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acromegaly

What is acromegaly

Acromegaly is a rare but serious condition caused by too much growth hormone (GH) in the blood, causing body tissues and bones to grow more quickly. Over time, the excess growth hormone (GH) leads to abnormally large hands and feet, and a wide range of other symptoms. In adults, too much growth hormone (GH) 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. Acromegaly is usually diagnosed in adults aged 30 to 50 but can affect people of any age. When it develops before puberty, it’s known as “gigantism”. The name “acromegaly” comes from the Greek words for “extremities” (akros) and “big” (megas). The acromegaly term was proposed by Pierre Marie, a famous French neurologist working in La Salpetrière Hospital, in Paris, who published the first description of the disease and its pathology in 1886 1.

Growth hormone (GH) is released into the bloodstream by the pituitary gland, located at the base of the brain. The blood carries growth hormone (GH) to other parts of the body where it has specific effects. In children, growth hormone (GH) stimulates growth and development. In adults, growth hormone (GH) affects energy levels, muscle strength, bone health, and one’s sense of well-being. Too much growth hormone (GH) in children is called gigantism and is extremely rare. Acromegaly in adults occurs mainly in middle-aged men and women. Acromegaly is a very rare condition. Each year, about three new cases of acromegaly occur for every million people.

Acromegaly is usually caused by a non-cancerous tumor in the pituitary gland called a pituitary adenoma 2. The tumor produces too much growth hormone (GH) and raises the level of growth hormone in the blood. When growth hormone (GH) is secreted into your bloodstream, it triggers your liver to produce a hormone called insulin-like growth factor-1 (IGF-1) 3. In turn, insulin-like growth factor-1 (IGF-1) stimulates the growth of bones and other tissues. If your pituitary gland makes too much growth hormone (GH), excessive amounts of IGF-1 can result. Too much insulin-like growth factor-1 (IGF-1) can cause abnormal growth of your soft tissues and skeleton and other signs and symptoms characteristic of acromegaly and gigantism. Rarely, acromegaly is caused by hormone-producing tumors in other parts of the body.

Acromegaly does sometimes run in families, but most of the time it’s not inherited. Adenomas usually spontaneously develop because of a genetic change in a cell of the pituitary gland. This change causes uncontrolled growth of the affected cells, creating the tumor.

In rare cases, acromegaly is caused by a tumor in another part of the body, such as the lungs, pancreas or another part of the brain. It may also be linked to some genetic conditions.

Because acromegaly is uncommon and physical changes occur gradually, the condition often isn’t recognized immediately: sometimes not for years. Most of the symptoms of acromegaly are due to the excess of growth hormone itself, but some come from the tumor pressing on nearby tissues. For example, you may get headaches and vision problems if a tumor pushes against the nearby nerves. The earlier the tumor is detected, the sooner the treatment can occur, and the fewer long-term changes in appearance the individual will experience, which is why knowing the definition of acromegaly is important. Those who suspect they may be suffering from this pituitary condition should consult with a doctor as soon as possible.

Figure 1. Acromegaly

acromegaly

Footnote: Characteristic appearance of patients with acromegaly: increased head circumference, enlarged jaw (prognathism), swollen soft tissues of heads, thicken lips, etc.

[Source 4 ]

Figure 2. Acromegaly hands

acromegaly hands

Footnote: As compared with the hand of a normal person (left), the hand of a patient with acromegaly (right) is enlarged, the fingers are widened, thickened and stubby, and the soft tissue is thickened.

[Source 5 ]

Figure 3. Acromegaly hands

acromegaly hands

Footnote: (A) The patient’s hands and fingers were widened, thickened and stubby. (B) When asked to make tight fists, he was unable to cover his fingernails with the center of the palms, suggesting positive “fist sign”.

[Source 6 ]

Figure 4. Acromegaly face

Acromegaly face

Footnote: Facial aspect of a patient with acromegaly. The nose is widened and thickened, the cheekbones are obvious, the forehead bulges, the lips are thick and the facial lines are marked. The forehead and overlying skin is thickened, sometimes leading to frontal bossing.

[Source 1 ]

Figure 5. Acromegaly mandibular prognathism

Acromegaly mandibular prognathism

Footnote: Mandibular overgrowth leads to prognathism, maxillary widening, teeth separation and jaw malocclusion.

[Source 7 ]

Figure 6. Acromegaly signs and symptoms

acromegaly signs and symptoms
[Source 8 ]

Gigantism vs Acromegaly

Gigantism causes children to grow taller than average. This condition, which most often affects children, occurs due to a noncancerous tumor on the pituitary gland that creates too much growth hormone. Children with gigantism will grow unusually tall, and many will experience delayed puberty.

Unfortunately, diagnosing gigantism can be difficult for parents, because the condition does not cause many signs other than unusual height. If the family is an unusually tall family, this may simply be attributed to a growth spurt or the child’s genetic makeup.

Early diagnosis of gigantism is important for the child’s health and well-being. The condition is treatable by removing the tumor, but once the growth has occurred the child is not going to shrink back to an average height. For this reason, the earlier the condition is treated, the better the outcome is for the child.

The definition of acromegaly is a disease caused by noncancerous tumors in the pituitary gland that cause secretions of growth hormone. The difference between acromegaly and gigantism is that acromegaly occurs in adults, typically between the ages of 30 and 50.

Hypothalamus and Pituitary Gland

The pituitary gland is a pea-shaped structure that measures 1–1.5 cm (0.5 in.) in diameter and lies in the hypophyseal fossa of the sella turcica of the sphenoid bone (see Figure 7). The pituitary gland attaches to the hypothalamus by a stalk, the infundibulum and has two anatomically and functionally separate portions:

  • the anterior pituitary and
  • the posterior pituitary.

The anterior pituitary (anterior lobe), also called the adenohypophysis, accounts for about 75% of the total weight of the gland and is composed of epithelial tissue. The anterior pituitary consists of two parts in an adult: The pars distalis is the larger portion, and the pars tuberalis forms a sheath around the infundibulum.

The posterior pituitary (posterior lobe), also called the neurohypophysis, is composed of neural tissue. It also consists of two parts: the pars nervosa, the larger bulbar portion, and the infundibulum.

A third region of the pituitary gland called the pars intermedia atrophies during human fetal development and ceases to exist as a separate lobe in adults. However, some of its cells migrate into adjacent parts of the anterior pituitary, where they persist.

Anterior Pituitary

The anterior pituitary secretes hormones that regulate a wide range of bodily activities, from growth to reproduction.

Types of Anterior Pituitary Cells and Their Hormones

Five types of anterior pituitary cells—somatotrophs, thyrotrophs, gonadotrophs, lactotrophs, and corticotrophs—secrete seven hormones:

  • 1. Somatotrophs secrete growth hormone (GH), also known as human growth hormone (hGH) or somatotropin. Growth hormone stimulates general body growth and regulates aspects of metabolism.
  • 2. Thyrotrophs secrete thyroid-stimulating hormone (TSH), also known as thyrotropin. TSH controls the secretions and other activities of the thyroid gland.
  • 3. Gonadotrophs secrete two gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH both act on the gonads (testes and ovaries). In men, they stimulate the testes to produce sperm and to secrete testosterone. In women, they stimulate the ovaries to mature oocytes (eggs) and to secrete estrogens and progesterone.
  • 4. Lactotrophs secrete prolactin (PRL), which initiates milk production in the mammary glands.
  • 5. Corticotrophs secrete adrenocorticotropic hormone (ACTH), also known as corticotropin, which stimulates the adrenal cortex to secrete glucocorticoids such as cortisol. Some corticotrophs, remnants of the pars intermedia, also secrete melanocyte stimulating hormone (MSH).

Hypothalamic Control of the Anterior Pituitary

Release of anterior pituitary hormones is regulated in part by the hypothalamus. The hypothalamus secretes five releasing hormones, which stimulate secretion of anterior pituitary hormones:

  • 1. Growth hormone-releasing hormone (GHRH), also known as somatocrinin, stimulates secretion of growth hormone.
  • 2. Thyrotropin-releasing hormone (TRH) stimulates secretion of thyroid-stimulating hormone.
  • 3. Corticotropin-releasing hormone (CRH) stimulates secretion of adrenocorticotropic hormone.
  • 4. Prolactin-releasing hormone (PRH) stimulates secretion of prolactin.
  • 5. Gonadotropin-releasing hormone (GnRH) stimulates secretion of FSH and LH.

The hypothalamus also produces two inhibiting hormones, which suppress secretion of anterior pituitary hormones:

  • 1. Growth hormone-inhibiting hormone (GHIH), also known as somatostatin, suppresses secretion of growth hormone.
  • 2. Prolactin-inhibiting hormone (PIH), which is dopamine, suppresses secretion of prolactin.

Figure 7. Pituitary gland and hypothalamus

pituitary gland

Figure 8. Hypothalamic Control of Pituitary Gland

hypothalamus controlling pituitary gland

Acromegaly complications

Acromegaly is treatable in most people. But because symptoms come on slowly, health problems can develop before the disorder is diagnosed and treated.

If you do not get treatment for acromegaly, you may be at risk of developing:

  • type 2 diabetes
  • high blood pressure (hypertension)
  • heart disease, particularly enlargement of the heart (cardiomyopathy)
  • disease of the heart muscle (cardiomyopathy)
  • osteoarthritis
  • bowel polyps, which can potentially turn into bowel cancer if left untreated
  • goiter
  • precancerous growths (polyps) on the lining of your colon
  • sleep apnea, a condition in which breathing repeatedly stops and starts during sleep
  • Carpal tunnel syndrome
  • reduced secretion of other pituitary hormones (hypopituitarism)
  • uterine fibroids, benign tumors in the uterus
  • spinal cord compression
  • vision loss

People with acromegaly also have an increased risk for colon polyps, which may develop into colon cancer if not removed. Because of the risk of bowel polyps, a colonoscopy might be recommended for anyone diagnosed with acromegaly, and regular colonoscopy screening may be necessary.

Some people with acromegaly may have a genetic condition that can lead tumors to develop in different parts of their bodies. Increased growth hormone (GH) can cause these other tumors to grow.

Early treatment of acromegaly can prevent these complications from developing or becoming worse. Life expectancy may return to normal 9. If untreated, acromegaly and its complications can lead to premature death.

Musculoskeletal complications

Both growth hormone (GH) and insulin-like growth factor-1 (IGF-1) stimulate the production of periosteal bone formation 1. IGF-1 creates somatic growth by binding to insulin-like growth factor-1 receptor (IGF-1R), which is relatively ubiquitous. IGF-1R is a receptor tyrosine kinase that brings about phosphorylation and activation of several intracellular signaling pathways, one of which is the AKT pathway activation that results in somatic cell growth and proliferation. In the craniofacial region, this manifests as characteristic features such as prognathism, teeth separation, jaw thickening, frontal bossing as well as nasal bone hypertrophy. The changes noted in the extremities are due to a combination of increased soft tissue, cartilage, and bone overgrowth, and deformity. Cartilage hypertrophy results in the widening of joint spaces and widening of the phalanges occur due to thickening of the base of the bone and the diaphysis. The spine is also affected by cartilage and bone overgrowth, the phenotype of which is dorsal kyphosis and lumbar hyperlordosis. Deformity due to overgrowth of the costochondral joints can cause splaying of the ribs. Bone mass can give differing results in these patients because acromegaly is associated with other endocrinopathies that may contribute to a low bone mineral density. An example of this would be hypogonadism. Peripheral arthralgias and myalgias are also common.

Skin manifestations

The major changes seen with the skin are a result of hyperhidrosis (abnormally excessive sweating) and patients may complain of excessive sweating and general oiliness of their skin 1. Additional findings may include skin tags. Skin is also generally thickened as a result of glycosaminoglycan deposition and connective tissue overgrowth.

Neurologic complication

Carpal tunnel syndrome remains the most common neuropathy 1. Interestingly, the mechanism is thought to be swelling of the median nerve and not external compression of the nerve from soft tissue and bone overgrowth. Also, cerebral aneurysms have been reported with increased frequency in patients with acromegaly, often found incidentally on imaging during an evaluation, but they can also present as cerebral hemorrhage if they should rupture.

Cardiovascular complications

Hypertension (high blood pressure) is frequent in these patients 1. The pathophysiology seems multifactorial. Primarily, there is an increased plasma volume and perhaps an element of endothelial dysfunction as well. Secondary contributors to the development of hypertension include sleep apnea and insulin resistance. Myocardial biventricular hypertrophy can also occur as a direct result of GH on the myocardium, leading to diastolic dysfunction. Histologically there is necrosis of myocardial cells, interstitial fibrosis, and infiltration of lymphocytes. Initially, this presents as a hyperkinetic heart, then evolving to biventricular hypertrophy and eventually diastolic and then systolic dysfunction 10. Arrhythmias can also occur but are seldom symptomatic. They occur due to the combination of fibrotic changes, cardiac remodeling, and associated cardiomyopathy. Valvular abnormalities can also occur with increased frequency in acromegalic patients. It has been postulated that this may, in part, be related to some fibrotic changes.

Metabolic complications

Both insulin resistance and diabetes occur in acromegaly 11. This is because GH in excess causes insulin resistance at the level of the liver and peripheral tissues. There is then an increase in beta-cell function as compensation to attempt the maintain euglycemia. Physiologically, GH stimulates the hydrolysis of triglycerides into free fatty acids and glycerol. The combination of chronic insulin resistance and lipotoxicity eventually results in beta-cell dysfunction and eventual apoptosis with subsequent development of diabetes 11.

Respiratory complications

The most common respiratory complication is sleep apnea 1. The majority of acromegalic patients with sleep apnea have the obstructive kind due to craniofacial anatomic changes such as macroglossia, soft tissue overgrowth of the palate and uvula, and alterations of the jaw. However, one-third of patients do have central sleep apnea. Other abnormalities that can occur again are due to anatomic changes related to the ribcage, thus altering ventilatory mechanics.

Neoplastic complications

The risk of colon cancer in acromegaly remains a very controversial topic 1. A large meta-analysis evaluating the presence of colorectal malignancy in acromegaly was published in 2008. It included around 700 patients with acromegaly compared to around 1500 controls. They found that the odds ratios of developing colon adenomas and colon cancer in patients with acromegaly were 2.5 and 4.3, respectively 12. There remains no true consensus among different guidelines concerning colonoscopy surveillance. Some guidelines recommend screening at the time of diagnosis, and others starting at age 40. Repeat colonoscopies depend on the findings of the initial colonoscopy 13. Thyroid nodules can also occur. Sometimes these patients can develop a multinodular goiter and become clinically thyrotoxic.

Acromegaly causes

Acromegaly develops when the pituitary gland releases too much GH (growth hormone) 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 1 (IGF-1). Consequently, individuals with acromegaly also have elevated levels of IGF-1. Insulin-like growth factor 1 (IGF-1) is the hormone that actually causes bones and body tissue to grow. High levels of insulin-like growth factor-1 (IGF-1) 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 adults, a tumor is the most common cause of too much growth hormone (GH) production:

  • Pituitary tumors. In more than 9 out of 10 cases of acromegaly are caused by a noncancerous (benign) tumor of the pituitary gland called a pituitary adenoma 2. The tumor secretes excessive amounts of growth hormone (GH), causing many of the signs and symptoms of acromegaly. Some of the symptoms of acromegaly, such as headaches and impaired vision, are due to the tumor mass pressing on nearby brain tissues. The pituitary tumor may also 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
  • Pituitary adenomas size:
    • Microadenomas are smaller than 1 centimeter across. Most pituitary adenomas are this size.
    • Macroadenomas are 1 centimeter across or larger.
  • Some pituitary tumors that create growth hormone can also increase the levels of other hormones in the body. For example, the pituitary 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. In a few people with acromegaly, tumors in other parts of the body, such as the lungs, pancreas or adrenal glands, cause acromegaly. Sometimes, these tumors actually secrete growth hormone (GH). In other cases, the tumors produce a hormone called growth hormone-releasing hormone (GH-RH), which stimulates the pituitary gland to make more growth hormone.
  • 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.

Rarely acromegaly may be caused by the ineffective control of growth hormone-secreting cells by the hypothalamus (a gland in the brain that regulates hormone secretions). Growth hormone excess may sometimes be due to over-stimulation by production of too much growth hormone-releasing hormone (GH-RH) secreted by the hypothalamus or other tissues.

In some patients, acromegaly may occur as part of certain genetic syndromes including multiple endocrine neoplasia type 1, familial isolated pituitary adenoma, Carney complex and McCune-Albright syndrome. X-linked acrogigantism causes gigantism and is due to microduplications of segments of the X chromosome.

Acromegaly symptoms

The symptoms of acromegaly generally occur very slowly over time and become more noticeable as affected individuals age. The specific symptoms that develop may vary greatly from one person to another. Acromegaly can potentially cause a wide variety of symptoms and physical findings.

Early symptoms include:

  • swollen hands and feet – you may notice a change in your ring or shoe size
  • tiredness and difficulty sleeping, and sometimes sleep apnea (breathing repeatedly stops and starts during sleep)
  • gradual changes in your facial features, such as your brow, lower jaw and nose getting larger, or your teeth becoming more widely spaced
  • numbness and weakness in your hands, caused by a compressed nerve (Carpal tunnel syndrome)
  • high blood glucose (sugar)
  • coarse, oily, thickened skin
  • excessive sweating and body odor
  • small outgrowths of skin tissue (skin tags)
  • fatigue and muscle weakness
  • deepened, husky voice due to enlarged vocal cords and sinuses
  • enlarged tongue

Children and teenagers will be abnormally tall.

As time goes on, common symptoms include:

  • abnormally large hands and feet
  • large, prominent facial features (such as the nose and lips) and an enlarged tongue
  • skin changes – such as thick, coarse, oily skin; skin tags; or sweating too much
  • deepening of the voice, as a result of enlarged sinuses and vocal cords
  • joint pain
  • tiredness and weakness
  • headaches
  • blurred or reduced vision
  • loss of sex drive
  • abnormal periods (in women) and erection problems (in men)
  • heart failure or enlarged heart
  • high blood pressure (hypertension)
  • arthritis
  • goiter (enlarged thyroid gland)
  • enlarged liver, heart, kidneys, spleen and other organs
  • increased chest size (barrel chest)

Symptoms often become more noticeable as you get older.

Symptoms caused by hypopituitarism:

  • Menstrual disorders (irregular bleeding; absence of periods)
  • Lower sexual desire
  • Tiredness

Symptoms caused by tumor volume:

  • Headaches
  • Vision problems (tunnel vision; vision loss)

Acromegaly signs and symptoms

Signs and symptoms of acromegaly can vary from person to person and generally occur very slowly over time and become more noticeable as affected individuals age. The specific symptoms that develop may vary greatly from one person to another.

Table 1. Clinical symptoms and signs of acromegaly 14

Facial change, acral enlargement, and soft-tissue swelling100%
Excessive sweating83%
Acroparesthesiae/ carpal tunnel syndrome68%
Tiredness and lethargy53%
Headaches53%
Oligomenorrhea (infrequent or light menstrual cycles) or amenorrhea (absence of menstruation), infertility55*
Erectile dysfunction and/or decreased libido42#
Arthropathy37%
Impaired glucose tolerance/ diabetes37%
Goiter35%
Ear, nose throat and dental problems32%
Congestive cardiac failure/ arrhythmia25%
Hypertension23%
Visual field defects17%
* percentage of female patients # percentage of male patients

Facial features gradually become coarse because of the overgrowth of soft tissues and cartilage. Facial bones gradually become prominent, the lower jaw protrudes (prognathism) and an underbite may cause a wide separation and misalignment between the teeth (malocclusion). Affected individuals may also have an abnormally large tongue and unusually thick, full lips. People with acromegaly eventually develop a deep and husky voice due to thickening of the vocal cords and enlargement of the sinuses.

Acromegaly also results in a gradual enlargement of the hands and feet. Affected individuals may notice that rings feel tighter or no longer fit at all, and that their shoe size and width has increased. Overgrowth (hypertrophy) of bone and enlargement of cartilage in the joints may result in inflammation and gradual degeneration of involved joints (osteoarthritis). Joint and muscle pain (arthralgia and myalgia) often develops, especially affecting the large joints such as the knees, shoulders, hands, wrists and hips.

In some people with acromegaly, the spine may abnormally curve from side to side and from front to back (kyphoscoliosis). Overgrowth of tissue may trap nerves, causing numbness and weakness of the hands (carpal tunnel syndrome). Abnormal darkening and thickening of patches of skin in certain areas of the body (acanthosis nigricans), an excessive amount of body hair (hirsutism) and small abnormal outgrowths of extra skin (skin tags) may also be present.

In some patients, acromegaly may cause abnormal enlargement of certain organs including the heart. Symptoms may include difficulty breathing upon exertion (dyspnea) and/or irregular heartbeats (arrhythmias). Heart involvement in acromegaly can ultimately lead to congestive heart failure, in which the heart cannot properly circulate blood to the lungs and the rest of the body, resulting in fluid buildup in the heart, lung and various body tissues.

Additional symptoms of acromegaly may include abnormal enlargement of the liver (hepatomegaly), spleen (splenomegaly), intestines and/or kidneys. The thyroid (goiter) and/or the adrenal glands may also become abnormally enlarged.

Approximately 25 percent of people with acromegaly have elevated blood pressure (hypertension). Abnormal enlargement of the pituitary gland, located at the base of the skull, may cause headaches, visual abnormalities and/or hormonal deficiencies. In approximately 50 percent of people with acromegaly, excessive levels of growth hormone (GH) secreted by the pituitary gland may influence the production of insulin, a hormone produced by the pancreas that regulates blood sugar (glucose) levels by promoting the movement of glucose into cells in the body. Abnormalities in insulin action may result in elevated levels of blood sugar (glucose) and some individuals with acromegaly may develop insulin resistance or type 2 diabetes mellitus. Some people with acromegaly may have an increased metabolic rate, excessive sweating (hyperhidrosis) and/or increased production of oil (sebum) by the sebaceous glands in the skin, resulting in abnormally oily skin.

Individuals with acromegaly may develop breathing (respiratory) abnormalities including sleep apnea, a common sleep disorder characterized by temporary, recurrent interruptions of breathing during sleep. Symptoms of the disorder include wakefulness during the night, excessive sleepiness during the day, loud snoring and/or obesity. In obstructive apnea, the most common form of sleep apnea, labored breathing is interrupted by airway collapse or blockage from enlarged soft tissue. Partial awakening may then occur and the person may gasp for air. Sleep is resumed as breathing begins again. Untreated sleep apnea may be associated with high blood pressure, irregular heartbeats, swelling in the arms and/or legs, hallucinations, anxiety and/or irritability.

Females with acromegaly may experience an abnormal flow of milk from the breasts (galactorrhea), and infrequent or delayed menstrual flow (oligomenorrhea). Males with acromegaly may experience impotence and a decrease in sexual drive (decreased libido). Individuals with acromegaly have an increased risk of developing polyps in the colon. Individuals with acromegaly may have a slightly greater risk of developing colon cancer than the general population.

Symptoms that may develop late during the course of acromegaly include muscle weakness and impaired function of peripheral nerves (i.e., nerves that lie outside the brain and spinal cord). Vision of some affected individuals may become impaired and possibly progress to blindness. If untreated, 25 percent of people with acromegaly experience symptoms associated with uncontrolled diabetes including an increase in the amount of sugar in their urine (glycosuria), abnormally excessive thirst (polydipsia) and/or an abnormally increased appetite (polyphagia).

Diagnosing acromegaly

Because the symptoms of acromegaly often develop gradually over several years, you may not get a diagnosis straight away. Your doctor may ask you to bring in photographs of yourself that span the past few years to look for the tell-tale gradual changes.

Acromegaly diagnosis is made based upon a detailed patient history, a thorough clinical evaluation, identification of characteristic findings and specialized tests such as blood tests, a glucose tolerance test, magnetic resonance imaging (MRI) or computerized tomography (CT).

Your doctor may test your blood for elevated levels of growth hormone or IGF-1 (insulin growth factor 1) associated with acromegaly. Measurement of IGF-1 is the most accurate available screening blood test. Measurement of growth hormone is often done in conjunction with a glucose tolerance test. During a glucose tolerance test, individuals ingest a specific amount of sugar that should lower GH levels in the blood. In individuals with overproduction of growth hormone, this reduction does not occur.

Your doctor may also order an MRI (magnetic resonance imaging), preferably, or CT (computed tomography) scan of the brain to reveal the presence and size of a pituitary tumor. During MRI, a magnetic field and radio waves are used to create cross-sectional images of organs and structures in the body. During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of an organ’s tissue structure.

Additional tests may be performed to assess the extent of acromegaly in an individual including echocardiography to evaluate whether the heart is involved, tests to determine whether sleep apnea is present and a colonoscopy to assess the health of the colon and establish a baseline for further testing. Patients with acromegaly may be at increased risk for bone fractures, and testing with X-rays or assessment of bone mineral density with a DXA (dual X-ray absorptiometry) scan may be ordered.

Blood tests

If your doctor suspects you have acromegaly, you will need to have a blood test to measure your growth hormone levels.

  • To make sure the blood test gives an accurate result, you may be asked to drink a sugary solution before having a series of blood samples taken. This is called a glucose tolerance test. For people without acromegaly, drinking the solution should stop growth hormone being released. In people with acromegaly, the level of growth hormone in the blood will remain high.
  • Your doctor will also measure the level of another hormone, called insulin-like growth factor 1 (IGF-1). A higher level of IGF-1 is a very accurate indication that you might have acromegaly. High IGF-1 levels can mean that your levels of growth hormone are also high.
  • Another way to diagnose acromegaly is with an oral glucose tolerance test (OGTT). In this test, growth hormone levels in the blood are measured after you drink sugar water. Normally, the sugar water will make the pituitary gland stop producing growth hormone and blood levels drop. However, a growth hormone-producing pituitary tumor will not stop making growth hormone, so the levels of growth hormone in the blood will not change.
  • Other dynamic tests exist but are seldom necessary. They can be done if acromegaly is suspected, but the IGF-1 and GH suppression test with oral glucose tolerance test (OGTT) are both normal. Thyrotropin-releasing hormone (TRH) 500 mg can be given intravenously, and in about half of acromegalic patients, the GH level would increase by 50% within 30 minutes. This effect is not observed in the general population 15.

Brain scans

If your blood tests show a high level of growth hormone and IGF-1, you might have an MRI scan of your brain. This will show where the adenoma is in your pituitary gland and how big it is. If you can’t have an MRI scan, a CT scan can be carried out, but this is less accurate.

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.

  • Magnetic resonance imaging (MRI). 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 (CT) 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.

Acromegaly treatment

Acromegaly requires expert care. Too much growth hormone and IGF-1 in your blood lower both your quality of life and how long you might live. The main goal of treatment is to lower growth hormone and IGF-1 levels to normal. Treatment may be surgery, pituitary irradiation (radiation therapy on the pituitary gland), medication, or a combination of these options.

The type of treatment offered for acromegaly depends on the symptoms you have. Usually the goal is to:

  • reduce growth hormone production to normal levels
  • relieve the pressure a tumour may be putting on surrounding tissues
  • treat any hormone deficiencies
  • improve your symptoms

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 and general health, the size and location of the pituitary tumor, severity of symptoms, GH and IGF-1 levels, and other issues.

Most people with acromegaly will have a pituitary tumor that needs to be surgically removed. Medication or radiotherapy may sometimes be needed after, or instead of, surgery.

Surgery

Surgery is effective in most people and can completely cure acromegaly. But sometimes the tumor is too large to be removed entirely, and you may need another operation or further treatment with medication or radiotherapy.

Surgical techniques

  • Endoscopic Transsphenoidal Surgery: A minimally invasive surgery using a long, thin, flexible tube with a light and video camera at one end, called an endoscope, through a small cut inside your nose or behind your upper lip to remove the pituitary adenoma. Removing the tumor should instantly lower your levels of growth hormone and relieve pressure on the surrounding tissue. Often, facial features start to return to normal and swelling improves within a few days. The proposed benefit of using an endoscope is the enhanced ability to visualize the tumor in a panoramic fashion and not miss any residual tumor when resecting 16.
  • Transsphenoidal Microscopic Surgery: The tumor is directly visualized using a microscope, and this is the traditional method of transsphenoidal surgery. A meta-analysis compared endoscopic and traditional microscopic transsphenoidal surgeries. It found they have comparable endocrine remission and complication rates. As expected, microadenomas had higher remission rates regardless of the surgical technique used, and the endoscopic technique confers the theoretical benefit of better visualization and, thus, better outcomes for macroadenomas. But, further studies are required to directly compare these surgical modalities 17.
  • Craniotomy: This approach is reserved for those adenomas with suprasellar extension. Other reasons for choosing this approach include unfavorable para-sellar sinuses and internal or external carotid artery aneurysms 16.

When the tumor that is creating too much growth hormone 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.

Figure 3. Endoscopic transnasal transsphenoidal surgery

Endoscopic transnasal transsphenoidal surgery

Note: In transnasal transsphenoidal endoscopic surgery, a surgical instrument is placed through the nostril and alongside the nasal septum to access a pituitary tumor.

With surgery, there is risk of:

  • causing damage to healthy parts of your pituitary gland
  • leakage of the fluid (cerebrospinal fluid) that surrounds and protects your brain
  • meningitis – although this is rare

Your surgeon will discuss these risks with you and answer any questions you have.

Surgery outcomes

The surgery is considered a success if blood levels of GH and IGF-1 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 2.

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.

Quality of life after treatment

Numerous studies have looked at the impact of different treatment modalities in first- or second-line therapies. Pituitary surgery compared with medical treatment seems superior in improving quality of life in patients with acromegaly 18 as in other types of pituitary tumor 19. A French study 20 found that patients who underwent surgery had a better quality of life than if they had received medical treatment only (65 ± 18% versus 54 ± 14%) and investigators concluded that neurosurgery was associated with greater improvement in quality of life when compared with medical therapy alone. Overall, greater GH suppression could be attained with surgery than with somatostatin receptor ligand injections 21. Patients with remission after surgery could avoid medication side effects and consequences of suboptimal biochemical control.

Postsurgery treatments

In most cases, levels of GH and IGF-1 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.

An oral glucose tolerance test (OGTT) can be done 1 week post-operatively. A GH value of <0.4ng/mL is used as defining disease control 22. Serology of GH and IGF-1 can be measured by 3 to 6 months post-operatively as it can take this long for IGF-1 levels to normalize. Remission is then defined when normal IGF-1 levels are seen, and GH after OGTT is measured at <1ng/mL (although some recommend the use of <0.4ng/mL). If remission is confirmed, serology should be repeated at least annually, as relapse has been known to occur in some patients even as long as 10 or more years later. Post-operative imaging should be done a minimum of 3 months after surgery as the fat and gel foam packing can take that long to be resorbed 16. If residual disease is noted, the patient may need further treatment with repeat surgery if possible and appropriate, medical management, or radiotherapy. Pathology specimens are helpful for further management and prognostication as, for example, when the tumor is densely granulated, this may predict response to octreotide 23. Also, staining should be done for Ki67 and p21 as these levels have also shown to have prognostic value 24. Also, if the adenoma stains positive for prolactin, this could predict response to dopamine agonists.

Medication

If your levels of growth hormone are still higher than normal after surgery, or surgery wasn’t possible, you may be prescribed medication. 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 analogues. The drugs octreotide (Sandostatin) and lanreotide (Somatuline Depot) are synthetic versions of the brain hormone somatostatin. They can interfere with the excessive secretion of GH by the pituitary gland and the tumor may decrease in size in some people, thus can produce rapid declines in GH levels. When starting octreotide treatment, you initially inject yourself with a short-acting preparation under your skin (subcutaneously) three times a day to determine if you have any side effects from the medication and if it’s effective. Then, if it’s tolerated and effective, you can take a long-acting form that requires an injection into the muscles of your buttocks (gluteal muscles) by a health care professional, administered once a month. Lanreotide is administered as a subcutaneous injection once a month. Several studies have shown that these drugs are safe and effective for long-term treatment, but scientists are currently studying other options, such as pills 25.
  • Dopamine agonists. The medications cabergoline and bromocriptine (Parlodel) are taken as pills. In some people, these drugs can lower levels of GH and IGF-1. The tumor may decrease in size in some people taking a dopamine agonist or somatostatin analogues. 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). Some people may develop compulsive behaviors, such as gambling, while taking these medications. Side effects can include nausea, stuffed nose, tiredness, headache, dizziness when standing, nightmares, and mood changes.
  • Growth hormone-receptor antagonist. The medication pegvisomant (Somavert), a growth hormone antagonist, acts to block the effect of GH on body tissues. Pegvisomant may be particularly helpful for people who haven’t had good success with other forms of treatment. You administer this medication yourself daily by subcutaneous injection. This medication can normalize IGF-1 levels and relieve symptoms in most people with acromegaly, but doesn’t lower GH levels or reduce the tumor size. Pegvisomant can have a beneficial effect on glucose homeostasis and can improve insulin sensitivity 26. Pegvisomant side effects can include liver problems, diarrhea and nausea.

Three different types of medicine are used:

  • A monthly injection of either octreotide, lanreotide or pasireotide: this slows down the release of growth hormone and can sometimes also shrink tumors.
  • A daily pegvisomant injection: this blocks the effects of growth hormone and can significantly improve symptoms.
  • Bromocriptine or cabergoline tablets: these can stop growth hormone being produced, but they only work in a small proportion of people.

Each of these medications has different advantages and disadvantages. Speak to your doctor about the options available to you, and the benefits and risks of each.

Combination medical therapy has also been described. Combining cabergoline with a somatostatin analog has been seen to be effective in a subset of patients, even in the absence of hyperprolactinemia 22. Another common combination is that of a somatostatin analog with Pegvisomant. A study demonstrated that by adding Pegvisomant to a somatostatin analog in patients seemingly resistant to the somatostatin analog, IGF-1 levels normalized in 95% of patients 27. Importantly, if this combination is used, one needs to monitor hepatic function as the liver derangement is more common with the combination of drugs than with Pegvisomant alone 27.

A combination of a low-dose somatostatin analog with weekly pegvisomant is not an on-label or approved regimen for acromegaly; however, a study has shown promise for this novel dosing regimen to be effective in biochemical control in addition to being cost-effective in those requiring combination therapy for control of their acromegaly 28.

Radiotherapy

If surgery isn’t possible, not all of the tumor could be removed or medication hasn’t worked, then you may be offered radiotherapy.

Radiotherapy can eventually reduce your growth hormone levels, but it may not have a noticeable effect for several years and you may need to take medication in the meantime.

Patients treated with radiotherapy need to be closely monitored for hypopituitarism.

Three main types of radiotherapy are used to treat acromegaly:

  • Stereotactic radiotherapy (stereotactic radiation therapy): Also known as Gamma Knife radiosurgery, stereotactic radiosurgery can deliver a high dose of radiation to the tumor cells in a single dose while limiting the amount of radiation to the normal surrounding tissues. A high-dose beam of radiation aimed very precisely at your adenoma. You will need to wear a rigid head frame or a plastic mask to hold your head still during the treatment. This can usually be done in one session. This type of radiation may bring growth hormone levels back to normal within three to five years. However, a single dose may not work for very large tumors and tumors located close to optic nerves that affect your vision. The remission rate with stereotactic radiosurgery ranges from 17 to 50% in the absence of medical management at 2 to 5 years 29.
  • Conventional radiotherapy (conventional radiation therapy): this also uses a beam of radiation to target the adenoma, but it is wider and less precise than the one used in stereotactic radiotherapy. This means this treatment can damage your surrounding pituitary gland and brain tissue, so it’s given in small doses over four to six weeks to give your tissues time to heal between treatments. You may not realize the full effect of conventional radiation therapy for 10 or more years after treatment. Your doctor is likely to prescribe medicines while you wait for GH and IGF-1 levels to go back to normal and for symptoms to improve.
  • Proton beam therapy. Proton beam therapy delivers a targeted, high dose of radiation to the tumor, sparing radiation exposure to normal tissues. Proton beam therapy is provided in fractions over time, but treatment times are generally less than conventional radiation.

Stereotactic radiotherapy is more commonly used to treat adenomas because it minimises the risk of damage to nearby healthy tissue.

However, stereotactic radiosurgery is available at only a few U.S. medical centers and is not recommended for all people undergoing radiation for acromegaly. Your doctor will determine which type of radiation therapy is right for you based on:

  • The size and location of your remaining tumor cells
  • Your levels of insulin-like growth factor-1 (IGF-1)

Even after initial treatment, acromegaly requires periodic monitoring by your doctor to make sure that your pituitary gland is functioning properly. This follow-up care may last for the rest of your life.

Radiotherapy can have a number of side effects. It will often cause a gradual drop in the levels of other hormones produced by your pituitary gland, so you’ll usually need hormone replacement therapy for the rest of your life. It may also have an effect on your fertility.

Your doctor will be able to talk to you about these risks and other possible side effects.

Follow-up

Treatment is often effective at stopping the excessive production of growth hormone and improving the symptoms of acromegaly.

After treatment, you’ll need regular follow-up appointments with your specialist for the rest of your life. These will be used to monitor how well your pituitary gland is working, check you’re on the correct hormone replacement treatment and make sure the condition does not return.

Acromegaly in Pregnancy

GH secretion varies during normal pregnancy. GH-secreting tumors have estrogen receptors, particularly those who co-secrete prolactin. The concern is whether the pregnant state would increase the size of the tumor; however, in some studies, it has been found that tumor size does not change significantly during pregnancy in most women. But, given that the risk is still present, women need to be monitored closely with serial visual field monitoring.

In a pregnant patient with acromegaly due to a microadenoma, the clinician should discontinue medical management, and these patients can just be closely monitored. The same applies to those with macroadenomas not affecting the optic chiasm with very close monitoring of visual fields. If a woman were to develop worsening symptoms of any kind related to acromegaly, medical management could be reinstituted to help alleviate those symptoms (no biochemical monitoring due to alterations of IGF-1 and GH during pregnancy). Bromocriptine has been used in pregnant women with acromegaly to manage the signs and symptoms without causing adverse fetal harm. However, cabergoline has not been extensively studied in pregnancy. Somatostatin analogs can cross the placenta and potentially decrease uterine blood flow, but longer use of octreotide does not seem to adversely affect the pregnancy or fetal development. Pegvisomant is not recommended as it has not been studied in pregnancy, and its use in pregnancy is limited to case reports. Should visual complaints arise, an MRI is a necessity to determine whether medical management or surgery is necessary at that point.

Acromegaly prognosis

Acromegaly is associated with high mortality rates, chiefly due to cancers, cardiovascular and respiratory disorders 30. Individuals with acromegaly have 1.2 to 3.3 times the mortality rate compared to the general population as per the standardized mortality index 22. However, it has also been postulated that post-operative growth hormone (GH) levels correlate the best with overall survival. Thus, if growth hormone (GH)/insulin-like growth factor-1 (IGF-1) levels are controlled, the life expectancy becomes the same as that of age-matched controls 31. Factors associated with a worse prognosis include high GH/IGF-1 levels, cardiomyopathy, and high blood pressure (hypertension) 32. Morbidity related to the condition often remains despite normalizing GH/IGF-1 levels, but treatment can reduce the severity and partially improves the quality of life 33.

Multiple factors influence the prognosis in acromegaly. Patient factors such as age, biochemical factors such as how high GH/IGF-1 levels are at diagnosis, tumor factors including tumor granularity, receptor expression (SSTR2, SSTR5, and D2), markers such as Ki67 and p21, specific mutations, how the tumor behaves in terms of its size and invasion and the T2 intensity of the tumor on MRI. Using this information, a classification of acromegaly into three subtypes has been proposed, guiding prognosis, predicting treatment responsiveness, and thus patient outcomes 34:

  • Type 1 (best prognosis): Older patients, fewer symptoms, and lower levels of IGF-1. They have densely granulated micro or macroadenomas that are less aggressive, as evidenced by lower Ki67 (a proliferation marker), high p21 (a marker of senescence), very uncommonly have a suprasellar extension. Rather, they tend to exhibit extension laterally to the sphenoid sinuses, which are more accessible to surgery. Also, these tumors more frequently express SSTR2 predicting a better response to medical treatment.
  • Type 2 (intermediate prognosis): These macroadenomas can be either dense or sparsely granulated but do not demonstrate any invasive features. Compared with type 1, IGF-1 levels are higher at diagnosis.
  • Type 3 (worst prognosis): These patients are young, experience severe symptoms and have high levels of IGF-1 at diagnosis. Their tumors are macroadenomas and are sparsely granulated and more aggressive as supported by low levels of p21. These tumors also extend to both the sphenoid sinus and the suprasellar region and frequently compress the optic chiasm. Low expression of SSTR2 may indicate poor response to medical therapy.
References
  1. Chanson, P., & Salenave, S. (2008). Acromegaly. Orphanet journal of rare diseases, 3, 17. https://doi.org/10.1186/1750-1172-3-17
  2. Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism. 2014;99(11):3933–3951.
  3. Frara S, Maffezzoni F, Mazziotti G, Giustina A. The Modern Criteria for Medical Management of Acromegaly. Prog Mol Biol Transl Sci. 2016;138:63-83. doi: 10.1016/bs.pmbts.2015.10.015
  4. Liu, Z. H., Li, K., Ding, Y. S., Qiu, J. X., Meng, S. S., Momin, M., Liu, S. C., Yi, T. C., & Li, J. P. (2018). Normalization of plasma growth hormone alleviated malignant ventricular tachycardia in acromegaly. Journal of geriatric cardiology : JGC, 15(8), 547–550. https://doi.org/10.11909/j.issn.1671-5411.2018.08.003
  5. Acromegalic hands (photo). https://radiopaedia.org/cases/acromegalic-hands-photo
  6. Harada K, Hasegawa K, Otsuka F. Swollen Hands and “Fist Sign” in Acromegaly. Am J Med. 2019 Jul;132(7):e618-e619. https://doi.org/10.1016/j.amjmed.2019.02.022
  7. Gosau, M., Vogel, C., Moralis, A. et al. Mandibular prognathism caused by acromegaly – a surgical orthodontic case. Head Face Med 5, 16 (2009). https://doi.org/10.1186/1746-160X-5-16
  8. Adelman, D. T., Liebert, K. J., Nachtigall, L. B., Lamerson, M., & Bakker, B. (2013). Acromegaly: the disease, its impact on patients, and managing the burden of long-term treatment. International journal of general medicine, 6, 31–38. https://doi.org/10.2147/IJGM.S38594
  9. Chanson P, Salenave S, Kamenicky P. Acromegaly. In: Fliers E, Korbonits M, Romijn JA, eds. Handbook of clinical neurology. Vol 124. 1st ed. Waltham, MA: Elsevier B.V.; 2014:197–219.
  10. Sharma, M. D., Nguyen, A. V., Brown, S., & Robbins, R. J. (2017). Cardiovascular Disease in Acromegaly. Methodist DeBakey cardiovascular journal, 13(2), 64–67. https://doi.org/10.14797/mdcj-13-2-64
  11. Vila, G., Jørgensen, J., Luger, A., & Stalla, G. K. (2019). Insulin Resistance in Patients With Acromegaly. Frontiers in endocrinology, 10, 509. https://doi.org/10.3389/fendo.2019.00509
  12. Rokkas, T., Pistiolas, D., Sechopoulos, P., Margantinis, G., & Koukoulis, G. (2008). Risk of colorectal neoplasm in patients with acromegaly: a meta-analysis. World journal of gastroenterology, 14(22), 3484–3489. https://doi.org/10.3748/wjg.14.3484
  13. Lois K, Bukowczan J, Perros P, Jones S, Gunn M, James RA. The role of colonoscopic screening in acromegaly revisited: review of current literature and practice guidelines. Pituitary. 2015 Aug;18(4):568-74. doi: 10.1007/s11102-014-0586-5
  14. Carroll PV, Jenkins PJ. Acromegaly. [Updated 2016 Feb 1]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279097
  15. Irie M, Tsushima T. Increase of serum growth hormone concentration following thyrotropin-releasing hormone injection in patients with acromegaly or gigantism. J Clin Endocrinol Metab. 1972 Jul;35(1):97-100. doi: 10.1210/jcem-35-1-97
  16. Marquez, Y., Tuchman, A., & Zada, G. (2012). Surgery and radiosurgery for acromegaly: a review of indications, operative techniques, outcomes, and complications. International journal of endocrinology, 2012, 386401. https://doi.org/10.1155/2012/386401
  17. Chen, C. J., Ironside, N., Pomeraniec, I. J., Chivukula, S., Buell, T. J., Ding, D., Taylor, D. G., Dallapiazza, R. F., Lee, C. C., & Bergsneider, M. (2017). Microsurgical versus endoscopic transsphenoidal resection for acromegaly: a systematic review of outcomes and complications. Acta neurochirurgica, 159(11), 2193–2207. https://doi.org/10.1007/s00701-017-3318-6
  18. Geraedts, V. J., Andela, C. D., Stalla, G. K., Pereira, A. M., van Furth, W. R., Sievers, C., & Biermasz, N. R. (2017). Predictors of Quality of Life in Acromegaly: No Consensus on Biochemical Parameters. Frontiers in endocrinology, 8, 40. https://doi.org/10.3389/fendo.2017.00040
  19. Waddle, M. R., Oudenhoven, M. D., Farin, C. V., Deal, A. M., Hoffman, R., Yang, H., Peterson, J., Armstrong, T. S., Ewend, M. G., & Wu, J. (2019). Impacts of Surgery on Symptom Burden and Quality of Life in Pituitary Tumor Patients in the Subacute Post-operative Period. Frontiers in oncology, 9, 299. https://doi.org/10.3389/fonc.2019.00299
  20. Matta MP, Couture E, Cazals L, Vezzosi D, Bennet A, Caron P. Impaired quality of life of patients with acromegaly: control of GH/IGF-I excess improves psychological subscale appearance. Eur J Endocrinol. 2008 Mar;158(3):305-10. doi: 10.1530/EJE-07-0697
  21. Rubeck KZ, Madsen M, Andreasen CM, Fisker S, Frystyk J, Jørgensen JO. Conventional and novel biomarkers of treatment outcome in patients with acromegaly: discordant results after somatostatin analog treatment compared with surgery. Eur J Endocrinol. 2010 Nov;163(5):717-26. doi: 10.1530/EJE-10-0640
  22. Adigun OO, Nguyen M, Fox TJ, et al. Acromegaly. [Updated 2021 Dec 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431086
  23. Bhayana S, Booth GL, Asa SL, Kovacs K, Ezzat S. The implication of somatotroph adenoma phenotype to somatostatin analog responsiveness in acromegaly. J Clin Endocrinol Metab. 2005 Nov;90(11):6290-5. doi: 10.1210/jc.2005-0998
  24. Alimohamadi, M., Ownagh, V., Mahouzi, L., Ostovar, A., Abbassioun, K., & Amirjmshidi, A. (2014). The impact of immunohistochemical markers of Ki-67 and p53 on the long-term outcome of growth hormone-secreting pituitary adenomas: A cohort study. Asian journal of neurosurgery, 9(3), 130–136. https://doi.org/10.4103/1793-5482.142732
  25. Paragliola RM, Salvatori R. Novel somatostatin receptor ligands therapies for acromegaly. Frontiers in Endocrinology. 2018;9:78.
  26. Giustina, A., Arnaldi, G., Bogazzi, F., Cannavò, S., Colao, A., De Marinis, L., De Menis, E., Degli Uberti, E., Giorgino, F., Grottoli, S., Lania, A. G., Maffei, P., Pivonello, R., & Ghigo, E. (2017). Pegvisomant in acromegaly: an update. Journal of endocrinological investigation, 40(6), 577–589. https://doi.org/10.1007/s40618-017-0614-1
  27. Feenstra J, de Herder WW, ten Have SM, van den Beld AW, Feelders RA, Janssen JA, van der Lely AJ. Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly. Lancet. 2005 May 7-13;365(9471):1644-6. doi: 10.1016/S0140-6736(05)63011-5. Erratum in: Lancet. 2005 May;365(9471):1620.
  28. Bonert V, Mirocha J, Carmichael J, Yuen KCJ, Araki T, Melmed S. Cost-Effectiveness and Efficacy of a Novel Combination Regimen in Acromegaly: A Prospective, Randomized Trial. J Clin Endocrinol Metab. 2020 Sep 1;105(9):dgaa444. doi: 10.1210/clinem/dgaa444
  29. Castinetti F, Taieb D, Kuhn JM, Chanson P, Tamura M, Jaquet P, Conte-Devolx B, Régis J, Dufour H, Brue T. Outcome of gamma knife radiosurgery in 82 patients with acromegaly: correlation with initial hypersecretion. J Clin Endocrinol Metab. 2005 Aug;90(8):4483-8. doi: 10.1210/jc.2005-0311
  30. Holdaway IM, Rajasoorya C. Epidemiology of acromegaly. Pituitary. 1999 Jun;2(1):29-41. doi: 10.1023/a:1009965803750
  31. Ayuk J, Clayton RN, Holder G, Sheppard MC, Stewart PM, Bates AS. Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J Clin Endocrinol Metab. 2004 Apr;89(4):1613-7. doi: 10.1210/jc.2003-031584
  32. Melmed S. Acromegaly and cancer: not a problem? J Clin Endocrinol Metab. 2001 Jul;86(7):2929-34. doi: 10.1210/jcem.86.7.7635
  33. Biermasz NR, van Thiel SW, Pereira AM, Hoftijzer HC, van Hemert AM, Smit JW, Romijn JA, Roelfsema F. Decreased quality of life in patients with acromegaly despite long-term cure of growth hormone excess. J Clin Endocrinol Metab. 2004 Nov;89(11):5369-76. doi: 10.1210/jc.2004-0669
  34. Cuevas-Ramos, D., Carmichael, J. D., Cooper, O., Bonert, V. S., Gertych, A., Mamelak, A. N., & Melmed, S. (2015). A structural and functional acromegaly classification. The Journal of clinical endocrinology and metabolism, 100(1), 122–131. https://doi.org/10.1210/jc.2014-2468
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