symptoms of gigantism are primarily caused by excess growth hormone (GH). In addition, children with gigantism may experience symptoms related to the pressure of a pituitary tumor on nearby brain and nervous tissues. The hallmark sign of gigantism is abnormally rapid growth. Affected children will experience accelerated weight gain and exhibit certain physical characteristics, such as:

• A very prominent forehead and protruding jaw
• Gaps between the teeth
• Thickening of facial features
• Large hands and feet with thick fingers

Other symptoms of gigantism include:

• Enlargement of internal organs, especially the heart
• Excessive sweating (hyperhidrosis)
• Double vision or impaired peripheral vision
• Headaches
• Joint pain
• Delayed puberty
• Irregular menstrual periods
• Sleep disorders, such as sleep apnea
• Muscle weakness

Diagnosis

Diagnosing gigantism can be challenging due to its rarity and the wide variation in normal growth patterns among children. Doctors may suspect gigantism if a child’s height is more than 3 standard deviations above the average for their age and sex, or more than 2 standard deviations above the average for the child's biological parents. The following tests may be recommended to confirm the diagnosis:

• GH and IGF-1 blood tests: These assess hormone levels in a blood sample. Elevated GH and IGF-1 levels may indicate gigantism.
• Glucose tolerance test: This test checks whether GH levels respond appropriately to glucose. Blood samples are drawn after the child drinks a sugar solution.
• Imaging tests: If blood tests confirm gigantism, imaging tests such as MRI or CT scans can reveal the size and location of the pituitary tumor.

If gigantism is diagnosed, further tests might be needed to evaluate the impact on other parts of the body, such as:

• Echocardiogram: To check for heart problems.
• Sleep study test: To assess sleep apnea.
• X-ray or DEXA scan: To evaluate bone health.

Management

Treatment for gigantism usually involves a combination of surgery, radiation therapy, and sometimes medication. The primary goal is to reduce GH levels and manage symptoms effectively.

• Surgery: This is the most common treatment, aiming to remove or shrink the pituitary tumor. Because pituitary tumors causing gigantism are often large, multiple surgeries may be needed to fully regulate GH levels. A common surgical approach involves inserting instruments through the nose and sphenoid sinus to access the tumor.
• Radiation therapy: If surgery is not entirely effective, radiation therapy may be used to reduce GH levels. This method targets the tumor with radiation, but its effects are slow, often requiring multiple rounds over time, with visible results taking years.

Complications

Long-term complications of gigantism arise from both the increased height and the effects of excess growth hormone (GH). These complications include:

• Impaired mobility due to muscle weakness
• Joint calcification
• Peripheral nerve disorders
• Sleep disturbances
• Heart enlargement and heart valve disorders
• Metabolic complications such as type 2 diabetes

Prevention

There are no preventive measures for gigantism. However, early diagnosis is crucial, as prompt treatment can prevent or slow excessive growth and reduce the risk of complications.

When to See a Doctor?

It can be challenging for parents to detect gigantism since the symptoms may resemble a typical growth spurt. If there are concerns about a child’s growth rate or physical development, consulting a doctor is essential.

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