Acromegaly

Overview

Acromegaly is a rare hormonal disorder that results from the body producing excess growth hormone. This condition usually originates from a benign tumor in the pituitary gland (a small hormone gland at the base of the brain). Excess growth hormone leads to abnormal growth of bones and soft tissues.

The word "acromegaly" comes from the Greek words "akron" (extremities) and "megalos" (large). This name derives from the disease causing noticeable enlargement in the hands, feet, and face. The disease progresses slowly and symptoms develop so gradually that most people do not notice for years. The change becomes more apparent when family members or old photographs are compared.

Acromegaly develops in adulthood. Excess growth hormone secretion begins after the growth plates have closed. If the same condition occurs during childhood or adolescence, before the growth plates close, this is called "gigantism" and the person becomes abnormally tall. In acromegaly, however, there is no height increase but instead bones thicken and widen.

If left untreated, acromegaly can lead to serious health problems and premature death. Heart disease, diabetes, high blood pressure, joint problems, and other complications can develop. However, with early diagnosis and appropriate treatment, growth hormone levels can be brought to normal and complications can be prevented or controlled.

Acromegaly is quite a rare disease. Approximately 3-4 new cases are seen per million people. The disease is generally diagnosed in middle-aged adults (ages 40-50) but symptom onset dates back years earlier. It occurs with equal frequency in men and women.

Symptoms

Acromegaly symptoms develop very slowly. They generally emerge gradually over 10-15 years. This is why the disease is usually diagnosed late. Symptoms progress so slowly that both the patient and relatives may not notice the change for a long time.

Acromegaly symptoms include the following:

• Enlargement of hands and feet. This is the most common and most obvious symptom. Hands and feet thicken and widen. Ring, bracelet, or shoe size changes. Rings previously worn no longer fit on the finger. Shoe size increases by one or two sizes.
• Change in facial features. Facial bones thicken and features coarsen. The lower jaw protrudes forward and enlarges (prognathism). Forehead bones become prominent and eyebrows become protruding. The nose enlarges and flesh thickens. The tongue enlarges. Gaps form between teeth. When compared with old photographs, the face is seen to have changed noticeably.
• Voice deepening. When the larynx and vocal cords enlarge, the voice deepens and becomes hoarse. This change is more noticeable especially in women.
• Skin thickening and oiliness. The skin thickens and takes on an oily and porous structure. Sweating increases and excessive body odor may develop. Dark-colored and velvety thickenings (acanthosis nigricans) may be seen on the skin.
• Joint pain. Abnormal growth of bones and cartilage leads to pain, stiffness, and limited movement in the joints. Arthritis can develop. Especially the knees, hips, and spine are affected.
• Muscle weakness and fatigue. A general weakness, energy loss, and muscle frailty is felt. Even daily activities become tiring.
• Headache. As the pituitary tumor grows, it presses on surrounding tissues and causes chronic headache. Headache is generally felt in the front part of the forehead or behind the temples.
• Vision problems. The pituitary gland is located very close to the optic nerves. When the tumor grows, it can press on these nerves, causing narrowing in the visual field (especially peripheral vision), double vision, or decreased visual acuity.
• Sleep apnea. Due to soft tissue enlargement and tongue enlargement, breathing cessations develop during sleep. Snoring, nighttime choking sensation, and excessive daytime sleepiness are observed.
• Menstrual irregularities in women. The menstrual cycle may be disrupted or stop completely. Milk discharge from the nipples (galactorrhea) may occur. Fertility can be affected.
• Sexual dysfunction in men. Erectile dysfunction (erection problem), loss of libido, and fertility problems may be seen.
• Rise in blood pressure. High blood pressure is a frequently seen complication of acromegaly.
• Rise in blood sugar. Growth hormone leads to insulin resistance and the risk of developing diabetes increases.

When to See a Doctor

Because acromegaly is a slowly progressive disease, symptoms can be ignored for a long time. However, early diagnosis is very important to prevent complications.

See a doctor in the following situations:

• If you have noticed noticeable changes in your hands, feet, or facial features
• If your ring, bracelet, or shoe size is continuously increasing
• If your facial features have changed noticeably when you compare with old photographs
• If you have persistent headache
• If you are experiencing vision problems (especially loss of peripheral vision)
• If you have joint pain and limited movement
• If there is excessive sweating and skin thickening
• If sleep apnea symptoms are seen
• If there are menstrual irregularities in women or sexual dysfunction in men

Acromegaly is usually diagnosed late because changes occur so slowly they become normalized. Your relatives or doctor may draw attention to physical changes. Taking these warnings seriously is important.

Causes

The cause of acromegaly is the body producing excessive amounts of growth hormone. Growth hormone (GH) is secreted by the pituitary gland and controls bone, muscle, and organ growth. Conditions leading to excess growth hormone production are as follows:

• Pituitary adenoma (pituitary tumor). This is the cause of more than 95 percent of acromegaly cases. A benign tumor develops in the pituitary gland and this tumor secretes growth hormone in an uncontrolled manner. The tumor grows slowly and is not noticed for years. As the tumor grows, symptoms appear both due to excess hormone production and pressure on surrounding tissues. These tumors do not turn into cancer but lead to serious health problems if left untreated.
• Extra-pituitary tumors. Very rarely, tumors in the lung, pancreas, or adrenal glands can produce growth hormone or growth hormone-releasing hormone (GHRH). This is called "ectopic" hormone production.
• Familial causes. Most cases of acromegaly are sporadic (random). However, in very rare cases there is genetic predisposition. Hereditary syndromes such as multiple endocrine neoplasia type 1 (MEN1), Carney complex, or familial acromegaly increase acromegaly risk. In these cases, similar hormonal disorders may also be seen in family members.

Why the pituitary tumor develops is not fully known in most cases. Genetic factors, radiation exposure, or other environmental factors may play a role but the exact cause is usually unclear.

Risk Factors

Risk factors for acromegaly are as follows:

• Middle age. Although the disease can be seen at any age, it is most commonly diagnosed between ages 40-50. However, symptoms usually began years earlier.
• Genetic syndromes. Rare genetic conditions such as multiple endocrine neoplasia type 1 (MEN1), Carney complex, McCune-Albright syndrome, or familial isolated pituitary adenoma (FIPA) increase risk.
• Family history of pituitary tumor. If there is a pituitary tumor in first-degree relatives, risk increases slightly. However, the vast majority of acromegaly cases are non-familial (sporadic).

There are no known modifiable risk factors for acromegaly. The contribution of lifestyle, diet, or environmental factors to disease development has not been clearly demonstrated.

Diagnosis

Acromegaly is diagnosed with clinical examination, hormone tests, and imaging methods. Early diagnosis is important to prevent complications and increase the chance of treatment success.

The methods used in acromegaly diagnosis are as follows:

• Physical examination and medical history. The doctor examines physical characteristics. Changes in hands, feet, and facial features are evaluated. Old photographs are requested and changes over time are compared. When symptoms started, how they progressed, and family history are queried.
• Growth hormone (GH) and IGF-1 measurement. Hormone levels are measured with blood tests. Growth hormone fluctuates throughout the day, so a single measurement can be misleading. Insulin-like growth factor-1 (IGF-1) is produced in the liver under the influence of growth hormone and its levels are more stable. High IGF-1 level is a strong indicator for acromegaly.
• Glucose suppression test. This is the most reliable diagnostic test. The patient is given a sugary drink and growth hormone levels are measured over several hours. In normal people, when blood sugar rises, growth hormone is suppressed and decreases. In acromegaly, however, growth hormone does not decrease or may even increase.
• Pituitary MRI (magnetic resonance imaging). When acromegaly is diagnosed, MRI is taken to search for a tumor in the pituitary gland. This imaging shows the presence, size, and relationship with surrounding structures of the tumor. In most cases, a macroadenoma (tumor larger than 1 cm) is found.
• Visual field testing. If the tumor is pressing on the optic nerves, there may be losses in the visual field. Ophthalmology examination and perimetry (visual field testing) are performed.
• Measurement of other pituitary hormones. The pituitary gland secretes multiple hormones. The tumor can also affect other hormone levels. Thyroid hormone (TSH), cortisol (ACTH), prolactin, sex hormones (LH, FSH, testosterone, or estrogen) are measured.
• Cardiac, metabolic, and other screening tests. To evaluate complications of acromegaly, echocardiography (heart ultrasound), blood sugar tests, colonoscopy (because colon cancer risk is increased), and polysomnography for sleep apnea may be performed.

Treatment

The goals of acromegaly treatment are to normalize growth hormone and IGF-1 levels, shrink or eliminate the tumor, relieve symptoms, and prevent complications. Treatment usually includes more than one method.

The methods used in acromegaly treatment are as follows:

Surgical treatment (transsphenoidal surgery). This is the first choice treatment in most patients. The pituitary tumor is removed surgically. The procedure is done through the nose or under the upper lip and the skull is not opened. The surgeon uses a thin tube (endoscope) to reach and remove the tumor.

Surgery generally takes 2-3 hours and requires a few days of hospital stay. In small tumors (microadenomas), the success rate is 80-90 percent. In large tumors, the success rate is lower. After surgery, growth hormone levels drop rapidly and return to normal in many patients.

Medication treatment. Used in patients who cannot have surgery, in whom hormone levels do not return to normal after surgery, or who do not want surgery.

There are three main drug groups.

• Somatostatin analogs (octreotide, lanreotide, pasireotide) reduce growth hormone secretion and can shrink the tumor. They are administered as injections once a month or every 4-6 weeks.
• Dopamine agonists (cabergoline, bromocriptine) reduce growth hormone in some patients and are generally preferred if prolactin is also high. Taken as a daily tablet.
• Growth hormone receptor blockers (pegvisomant) block the effect of growth hormone in the body. They very effectively lower IGF-1 levels but do not shrink tumor size. Administered as a daily injection.

Radiotherapy. Used in cases that do not respond to surgery and medication or when the tumor cannot be completely removed. Conventional radiotherapy lasts several weeks with small daily doses of radiation. Stereotactic radiosurgery (Gamma Knife or CyberKnife) delivers a high dose of focused radiation in a single session.

The effect of radiotherapy is slow. It may take years for hormone levels to return to normal. After radiotherapy, the pituitary gland's other hormone production may also decrease and lifelong hormone replacement therapy may be needed.

Combined treatment. In many patients, the best result is obtained with a combination of different treatment methods. For example, medication or radiotherapy may be added for tumor remaining after surgery.

Treatment response is monitored with regular blood tests (GH and IGF-1 levels) and MRI imaging. The goal is to bring GH level below 1 ng/mL and IGF-1 into the normal range for age.

Complications

If acromegaly is left untreated or diagnosed late, it can lead to serious complications. These complications reduce quality of life and can shorten lifespan.

Complications that may be seen in acromegaly are as follows:

• Heart disease. This is the most important and most commonly seen complication. The heart muscle enlarges (cardiomegaly) and thickens. Risk of heart failure, heart valve problems, rhythm disorders (arrhythmia), and coronary artery disease increases. Acromegaly patients have a 2-3 times higher risk of dying from heart disease compared to the normal population.
• High blood pressure (hypertension). Seen in approximately one-third of patients. High blood pressure further increases the risk of heart and vascular disease.
• Type 2 diabetes. Growth hormone leads to insulin resistance. Diabetes develops in approximately 20-30 percent of patients. High blood sugar increases complication risk.
• Joint damage (arthropathy). Bone and cartilage growth leads to permanent damage in joints. Especially the knees, hips, spine, and hand joints are affected. Chronic pain, limited movement, and deformity develop. In advanced cases, joint prosthesis may be needed.
• Sleep apnea. Seen in approximately 60-70 percent of patients. Soft tissue growth narrows the upper airway. If sleep apnea is not treated, it increases heart disease risk and reduces quality of life.
• Colon polyps and colon cancer. Acromegaly increases the risk of colon polyps and cancer. Regular colonoscopy screening is recommended from the time of diagnosis.
• Vision loss. If the tumor presses on the optic nerves, permanent vision loss can develop. With early treatment, vision generally improves or is preserved.
• Hypopituitarism. Due to the tumor or treatment (surgery, radiotherapy), the pituitary gland's other hormones may also decrease. Thyroid hormone, cortisol, sex hormone deficiency can develop. Lifelong hormone replacement therapy is required.
• Carpal tunnel syndrome. Due to nerve compression at the wrist, numbness, tingling, and pain occur in the hand and fingers.
• Thyroid nodules and goiter. The thyroid gland can enlarge and nodules can form.

With early diagnosis and treatment, many of these complications can be prevented or reversed. Some changes such as heart and joint damage may not completely improve after treatment.

Living with Acromegaly

Receiving an acromegaly diagnosis is a difficult experience but with appropriate treatment and follow-up, many patients can lead a normal or near-normal life. The basic principles of living with the disease are regular follow-up, adherence to treatment, and healthy lifestyle.

Continuing Treatment Regularly

If you are taking medication, it is very important to use it regularly without skipping doses. Do not miss your appointments for injections such as somatostatin analogs. If you feel medication side effects, do not stop on your own but consult your doctor.

The recovery process after surgery may take several weeks. Follow the restrictions your doctor recommends. Avoid heavy lifting and pay attention to warning signs such as nosebleeds or headache.

Regular Follow-up and Tests

Lifelong regular follow-up is required after treatment. Go for checkups more frequently in the first year (every 3-6 months), then once or twice a year afterward. During follow-ups, growth hormone and IGF-1 levels are measured, MRI imaging is performed, and complications are evaluated.

Monitor your heart health. Echocardiography, EKG, and blood pressure measurement should be done regularly. Get blood sugar and HbA1c tests for diabetes screening. Colonoscopy colon cancer screening should begin from diagnosis and be repeated regularly.

If you have sleep apnea, get it treated. CPAP (continuous positive airway pressure) device use increases sleep quality and protects heart health.

Physical Activity and Joint Health

Avoiding movement due to joint pain increases joint stiffness. Low-impact exercises (swimming, cycling, walking) preserve joint flexibility and increase muscle strength. You can work with a physiotherapist to create an appropriate exercise program.

If overweight, losing weight reduces the load on joints. Healthy eating and regular exercise help with both weight control and reducing diabetes and heart disease risk.

Emotional and Psychological Support

Physical changes can affect self-image and self-confidence. Especially changes in facial features can lead to social anxiety. Share your feelings with loved ones. If necessary, seek support from a psychologist or psychiatrist.

Joining acromegaly support groups can be very valuable. Connecting with people who have had similar experiences makes you feel you are not alone and allows you to learn practical tips.

Daily Life Adjustments

Special shoes or gloves may be needed due to hand and foot enlargement. Prefer comfortable and wide shoes. Remove jewelry such as rings and bracelets if they are tight.

If you have carpal tunnel syndrome, you can use wrist splints and avoid repetitive hand movements. Using an ergonomic keyboard and mouse can help.

If you are having difficulty speaking due to voice deepening, you can work with a speech therapist.

Hormone Replacement Therapy

If the pituitary gland's other hormones have also decreased after surgery or radiotherapy, lifelong hormone replacement therapy is required. Thyroid hormone, cortisol, or sex hormones should be used regularly. Stopping these medications can lead to serious health problems.

If you have cortisol deficiency, dose increase may be needed in situations such as stress, infection, or surgery. Create an emergency plan with your doctor and carry a medical identification card with you.

Preparing for Your Appointment

What you can do:

• Note the physical changes you have noticed and when they started
• If possible, bring old photographs from various years (especially showing face, hands, and feet)
• Record changes in your ring, bracelet, or shoe size
• List all your symptoms (joint pain, fatigue, sweating, etc.)
• Write down the medications, vitamins, and supplements you use
• Mention if there is a family history of pituitary tumor or hormonal disease
• Write your questions down in advance

Questions you can ask your doctor are as follows:

• Are these symptoms caused by acromegaly?
• What tests do I need to have?
• How large is my pituitary tumor?
• What are my treatment options?
• Is surgery or medication more appropriate?
• Will physical changes improve after treatment?
• What are my complication risks?
• How often should I have checkups?
• What changes should I make in my daily life?
• Does this disease pose a risk for my family?

Questions your doctor may ask you are as follows:

• When did your symptoms start?
• When did you notice your hand or foot enlargement?
• Has your ring or shoe size changed?
• Do you have headache?
• Are you experiencing vision problems?
• Do you have joint pain?
• Are there sleep apnea symptoms (snoring, nighttime breathing cessation)?
• Do you have menstrual irregularity or sexual problems?
• Is there a family history of pituitary tumor?
• Do you have chronic diseases (diabetes, hypertension)?