What does acromegaly affect. Acromegaly: Causes, Symptoms, and Treatment of Excessive Growth Hormone Production
What are the main symptoms of acromegaly. How is acromegaly diagnosed and treated. What complications can arise from untreated acromegaly. Who is most likely to develop this rare endocrine disorder.
Understanding Acromegaly: A Rare Endocrine Disorder
Acromegaly is an uncommon endocrine disorder characterized by excessive production of growth hormone (GH) in adults. This condition occurs when the body produces too much GH, typically due to a benign tumor in the pituitary gland. The overproduction of GH leads to abnormal growth of bones, tissues, and organs, resulting in distinctive physical changes and potential health complications.
How rare is acromegaly? Estimates suggest that only 3 to 14 out of every 100,000 people are diagnosed with this condition. Despite its rarity, understanding acromegaly is crucial for early detection and proper management of the disorder.
The Underlying Causes of Acromegaly
What triggers the excessive production of growth hormone in acromegaly? In more than 90% of cases, acromegaly is caused by a pituitary adenoma, a benign tumor in the pituitary gland. These tumors can vary in size and growth rate, affecting the severity and progression of symptoms.
The pituitary gland, often referred to as the “master gland,” plays a crucial role in hormone regulation. When a tumor develops in this gland, it can disrupt the normal production and release of growth hormone. This excess GH signals the liver to produce more insulin-like growth factor I (IGF-I), which is responsible for the actual tissue and bone growth seen in acromegaly.
Genetic Factors and Rare Causes
While the exact cause of pituitary tumors remains unclear, genetic factors may play a role in some cases. In young adults, certain gene defects have been linked to the development of acromegaly. Additionally, in rare instances, tumors in other parts of the body can lead to excess GH production, causing acromegaly without direct involvement of the pituitary gland.
Recognizing the Symptoms of Acromegaly
The symptoms of acromegaly often develop gradually over several years, making early diagnosis challenging. What are the telltale signs of this condition? Here are some of the most common physical changes and symptoms associated with acromegaly:
- Enlargement of hands and feet, often noticed through changes in ring or shoe size
- Facial changes, including enlarged lips, nose, and tongue
- Protruding brow and lower jaw
- Increased spacing between teeth
- Thickening and coarsening of the skin
- Increased sweating and body odor
- Deepening of the voice
- Development or enlargement of skin tags
Beyond these visible changes, individuals with acromegaly may experience:
- Persistent headaches
- Joint pain and arthritis
- Vision problems
- Fatigue and weakness
- Sleep apnea
- Carpal tunnel syndrome
Diagnosing Acromegaly: A Multifaceted Approach
Given the gradual onset of symptoms, how do doctors diagnose acromegaly? The diagnostic process typically involves a combination of methods:
- Physical examination: Doctors look for characteristic features of acromegaly, such as enlarged hands and feet, facial changes, and skin thickening.
- Blood tests: Measurements of GH and IGF-I levels in the blood are crucial for diagnosis.
- Glucose tolerance test: This test helps assess GH levels in response to glucose intake.
- Imaging studies: MRI scans of the pituitary gland can reveal the presence and size of tumors.
Early diagnosis is vital for preventing the progression of symptoms and reducing the risk of complications. If you suspect you may have acromegaly, it’s essential to consult with an endocrinologist for a thorough evaluation.
Treatment Options for Acromegaly
Once diagnosed, what treatment options are available for individuals with acromegaly? The primary goals of treatment are to:
- Reduce excess GH production
- Relieve pressure caused by the tumor
- Preserve normal pituitary function
- Improve symptoms and prevent complications
Treatment strategies may include:
1. Surgery
Transsphenoidal surgery is often the first-line treatment for most cases of acromegaly. This minimally invasive procedure involves removing the pituitary tumor through the nose and sinuses. When successful, surgery can lead to rapid improvement of symptoms and normalization of GH and IGF-I levels.
2. Medication
Several types of medications can be used to manage acromegaly:
- Somatostatin analogs: These drugs inhibit GH production and can shrink tumor size.
- GH receptor antagonists: These medications block the effects of GH on body tissues.
- Dopamine agonists: These drugs can be effective in some cases, particularly when the tumor also produces prolactin.
3. Radiation Therapy
In cases where surgery and medication are not fully effective, radiation therapy may be recommended. This treatment can gradually reduce tumor size and GH production over time.
Potential Complications of Untreated Acromegaly
Why is timely treatment of acromegaly so crucial? Untreated acromegaly can lead to several serious health complications, including:
- Type 2 diabetes
- Hypertension (high blood pressure)
- Cardiovascular disease
- Sleep apnea
- Osteoarthritis
- Carpal tunnel syndrome
- Increased risk of colon polyps and potential colon cancer
- Spinal cord compression
- Visual impairment due to tumor growth
Moreover, individuals with untreated acromegaly may face a shortened life expectancy. However, with proper treatment, many of these complications can be prevented or managed effectively, and life expectancy can return to normal.
Living with Acromegaly: Long-term Management and Care
For individuals diagnosed with acromegaly, long-term management is essential for maintaining quality of life and preventing complications. What does ongoing care for acromegaly involve?
- Regular medical check-ups and hormone level monitoring
- Management of comorbid conditions such as diabetes or hypertension
- Periodic imaging studies to monitor tumor size
- Lifestyle modifications, including a balanced diet and regular exercise
- Psychological support to address the emotional impact of the condition
It’s important to work closely with an endocrinologist and a multidisciplinary team of healthcare professionals to ensure comprehensive care. With proper management, many individuals with acromegaly can lead fulfilling lives and effectively control their symptoms.
Research and Future Directions in Acromegaly Treatment
The field of acromegaly research continues to evolve, with ongoing efforts to improve diagnosis, treatment, and quality of life for affected individuals. What are some promising areas of research in acromegaly?
- Development of new, more effective medications with fewer side effects
- Improved surgical techniques for tumor removal
- Gene therapy approaches to target the underlying causes of pituitary tumors
- Enhanced imaging technologies for earlier and more accurate diagnosis
- Studies on the long-term outcomes of various treatment approaches
Clinical trials play a crucial role in advancing our understanding and treatment of acromegaly. Patients interested in participating in research studies should discuss options with their healthcare providers or search for ongoing trials through reputable databases.
Raising Awareness: The Importance of Early Detection
Given the gradual onset of symptoms and the rarity of acromegaly, raising awareness about this condition is crucial for early detection and treatment. How can we improve recognition of acromegaly?
- Educating healthcare providers about the subtle early signs of the disorder
- Promoting public awareness through information campaigns
- Encouraging individuals with persistent changes in hand or foot size to seek medical evaluation
- Supporting patient advocacy groups that provide resources and community for those affected by acromegaly
By increasing awareness and understanding of acromegaly, we can help ensure that individuals receive timely diagnosis and appropriate care, ultimately improving outcomes and quality of life for those affected by this rare but significant endocrine disorder.
Acromegaly, while uncommon, presents a complex set of challenges for both patients and healthcare providers. From its gradual onset and varied symptoms to the potential for serious complications if left untreated, this condition requires vigilance, comprehensive care, and ongoing management. With advances in treatment options and a growing understanding of the disorder, individuals with acromegaly have more resources than ever to effectively manage their condition and lead healthy, fulfilling lives. As research continues and awareness grows, we can hope for even better outcomes and support for those affected by this unique endocrine disorder.
Acromegaly – NIDDK
On this page:
- What is acromegaly?
- How common is acromegaly?
- Who is more likely to develop acromegaly?
- What are the complications of acromegaly?
- What are the symptoms of acromegaly?
- What causes acromegaly?
- How do doctors diagnose acromegaly?
- How do doctors treat acromegaly?
- Clinical Trials for Acromegaly
What is acromegaly?
Acromegaly is a disorder that occurs when your body makes too much growth hormone (GH). Produced mainly in the pituitary gland, GH controls the physical growth of the body. In adults, too much of this hormone causes bones, cartilage, body organs, and other tissues to increase in size. Common changes in appearance include enlarged or swollen nose, ears, hands, and feet.
The pituitary gland sits at the base of the brain.
How common is acromegaly?
Acromegaly is rare. Scientists estimate that about 3 to 14 of every 100,000 people have been diagnosed as having acromegaly. 1
Who is more likely to develop acromegaly?
Acromegaly is most often diagnosed in middle-aged adults, but symptoms can appear at any age. In children, too much growth hormone causes a condition called gigantism rather than acromegaly. Gigantism occurs when excess GH begins before the end of puberty, when children’s growth plates fuse or close. Having too much GH before the growth plates close causes children to grow tall in height.
What are the complications of acromegaly?
Acromegaly is treatable in most people. But because symptoms come on slowly, health problems can develop before the disorder is diagnosed and treated.
Health problems can include
- type 2 diabetes
- high blood pressure
- heart disease
- sleep apnea
- arthritis
- carpal tunnel syndrome
- other conditions affecting the bones and muscles
People with acromegaly also have an increased risk for colon polyps, which may develop into colon cancer if not removed.
Some people with acromegaly may have a genetic condition that can lead tumors to develop in different parts of their bodies. Increased GH can cause these other tumors to grow.
Untreated, acromegaly can lead to serious health problems and early death. But when successfully treated, symptoms generally improve and may go away altogether. Life expectancy may return to normal.2
What are the symptoms of acromegaly?
Symptoms of acromegaly can vary from person to person. Common changes in physical appearance include
- hands and feet become larger and swollen—you may notice a change in ring or shoe size, especially shoe width
- lips, nose, and tongue become larger
- bone changes: brow and lower jaw jut out, bridge of the nose gets bigger, and space between teeth increases
- skin becomes thick, coarse, and oily
- sweating and skin odor increase
- voice becomes deeper
- skin tags—small, usually flesh-colored growths of skin that have a raised surface—may get larger or darker
Other common symptoms include
- headaches
- joint aches
- vision problems
What causes acromegaly?
Acromegaly develops when the pituitary gland releases too much GH into the body over a long period of time. When GH enters the blood, this signals the liver to produce another hormone, called insulin-like growth factor I (IGF-I). IGF-I is the hormone that actually causes bones and body tissue to grow. High levels of this hormone also cause changes in how the body processes blood glucose (blood sugar) and lipids (fats), which can lead to type 2 diabetes, high blood pressure, and heart disease.
In more than 9 out of 10 cases, acromegaly is caused by a tumor in the pituitary gland, called a pituitary adenoma.3 More rarely, the cause may be a tumor in another part of the body.
Although scientists don’t know what causes these tumors to develop, genetic factors may play a role. In young adults, acromegaly has been linked to defects in certain genes.
Pituitary tumors
Pituitary tumors are almost always benign, or noncancerous. Some tumors grow slowly, and symptoms of too much GH may not be noticed for many years. Other tumors may grow rapidly.
Depending on its size and location, the tumor may press against other pituitary tissue. Possible effects include
- changes in menstruation in women
- erectile dysfunction in men
- changes in thyroid hormone, which can affect weight, energy levels, hair, and skin
- decreases in cortisol, which can cause weight loss, dizziness, tiredness, low blood pressure, and nausea
A tumor that grows large in size may also press against nearby parts of the brain. This can lead to other symptoms, such as headaches and vision problems.
Some pituitary tumors that create growth hormone can also increase the levels of other hormones in the body. For example, the tumor may produce prolactin, the hormone that prompts the mammary glands to produce milk. This can lead to breast milk discharge in women.
Nonpituitary tumors
Rarely, acromegaly is caused by tumors located in the hypothalamus—a small area of the brain near the pituitary gland, pancreas, lungs, or other parts of the chest or abdomen. Some of these tumors make growth hormone themselves. But more often, the tumors produce growth hormone-releasing hormone (GHRH), a hormone that signals the pituitary gland to make growth hormone.
How do doctors diagnose acromegaly?
Blood tests
Doctors most often diagnose acromegaly by ordering two blood tests that help determine if your body is making too much GH.
- IGF test. Levels of GH in the blood can change throughout the day. A reliable way to track GH in the body is by measuring the level of IGF-I in the blood. In most cases, a high IGF-I level suggests that you have acromegaly.
- Oral glucose tolerance test. To confirm the diagnosis, your doctor will order an oral glucose tolerance test. For this test, you will drink a sugary liquid. A health professional will then test your blood every half hour for 2 hours to measure growth hormone levels. The sugar in the drink will normally cause GH levels to fall. But if your body is making too much of the hormone, these levels will not go down enough—thereby confirming the diagnosis of acromegaly.
Imaging tests
If the blood tests confirm that your body is making too much GH, your doctor will conduct imaging tests to locate and measure the tumor that may be causing the problem. Two commonly used tests are
- Magnetic resonance imaging. The preferred test for viewing a pituitary tumor is the magnetic resonance imaging (MRI) scan. The MRI scan uses radio waves and magnets to create detailed images of your internal organs and soft tissues without x-rays.
- Computed tomography scan. If an MRI is not a good option for you (for example, if you have a pacemaker or other implant that has metal), your doctor may order a computed tomography (CT) scan instead. The CT scan uses a combination of x-rays and computer technology to create images of your organs and other internal parts of your body.
An MRI can show the location and size of a pituitary tumor.
If the imaging test doesn’t find a pituitary tumor, your doctor will look for nonpituitary tumors as the cause of your high GH levels.
How do doctors treat acromegaly?
Treatment options include surgery, medicines, and radiation therapy. The goals of treatment are to control tumor size, return GH and IGF-I levels back to normal, improve symptoms, and manage related health problems. No single treatment is right for everyone. Your doctor will recommend a treatment plan that works for you, depending on factors such as your age, tumor size, severity of symptoms, GH and IGF-I levels, and health status.
Surgery
Doctors can remove most pituitary tumors using a method called transsphenoidal surgery. The operation is done through the nose and sphenoid sinus, a hollow space in the skull behind the nasal passages and below the brain. Two approaches to this surgery are
- with a microscope—a magnifying tool
- with an endoscope—a thin, lighted tube with a tiny camera
In both approaches, the surgeon uses advanced MRI imaging to scan the area around the tumor before surgery. He or she then makes a small cut inside your nostril to view the area and remove the tumor using tiny, special tools. In microscopic surgery, the surgeon uses a microscope to magnify the area. In endoscopic surgery, an endoscope camera sends images to a television monitor instead. Risks and results are similar for both approaches.3
When the tumor that is creating too much GH is not located in the pituitary gland, other types of surgery are used to remove the tumor. Removing these nonpituitary tumors also lowers GH levels and improves acromegaly symptoms.
Risks. Complications from surgery can include bleeding, cerebrospinal fluid leaks, meningitis, sodium (salt) and water imbalance, and low levels of pituitary hormones.3
Outcomes. The surgery is considered a success if blood levels of GH and IGF-I return to normal after 12 weeks. The cure rate right after surgery is about 85 percent for small tumors and 40 to 50 percent for large tumors. 3
When successful, the surgery relieves pressure on nearby areas of the brain and causes GH levels to drop right away. Soft tissue swelling may get better within a few days but facial changes may take longer to improve.
Surgery is most successful in people with smaller pituitary tumors. Success largely depends on the skill and experience of the surgeon, as well as the location of the tumor. Even experienced surgeons may not be able to remove the tumor if it’s too close to parts of the brain where surgery would be risky. However, surgeons may be able to remove part of the tumor.
Postsurgery treatments. In most cases, levels of GH and IGF-I improve but don’t go back to normal. If levels of these hormones are still too high or begin to rise again, you may need further treatment. Most often, this will involve taking medicines. In some cases, your doctor may recommend a second surgery.
Medicines
Currently, three types of medicines are used to treat acromegaly, but they are not a cure. The medicines may be used alone or in combination with each other.
Somatostatin analogs. The medicines most often used to treat acromegaly are called somatostatin analogs (SSAs). These drugs curb the release of GH and may also reduce the size of the pituitary tumor. Several studies have shown that these drugs are safe and effective for long-term treatment. The medicines are delivered by injection, but scientists are currently studying other options, such as pills.4 The most common side effects of SSAs are cramps, gas, and diarrhea. These effects are usually mild and go away over time. Some people may develop gallstones that usually do not cause symptoms. Hair loss is possible and, in rare cases, permanent. Control of blood sugar usually improves but, rarely, may worsen.
Dopamine agonists. These medicines inhibit GH production and tumor growth, but not as well as SSAs do. Dopamine agonists are most likely to work in people who have mild GH excess and those who have both acromegaly and hyperprolactinemia (too much of the hormone prolactin). The medicines are taken by mouth. Side effects can include nausea, stuffed nose, tiredness, headache, dizziness when standing, nightmares, and mood changes.
Growth hormone-receptor antagonists. Unlike the other two medicines, GH-receptor antagonists do not stop the body from making too much GH. Instead, they block GH from signaling the body to make more IGF-I. The drug is taken in the form of a daily injection under the skin that patients can administer themselves. Side effects can include liver problems.
Radiation therapy
The third treatment option is radiation therapy, which uses high-energy x-rays or particle waves to kill tumor cells. This type of treatment may be recommended if surgery isn’t possible or fails to remove all tumor tissue, and medicines are not an option or working for you.
Stereotactic. The preferred type of radiation therapy is stereotactic radiation therapy, which uses 3-D imaging to precisely aim high doses of radiation to the tumor from various angles. 3 The treatment can sometimes be done in a single session, reducing the risk of damage to nearby tissue. However, a single dose may not work for very large tumors and tumors located close to nerves that affect vision.
Conventional. The second option is conventional radiation therapy, which also targets the tumor with external beams. This type of radiation therapy delivers small doses of radiation in a series of treatments over 4 to 6 weeks.
Radiation therapy uses high-energy rays to destroy tumor cells in the pituitary gland.
As radiation treatment lowers GH and IGF-I levels over time, it may take years for this treatment to noticeably improve acromegaly symptoms. Your doctor is likely to prescribe medicines while you wait for GH and IGF-I levels to go back to normal and for symptoms to improve.
All forms of radiation therapy cause other pituitary hormones to slowly decrease over time. About half of people treated with radiation therapy will need hormone replacement after treatment ends. Radiation can also impair a patient’s fertility.
Vision loss and brain injury are rare complications. Rarely, other types of tumors can develop many years later in areas that were in the path of the radiation beam.
Clinical Trials for Acromegaly
The NIDDK conducts and supports clinical trials in many diseases and conditions, including endocrine diseases. The trials look to find new ways to prevent, detect, or treat disease and improve quality of life.
What are clinical trials for acromegaly?
Clinical trials—and other types of clinical studies—are part of medical research and involve people like you. When you volunteer to take part in a clinical study, you help doctors and researchers learn more about disease and improve health care for people in the future.
Researchers are studying many aspects of acromegaly and gigantism, such as
- use of medicine to treat gigantism in children and adolescents
- genetic factors that may cause pituitary tumors to develop, and how to treat the tumors and related complications in children and adults
Find out if clinical studies are right for you.
What clinical studies for acromegaly are looking for participants?
You can view a filtered list of clinical studies on acromegaly that are open and recruiting at
www.ClinicalTrials.gov. You can expand or narrow the list to include clinical studies from industry, universities, and individuals; however, the NIH does not review these studies and cannot ensure they are safe. Always talk with your health care provider before you participate in a clinical study.
References
Acromegaly | Johns Hopkins Medicine
What is acromegaly?
When your pituitary gland makes too much growth hormone, abnormal growth occurs. This is called acromegaly. The abnormal
growth starts in your hands and feet, as soft tissue begins to swell. This rare disease
affects mostly middle-aged adults. It can lead to severe illness and even death if not
treated.
In children, too much growth
hormone causes a condition called gigantism. This leads to a large increase in
height.
What causes acromegaly?
Acromegaly happens when the
pituitary gland makes too much growth hormone for a long time. Several reasons may cause
this extra amount of hormone to be made. The most common is a noncancer (benign) tumor
in the pituitary gland. Tumors in other parts of the body can also cause acromegaly.
But that is rare.
What are the symptoms of acromegaly?
Each person’s symptoms may vary. They depend on how long you have had
the disease. Symptoms may include:
- Swelling of your hands and feet. You
may find your rings no longer fit and you need to buy larger shoes. - Larger lips, nose, and tongue, as your
bones grow - Larger jaw that sticks out more
(protrudes) - Thicker body hair
- Thicker, darker skin and skin
tags - More sweat and body odor
- Deeper voice
- Larger chest as your ribs get
thicker - Joint pain
- Degenerative arthritis
- Increased size of your heart and other
organs - Strange feelings and weakness in your
arms and legs, including carpal tunnel syndrome - Snoring and breaks in breathing during
sleep (sleep apnea) - Lack of energy (fatigue) and
weakness - Headaches
- Loss of eyesight
- Irregular menstrual cycles
(women) - Breast discharge (women)
- Impotence (men)
- Enlarged thyroid gland
These symptoms may look like other health problems. Always see
your healthcare provider for a diagnosis.
How is acromegaly diagnosed?
Symptoms may not be seen right
away. So acromegaly is often not found until years later. Your healthcare provider will
take your health history and give you a physical exam. In addition, you may need:
- Photos
taken regularly over the years. These are used to see physical changes. - X-rays. These are done to see bone thickening.
- Blood
tests. These are done to check your growth hormone level and levels of other
related hormones. - MRI or
CT scan. These can help find tumors.
How is acromegaly treated?
Treatment will depend on your symptoms, age, and general health. It
will also depend on how severe the condition is.
Treatment of acromegaly depends on
what is causing the disease. The main goal of treatment is to get your growth hormone
levels back to normal.
Most cases are caused by benign
tumors on the pituitary gland. Others are caused by tumors in the pancreas, lungs, or
adrenal glands. Treatment may include:
- Surgery to remove or reduce the size
of a tumor - Radiation therapy
- Shots (injections) of medicines to
block growth hormone
What are the possible complications of acromegaly?
If acromegaly isn’t treated, it can lead to several problems. These may include:
- Heart disease
- Arthritis
- Diabetes and impaired glucose
tolerance - High blood pressure
- Vision problems
The disease also raises your risk for colon polyps. These are small growths on the lining of your colon. They may lead to colorectal cancer.
Living with acromegaly
You should see your healthcare
provider on a regular basis. Your provider can make sure your treatment is working. Your
provider can also check for any problems. Early treatment can then be started if
needed.
When should I call my healthcare provider?
Tell your healthcare provider if your symptoms get worse or you have new symptoms.
Key points about acromegaly
- Acromegaly is a rare disease. It occurs when your pituitary gland makes too much growth hormone for a long time. That causes abnormal growth.
- Acromegaly starts in the hands and feet. It affects mostly middle-aged adults.
- Most people with this condition have a
noncancer (benign) tumor in the pituitary gland. - Symptoms depend on how long you have
had the disease. Symptoms can be missed. So the disease is often not diagnosed until
years later. - If not treated, acromegaly can lead to
heart problems, arthritis, diabetes, vision problems, high blood pressure, or even
death.
Next steps
Tips to help you get the most from a visit to your healthcare provider:
- Know the reason for your visit and what you want to happen.
- Before your visit, write down questions you want answered.
- Bring someone with you to help you ask questions and remember what your provider tells you.
- At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you.
- Know why a new medicine or treatment is prescribed, and how it will help you. Also know what the side effects are.
- Ask if your condition can be treated in other ways.
- Know why a test or procedure is recommended and what the results could mean.
- Know what to expect if you do not take the medicine or have the test or procedure.
- If you have a follow-up appointment, write down the date, time, and purpose for that visit.
- Know how you can contact your provider if you have questions.
Acromegaly
Departments and centers
Methods of treatment
Methods of diagnosis
Diseases and symptoms
Growth hormone is a hormone produced in the pituitary gland. The main function of growth hormone is to stimulate the growth of various body tissues.
The biological effects of the hormone are as follows: stimulation of the linear dimensions of the body, support for the integrity of organ tissues, acceleration of the growth of bones and soft tissues (together with insulin growth factors), regulation of protein secretion, slows down the excretion of sodium and potassium in the urine, regulation of glucose metabolism and fat, increased sweating.
Acromegaly – is an endocrine disease resulting from chronic excess production of growth hormone. It is characterized by excessive disproportionate growth of cartilage, bones and internal organs.
Causes of acromegaly:
- Tumor formation of the pituitary gland excessively producing somatotropic hormone (growth hormone).
- Neuroendocrine tumors outside the pituitary gland (tumor of the mediastinum, lung, pancreas.)
- Malignant tumors of the bronchi, organs of the gastrointestinal tract, pancreas.
- Genetic syndromes (MEN-1 syndrome, McCunean-Albright syndrome, Carney complex)
Pathogenesis of acromegaly: Normally, the pituitary gland produces growth hormone, or somatotropin (GH). This hormone affects the growth zones – epiphyseal plates, areas of growing tissue in tubular bones. As a result, cartilage tissue is gradually replaced by bone and tubular bones are lengthened. In people who do not have these growth zones closed (mostly children), with an excess of growth hormone, an increase in the linear dimensions of the body (height, limb length) is noted. In adults, these growth zones are closed and the clinic changes fundamentally, there is a thickening of the bones, their deformation and an increase in the size of the organs. The appearance of the patient acquires a characteristic appearance.
Growth hormone has a contrainsular effect, which leads to an increase in blood sugar levels, protein synthesis increases, amino acid transport to muscle cells increases, internal organs work more actively and become larger.
Complaints. The first thing that most patients with acromegaly pay attention to is, of course, a change in appearance: there is an increase in the size of the lips, nose, tongue (sometimes it ceases to fit in the mouth, teeth marks appear on the tongue), thickening of the lower jaw, superciliary arches, toes and hands, excessive sweating. There may be complaints associated with the localization of the tumor (with pituitary adenoma (especially if they are large) – this is a headache, dizziness, blurred vision, visual fields may fall out, epilepsy is possible). There is a violation of carbohydrate metabolism (increased blood sugar), blood pressure usually also rises. In women, there is a violation of the ovarian-menstrual cycle, a decrease in libido. Men have erectile dysfunction.
As the disease progresses, symptoms progress. Changes in appearance are increasing, damage to internal organs (heart failure, poorly controlled arterial hypertension, which often causes vascular catastrophes (heart attacks, strokes), complications of diabetes mellitus) join this, a clinic of damage to the musculoskeletal system appears.
Examination for acromegaly: diagnosis of acromegaly confirmed by investigations:
- Investigation of somatotropic hormone and insulin-like growth factor-1,
- Study of prolactin, ACTH, cortisol, TSH, ST4, FSH, LH.
- In doubtful cases and when monitoring the activity of somatotropinoma after treatment, an oral glucose tolerance test (OGTT) is performed – normally, after taking glucose, suppression of GH secretion is noted, with acromegaly, GH does not decrease below 1 ng / ml.
- An MRI of the pituitary gland is done to visualize the tumor.
- Determination of visual fields, examination of the fundus, to assess the damage to the visual apparatus.
- If necessary, an additional examination is carried out for suspected GH-secreting tumors that are located outside the pituitary gland.
(PET CT, colonoscopy, CT of the chest, fibrobronchoscopy, examination of the intestines)
If a carcinoid origin of growth hormone excess is suspected, an oncologist joins the additional examination and treatment.
Treatment of acromegaly
The main treatment is surgery and radiotherapy.
Conservative therapy is carried out as a preoperative preparation, in the postoperative period and when it is impossible to carry out a radical treatment of the tumor. Somatostatin analogues (Octreotide, Lanreotide) are used. In addition to them, dopamine agonists (cabergoline, bromocriptine) can be prescribed. Drugs are often prescribed for a long period (5-7 years or more). The drugs can be canceled with stable normalization of the level of somatotropic hormone and insulin-like growth factor -1, after a negative oral glucose tolerance test.
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Attention, Acromegaly! — “InfoMedPharmDialogue”
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Attention, Acromegaly!Nataliya2021-12-14T10:40:35+03:00
ATTENTION, Acromegaly!
Dear friends!
InfoMedPharm Dialog and pharmaceutical company Pfizer present a joint project dedicated to modern diagnostic and treatment options for acromegaly.
Acromegaly is a rare neuroendocrine disease. Late diagnosis and lack of adequate therapy lead to a significant loss in the quality of life and a decrease in the life expectancy of patients. People with acromegaly die three times more often and live 6-8 years less than the average inhabitant of the Earth. With acromegaly, cardiovascular risks increase significantly (3-4 times), the most common cause of death in patients is cardiovascular events and disorders in the respiratory system. According to expert estimates, in Russia the average time to diagnosis is 8.7 years, and sometimes a patient waits for a diagnosis for more than 10 years.
Such a prolonged progression of the disease without proper treatment triggers irreversible processes, increasing the risk of death.*
It is with the aim of preventing the development of serious complications of acromegaly, early verification of the diagnosis and timely initiation of treatment that the project “Attention, Acromegaly!” was conceived and implemented. As part of the project, we share with you information about the features of the diagnosis and treatment of acromegaly. How to suspect a disease? What examinations should the patient be sent to? How to confirm the diagnosis? What are the current treatment options for acromegaly? On the project page you will find answers to all these questions.
*According to A.V. Andreeva, head of the endocrinology department GBUZ "GKB im. V.V. Veresaeva DZM. The data is given in the article "Overcoming clinical inertia" (Paradigm. Special issue: endocrinology, 04.2021, https://imfd.ru/2021/05/17/rpeodaklininertno/)
SYMPTOMS OF ACROMEGALIA
WORRY*
90 143
Drowsiness
51% of patients
SHIPPING
80% of patients patients
NIGHT APNEA
APPEARANCE CHANGED*
- 9 0002 frontal prominence
-
increased interdental spaces
-
protruding lower jaw
-
malocclusion
-
hand and foot augmentation
9019 2
joint pain (70% of patients)
arthritis
joint stiffness
carpal tunnel syndrome (30-50% of patients)
Symptoms *
Cardiovascular diseases
-
difficult to treat hypertension 9000 9000
-
Biventricular hypertrophy
-
Diastolic or systolic dysfunction
Diabetes mellitus
Infertility
Gastrointestinal tumors
*Chanson P, Salenave S. Orphanet J Rare Dis 2008;3:1–17; Katznelson L, et al. J Clin Endocrinol Metab 2014;99:3933–3395; Lugo G, et al. Int J Endocrinol 2012;2012:540398; Katznelson L, et al. Endocr Pract 2011;17(suppl 4).
PP-SOM-RUS-0045 24.06.2021
KEY GOAL OF TREATMENT
Normalization of IGF-1 levels is a key goal in the treatment of acromegaly, along with control of hormone-producing tumor * 9001 2
HOW TO CONTROL IGF-1 AFFECTS MORTALITY IN Acromegaly?
Controlling IGF-1 can potentially reduce the risk of death, which is increased by 3.5 times in acromegaly 1
Effective treatment reduces the risk of death associated with active acromegaly 2
- p<0.001, based on Holdaway, et al 2004. H/A ratio: ratio of observed to expected mortality
- Esposito D et al. Decreasing mortality and changes in treatment patterns in patients with acromegaly from a nationwide study. Eur J Endocrinol 2018;178(5):459–69.
*Melmed S, Bronstein MD, Chanson P, et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552-561
PP-SOM-RUS-0048 29.09.2021
Acromegaly and carbohydrate metabolism disorders
About 54% of patients with acromegaly suffer from carbohydrate metabolism disorders, and one in four is diagnosed with diabetes! 1
Carbohydrate metabolism disorders in acromegaly are based on changes in the central regulation of insulin and glucagon secretion in combination with impaired protein transport of glucose at the post-receptor level, as well as impaired formation of biologically active forms of insulin 1 .
An endocrinologist should suspect acromegaly if a patient has two or more of the following clinical manifestations: 2
-
0012
-
Generalized arthralgias
-
Increased fatigue
-
Headaches
-
Carpal tunnel syndrome
-
Sleep apnea syndrome
-
9 0011 Excessive sweating
-
Daytime sleepiness
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Newly diagnosed or difficult to treat hypertension
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Biventricular hypertrophy, diastolic or systolic dysfunction
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Narrowing of visual fields
-
Colon polyps 4
Progression of malocclusion
1. Acromegaly: clinical picture, diagnosis and treatment (textbook) . M. FSBI “NMITs of Endocrinology of the Ministry of Health of Russia, 2020. – 29 p. A38.
TEAM OF AUTHOR Ph.D. Knyazeva O.V., MD Pigarova E.A., MD Dzeranova L.K., Vorotnikova S.Yu.
2. Federal Clinical Guidelines. Acromegaly: CLINIC, DIAGNOSIS, DIFFERENTIAL DIAGNOSIS, TREATMENT METHODS Moscow 2014 rec_acromegalia_2014.pdf (endocrincentr.ru)
PP-SOM-RUS-0049 10/29/2021
DIFFICULTLY CONTROLLED BP AS A SYMPTOM OF Acromegaly
CARDIOVASCULAR ALTERATIONS ARE SIGNIFICANT COMPLICATIONS OF Acromegaly 1
25-50% of patients with acromegaly have arterial hypertension – 3-4 times more often than in the general population
Enlargement of the heart and the development of heart failure are characteristic
Cardiomegaly is one of the manifestations of splanchnomegaly. The mass of the myocardium is directly proportional to the duration of the disease and can reach 1300 g. 0002 More than 88% of patients, regardless of age, have diffuse changes in the myocardium, circulatory disorders, cardiac arrhythmias up to complete AV blockade
Gradually progressing, myocardial dystrophy leads to the development of heart failure and is often the cause of death CARDIOVASCULAR DISEASE 2
Cardiovascular disease (CVD) is still a common cause of death in patients with acromegaly
In patients with well-controlled acromegaly, CVD rates are now very similar to those in the aging population without acromegaly blood and cause arterial hypertension. Treatment of arterial hypertension in acromegaly should be carried out in accordance with recommendations for the general population
Arterial hypertension (AH) is a major factor in mortality from complications of cardiovascular diseases in acromegaly, while recent publications indicate a positive effect of effective drug treatment
60%, with significantly higher rates observed among patients who have not achieved biochemical control of acromegaly
Echocardiography should be performed prior to initiation of treatment given the possibility of asymptomatic cardiomyopathy
Biochemical control of acromegaly with pegvisomant* reduces the rate of progression of left ventricular hypertrophy and improves other markers of structural heart dysfunction, including ejection fraction left ventricle
1. Acromegaly: clinical picture, diagnosis and treatment (textbook). M. FGBU “NMITs Endocrinology” of the Ministry of Health of Russia, 2020. -29With.
2. Giustina. Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update JCEM-2019
011 THERAPY APPROACHES Acromegaly
Surgical resection of the pituitary tumor
is traditionally the main treatment for most patients with acromegaly 1
If surgery is not possible, the patient may receive medical treatment with or without radiotherapy 1
Medical therapy
is recommended for patients with persistent disease despite surgical resection of the adenoma, and for patients in whom surgical treatment is not suitable 9032 8 1.2
Somatostatin analogues : block related receptors in adenoma and suppress growth hormone secretion 2
Dopamine agonists : inhibit prolactin secretion and stimulate dopamine receptors 3
Growth hormone receptor antagonists peripherals and IGF-I production** 2
Radiation therapy
is usually used as an adjuvant treatment in patients with active disease despite surgery and medical treatment, or in patients who prefer radiotherapy given the cost of long-term treatment 1. 2
Can be used to control excess growth hormone secretion or tumor enlargement (or both) 1
Two main types are used 1 :
– standard fractionated radiotherapy 9 0003
– stereotactic radiosurgery
*GH = growth hormone
**IGF-I = insulin-like growth factor I
1. Katznelson L, et al. Endocr Practice. 2011;17(suppl 4):1-44.
2. Melmed S, et al. Nat Rev Endocrinol 2018;14:552–561.
3. Instructions for use of Bromocriptine P N011972/01 02/18/2021
PP-SOM-RUS-0050 11/01/2021
Somatostatin analogues (octreotide or lanreotide). The Pituitary Research Society’s updated international clinical guidelines for the treatment of acromegaly do not separate first-generation somatostatin analogs within the group and there is no mention of switching first-generation somatostatin analogs within the group if the target level of IGF-1 is not achieved 1 .
A meta-analysis of 44 studies found no benefit between long-acting formulations of octreotide and lanreotide in biochemical control, but tumor reductions greater than 10% were more frequently achieved with octreotide than with lanreotide 2 .
Complete normalization of GH and IGF-1 levels is achieved in 30% of patients who did not undergo surgical treatment, and in 50% after surgical treatment, which did not allow achieving biochemical remission 3 , which is due to the variability of somatostatin receptors in various pathomorphological variants of somatotropin. 4
If biochemical control is not achieved after 3 months of use of somatostatin analogues, it is recommended to increase the dose of the selected somatostatin analogue or shorten the intervals between injections (in the case of lanreotide). If biochemical control is not achieved after 6 months of therapy with somatostatin analogs, second-line therapy is recommended 3 .
An increasing number of publications are now arguing in favor of earlier prescribing of pegvisomant* and deeming it necessary to shift the paradigm towards early prescribing of pegvisomant* as it is safer and more effective than first and second generation somatostatin analogues 5 .
Growth hormone antagonist pegvisomant* is indicated as second-line drug therapy. With proper dose selection, the drug allows you to achieve target levels of IGF-1 in more than 90% of cases 6 . Pegvisomant has a positive effect on glucose metabolism, namely, it reduces the level of HbA1c, insulin concentration and insulin resistance, which is important for patients with acromegaly and diabetes mellitus.
1. M. Fleseriu; B. M. K. Biller; P.U. Freda; Monica R. Gadelha; Andrea Giustina; L.Katznelson; M.E. Molitch; S. L. Samson; C. J. Strasburger; A. J. van der Lely; S. Melmed; A Pituitary Society update to acromegaly management guidelines. Pituitary (2021) 24:1–13
2 Freda et al. J Clin Endocrinol Metab, August 2005, 90(8):4465–4473
3. O. V. Knyazeva, E. A. Pigarova, L. K. Dzeranova, S. Yu. Acromegaly: clinical picture, diagnosis and treatment (textbook). M. Federal State Budgetary Institution “NMIC of Endocrinology” of the Ministry of Health of Russia, 2021. -32p.
4. Pronin V.S., Pronin E.V. New opportunities for secondary drug therapy of acromegaly. Medical advice. 2020;(7):137–144. doi: 10.21518/2079-701X-2020-7-137-144
5. Aart J van der Lely et al; European Journal of Endocrinology (2020) 182, D17–D29
6. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Van der Lely AJ, et al. Lancet 2001;358:1754-59
* You can read the full version of the instructions for Somavert® (pegvisomant) here
PP-SOM-RUS-0052 RATE OF PROGRESSION OF PITUITARY TUMOR AND METHODS OF TREATMENT OF Acromegaly
Treatment of acromegaly is aimed at removing somatotropinoma, as a source of excess production of growth hormone (GH), at reducing the symptoms of the disease and normalizing the level of insulin-like growth factor type 1 (IGF-1).
For this, three main methods are used: surgical, medical and radiation 1 .
According to the literature, it has been shown that an increase in a tumor resistant to treatment occurs in an extremely small number of patients, regardless of the type of therapy 2 .
TUMOR GROWTH RATE WITH PEGWISOMANT MONOTHERAPY* CORRECTS WITH CHANGES IN TUMOR SIZE OBSERVED WITH OTHER DRUG THERAPY 3.4 .
“It is clear that long-term treatment with pegvisomant* is not associated with tumor growth. Drug treatment should be individualized taking into account the size of the tumor, especially its proximity to the optic chiasm, the presence of comorbidities, glucose tolerance, headache, and patient comfort” 5 .
“PEGVISOMANT* REMAINS THE MOST EFFECTIVE TREATMENT OF ACROMEGALIA TODAY” 6 .
1. Knyazeva O.V., Pigarova E.A., Dzeranova L.K., Vorotnikova S.Yu., Molitvoslovova N.N. Acromegaly: clinical picture, diagnosis and treatment (textbook). M. FGBU “NMITs Endocrinology” of the Ministry of Health of Russia, 2021.-32s
2. Besser G M et al. Predictors and rates of treatment-resistant tumor growth in acromegaly. Eur J Endocrinol 2005;153:187–93
3. Freda et al. ENDOCRINE PRACTICE Vol 21 No. 3 March 2015
4.Freda et al. J Clin Endocrinol Metab, August 2005, 90(8):4465–4473
Arch Endocrinol Metab. 2019;63/6
6. Sebastian J. Neggers et Aart J. van der Lely; Pegvisomant for acromegaly: does it always work? Arch Endocrinol Metab. 2019;63/4
* You can read the full version of the instructions for Somavert® (pegvisomant) here
PP-SOM-RUS-0057 11/19/2021
UPDATES TO THE PITUITARY RESEARCH SOCIETY CLINICAL RECOMMENDATIONS FOR THE TREATMENT OF Acromegaly 2021 90 328 1
IN THE SECTION ON SURGICAL TREATMENT OF ACROMEGALIA
When to evaluate remission after surgery treatment:
- Insulin-like growth factor-1 (IGF-1) level 6 weeks after surgery can be used to assess remission in most patients, but in patients with a slight increase in IGF-1 level, the level may normalize to 3–6 month 1
IN THE SECTION ON LONG-ACTING SOMATOSTATIN ANALOGUES (ACS) tomography (MRI) in T2 mode initially, are favorable predictors of long-term biochemical response to initial treatment with lanreotide 120 mg every 4 weeks 1 IN THE SECTION ON GROWTH HORMONE RECEPTOR BLOCKING DRUGS (PEGVISOMANT*) 1. In the ACROSTUDY study, continued (>10 years) follow-up of pegvisomant* showed that biochemical control was achieved in 73% of patients with a very low incidence of transient transaminase elevations, and 6.8%** of patients had an increase MRI tumor size1 ** 16.8% had a decrease in tumor size, 6.8% had an increase, and 4.3% had both an increase and a decrease. Only in 1% of patients, that is, in 21 out of 2025 patients studied over 12 years of observation , an increase in tumor size was interpreted as an adverse event associated with the use of pegvisomant 2 2. Pegvisomant* in patients with diabetes mellitus (DM) improves glucose metabolism independent of IGF-1 control but does not affect glycemic control endpoints in non-DM1 patients 3. Patients with diabetes and patients with higher body mass index (BMI) require higher doses of pegvisomant* to normalize IGF-11 levels AcroQoL (Acromegaly Quality of Life Questionnaire) and PASQ (Acromegaly Symptoms Questionnaire)1 1. M. Fleseriu; B. M. K. Biller; P.U. Freda; Monica R. Gadelha; Andrea Giustina; L.Katznelson; M.E. Molitch; S. L. Samson; C. J. Strasburger; A. J. van der Lely; S. Melmed; A Pituitary Society update to acromegaly management guidelines. Pituitary (2021) 24:1–13 * You can read the full version of the instructions for Somavert® (pegvisomant) here PP-SOM-RUS-0058 NOGO ACTION (ACC) – OCTREOTIDE AND LANREOTIDE AND WAYS TO OVERCOME IT
2. Buchfelder M., van der Lely A. J., Biller B.M.K., Webb S., Brue T., Strasburger C.J. et al. Long-term Treatment With Pegvisomant: Observations From 2090 Acromegaly Patients in ACROSTUDY. Eur J Endocrinol. 2018;179(6):419-427.
Randomized prospective studies in patients not previously treated with somatostatin analogues have shown that ASS therapy was effective in no more than 30% – 45% of cases 1
Criteria for resistance to therapy with somatostatin analogs 2
8 3
There are several ways to improve the effectiveness of therapy with first-generation somatostatin analogues in patients with partial resistance to them (i.e. e. a decrease in GH and IGF-1 during treatment by more than 50% of the initial level without reaching the norm).
Thus, surgical removal of a large part of the tumor (debulking) significantly increases the effectiveness of drug therapy.
On the other hand, increasing the dose of extended-release octreotide or shortening the interval between injections of long-acting lanreotide may also help achieve disease remission.
Treatment with a growth hormone receptor antagonist (pegvisomant) as monotherapy is indicated in patients who are completely resistant to treatment with conventional somatostatin analogues.
1. Paragliola RM et al. Somatostatin receptor ligands in acromegaly: clinical response and factors predicting resistance Pituitary. 2017 Feb;20(1):109-115
2. Giustina, A. et al. Pegvisomant in acromegaly: an update. J Endocrinol Invest. 2017; 40(6): 577–589
3. Knyazeva O.V., Pigarova E.A., Dzeranova L.K., Vorotnikova S.Yu., Molitvoslovova N.N. Acromegaly: clinical picture, diagnosis and treatment
(textbook). M. Federal State Budgetary Institution “NMITs Endocrinology” of the Ministry of Health of Russia, 2021.