Acromegaly is an endocrine disorder where there is a hormonal imbalance in the body. The condition is caused by too much growth hormone (GH).
Growth hormone is normally produced by the pituitary gland. This is a small pea-sized gland that lies within the brain. In acromegaly, the pituitary produces excessive amounts of GH.
The excess production may be due to a benign, or noncancerous, tumor on the pituitary. These tumors are called adenomas.
Without treatment acromegaly can cause severe complications and even death. Acromegaly is treatable in most patients. It has a slow and gradual onset and often goes un-noticed in its initial phases.
Acromegaly may lead to other disorders including:
If the disorder occurs in childhood, it leads to gigantism rather than acromegaly. In children excess growth hormone leads to excess prolongation of the long bones (in the legs) and this leads to excessive height gain.
The long bones in response to the growth hormone especially grow at the growth plates—areas near either end of the bone. Once the child attains puberty, the growth plates fuse and thus after attainment of puberty excess growth hormone does not lead to gigantism or excessive height gain.
Those with acromegaly usually have no growth of their limbs. However bones of the hands, feet, and face can still grow and these begin to grow. The hands appear like spades. The face bones grow to alter the shape of the face. The jaw becomes larger, with spaces appearing between the teeth, and the eyebrows become more prominent. The skin becomes rough and oily and there is excessive growth of the tongue as well.
Acromegaly is most often diagnosed in middle-aged adults between ages 40 and 45. Symptoms of the condition may appear at any age. Around 3 to 4 million persons are affected annually.
Treatment is targeted towards the pituitary tumor. The tumor may be treated using a combination of surgery to remove the tumour, radiotherapy to destroy any tumour cells and drugs to suppress the production of further growth hormone.
Acromegaly has a slow or gradual onset and the symptoms are also slow to appear. Obvious changes in appearance may not be detected immediately unless present photographs or appearance is compared with earlier photographs.
Some of the symptoms of acromegaly include:-
Growth hormone is produced and released by the pituitary gland. This is a pea-sized gland just below the brain. Normal release of growth hormone before attainment of puberty allows for normal growth of humans.
Growth hormone release is stimulated by the hypothalamus of the brain. The hypothalamus makes hormones that regulate the pituitary. One of the hormones that regulates the growth hormone is the growth hormone-releasing hormone (GHRH), which stimulates the pituitary gland to produce GH.
When growth hormone is released into the blood, it stimulates the liver to produce another hormone – insulin-like growth factor 1 (IGF-1). This IGF-1 causes growth of muscle, bones and cartilage throughout the body. In adults this process is required for growth and repair of body tissues.
The hypothalamus makes another hormone called somatostatin. This inhibits GH production and release. Normally the levels of each of the four hormones – GHRH, Somatostatin, Growth Hormone and IGF-1 are tightly regulated by each other and by other factors such as sleep, exercise, blood sugar levels, stress etc.
Acromegaly is caused by prolonged overproduction of GH by the pituitary gland. This leads to excessive rise of IGF-1 as well leading to bone overgrowth and organ enlargement. Rise in levels of IGF-1 changes glucose and fat metabolism leading to an increased risk of heart disease and diabetes.
Causes of acromegaly may be due to pituitary tumors or non-pituitary tumors.
This is the cause of acromegaly in more than 95 percent of people with the condition. Acromegaly results from a benign or non cancerous tumor of the pituitary gland, called an adenoma. This tumor produces excess GH.
Pituitary tumors may be micro- or macro-adenomas determined by their size. Acromegaly is commonly caused by macro-adenomas. This means they are over 1cm in size.
These larger tumors may also press upon the nearby structures of the brain. If the tumor grows upwards, it presses on the optic chiasm. At this site the optic nerves that carry information about vision from the eyes to the brain from either eye cross each other. If the tumor presses on the optic chiasm, there may be vision problems and loss of vision.
Similarly if the tumor grows to its sides an area of the brain called the cavernous sinus may be encroached. This site contains several nerves that may be damaged.
Growth of the tumor also causes a derangement of other hormones produced by the pituitary gland. This can lead to problems like sexual dysfunction, loss of libido, abnormal menstruation and breast discharge in women. Thyroid hormone production may also be altered leading to underactive thyroids or hypothyroidism.
The adrenal gland functions of releasing hormone cortisol may also be affected if the pituitary gland functioning is altered. Decline in cortisol levels can cause weight loss, fatigue, low blood pressure etc. Excess secretion of other pituitary hormones like prolactin may be seen from the pituitary adenomas. Prolactin stimulates the breast to produce milk.
Most pituitary tumors develop on their own and are usually not linked to genes and are not inherited. The DNA of the pituitary cell may be altered to give rise to the tumor. This is called a mutation and is not present since birth. The mutation occurs in a gene that regulates the transmission of chemical signals and permanently switches on the signal that asks the cells to continue dividing uncontrolled.
Acromegaly in very rare cases may also be caused by non-pituitary tumors. The other tumors include those of the lungs, pancreas, and other parts of the brain. These tumors also lead to excess GH, either because they produce GH themselves or because they produce GHRH that stimulates the pituitary to release GH.
If there is excess production of GHRH from these secondary tumors, the size of the pituitary may be increased leading to mistaken suspicion of a pituitary tumor.
Acromegaly has a slow course and symptoms often take months or even years to develop. If the condition is suspected, diagnostic tests are prescribed. The tests are outlined as follows.
Blood tests are prescribed to detect the levels of growth hormone in the body. In persons with Acromegaly the levels of growth hormone is elevated.
For diagnosis, a single measurement of an elevated blood level of growth hormone is not enough. This is because normally this hormone is secreted by the pituitary in impulses or spurts and has several spikes and waves that may change the concentration in the blood from minute to minute. Thus those with Acromegaly may have normal levels of growth hormone at one point in time and someone who has normal pituitary function may have a level several times higher at the same point in time.
Thus to get an accurate idea about abnormal levels of growth hormone secretion the person is subjected to test conditions. Health care professionals often use the oral glucose tolerance test to diagnose Acromegaly.
In a normal person drinking 75 to 100 grams of glucose solution lowers blood levels of growth hormone to less than 1 nanogram per millilitre (ng/ml). In those with Acromegaly and growth hormone overproduction this suppression does not occur. Thus the oral glucose tolerance test is a reliable method for confirming a diagnosis of Acromegaly.
Tests are also prescribed to measure blood levels of Insulin-like growth factor 1 (IGF-1). This level rises as the levels of growth hormone rises. Because IGF-I levels are much more stable than growth hormone throughout the day, screening for Acromegaly with IGF-1 levels is a more reliable method.
Elevated IGF-I levels almost always indicate Acromegaly. It must be remembered however that pregnancy causes a physiological rise in IGF-1 by two to three times and with age the IGF-1 levels decline. Levels may be low in persons with poorly controlled diabetes or liver or kidney disease.
IGF-binding protein-3 (IGFBP-3) is a protein that binds to circulating IGF in the body. When levels of IGF-1 are raised this protein levels also rises. This can be used in diagnosis of Acromegaly. Growth hormone-releasing hormone (GHRH) concentration can be estimated.
With involvement of the pituitary gland, other hormones may be affected. Assessment of these hormones including prolactin, adrenal, thyroid, and gonadal hormones may help detect abnormalities.
In addition, blood glucose, serum phosphate, and serum triglycerides may also be raised. Urine examination may reveal raised urinary calcium levels.
After blood levels are found to be indicative of Acromegaly, imaging studies are prescribed. A magnetic resonance imaging (MRI) scan of the brain and pituitary gland especially is the first choice of investigation. This helps in detection of the location and size of the tumor.
MRI is the most sensitive imaging technique but as an alternative computerized tomography (CT) scans can be used.
In patients who have nonpituitary tumors elsewhere which are secreting growth hormone or Growth hormone releasing hormone (GHRH) a CT scan or a whole body MRI scan may be prescribed.
Total body scintigraphy with radio-labelled OctreoScan® (somatostatin) is prescribed in some patients for detection of these non-pituitary tumors.
Visual field tests are conducted to see the extent of damage to the optic chiasma and the optic nerves.
Patients are screened for heart disease with Electrocardiogram and echocardiogram. Since there is a high risk of colon cancers and colonic polyps among Acromegaly patients, an assessment of the same is indicated.
Treatment of Acromegaly aims to reduce excess growth hormone, relieve the pressure that the tumour is exerting on the surrounding structures and thus improve symptoms of the disease. If not treated the condition may worsen and eventually lead to severe symptoms and death.
Treatment can be achieved in two manners – surgery or medications.
In most cases of acromegaly (85%) the cause of the condition is an adenoma in the pituitary gland. This is a non-cancerous and benign tumor but can press upon surrounding vital structures of the brain causing severe symptoms such as vision loss.
Surgery is undertaken to remove this tumor. Sometimes the tumour is too large to be removed completely. Removal of a pituitary adenoma is usually undertaken under general anaesthesia wherein the patient is made unconscious during surgery. The surgeon will make an incision though the nose or inside the upper lip to access the gland. The tumor is then removed and this may cause a dramatic relief of pressure on the surrounding structures and a lowering of growth hormone levels.
Trans-sphenoidal surgery is the treatment of choice in most cases. It has a remission rate or cure rate of 80-85% for microadenomas and 50-65% for macroadenomas. Patients may need drug treatment after surgery in order to reduce growth hormone levels.
In most cases surgery is the successful treatment if the tumor is not too big. After surgery there may be some soft tissue swelling and bruises that may disappear in a few days.
Although successful, pituitary surgery is a complex one and may lead to several complications like damage to the healthy parts of the pituitary gland, leakage of cerebrospinal fluid, bleeding and infection etc.
If the pituitary tumor is large and surgery is not possible, the tumor may be shrunk using radiation therapy. Radiation therapy has one disadvantage: reduction in growth hormone levels after radiation is very slow.
In addition, there is a risk of damage to the whole gland which may cause a gradual decline in the production of other hormones from the gland. This necessitates hormone replacement therapy for the rest of the patient’s life. Also, due to effects on the reproductive hormones from the pituitary, radiation may cause infertility.
Radiation may be given as conventional form where the tumour is targeted with external beams. The patient needs to attend the office of the radiologist to receive the radiation from a large X ray like machine in small doses over four to six weeks. Weekends are let off to allow normal tissues to heal. This type of radiation causes damage to the structures surrounding pituitary gland and brain tissues.
Radiation may also be given as stereotactic delivery. In this method high-dose beam of radiation can be precisely aimed at the tumour. The head is kept still by wearing a rigid head frame. The beam kills the tumors cells usually in a single session.
Medications used in treatment of acromegaly include:-
Acromegaly can cause several complications if left untreated. These complications, like the symptoms of the disease, are gradual in onset and may take months or years to develop.
Vigilance regarding these complications is part of management of acromegaly. Some of the complications include:-