Gigantism

Definitions & Key takeaways

Gigantism is a hormonal disorder that results in an individual growing to an excessive size. The condition is caused by the overproduction of growth hormone (GH) and insulin-like growth factor-1, usually due to a tumor on the pituitary gland.

Symptoms of gigantism include excessive growth, particularly in the facial area and hands; a deep, hoarse voice; and enlarged organs. Gigantism is also associated with other health problems, including heart disease, joint pain, and diabetes.

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Introduction0:00–0:34

With gigantism, “gigant” refers to giant, so gigantism is a rare hormonal disorder in children and adolescents where there is an excess of growth hormone, and it causes rapid and excessive growth of long bones, like the tibia and humerus.
As an example, the French wrestler André the Giant who played Fezzik in the movie The Princess Bride had gigantism. In adults, excess growth hormone causes a different disorder, called acromegaly, because their long bones have stopped growing.

Physiology0:34–2:33

Let’s start with how growth hormone, or somatotropin, is made. Normally, the hypothalamus which is at the base of the brain, secretes growth hormone-releasing hormone in bursts throughout the day - every couple hours, and this can increase based on things like low blood glucose levels, lack of food, increased exercise, increased sleep, and increased stress like trauma.
The growth hormone-releasing hormone goes into the hypophyseal portal system - which is a network of capillaries linking the hypothalamus to the anterior pituitary which is smaller in size than a pea.
The growth hormone-releasing hormone binds to a surface protein on somatotroph and mammosomatotroph cells of the anterior pituitary gland, and in response, they release growth hormone.
Now, growth hormone affects lots of tissues directly and indirectly throughout the body. Direct effects occur in certain tissues where growth hormone stimulates cellular metabolism and leads to organ growth.
The liver releases more glucose into the blood, the body retains nitrogen leading to more muscle growth, and osteoblasts get stimulated which causes the bones to thicken.
Another direct effect of growth hormone is to increase insulin resistance - making it harder for cells to take in glucose - which leads to an increase in blood insulin levels.
Because it is like what happens in individuals with diabetes, this effect of growth hormone is called diabetogenic. An important indirect effect, is that growth hormone stimulates certain tissues like the liver, skeletal muscles, bones, and kidneys to produce somatomedin C, also called insulin-like growth factor 1.
Insulin-like growth factor 1 promotes cellular metabolism, prevents cell death, and helps cell divide and differentiate throughout the body.
It’s also the key hormone that stimulates the growth in length of long bones. Gigantism is often caused by a pituitary adenoma, which specifically involves the mammosomatotroph cells, or sometimes the somatotroph cells, in the anterior pituitary gland.

Pathology2:33–3:31

This specific type of tumor is usually benign, meaning that it doesn’t invade into neighboring tissues. These tumor cells continuously make excess growth hormone and that in turn leads to excess insulin-like growth factor 1 as well.
Gigantism can also be caused by a hypothalamic tumor that releases too much growth-hormone-releasing hormone or from other tumors that might start producing growth hormone ectopically.
In this situation the cells in the pituitary are secreting lots of growth hormone simply because they’re being overstimulated.
On rare occasions, gigantism can be associated with a congenital syndrome like McCune Albright syndrome, a genetic condition which causes overproduction of several hormones including growth hormone.

Signs and symptoms3:31–4:41

The symptoms of gigantism usually appear pretty dramatically, because children’s bodies are very responsive to growth hormone and insulin-growth factor 1.
The primary symptom is excessively fast growth in height, often followed by rapid weight gain, because of excess insulin-growth factor 1.
Other growth effects include macrocephaly, or enlargement of the skull bones; projection of the lower jaw; soft tissue swelling in the hands and feet; and increased size of organs like the heart.
These changes also lead to additional problems like carpal tunnel syndrome because of increased pressure on nerves from muscle growth and diabetes mellitus from the diabetogenic effects of growth hormone.
If gigantism is caused by a tumor of the mammosomatotroph cells, there will be an excess of prolactin, the hormone that stimulates production of breast milk, because these cells make both growth hormone and prolactin.
Too much prolactin can cause symptoms like decreased menstruation in adolescent girls and enlarged breasts in adolescent boys.
Finally, the mass of a tumor in the anterior pituitary can cause headaches and compress the optic nerve. The diagnosis of gigantism can be made when there are elevated levels of insulin-like growth factor 1 and growth hormone, particularly if the levels of growth hormone are elevated in spite of receiving a large dose of glucose.

Diagnosis4:41–5:05

Often, the level of prolactin will also be high if mammosomatotroph cells are involved. An MRI can help confirm the presence of the pituitary tumor.

Treatment5:05–5:35

Treatment of gigantism usually involves surgery to remove the pituitary adenoma or other tumor that is causing the disorder.
In cases where that doesn’t work, medications can be used, like somatostatin analogs which limit growth hormone production or growth hormone receptor antagonists which stop growth hormone from binding to target tissues.
Radiation therapy is rarely used because the risks of this treatment are high for children and adolescents. All right, as a quick recap, gigantism is a hormonal disorder caused by a benign tumor of the anterior pituitary gland or of the hypothalamus.

Review5:35–6:02

It results in excessive growth hormone and insulin-like growth factor 1 production, which leads to symptoms like excessively fast growth in height, soft tissue growth, and organ growth.
When it involves mammosomatotroph cells, it can decrease menstruation in adolescent girls and cause enlarged breasts in adolescent boys.