Gigantism

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.

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.

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.