Acromegaly
Acromegaly is an uncommon disorder caused by the production of excessive growth hormone in the body resulting in a slow progression of multiple symptoms. The most obvious symptoms are enlarged hands and feet and a prominent facial profile. The cause is usually a non-cancerous tumor growing in the pituitary gland. Treatment includes surgical removal of the tumor, medication to inhibit the release of growth hormone or to block the effects of growth hormone. Chen Ge, Department of Neurosurgery, Xuanwu Hospital, Capital Medical University
Understanding the pituitary gland and growth hormone
The pituitary gland is located at the base of the brain. It produces several hormones, including growth hormone. (Hormones are chemicals that are produced in one part of the body and then enter the bloodstream to produce effects in other parts of the body.)
The amount of growth hormone (GH) produced can be controlled by a small part of the brain, the part of the hypothalamus that produces other hormones. The hypothalamus, which is located just above the pituitary gland, produces growth hormone-releasing hormone (GHRH), which stimulates the pituitary gland to produce growth hormone when blood levels of growth hormone are low. Another hormone it produces, growth hormone inhibitor, prevents the pituitary gland from producing growth hormone when blood levels of growth hormone are high.
Growth hormone helps stimulate the growth and repair of various body tissues. It is needed during childhood to help children grow. Growth hormone acts directly on certain tissues. It also stimulates the liver to produce another hormone called insulin-like growth factor- 1 (IGF- 1). Many of the effects of growth hormone are actually produced by IGF-1 acting on various cells in the body.
What is acromegaly and what causes it?
Acromegaly is a condition that occurs when too much growth hormone is produced. In more than 99 out of 100 patients, the excess hormone comes from a small tumor in the pituitary gland. This is a benign, non-cancerous growth called a pituitary adenoma. The adenoma may grow to be 1 – 2 cm or larger. However, because it is benign, it does not spread to other parts of the body. The abnormal cells in an adenoma produce large amounts of growth hormone. How adenomas occur remains unclear.
In a few cases, acromegaly is caused by excessive production of GHRH by the hypothalamus, which produces too much growth hormone by stimulating the cells of the pituitary gland. In rare cases, other tumors in the body also produce growth hormone.
Who gets acromegaly?
Acromegaly is relatively rare. The annual incidence of acromegaly is about 3 to 10 per million people. It is mainly seen in adults between the ages of 25 and 50. The difference in incidence between men and women is not significant.
In rare cases, it affects children. If it occurs in childhood (usually occurs between the ages of 15 and 17), it is often called gigantism because growth hormone promotes bone growth in the body.
Note: Everything covered below is about acromegaly in adults.
What are the symptoms and problems of acromegaly?
Acromegaly literally means “enlargement of the limbs” or “enlargement of the hands and feet”. This is a typical feature, but there are many other symptoms. The symptoms progress gradually, in some cases over 10 to 15 years before a definitive diagnosis is made.
Symptoms can be divided into two categories: those caused by too much growth hormone and those caused by enlarged pituitary tumors.
Symptoms caused by too much growth hormone
Too much growth hormone in the blood can affect many tissues in the body, causing them to thicken or grow.
Therefore, over time, one or more of the following symptoms may occur.
l The hands and feet become larger and wider; the size of gloves and shoes may increase over the years; wedding rings may not come off.
l Skin may thicken (especially on the face) and become more oily and sweaty.
l Facial changes may include thickened lips and nose, thickened scalp, and a more prominent chin. These changes develop so slowly that they go unnoticed by family or friends. However, looking back at old photographs can suggest changes that have occurred in the face.
l Vocal cords become thicker, which may lead to a low voice.
l The tongue becomes larger so you may bite it more often.
l Thickening of cartilage may lead to arthritis in multiple joints.
l Thickening of the nasal cavity may cause loud snoring and lead to airway obstruction during sleep (i.e., respiratory sleep apnea), resulting in poor sleep at night and grogginess during the day.
l Carpal tunnel syndrome. The nerve is compressed by thickened tissue at the point where it crosses the wrist. It can cause pain, tingling and weakness in parts of the hand or arm.
l Irregular menstruation or amenorrhea may occur in women.
Other effects of too much growth hormone may include:
l Fatigue throughout the body.
Partial muscle weakness.
Diabetes occurs in about 1 in 5 cases of acromegaly because growth hormone can resist the action of insulin.
l Hypertension in 1/3 of patients.
l There is an increased risk of heart disease and stroke. This is likely due to the increased risk of developing hypertension and diabetes mellitus.
l Patients with acromegaly have an increased chance of developing intestinal polyps (small benign growths) and a mildly increased chance of developing bowel cancer. Patients with acromegaly are now routinely screened for these conditions (see below).
In addition, in about 1/3 of cases, adenomas can also produce too much of another hormone called prolactin. Prolactin can cause problems with sexual function and menstruation, as well as nipple discharge. Many men with acromegaly develop erectile dysfunction (impotence).
Symptoms caused by an enlarged tumor
In many cases, the tumor is small and does not cause compression symptoms. In some cases, however, the tumor can grow to such an extent that it can compress adjacent tissues, which may result in
l Headache.
l Visual problems. The tumor may compress the optic nerve in the adjacent pituitary gland (the optic nerve runs from the eye to the brain).
l Other normal cells of the pituitary gland may be compressed and damaged. As a result, there may be a deficiency of a certain hormone produced by the pituitary gland. This may lead to hypothyroidism and/or hypoadrenalism, which can cause a variety of other symptoms.
How is acromegaly diagnosed?
l A blood test can detect levels of growth hormone. However, a single test is not reliable because growth hormone levels in all people fluctuate greatly from one day to the next.
A glucose tolerance test is required to diagnose acromegaly. In this test, a sugary drink containing 75 grams of glucose is drunk and then subjected to a blood test for more than two hours. Glucose lowers the level of growth hormone in the blood, which remains high in people with acromegaly.
A blood test to measure IGF-1 levels (see above) is required for those suspected of having acromegaly. This can also be used as an index of disease activity to assess the effectiveness of treatment.
Magnetic resonance imaging (MRI) scans can show the size of the tumor.
l Eye and visual tests can assess whether the tumor is compressing the optic nerve.
If acromegaly is confirmed, other tests are needed to see if the tumor is causing a deficiency or excess of other pituitary hormones.
Other tests include chest x-ray, electrocardiogram (ECG) and x-ray of certain joints.
What are the treatment measures for acromegaly?
The goal of treatment is to reduce the level of growth hormone in the blood to normal and to reduce the size of the tumor. Many of the symptoms and functions of acromegaly will reverse or improve with successful treatment (except for skeletal changes that have already occurred and are fixed).
Surgical treatment
Surgical resection is preferred for most pituitary GH adenomas. The basic surgical approaches are divided into transsphenoidal pituitary tumor resection and transcranial pituitary tumor resection.
l The first surgical approach is known as transnasal pterygoid sinus surgery. The surgeon makes a small endoscopic or microscopic incision through one or both nostrils to reach the pituitary gland, and surgical instruments are passed through the base of the skull, the pterygoid bone, to remove the adenoma, leaving the rest of the pituitary gland intact. The current trend is to remove pituitary tumors through the endoscopic transnasopterygoid approach with minimal trauma and pain. Transnasal pterygoid sinus surgery can be performed in about 95% of pituitary tumors.
The second surgical approach is transcranial surgery. It requires craniotomy to remove an invasive giant pituitary tumor and is indicated in about 5% of patients.
Complete removal of the GH adenoma can effectively restore normal GH levels, with a dramatic decrease in serum GH levels and a concomitant decrease in IGF-1 levels, as well as partial or complete recovery of normal pituitary function damaged by compression, and other symptoms of tumor compression. About 90% of patients with smaller tumors do not require further treatment after total surgical excision. The surgical outcome depends greatly on the surgeon’s technique, the extent and size of the tumor, and the preoperative GH level. In large GH adenomas, where the tumor may have invaded surrounding tissues, surgery may reduce the tumor load, if not completely remove the tumor, while using adjuvant therapeutic measures such as radiotherapy, medication or a combination of both to obtain the best results.
The surgeon will advise of the possible complications of surgery, for example, sometimes surgery may damage other parts of the pituitary gland, which may result in decreased production of other hormones. If this happens, hormone replacement therapy will be required.
Medication
If surgery is not possible or is not desired, medications may be used. They may also be used to relieve symptoms while waiting for surgery or radiation therapy and in cases where surgery does not completely remove the tumor and growth hormone levels remain high.
Growth hormone analogs (octreotide and lanreotide) can reduce growth hormone levels to normal in more than half of patients and reduce tumor size in about 80% of patients. However, these drugs need to be given by injection. They work in a similar way to growth inhibitors (as described above), which are hormones that block the release of growth hormone from pituitary cells. Short-acting drugs require multiple injections a day. Long-acting preparations can be injected monthly or biweekly. Side effects of these drugs are uncommon; some people experience abdominal pain and diarrhea, but these usually go away with time. Gallstones may also occur, but they rarely cause problems.
Dopamine receptor agonists (such as carte blanche, bromocriptine, and quinagolide) can be taken as pills. They work by blocking the release of growth hormone from tumor cells. However, they are only effective in about 1 in 5 patients. Side effects such as nausea and dizziness are also fairly common.
Pevisomant (Somavo®) requires daily injections. Unlike the other drugs mentioned above, it does not act directly on the pituitary gland. Pevisomant works by blocking the action of growth hormone on the body’s cells. Therefore, it does not reduce the size of the tumor or relieve headaches, although it may relieve many of the symptoms that occur as a result of excessive hormone production.
Radiotherapy
Radiation therapy is an option that can reduce the size of the tumor, thereby reducing the production of growth hormone. It can be used for patients who are unable to undergo surgery, or for whom surgery is only a partial removal of the tumor. It may take several months or years after radiation therapy for growth hormone levels to drop to normal. Medications may be taken while waiting for the radiation therapy to take effect.
There are two methods of radiation therapy
l Conventional radiation therapy: This method of radiation therapy is usually given 5 days a week for 4-6 weeks. It takes several years for the treatment to take effect.
l Stereotactic Radiation Therapy: Also known as Gamma Knife, this is a high dose of radiation focused on the tumor cells in the pituitary gland, while irradiating the normal pituitary gland and tissues around the tumor, such as the optic nerve, at a smaller dose, usually only once, and it takes 3 to 5 years before the growth hormone may be reduced to normal.
Your doctor will choose the radiation therapy that is right for you based on your condition.
A possible side effect of pituitary radiation therapy is damage to other normal pituitary cells. This may result in lower levels of some other hormones. If this happens hormone replacement therapy may be used.
Follow-up
Even after treatment, acromegaly requires regular monitoring of your pituitary function by your doctor. Hormone levels are usually reviewed every 6 months after surgery, and MRIs are reviewed annually for 5 years, and then every 2-3 years depending on your condition. And lifelong follow-up is required.
Screening for acromegaly and bowel cancer
As mentioned earlier, patients with acromegaly have an increased chance of developing intestinal (colon) polyps and bowel cancer. Therefore, patients over the age of 40 diagnosed with acromegaly usually require routine colonoscopy every 3 – 5 years. During a colonoscopy, the operator (doctor or nurse) uses a flexible endoscope to look directly into the colon (large intestine) and can diagnose intestinal problems such as polyps and bowel cancer. The goal is to detect patients with cancer early (before symptoms occur), when the probability of a complete cure is higher.
The doctor should be informed of any new bowel symptoms such as persistent diarrhea, mucus stools, blood in the stool, or abdominal pain.