Acromegaly is a disorder that results from excess

growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...

(GH) after the

growth plates The epiphyseal plate (or epiphysial plate, physis, or growth plate) is a hyaline cartilage plate in the metaphysis at each end of a long bone. It is the part of a long bone where new bone growth takes place; that is, the whole bone is alive, with ...

have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Other symptoms may include

joint pain Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...

, thicker skin, deepening of the voice,

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

s, and problems with vision. Complications of the disease may include

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...

sleep apnea Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times ...

, and

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

. Acromegaly is usually caused by the

pituitary gland In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...

producing excess growth hormone. In more than 95% of cases the excess production is due to a

benign tumor A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize (spread throughout the body). Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have re ...

, known as a

pituitary adenoma Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas.inherited from a person's parents. Acromegaly is rarely due to a tumor in another part of the body. Diagnosis is by measuring growth hormone after a person has consumed a

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

solution, or by measuring

insulin-like growth factor I Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. IGF-1 is a protein that in humans is ...

in the blood. After diagnosis,

medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...

of the pituitary is carried out to determine if an adenoma is present. If excess growth hormone is produced during childhood, the result is the condition

gigantism Gigantism ( el, γίγας, ''gígas'', "giant", plural γίγαντες, ''gígantes''), also known as giantism, is a condition characterized by excessive growth and height significantly above average. In humans, this condition is caused by ove ...

rather than acromegaly, and it is characterized by excessive height. Treatment options include

surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...

to remove the tumor, medications, and

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...

. Surgery is usually the preferred treatment; the smaller the tumor, the more likely surgery will be curative. If surgery is contraindicated or not curative,

somatostatin analogue Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coup ...

s or

GH receptor antagonist Growth hormone receptor is a protein that in humans is encoded by the ''GHR'' gene. GHR orthologs have been identified in most mammals. Structure Growth hormone receptor (GHR) is a transmembrane protein consisting of 620 amino acids. The rece ...

s may be used. Radiation therapy may be used if neither surgery nor medications are completely effective. Without treatment, life expectancy is reduced by 10 years; with treatment, life expectancy is not reduced. Acromegaly affects about 3 per 50,000 people. It is most commonly diagnosed in middle age. Males and females are affected with equal frequency. It was first described in the medical literature by Nicolas Saucerotte in 1772. The term is from the

Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...

() meaning "extremity", and () meaning "large".

Signs and symptoms

Features that may result from a high level of GH or expanding tumor include: *

Headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

s – often severe and prolonged *

Soft tissue Soft tissue is all the tissue in the body that is not hardened by the processes of ossification or calcification such as bones and teeth. Soft tissue connects, surrounds or supports internal organs and bones, and includes muscle, tendons, ligam ...

swelling visibly resulting in enlargement of the hands, feet, nose, lips, and ears, and a general thickening of the skin * Soft tissue swelling of internal organs, notably the heart with the attendant weakening of its muscularity, and the kidneys, also the

vocal cords In humans, vocal cords, also known as vocal folds or voice reeds, are folds of throat tissues that are key in creating sounds through vocalization. The size of vocal cords affects the pitch of voice. Open when breathing and vibrating for speech ...

resulting in a characteristic thick, deep voice and slowing of speech * Generalized expansion of the skull at the

fontanelle A fontanelle (or fontanel) (colloquially, soft spot) is an anatomical feature of the infant human skull comprising soft membranous gaps ( sutures) between the cranial bones that make up the calvaria of a fetus or an infant. Fontanelles allow f ...

* Pronounced brow protrusion, often with ocular distension (

frontal bossing Skull bossing is a descriptive term in medical physical examination indicating a protuberance of the skull, most often in the frontal bones of the forehead ("frontal bossing"). Although prominence of the skull bones may be normal, skull bossing m ...

) * Pronounced lower jaw protrusion ( prognathism) with attendant

macroglossia Macroglossia is the medical term for an unusually large tongue. Severe enlargement of the tongue can cause cosmetic and functional difficulties in speaking, eating, swallowing and sleeping. Macroglossia is uncommon, and usually occurs in children. ...

(enlargement of the tongue) and teeth spacing *

Hypertrichosis Hypertrichosis is an abnormal amount of hair growth over the body. The two distinct types of hypertrichosis are generalized hypertrichosis, which occurs over the entire body, and localized hypertrichosis, which is restricted to a certain area. H ...

hyperpigmentation Hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin. Causes Hyperpigmentation can be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris.James, William; Ber ...

and

hyperhidrosis Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psychologi ...

may occur in these people. *

Skin tags A skin tag, or acrochordon (pl. acrochorda), is a small benign tumor that forms primarily in areas where the skin forms creases (or rubs together), such as the neck, armpit and groin. They may also occur on the face, usually on the eyelids. Tho ...

Carpal tunnel syndrome Carpal tunnel syndrome (CTS) is the collection of symptoms and signs associated with median neuropathy at the carpal tunnel. Most CTS is related to idiopathic compression of the median nerve as it travels through the wrist at the carpal tunn ...

Complications

* Problems with bones and joints, including

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

nerve compression syndrome Nerve compression syndrome, or compression neuropathy, or nerve entrapment syndrome, is a medical condition caused by direct pressure on a nerve. It is known colloquially as a ''trapped nerve'', though this may also refer to nerve root compress ...

due to bony overgrowth, and

carpal tunnel syndrome Carpal tunnel syndrome (CTS) is the collection of symptoms and signs associated with median neuropathy at the carpal tunnel. Most CTS is related to idiopathic compression of the median nerve as it travels through the wrist at the carpal tunn ...

Hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

Diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

Cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...

, potentially leading to

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

Colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

Sleep Apnea Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times ...

Thyroid nodule Thyroid nodules are nodules (raised areas of tissue or fluid) which commonly arise within an otherwise normal thyroid gland. They may be hyperplastic or tumorous, but only a small percentage of thyroid tumors are malignant. Small, asymptomatic ...

s and

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...

Hypogonadism Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen ...

* Compression of the

optic chiasm In neuroanatomy, the optic chiasm, or optic chiasma (; , ), is the part of the brain where the optic nerves cross. It is located at the bottom of the brain immediately inferior to the hypothalamus. The optic chiasm is found in all vertebrate ...

by the growth of pituitary adenoma leading to visual problems

Causes

Pituitary adenoma

About 98% of cases of acromegaly are due to the overproduction of growth hormone by a

of the pituitary gland called an

adenoma An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenom ...

. These tumors produce excessive growth hormone and compress surrounding brain tissues as they grow larger. In some cases, they may compress the

optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual system, visual information from the retina to the brain. In humans, the optic nerve i ...

s. Expansion of the tumor may cause headaches and visual disturbances. In addition, compression of the surrounding normal pituitary tissue can alter production of other

hormones A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and beh ...

, leading to changes in

menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...

and breast discharge in women and

impotence Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...

in men because of reduced

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...

production. A marked variation in rates of GH production and the aggressiveness of the tumor occurs. Some adenomas grow slowly and symptoms of GH excess are often not noticed for many years. Other adenomas grow rapidly and invade surrounding brain areas or the

sinuses Paranasal sinuses are a group of four paired air-filled spaces that surround the nasal cavity. The maxillary sinuses are located under the eyes; the frontal sinuses are above the eyes; the ethmoidal sinuses are between the eyes and the sphenoid ...

, which are located near the pituitary. In general, younger people tend to have more aggressive tumors. Most pituitary tumors arise spontaneously and are not genetically inherited. Many pituitary tumors arise from a genetic alteration in a single pituitary cell that leads to increased cell division and tumor formation. This genetic change, or

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

, is not present at birth but is acquired during life. The mutation occurs in a gene that regulates the transmission of chemical signals within pituitary cells; it permanently switches on the signal that tells the cell to divide and secrete growth hormones. The events within the cell that cause disordered pituitary

cell growth Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...

and GH oversecretion currently are the subject of intensive research. Pituitary adenomas and diffuse somatomammotroph hyperplasia may result from somatic mutations activating ''GNAS'', which may be acquired or associated with McCune-Albright syndrome.

Other tumors

In a few people, acromegaly is caused not by pituitary tumors, but by

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s of the

pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

s, and

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...

s. These tumors also lead to an excess of GH, either because they produce GH themselves or, more frequently, because they produce GHRH (growth hormone-releasing hormone), the hormone that stimulates the pituitary to make GH. In these people, the excess GHRH can be measured in the blood and establishes that the cause of the acromegaly is not due to a pituitary defect. When these nonpituitary tumors are surgically removed, GH levels fall and the symptoms of acromegaly improve. In people with GHRH-producing, non-pituitary tumors, the pituitary still may be enlarged and may be mistaken for a tumor. Therefore, it is important that physicians carefully analyze all "pituitary tumors" removed from people with acromegaly so as to not overlook the possibility that a tumor elsewhere in the body is causing the disorder.

Diagnosis

If acromegaly is suspected,

medical laboratory A medical laboratory or clinical laboratory is a laboratory where tests are conducted out on clinical specimens to obtain information about the health of a patient to aid in diagnosis, treatment, and prevention of disease. Clinical Medical labor ...

investigations followed by

if the lab tests are positive confirms or rules out the presence of this condition.

IGF1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. IGF-1 is a protein that in humans is ...

provides the most sensitive lab test for the diagnosis of acromegaly, and a GH suppression test following an oral

load, which is a very specific lab test, will confirm the diagnosis following a positive screening test for IGF1. A single value of the GH is not useful in view of its pulsatility (levels in the blood vary greatly even in healthy individuals). GH levels taken 2 hours after a 75- or 100-gram

glucose tolerance test The glucose tolerance test (GTT, not to be confused with GGT test) is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, ...

are helpful in the diagnosis: GH levels are suppressed below 1 μg/L in normal people, and levels higher than this cutoff are confirmatory of acromegaly. Other pituitary hormones must be assessed to address the secretory effects of the tumor, as well as the mass effect of the tumor on the normal pituitary gland. They include

thyroid stimulating hormone Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of ...

(TSH), gonadotropic hormones (FSH, LH),

adrenocorticotropic hormone Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...

, and

prolactin Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...

. An

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

of the brain focusing on the

sella turcica The sella turcica (Latin for 'Turkish saddle') is a saddle-shaped depression in the body of the sphenoid bone of the human skull and of the skulls of other hominids including chimpanzees, gorillas and orangutans. It serves as a cephalometric la ...

after

gadolinium Gadolinium is a chemical element with the symbol Gd and atomic number 64. Gadolinium is a silvery-white metal when oxidation is removed. It is only slightly malleable and is a ductile rare-earth element. Gadolinium reacts with atmospheric oxygen ...

administration allows for clear delineation of the pituitary and the hypothalamus and the location of the tumor. A number of other

overgrowth syndrome Overgrowth syndromes in children constitute a group of rare disorders that are characterised by tissue hypertrophy. Individual overgrowth syndromes have been shown to overlap with regard to clinical and radiologic features. The details of the gene ...

s can result in similar problems.

Differential diagnosis

Pseudoacromegaly Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Other ...

is a condition with the usual acromegaloid features, but without an increase in growth hormone and IGF-1. It is frequently associated with insulin resistance. Cases have been reported due to

minoxidil Minoxidil, sold under the brand name Rogaine among others, is a medication used for the treatment of high blood pressure and pattern hair loss. It is an antihypertensive vasodilator. It is available as a generic medication by prescription in ora ...

at an unusually high dose. It can also be caused by a selective post receptor defect of insulin signalling, leading to the impairment of metabolic, but preservation of mitogenic, signalling.

Treatment

The goals of treatment are to reduce GH production to normal levels thereby reversing or ameliorating the signs and symptoms of acromegaly, to relieve the pressure that the growing pituitary tumor exerts on the surrounding brain areas, and to preserve normal pituitary function. Currently, treatment options include surgical removal of the tumor,

drug therapy Pharmacotherapy is therapy using pharmaceutical drugs, as distinguished from therapy using surgery (surgical therapy), radiation (radiation therapy), movement (physical therapy), or other modes. Among physicians, sometimes the term ''medical ther ...

, and

of the pituitary.

Medications

Somatostatin analogues

The primary current medical treatment of acromegaly is to use somatostatin analogues –

octreotide Octreotide, sold under the brand name Sandostatin among others, is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was ...

(Sandostatin) or

lanreotide Lanreotide, sold under the brand name Somatuline among others, is a medication used in the management of acromegaly and symptoms caused by neuroendocrine tumors, most notably carcinoid syndrome. It is a long-acting analogue of somatostatin, like ...

(Somatuline). These somatostatin analogues are synthetic forms of a brain hormone,

somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...

, which stops GH production. The long-acting forms of these drugs must be injected every 2 to 4 weeks for effective treatment. Most people with acromegaly respond to this medication. In many people with acromegaly, GH levels fall within one hour and headaches improve within minutes after the injection. Octreotide and lanreotide are effective for long-term treatment. Octreotide and lanreotide have also been used successfully to treat people with acromegaly caused by non-pituitary tumors. Somatostatin analogues are also sometimes used to shrink large tumors before surgery. Because octreotide inhibits gastrointestinal and pancreatic function, long-term use causes digestive problems such as loose stools, nausea, and gas in one third of people. In addition, approximately 25 percent of people with acromegaly develop

gallstone A gallstone is a calculus (medicine), stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to ...

s, which are usually asymptomatic. In some cases, octreotide treatment can cause

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

due to the fact that

and its analogues can inhibit the release of

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

. With an aggressive adenoma that is not able to be operated on, there may be a resistance to octreotide and in which case a second generation SSA, pasireotide, may be used for tumor control. However, insulin and glucose levels should be carefully monitored as pasireotide has been associated with hyperglycemia by reducing insulin secretion.

Dopamine agonists

For those who are unresponsive to somatostatin analogues, or for whom they are otherwise contraindicated, it is possible to treat using one of the

dopamine agonists A dopamine agonist (DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D2-like and D1-like, and they are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the ...

bromocriptine Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic maligna ...

cabergoline Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth. Cabergoline is an e ...

. As tablets rather than injections, they cost considerably less. These drugs can also be used as an adjunct to somatostatin analogue therapy. They are most effective in those whose pituitary tumours cosecrete

. Side effects of these dopamine agonists include gastrointestinal upset, nausea, vomiting, light-headedness when standing, and nasal congestion. These side effects can be reduced or eliminated if medication is started at a very low dose at bedtime, taken with food, and gradually increased to the full therapeutic dose. Bromocriptine lowers GH and

IGF-1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. IGF-1 is a protein that in humans is ...

levels and reduces tumor size in fewer than half of people with acromegaly. Some people report improvement in their symptoms although their GH and IGF-1 levels still are elevated.

Growth hormone receptor antagonists

The latest development in the medical treatment of acromegaly is the use of

growth hormone receptor Growth hormone receptor is a protein that in humans is encoded by the ''GHR'' gene. GHR orthologs have been identified in most mammals. Structure Growth hormone receptor (GHR) is a transmembrane protein consisting of 620 amino acids. The recep ...

antagonists. The only available member of this family is

pegvisomant Pegvisomant, sold under the brand name Somavert, is a growth hormone receptor antagonist used in the treatment of acromegaly. It is primarily used if the pituitary gland tumor causing the acromegaly cannot be controlled with surgery or radiatio ...

(Somavert). By blocking the action of the endogenous growth hormone molecules, this compound is able to control the disease activity of acromegaly in virtually everyone with acromegaly. Pegvisomant has to be administered subcutaneously by daily injections. Combinations of long-acting somatostatin analogues and weekly injections of pegvisomant seem to be equally effective as daily injections of pegvisomant.

Surgery

Surgical removal of the pituitary tumor is usually effective in lowering growth hormone levels. Two surgical procedures are available for use. The first is endonasal transsphenoidal surgery, which involves the surgeon reaching the pituitary through an incision in the

nasal cavity The nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. The nasal septum divides the cavity into two cavities, also known as fossae. Each cavity is the continuation of one of the two nostrils. The nasal c ...

wall. The wall is reached by passing through the

nostril A nostril (or naris , plural ''nares'' ) is either of the two orifices of the nose. They enable the entry and exit of air and other gasses through the nasal cavities. In birds and mammals, they contain branched bones or cartilages called turbi ...

s with microsurgical instruments. The second method is transsphenoidal surgery during which an incision is made into the gum beneath the upper lip. Further incisions are made to cut through the

septum In biology, a septum (Latin for ''something that encloses''; plural septa) is a wall, dividing a cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate. Examples Human anatomy * Interatri ...

to reach the nasal cavity, where the pituitary is located. Endonasal transsphenoidal surgery is a less invasive procedure with a shorter recovery time than the older method of transsphenoidal surgery, and the likelihood of removing the entire tumor is greater with reduced side effects. Consequently, endonasal transsphenoidal surgery is the more common surgical choice. These procedures normally relieve the pressure on the surrounding brain regions and lead to a lowering of GH levels. Surgery is most successful in people with blood GH levels below 40 ng/ml before the operation and with pituitary tumors no larger than 10 mm in diameter. Success depends on the skill and experience of the surgeon. The success rate also depends on what level of GH is defined as a cure. The best measure of surgical success is the normalization of GH and IGF-1 levels. Ideally, GH should be less than 2 ng/ml after an oral glucose load. A review of GH levels in 1,360 people worldwide immediately after surgery revealed that 60% had random GH levels below 5 ng/ml. Complications of surgery may include

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

leaks,

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

, or damage to the surrounding normal pituitary tissue, requiring lifelong pituitary

hormone replacement Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vagina ...

. Even when surgery is successful and hormone levels return to normal, people must be carefully monitored for years for possible recurrence. More commonly, hormone levels may improve, but not return completely to normal. These people may then require additional treatment, usually with medications.

Radiation therapy

Radiation therapy has been used both as a primary treatment and combined with surgery or drugs. It is usually reserved for people who have tumor remaining after surgery. These people often also receive medication to lower GH levels. Radiation therapy is given in divided doses over four to six weeks. This treatment lowers GH levels by about 50 percent over 2 to 5 years. People monitored for more than 5 years show significant further improvement. Radiation therapy causes a gradual loss of production of other pituitary hormones with time. Loss of vision and brain injury, which have been reported, are very rare complications of radiation treatments.

Selection of treatment

The initial treatment chosen should be individualized depending on the person's characteristics, such as age and tumor size. If the tumor has not yet invaded surrounding brain tissues, removal of the pituitary adenoma by an experienced neurosurgeon is usually the first choice. After surgery, a person must be monitored long-term for increasing GH levels. If surgery does not normalize hormone levels or a relapse occurs, a doctor will usually begin additional drug therapy. The current first choice is generally octreotide or lanreotide; however, bromocriptine and cabergoline are both cheaper and easier to administer. With all of these medications, long-term therapy is necessary, because their withdrawal can lead to rising GH levels and tumor re-expansion. Radiation therapy is generally used for people whose tumors are not completely removed by surgery, for people who are not good candidates for surgery because of other health problems, and for people who do not respond adequately to surgery and medication.

Prognosis

Life expectancy of people with acromegaly is dependent on how early the disease is detected. Life expectancy after the successful treatment of early disease is equal to that of the general population. Acromegaly can often go on for years before diagnosis, resulting in poorer outcome, and it is suggested that the better the growth hormone is controlled, the better the outcome. Upon successful surgical treatment, headaches and visual symptoms tend to resolve. One exception is sleep apnea, which is present in around 70% of cases, but does not tend to resolve with successful treatment of growth hormone level. While hypertension is a complication of 40% of cases, it typically responds well to regular regimens of blood pressure medication. Diabetes that occurs with acromegaly is treated with the typical medications, but successful lowering of growth hormone levels often alleviates symptoms of diabetes. Hypogonadism without gonad destruction is reversible with treatment. Acromegaly is associated with a slightly elevated risk of cancer.

Notable people

A number of famous people have or have had acromegaly. For several people in this list, stark physical features associated with excess growth hormone have greatly contributed to their fame. Thus one should keep in mind that this list is tilted towards showing rather pronounced cases of acromegaly: *

Daniel Cajanus Daniel Cajanus (1704 – 27 February 1749) was a Finnish giant. He made his living by exhibiting himself for money; he appeared in many European countries and attracted the interest of scientists and laypeople, including royalty. After his death, ...

(1704–1749), "The Finnish Goliath". His natural size portrait and femur are still extant. His height was estimated to have been 247 cm (8' 1"). * Mary Ann Bevan (1874–1933), an English woman, who after developing acromegaly, toured the

sideshow In North America, a sideshow is an extra, secondary production associated with a circus, carnival, fair, or other such attraction. Types There are four main types of classic sideshow attractions: *The Ten-in-One offers a program of ten seq ...

circuit as "the ugliest woman in the world". *

André the Giant André René Roussimoff (; 19 May 1946 – 28 January 1993), better known by his ring name André the Giant, was a French professional wrestler and actor. Roussimoff was known for his great size, which was a result of gigantism caused by exce ...

(born André Roussimoff, 1946–1993), French professional wrestler and actor *

Salvatore Baccaro Salvatore Baccaro (6 May 1932 – 13 March 1984) was an Italian character actor. He was recognizable for his known acromegaly and appeared in more than sixty films from 1970 to 1984. He died on 13 March 1984 aged 52 after thyroid surgery. Filmo ...

(1932–1984), Italian character actor. Active in

B-movies A B movie or B film is a low-budget commercial motion picture. In its original usage, during the Golden Age of Hollywood, the term more precisely identified films intended for distribution as the less-publicized bottom half of a double featur ...

comedies Comedy is a genre of fiction that consists of discourses or works intended to be humorous or amusing by inducing laughter, especially in theatre, film, stand-up comedy, television, radio, books, or any other entertainment medium. The term origin ...

, and horrors because of his peculiar features and spontaneous sympathy *

Paul Benedict Paul Benedict (September 17, 1938 – December 1, 2008) was an American actor who made numerous appearances in television and films, beginning in 1965. He was known for his roles as The Number Painter on the PBS children's show ''Sesame Street' ...

(1938–2008), American actor. Best known for portraying Harry Bentley, ''

The Jeffersons ''The Jeffersons'' is an American sitcom television series that was broadcast on CBS from January 18, 1975, to July 2, 1985, lasting 11 seasons and a total of List of The Jeffersons episodes, 253 episodes. ''The Jeffersons'' is one of the longe ...

'' English next door neighbour *

Big Show Paul Donald Wight II (born February 8, 1972) is an American professional wrestler and actor. He is signed to All Elite Wrestling (AEW) as an in-ring performer, and as a commentator for its web television show, '' AEW Dark: Elevation,'' under ...

(born Paul Wight; 1972), American professional wrestler and actor, had his pituitary tumor removed in 1991. *

Eddie Carmel Eddie Carmel (born Oded Ha-Carmeili ; March 16, 1936 – August 14, 1972) was an Israeli-born American entertainer with gigantism and subsequent acromegaly resulting from a pituitary adenoma. He was popularly known as "The Jewish Giant", "The ...

, born Oded Ha-Carmeili (1936–1972), Israeli-born entertainer with gigantism and acromegaly, popularly known as "The Jewish Giant" *

Ted Cassidy Theodore Crawford Cassidy (July 31, 1932 – January 16, 1979) was an American actor noted for his tall stature at and deep voice. He tended to play unusual characters in offbeat or science-fiction series such as ''Star Trek'' and ''I Dream of ...

(1932–1979), American actor. Best known for portraying Lurch in the TV sitcom ''

The Addams Family ''The Addams Family'' is a fictional family created by American cartoonist Charles Addams. They originally appeared in a series of 150 unrelated single-panel cartoons, about half of which were originally published in ''The New Yorker'' over a ...

'' *

Rondo Hatton Rondo Hatton (April 22, 1894 – February 2, 1946) was an American journalist and actor. After writing for ''The Tampa Tribune'', Hatton found a career in film due to his unique facial features, which were the result of acromegaly. He headlin ...

(1894–1946), American journalist and actor. A Hollywood favorite in B-movie horror films of the 1930s and 1940s. Hatton's disfigurement, due to acromegaly, developed over time, beginning during his service in World War I. * Sultan Kösen, the world's tallest man *

Maximinus Thrax Gaius Julius Verus Maximinus "Thrax" ("the Thracian"; – 238) was Roman emperor from 235 to 238. His father was an accountant in the governor's office and sprang from ancestors who were Carpi (a Dacian tribe), a people whom Diocletian ...

, Roman emperor (, reigned 235–238). Descriptions, as well as depictions, indicate acromegaly, though remains of his body are yet to be found. *

The Great Khali Dalip Singh Rana (born 27 August 1972) is an Indian professional wrestler and wrestling promoter better known by his ring name The Great Khali. He is best known for his tenure in WWE where he became the first Indian-born WWE World Heavywe ...

(born Dalip Singh Rana), Indian professional wrestler, is best known for his tenure with WWE. He had his pituitary tumor removed in 2012 at age 39. *

Primo Carnera Primo may refer to: People *DJ Premier (born 1966), hip-hop producer, sometimes goes by nickname Primo * Primo Carnera (1906–1967), Italian boxer, World Heavyweight champion 1933–1934 *Primo Cassarino (born 1956), enforcer for the Gambino cr ...

(1906–1967), nicknamed the Ambling Alp, was an Italian professional boxer and wrestler who reigned as the boxing World Heavyweight Champion from 29 June 1933 to 14 June 1934. *

Maurice Tillet Maurice Tillet (23 October 1903 – 4 September 1954) was a Russian-born French professional wrestler, better known by his ring name, The French Angel. Tillet was a leading box office draw in the early 1940s and was twice World Heavyweight Cham ...

(1903–1954), Russian-born French professional wrestler, is better known by his ring name, the French Angel. *

Richard Kiel Richard Dawson Kiel (September 13, 1939 – September 10, 2014) was an American actor. Standing tall, he was known for portraying Jaws in '' The Spy Who Loved Me'' (1977) and '' Moonraker'' (1979). Kiel's next-most-recognized role is the t ...

(1939–2014), actor, "Jaws" from two James Bond movies and Mr. Larson in ''

Happy Gilmore ''Happy Gilmore'' is a 1996 American sports comedy film directed by Dennis Dugan and produced by Robert Simonds. It stars Adam Sandler as the title character, an unsuccessful ice hockey player who discovers a newfound talent for golf. The screenp ...

'' *

Pío Pico Don Pío de Jesús Pico (May 5, 1801 – September 11, 1894) was a Californio politician, ranchero, and entrepreneur, famous for serving as the last governor of California (present-day U.S. state of California) under Mexican rule. A member of ...

, the last Mexican Governor of California (1801–1894), manifested acromegaly without gigantism between at least 1847 and 1858. Some time after 1858, signs of the growth hormone-producing tumor disappeared along with all the secondary effects the tumor had caused in him. He looked normal in his 90s. His remarkable recovery is likely an example of spontaneous selective pituitary tumor apoplexy. *

Earl Nightingale Earl Nightingale V (March 12, 1921 – March 25, 1989) was an American radio speaker and author, dealing mostly with the subjects of human character development, motivation, and meaningful existence. He was the voice during the early 1950s of ...

(March 12, 1921 – March 25, 1989) was an American radio speaker and author, dealing mostly with the subjects of human character development, motivation, and meaningful existence. He was the voice during the early 1950s of Sky King, the hero of a radio adventure series, and was a WGN radio program host from 1950 to 1956. Nightingale was the author of The Strangest Secret, which economist Terry Savage has termed "…one of the great motivational books of all time." Nightingale’s daughter, Pamela, mentioned her father had acromegaly during a podcast about her father that aired in June 2022. *

Tony Robbins Anthony Jay Robbins (né Mahavoric, born February 29, 1960) is an American author, coach, speaker, and philanthropist. He is known for his infomercials, seminars, and self-help books including the books ''Unlimited Power'' and ''Awaken the Gia ...

, motivational speaker *

Carel Struycken Carel Struycken (; born 30 July 1948) is a Dutch actor. He is known for playing the Giant/Fireman in the television series ''Twin Peaks'' (1990–1991, 2017), the occasional guest role of Mr. Homn in '' Star Trek: The Next Generation'' (1987–1 ...

, Dutch actor, , is best known for playing Lurch in ''

'' film trilogy, The Giant in ''

Twin Peaks ''Twin Peaks'' is an American Mystery fiction, mystery serial drama television series created by Mark Frost and David Lynch. It premiered on American Broadcasting Company, ABC on April 8, 1990, and originally ran for two seasons until its cance ...

'', Lwaxana Troi's silent Servant

Mr. Homn This is a list of characters from the science fiction Science fiction (sometimes shortened to Sci-Fi or SF) is a genre of speculative fiction which typically deals with imaginative and futuristic concepts such as advanced science and t ...

in '' Star Trek: The Next Generation'', and The Moonlight Man in ''

Gerald's Game ''Gerald's Game'' is a 1992 suspense novel by American writer Stephen King. The story is about a woman whose husband dies of a heart attack while she is handcuffed to a bed, and, following the subsequent realization that she is trapped with lit ...

'', based on the Stephen King book. *

Peter Mayhew Peter William Mayhew (19 May 1944 – 30 April 2019) was a British-American actor. He was best known for portraying Chewbacca in the ''Star Wars'' film series. He played the character in all of his live-action appearances from the 1977 origin ...

(1944–2019), British-American actor, was diagnosed with gigantism at age eight. Best known for portraying

Chewbacca Chewbacca ( ), nicknamed "Chewie", is a fictional character in the ''Star Wars'' franchise. He is a Wookiee, a tall, hirsute, bipedal, intelligent species originating from the fictional planet of Kashyyyk. Chewbacca is the loyal friend and firs ...

in the ''

Star Wars ''Star Wars'' is an American epic film, epic space opera multimedia franchise created by George Lucas, which began with the Star Wars (film), eponymous 1977 film and quickly became a worldwide popular culture, pop-culture Cultural impact of S ...

'' film series. *

Irwin Keyes Irwin may refer to: Places ;United States * Irwin, California * Irwin, Idaho * Irwin, Illinois * Irwin, Iowa * Irwin, Nebraska * Irwin, Ohio * Irwin, Pennsylvania * Irwin, South Carolina * Irwin County, Georgia * Irwin Township, Venango County, ...

, American actor. Best known for portraying Hugo Mojoloweski, George's occasional bodyguard on ''

'' *

Morteza Mehrzad Morteza Mehrzadselakjani (born 17 September 1987) is an Iranian volleyball player who plays in the national sitting volleyball team of and Mes Shahr Babak. With a height of 247 cm, he is known as the tallest living man in Iran and the second tall ...

Iranian Iranian may refer to: * Iran, a sovereign state * Iranian peoples, the speakers of the Iranian languages. The term Iranic peoples is also used for this term to distinguish the pan ethnic term from Iranian, used for the people of Iran * Iranian lan ...

Paralympian The Paralympic Games or Paralympics, also known as the ''Games of the Paralympiad'', is a periodic series of international multisport events involving athletes with a range of physical disabilities, including impaired muscle power and impaire ...

and medalist. Member of the Iranian sitting volleyball team. Top scorer in the 2016 gold medal match * Neil McCarthy, British actor. Known for roles in '' Zulu'', ''

Time Bandits ''Time Bandits'' is a 1981 British fantasy adventure film co-written, produced, and directed by Terry Gilliam. It stars Sean Connery, John Cleese, Shelley Duvall, Ralph Richardson, Katherine Helmond, Ian Holm, Michael Palin, Peter Vaughan and ...

'', and many British television series *

Nikolai Valuev Nikolai Sergeyevich Valuev (, rus, Никола́й Серге́евич Валу́ев, p=vɐˈlujɪf; born 21 August 1973) is a Russian politician and former professional boxer. He competed in boxing from 1993 to 2009, and held the WBA heav ...

, Russian politician and former professional boxer * Antônio "Bigfoot" Silva, Brazilian

kickboxer Kickboxing is a combat sport focused on kicking and punching. The combat takes place in a boxing ring, normally with boxing gloves, mouthguards, shorts, and bare feet to favour the use of kicks. Kickboxing is practiced for self-defense, general ...

and

mixed martial arts Mixed martial arts (MMA), sometimes referred to as cage fighting, no holds barred (NHB), and ultimate fighting, and originally referred to as Vale Tudo is a full-contact combat sport based on striking, grappling and ground fighting, inc ...

fighter. * (Leonel)

Edmundo Rivero Leonel Edmundo Rivero (June 8, 1911 – January 18, 1986) was an Argentine tango singer, composer, and impresario. Biography Early days Rivero was born in the southern Buenos Aires suburb of Valentín Alsina. Joining his father in some of his ...

Argentine Argentines (mistakenly translated Argentineans in the past; in Spanish (masculine) or (feminine)) are people identified with the country of Argentina. This connection may be residential, legal, historical or cultural. For most Argentines, s ...

tango Tango is a partner dance and social dance that originated in the 1880s along the Río de la Plata, the natural border between Argentina and Uruguay. The tango was born in the impoverished port areas of these countries as the result of a combina ...

singer, composer and

impresario An impresario (from the Italian ''impresa'', "an enterprise or undertaking") is a person who organizes and often finances concerts, plays, or operas, performing a role in stage arts that is similar to that of a film or television producer. Hist ...

It has been argued that

Lorenzo de' Medici Lorenzo di Piero de' Medici (; 1 January 1449 – 8 April 1492) was an Italian statesman, banker, ''de facto'' ruler of the Florentine Republic and the most powerful and enthusiastic patron of Renaissance culture in Italy. Also known as Lorenzo ...

(1449–92) may have had acromegaly. Historical documents and portraits, as well as a later analysis of his skeleton, support the speculation. Pianist and composer

Sergei Rachmaninoff Sergei Vasilyevich Rachmaninoff; in Russian pre-revolutionary script. (28 March 1943) was a Russian composer, virtuoso pianist, and conductor. Rachmaninoff is widely considered one of the finest pianists of his day and, as a composer, one o ...

, noted for his hands that could comfortably stretch a 13th on the piano, was never diagnosed with acromegaly in his lifetime, but a medical article from 2006 suggests that he might have had it. The

Bogdanoff twins Igor Youriévitch Bogdanoff (; 29 August 1949 – 3 January 2022) and Grégoire "Grichka" Youriévitch Bogdanoff (; 29 August 1949 – 28 December 2021) were French twin television presenters, producers, and essayists who, from the 1970s on, pr ...

had shown some signs of acromegaly and their continued denials that they had plastic surgery that greatly altered their facial appearance made some consider the disease. However, acromegaly was not proven before they died.

References

External links

*
2011 American Association of Clinical Endocrinologists Guideline

{{Authority control Endocrine-related cutaneous conditions Growth disorders Growth hormones Neuroendocrinology Pituitary disorders Wikipedia medicine articles ready to translate Wikipedia neurology articles ready to translate

Signs and symptoms

Complications

Causes

Pituitary adenoma

Other tumors

Diagnosis

Differential diagnosis

Treatment

Medications

Somatostatin analogues

Dopamine agonists

Growth hormone receptor antagonists

Surgery

Radiation therapy

Selection of treatment

Prognosis

Notable people

See also

References

External links