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Gigantism

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Description:
Gigantism is a rare condition that causes abnormal growth in children. This change is most notable in terms of height, but girth is affected as well. It occurs when your child’s pituitary gland makes too much growth hormone, which is also known as somatotropin. This is most often due to abnormal tumor growths on the pituitary gland. Gigantism should not be confused with acromegaly, the adult form of the disorder, characterized by somatic enlargement specifically in the extremities and face.

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Early diagnosis is important. Prompt treatment can stop or slow the changes that may cause your child to grow larger than normal. However, the condition can be hard for parents to detect. The symptoms of gigantism might seem like normal childhood growth spurts at first.

Symptoms:
If your child has gigantism, you may notice that they’re much larger than other children of the same age. Also, some parts of the body may be larger in proportion to other parts. Common symptoms include:

*Very large hands and feet
*Thick toes and fingers
*A prominent jaw and forehead
*Coarse facial features

Sometimes children with gigantism may also have flat noses and large heads, lips, or tongues.

The symptoms your child has may depend on the size of the pituitary gland tumor. As the tumor grows, it may press on nerves in the brain. Many people experience headaches, vision problems, or nausea from tumors. Other symptoms of gigantism may include:

*Excessive sweating
*Severe or recurrent headaches
*Weakness
*Insomnia and other sleep disorders
*Delayed puberty in both boys and girls
*Irregular menstrual periods in girls
deafness

Causes:
A pituitary gland tumor is almost always the cause of gigantism. The pea-sized pituitary gland is located at the base of your brain. It makes hormones that control many functions in your body. Some tasks managed by the gland include:

*Temperature control
*Sexual development
*Growth
*Metabolism
*Urine production

When a tumor grows on the pituitary gland, the gland makes far more growth hormone than the body needs.

There are other less common causes of gigantism:

* McCune-Albright syndrome causes abnormal growth in bone tissue, patches of light-brown skin, and gland abnormalities.

* Carney complex is an inherited condition that causes non-cancerous tumors on connective tissue, cancerous or non-cancerous endocrine tumors, and spots of darker skin.

* Multiple endocrine neoplasia type 1 (MEN1) is an inherited disorder that causes tumors in the pituitary gland, pancreas, or parathyroid glands.

Neurofibromatosis is an inherited disorder that causes tumors in the nervous system.

Gigantism is characterized by an excess of growth hormone (GH). This overproduction of growth hormone that brings about gigantism is virtually always caused by pituitary growths (adenomas). These adenomas are on the anterior pituitary gland. They can also cause overproduction of GH’s hypothalamic precursor known as growth hormone releasing hormone (GHRH).

As a result of the excessive amounts of growth hormone, children achieve heights that are well above normal ranges. The specific age of onset for gigantism varies between patients and gender, but the common age that excessive growth symptoms start to appear has been found to be around 13 years onwards. Other health complications may occur in pediatric patients with hyper-secretion of growth hormone such as hypertension. Characteristics more similar to those seen in acromegaly may occur in patients that are closer in age to adolescence since they are nearing growth plate fusio.

Diagnosis:
If your child’s doctor suspects gigantism, they may recommend a blood test to measure levels of growth hormones and insulin-like growth factor 1 (IGF-1), which is a hormone produced by the liver. The doctor also may recommend an oral glucose tolerance test.

During an oral glucose tolerance test, your child will drink a special beverage containing glucose, a type of sugar. Blood samples will be taken before and after your child drinks the beverage. In a normal body, growth hormone levels will drop after eating or drinking glucose. If your child’s levels remain the same, it means their body is producing too much growth hormone.

If the blood tests indicate a pituitary gland tumor, your child will need an MRI scan of the gland. Doctors use this scan to see the size and position of the tumor.

Genetics:
Finding a specific genetic cause for gigantism has proven to be difficult. Gigantism is the primary example of growth hormone hyper-secretion disorders, a group of illnesses that are not yet deeply understood.

Some common mutations (errors in DNA) have been associated with gigantism. Pediatric gigantism patients have shown to have duplications of genes on a specific chromosome, Xq26. Typically, these patients also experienced an onset of typical gigantism symptoms before reaching the age of 5. This indicates a possible linkage between gene duplications and the gigantism.

Additionally, DNA mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are common in gigantism patients. They have been found to be present in about 29 percent of patients with gigantism. AIP is labeled as a tumor suppressor gene and a pituitary adenoma disposition gene.

Mutations in AIP sequencing can have deleterious effects by inducing the development of pituitary adenomas which in turn can cause gigantism.

Two specific mutations in the AIP gene have been identified as possible causes of pituitary adenomas. These mutations also have the ability to cause adenoma growth to occur early in life. This is typical in gigantism.

Additionally, a large variety of other known genetic disorders have been found to influence the development of gigantism such as multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, X-linked acrogigantism (X-LAG).

Although various gene mutations have been associated with gigantism, over 50 percent of cases cannot be linked to genetic causes, showing the complex nature of the disorder

Treatment:

Many treatments for gigantism receive criticism and are not accepted as ideal. Various treatments involving surgery and drugs have been used to treat gigantism.

Treatments for gigantism aim to stop or slow your child’s production of growth hormones.

Surgery:
Removing the tumor is the preferred treatment for gigantism if it’s the underlying cause.

The surgeon will reach the tumor by making an incision in your child’s nose. Microscopes or small cameras may be used to help the surgeon see the tumor in the gland. In most cases, your child should be able to return home from the hospital the day after the surgery.

Gamma Knife Radiosurgery:
Gamma knife radiosurgery is an option if your child’s doctor believes that a traditional surgery isn’t possible. The “gamma knife” is a collection of highly focused radiation beams. These beams don’t harm the surrounding tissue, but they’re able to deliver a powerful dose of radiation at the point where they combine and hit the tumor. This dose is enough to destroy the tumor.

Gamma knife treatment takes years to be fully effective and to return the levels of growth hormone to normal. It’s performed on an outpatient basis under general anesthetic.

However, since the radiation in this type of surgery has been linked to obesity, learning disabilities, and emotional issues in children, it’s usually used only when other treatment options don’t work.

Medication:
Surgery may not be an option. This can be the case if there’s high risk of injury to a critical blood vessel or nerve. Your child’s doctor may recommend medication if surgery is not an option. This treatment is meant to either shrink the tumor or stop the production of excess growth hormone. Your doctor may use the drugs octreotide or lanreotide to prevent the growth hormone’s release. These drugs mimic another hormone that stops growth hormone production. They’re usually given as an injection about once a month.

Bromocriptine and cabergoline are drugs that can be used to lower growth hormone levels. These are typically given in pill form. They may be used with octreotide. Octreotide is a synthetic hormone that, when injected, can also lower the levels of growth hormones and IGF-1. In situations where these drugs are not helpful, daily shots of pegvisomant might be used as well. Pegvisomant is a drug that blocks the effects of growth hormones. This lowers the levels of IGF-1 in your child’s body.

Pegvisomant is one pharmaceutical drug which has received attention for being a possible treatment route for Gigantism. Reduction of the levels of IGF-I as a result of pegvisomant administration can be incredibly beneficial for the pediatric gigantism patients.

After treatment with pegvisomant, high growth rates, a feature characteristic of gigantism, can be significantly decreased. Pegvisomant has been seen to be a powerful alternative to other treatments such as somatostatin analogues, a common treatment method for acromegaly, if drug treatment is paired with radiation.

Finding the optimal level of pegvisomant is important so normal body growth is not negatively affected. In order to do this, titration of the medication can be used as a way to find the proper administration level.

According to St. Joseph’s Hospital and Medical Center, 80 percent of gigantism cases are cured with surgery. If the tumor returns or if surgery cannot be safely attempted, medications can be used to reduce your child’s symptoms and to allow them to live a long and fulfilling life.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
https://en.wikipedia.org/wiki/Gigantism
https://www.healthline.com/health/gigantism

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