Acromegaly

Definitions & Key takeaways

Acromegaly is a rare disorder caused by too much growth hormone (GH) secreted by the anterior pituitary gland, a small organ at the base of the brain. In children, too much GH can lead to gigantism condition characterized by unusually tall stature. In adults, too much GH can cause acromegaly, which results in abnormal enlargement of the head, face, hands, and feet. It is usually accompanied by comorbidities like diabetes mellitus, hypertension, heart disease, and arthritis.

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Introduction0:00–0:46

With acromegaly, “acro” refers to extremity and “megaly” refers to enlargement. So acromegaly is a hormonal disorder in adults where there is an excess of growth hormone or somatotropin, which causes continued growth of the extremities in adults, leading to a large face, hands, feet.
As examples, the French wrestler André the Giant who played Fezzik in the movie The Princess Bride (one of our favourites) and actor Richard Kiel who played Jaws in the James Bond movies both had acromegaly.
In children, excess growth hormone causes a different disorder, called gigantism, because their long bones haven’t stopped growing yet.

Physiology0:46–3:19

So let’s talk about how growth hormone 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 cells of the anterior pituitary gland, and in response, they release growth hormone.
The body uses three main ways to help limit the amount of growth hormone that gets made. First, too much growth-hormone-releasing hormone signals the hypothalamus to stop making more.
Second, when growth hormone reaches tissues like the liver, bones, and muscles, they make somatomedins, which are small protein hormones.
These somatomedins signal the anterior pituitary to stop producing growth hormone. Third, growth hormone and somatomedins together signal to the hypothalamus to produce somatostatin, another hormone, whose role is also to signal the anterior pituitary to stop producing 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.
In the liver, more glucose is released into the blood. In the muscles, the body retains nitrogen leading to more muscle growth, and in the bones osteoblasts are stimulated, causing 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 this is similar to what happens in people 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.

Pathology3:19–4:09

The main cause of acromegaly is a pituitary adenoma which is a tumor of somatotroph cells in the anterior pituitary gland.
This tumor is benign, meaning that it doesn’t invade into neighboring tissues. These somatotroph cells continuously make excess growth hormone and this leads to excess insulin-like growth factor 1 as well.
More rarely, acromegaly can result from hypothalamic tumors that release too much growth-hormone-releasing hormone or even tumors from other parts of the body that start producing growth hormone ectopically - meaning that it comes from an unexpected location.
On rare occasions, acromegaly can be associated with a congenital syndrome like multiple endocrine neoplasia type 1, also called Wermer syndrome, which affects the parathyroid, pancreas, and pituitary glands.

Symptoms4:09–4:49

The symptoms of acromegaly, which can take years before they are even recognized, include growth of the bones of the hands, feet, and lower jaw and protrusion of the forehead.
It also includes soft tissue swelling in hands, feets, face, and tongue; increased size of organs; and excessive sweating.
These changes can lead to additional health problems like carpal tunnel syndrome because of increased pressure on nerves from muscle growth, diabetes mellitus from the diabetogenic effects of growth hormone, congestive heart failure due to enlargement of the heart, and gastrointestinal cancers from colon polyps - outgrowths in the large intestines.

Diagnosis4:49–5:08

The diagnosis of acromegaly 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.
An MRI can help confirm the presence of the pituitary tumor. Treatment of acromegaly depends on the underlying cause.

Treatment5:08–5:34

If there’s a pituitary adenoma, then surgery can be done to try to remove the growth, and in cases where that doesn’t work, radiation therapy can be used.
Medications like somatostatin analogs can also be used to limit growth hormone production. Alternatively, growth hormone receptor antagonists can be used to stop growth hormone from binding to target tissues.
All right, as a quick recap, acromegaly is a hormonal disorder typically caused by a benign tumor of the anterior pituitary gland.

Review5:34–5:57

It results in excessive growth hormone and insulin-like growth factor 1 production, which has a diabetogenic effect - it raises the blood sugar.
Overall, this leads to symptoms like bony growth, soft tissue growth, organ growth, and excess sweating.