User:IntentionallyDense/Acromegaly

IntentionallyDense/Acromegaly
Characteristic facial features of acromegaly

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Acromegaly is a disorder characterized by an excessive amount of growth hormone (GH). It is a chronic disorder affecting multiple organ systems, causing various symptoms. Acromegaly symptoms include facial changes, fatigue, joint pain, prominent brow ridges, enlarged tongue, thick skin, increased hand and foot size, increased sweating, and over- or underbites.

Somatotroph adenomas are hormone-producing tumours responsible for 95% of acromegaly cases. They form due to the uncontrolled growth of somatotroph cells, causing problems with the cell cycle and hormone production pathways. GH, a peptide hormone, is produced by somatotroph cells in the pituitary gland and stimulates insulin-like growth factor 1 (IGF-1) production, leading to acromegaly symptoms over time.

Acromegaly is diagnosed by increased IGF-1 levels and failure to lower growth hormone levels during an oral glucose tolerance test. Physical examination and history taking can help identify potential symptoms, and IGF-I levels above 1.3 times the upper limit of normal can confirm the diagnosis. Acromegaly is treated using surgery, medication, and radiation therapy, with pituitary surgery being the first-line treatment. If the disease persists, medication may be used, and if surgery doesn't result in remission or the tumour is large or invasive, radiation therapy may be considered. Those with acromegaly have twice the mortality rate of healthy individuals, primarily due to heart disease and cancer. However, mortality has decreased over time, likely due to treatment advancements.

Acromegaly affects 50 to 60 people per million. Acromegaly is typically diagnosed between the ages of 40-60, with 44 being the most common age at diagnosis. It affects all races and genders equally. Acromegaly is diagnosed only after the growth plates have fused. If high growth hormone levels occur before this fusion, it is typically diagnosed as gigantism. Therefore, acromegaly is seldom diagnosed in children, though some cases have been reported in teenagers.

Signs and symptoms

Acromegaly is a chronic disorder that can affect multiple different organ systems, meaning that those with acromegaly can experience several different symptoms. Changes in the face are often the most recognizable symptoms. Nonspecific symptoms, like fatigue and joint pain, can also be prominent symptoms. Physical examination of those with acromegaly can reveal prominent brow ridges, enlarged tongue, thick and oily skin, increase in hand and foot size, increased sweating and over or under bites. Those with acromegaly may visit several different specialists, such as neurologists, dentists, surgeons, rheumatologists, cardiologists, and gynecologists. The symptoms of acromegaly may develop slowly over time, or present more suddenly, with pituitary apoplexy.

Signs and symptoms of acromegaly

Type	Sign/symptom
Acral enlargement	Increased hand, shoe, and ring size
	Prominent crease running from the sides of the nose to the corners of the mouth (nasolabial fold)
	Prominent forehead (frontal bossing)
	Prominent brow ridge
Skin	Increased sweating
	Oiliness
	Excess hair (hirsutism)
	Increased skin pigmentation (hyperpigmentation)
	Tickened skin on the back of the hands
	Skin tags
	Furrowing of the skin on the forehead or back of the head (cutis verticis gyrata)
Cardiovascular	High blood pressure (hypertension)
	Congestive heart failure
	Ventricular hypertrophy
	Cardiomyopathy
Respiratory	Sleep apnea
	Enlarged sinuses
	Deep voice
Musculoskeletal	Knee, hip, and spine arthropathy
	Rounded upper back (kyphosis)
	Under or overbite (prognathism)
	Misaligned teeth (dental malocclusion)
	Muscle weakness
	Increased height
Alimentary	Enlarged tongue (macroglossia)
	Enlarged abdominal (liver, spleen, kidney, bowels, salivary glands) organs (visceromegaly)
	Colon polyps
	Constipation
Neurological	Headache
	Pituitary apoplexy
	Carpal tunnel syndrome
	Tingling and numbness (paraesthesia)
Reproductive	Loss of menses (amenorrhoea)
	Breast milk production (galactorrhoea)
	Impotence
	Enlarged prostate
Metabolic	Increased insulin resistance
	Diabetes mellitus
	High urinary calcium (hypercalciuria)
	High blood calcium (hypercalcaemia)
Endocrine	Concurrent secretion of prolactin or thyroid-stimulating hormone (TSH)
	Galactorrhoea
	Hypopituitarism
	Multinodular goitre
Psychological	Anxiety
	Fatigue
	Apathy
	Depression
Local tumour effects	Headache
	Visual field defects (bitemporal hemianopsia)
	Cranial nerve palsy

Facial features of acromegaly

Prognathism

Widened and thickened nose, prominant cheekbones, bulging forehead with thickened skin, thick lips and pronounced facial lines

Over half of those with acromegaly experience heart disease and 18–55% have high blood pressure. Acromegaly is a risk factor for valvular diseases such as aortic and mitral regurgitation. Other cardiovascular system manifestations of acromegaly include increased size of the left ventricle, cardiomyopathy, ischaemic heart disease, coronary arterial disease, and arrhythmias.

Respiratory symptoms such as narcolepsy and sleep apnea, sometimes caused by obstruction of the airway due to prognathism, macroglossia, and hypertrophy of the nasal structures, are common. Although obstructive sleep apnea is more common, up to 30% of those with acromegaly also have central sleep apnea. Too much growth hormone (GH) can increase the amount of air left in the lungs after exhaling (residual lung volume), small airway obstructions, and lower the lungs' ability to transfer oxygen into the blood (diffusion capacity).

Increased insulin resistance happens because GH directly counteracts insulin, which can lead to diabetes. High cholesterol affects 13–80% of those with acromegaly. About 80% of those with acromegaly develop hypercalciuria since GH helps produce vitamin D, which increases calcium absorption in the bowels and kidneys. High phosphate levels (hyperphosphatemia) can also occur due to GH and insulin-like growth factor 1 (IGF-1) affecting phosphate reabsorption in the kidneys. People with acromegaly are more likely to develop a multinodular goiter, which can lead to hyperthyroidism. A tumour pressing on nearby structures (mass effect), high prolactin levels, and too much GH or IGF-1 can all lead to reduced pituitary function (hypopituitarism). Treatments like surgery and radiation can increase this risk even more. About half of those with acromegaly have low sex hormones (hypogonadism) at the time of diagnosis; other hormone deficiencies are less common. Infertility is common and may be due to either reduced pituitary function, high prolactin levels, or both. Too much GH or IGF-1 can also interfere with the release of reproductive hormones and may lead to symptoms similar to polycystic ovary syndrome.

75% of those with acromegaly experience joint pain, often caused by degenerative joint disease and hypermobility. The most commonly affected joints include the hip and spine. Those with acromegaly are also at a higher risk for vertebral fractures. Excess bone growth and thickening of soft tissues can compress nerves, leading to conditions like carpal tunnel syndrome, seen in 19–64% of those with acromegaly, and cubital tunnel syndrome. About two-thirds of those with acromegaly experience headaches, which may be caused by high levels of GH or by the tumour pressing into nearby areas. Abdominal organs such as the liver, kidneys, spleen, and colon can become enlarged due to acromegaly. Constipation and colon polyps are other common symptoms of acromegaly.

Complications

Experimental studies have shown that the GH–IGF-1 pathway can play a role in cancer growth in people with acromegaly by promoting cell growth and division (cell proliferation). However, studies investigating the risk of cancer in those with acromegaly have had mixed results, with some studies finding an increased risk of certain cancers, notably thyroid and colorectal cancers, and others finding no significant increases in cancer among those with acromegaly compared to those without.

Causes

Pituitary macroadenoma

About 99% of the time, acromegaly is caused by a GH-secreting pituitary adenoma; larger pituitary adenomas (macroadenomas, over 1 cm in size) are more common than smaller ones (microadenomas), mainly because diagnosis is often delayed. Less than 1% of those with acromegaly have a tumour that produces growth hormone-releasing hormone (GHRH). These are usually rare neuroendocrine tumours found in the pancreas or the lungs. In extremely rare cases, they can come from a pheochromocytoma. Tumors in the hypothalamus, like gangliocytomas, can also produce GHRH. Pituitary cancers are very rare, making up only 0.1% of all pituitary tumours. Genetic disorders may also cause acromegaly.

Genetics

About 5% of all pituitary neuroendocrine tumors are caused by inherited genetic conditions. Acromegaly can be caused by genetic disorders that cause various symptoms, such as multiple endocrine neoplasia type 1, type 2, and type 4, McCune-Albright syndrome, Carney complex, three P association (phaeochromocytoma, paraganglioma and pituitary adenoma), neurofibromatosis type 1, and tuberous sclerosis complex, or genetic disorders which only effect the pituitary gland, including familial isolated pituitary adenoma, x-linked acrogigantism,, and mutations in the aryl hydrocarbon receptor interacting protein.

Mechanism

Somatotropine

Acromegaly is caused by the long-term hypersecretion of GH. GH is a peptide hormone made by somatotroph cells in the front part of the pituitary gland. Its release is triggered by GHRH from the hypothalamus. GH then stimulates the production of IGF-1, which helps body tissues grow. Excessive exposure to GH over time causes the symptoms of acromegaly.

Somatotroph adenomas make up about 15–20% of all pituitary tumours. Somatotroph adenomas are hormone-producing tumours that release too much growth hormone and are responsible for 95% of acromegaly cases. They form due to the uncontrolled growth of somatotroph cells, caused by problems with the cell-cycle and the pathways that control their growth and hormone production. Although these tumours are not cancerous and don’t spread to other parts of the body, they can grow into nearby tissues. Their development is linked to genetic mutations, changes in gene regulation (epigenetics), and chromosome instability.

Diagnosis

Growth hormone levels in healthy individuals (left) and those with acromegaly (right)

The diagnosis of acromegaly is commonly made based on increased levels of IGF-1 and a failure to lower growth hormone levels during an oral glucose tolerance test (OGTT). Physical examination and history taking can aid in the assessment of a person with potential acromegaly, as it can uncover signs and symptoms pointing to acromegaly. IGF-I > 1.3 times the upper limit of normal in a person with symptoms of acromegaly can confirm the diagnosis.

Random measurement of serum GH has little utility in making the diagnosis of acromegaly; GH is released in bursts, with long gaps in between where its levels can be so low that it's not detectable in the blood. Factors such as sleep, exercise, fasting, and stress may also affect GH levels. IGF-1 levels in the blood stay fairly steady throughout the day, making it a reliable test for diagnosing excess growth hormone. It’s usually measured using immunoassays or liquid chromatography with mass spectrometry.

If IGF-1 levels are high or borderline, a 75 g OGTT may be performed. In healthy people, GH levels drop after consuming glucose. A diagnosis of acromegaly is made if GH does not fall below 1 μg/L. After acromegaly has been diagnosed, a magnetic resonance image (MRI) of the pituitary gland may be performed to look for a pituitary adenoma.

Differential diagnosis

The diagnosis of acromegaly is generally pretty direct based on the person's history, symptoms, blood tests, and imaging. Some people with traits of acromegaly, such as tall stature and characteristic facial features, have normal levels of GH. Pseudoacromegaly refers to a group of different conditions where individuals show physical features similar to those seen in acromegaly or gigantism, but without any abnormalities in growth hormone. Acromegaloidism, also known as insulin-mediated pseudoacromegaly, is a condition where a person develops features similar to acromegaly—like an enlarged jaw, hands, and feet—along with dark, thickened skin (acanthosis nigricans), due to severe insulin resistance. However, their growth hormone (GH) and IGF-1 levels are normal. Pachydermoperiostosis is a genetic disorder that also causes acromegaly-like facial features and enlarged hands and feet, along with finger and toe clubbing. Cantu syndrome is another condition that can resemble acromegaly in facial appearance.

Pseudoacromegaly conditions

Traits	Disorders
Acromegaloid features and accelerated growth/tall stature	Beckwith-Wiedemann syndrome, Berardinelli-Seip congenital lipodystrophy, chromosome 11 pericentric inversion, fragile X syndrome, Malan syndrome, Marshall-Smith syndrome, Phelan-McDermid syndrome, Simpson-Golabi-Behmel syndrome, SHOX overdosage, Sotos syndrome, Sotos-like syndromes, Tatton-Brown-Rahman syndrome, Weaver syndrome, and 15q26 microduplications
Acromegaloid features and normal growth/stature	Antiretroviral-induced lipodystrophy, Barraquer-Simons syndrome, Cantú syndrome, Coffin-Siris syndrome, certain medications (minoxidil, antiretrovirals, and phenytoin), Fabry disease, long-standing untreated primary hypothyroidism, nonislet cell tumor-induced hypoglycemia, pachydermoperiostosis, Pallister-Killian syndrome, and severe insulin resistance (insulin-mediated pseudoacromegaly)
Acromegaloid features and growth retardation/short stature	Börjeson-Forssman-Lehmann syndrome, Coffin-Lowry syndrome, Cornelia de Lange syndrome, and Nicolaides-Baraitser syndrome
Accelerated growth/tall stature and no acromegaloid features	Beals syndrome, CATSHL syndrome, endocrine disorders (sexual precocity, hyperthyroidism, hypogonadism, and obesity), epiphyseal chondrodysplasia Miura-type syndromes, familial glucocorticoid deficiency, FIBP-related overgrowth, HMGA2-related overgrowth, Klinefelter syndrome, Loeys-Dietz syndrome, and Marfan and marfanoid syndromes

Treatment

Site of action of the different therapeutic tools in acromegaly. Surgery, radiotherapy, somatostatin analogues and dopamine agonists act at the level of the pituitary adenoma, while GH-receptor antagonists act in the periphery by blocking the GH receptor and thus impairing the effects of GH on the different tissues.

Surgery, medication, and radiation therapy are used to treat acromegaly, with pituitary surgery being the first-line treatment and medication or radiation therapy used as second- or third-line treatment. Medication may be used to manage acromegaly if the disease persists despite surgery; if medication and surgery do not result in remission or an individual has a particularly large or invasive tumour, then radiation therapy may be considered. The aims of acromegaly treatment are to get GH and IGF-1 levels back to a normal amount as well as reducing the tumour size and improving symptoms, mortality, comorbidities, complications, and quality of life (QoL).

Pituitary surgery is usually done through the nose with an endoscope, though a microscope may be used in some cases. For very large tumours that extend beyond the sellar region, surgery may be done through the skull. Among those with microadenomas, remission is reached 75–90% of the time, and 40–60% of those with macroadenomas achieve remission after pituitary surgery. Remission rates are often higher at specialized centers that treat a large number of cases. Surgical removal of part of the tumour (debulking) may be performed before starting medication if the individual isn’t likely to be fully cured by surgery or if a large portion of the tumour can still be removed. A second surgery may be considered for those who still have a significant amount of the tumour left and haven't responded well to medication, or if the remaining tumour looks like it can be safely removed. Potential complications of pituitary surgery include transient diabetes insipidus, hypopituitarism, and cerebrospinal fluid leak.

Medications used to treat acromegaly include somatostatin receptor ligands (SRLs), cabergoline, and pegvisomant. The Food and Drug Administration has approved pegvisomant and various SRLs for the treatment of acromegaly. Some people may require multiple different types of medications to treat their acromegaly.

Chemical structure of somatostatin

SRLs, such as octreotide, lanreotide, and pasireotide, are commonly the first medication chosen for treating acromegaly. This is due to their efficiency and milder adverse effects, which can affect the endocrine and gastrointestinal systems. SRLs have similar effects as somatostatin, a hormone that blocks the release of GH. GH-secreting tumours usually have high levels of somatostatin receptors, making these drugs effective at reducing GH production. SRLs are usually administered through injections, however, oral octreotide capsules allow for an alternative route of administration.

Pegvisomant is a GH receptor antagonist that blocks the action of GH at its receptor, rather than lowering how much GH is produced. It is sometimes used in individuals who do reach remission with high doses of SRLs.

Cabergoline, which is a dopamine agonist, can provide a more affordable treatment option for those with milder acromegaly. Cabergoline tends to be less effective than SRLs and is considered off-label for acromegaly. While dopamine agonists usually increase GH levels in healthy people, they can actually lower GH in people with acromegaly. This is because some pituitary tumours in acromegaly have dopamine D2 receptors, which respond differently and cause GH levels to drop.

Outlook

The mortality of those with acromegaly is twice as high as the mortality of healthy individuals. Factors that increase mortality in acromegaly include old age, glucocorticoids for adrenal insufficiency, hypogonadism, and a history of radiotherapy, with high GH levels being the most important factor. The main cause of excess mortality in those with acromegaly is heart disease and cancer. However, mortality in those with acromegaly has decreased over time, most likely due to advancements in acromegaly treatment.

Iceberg graphic representing acromegaly. The iceberg tip, above water symbolizes the aspects of acromegaly that the medical community is most often concerned about. The larger, underwater part of the iceberg represents the hidden, less managed aspects of acromegaly.

The QoL in those with acromegaly is negatively affected by factors such as poor acceptance of the disease, often due to frustration from a delayed diagnosis, noticeable changes in facial features and body shape, and resulting issues like negative body image, low self-esteem, and social withdrawal. Although treatment can improve QoL in people with acromegaly, studies have shown that those with treated acromegaly report lower QoL compared to healthy individuals.

Joint disease affects about 80% of those with acromegaly, despite treatment, causing chronic pain and joint stiffness. A major factor that leads to disability in people with acromegaly is the loss of other hormone functions from the pituitary gland. Over 40% of those with acromegaly experience hypopituitarism. Amongst the different hormone deficiencies, adrenal insufficiency is linked to poor quality of life and disability.

Even with medical care, people with acromegaly often face mental health challenges and personality changes. One study found that 63% of those with acromegaly had psychiatric conditions, with depression being the most common, followed by psychosis and anxiety. Other emotional and psychological changes seen in those with acromegaly include shifts in personality due to lower self-esteem, a distorted sense of body image, trouble in relationships, pulling away from social interactions, and a noticeable drop in motivation, spontaneity, and decision-making. Some studies have found no issues with cognitive function in people with acromegaly, while others have reported problems, especially with attention. These issues may be linked to changes in brain volume seen in some people with acromegaly. People with acromegaly often report more sexual health issues than those without the condition, including reduced interest in sex (low libido) and difficulty reaching orgasm.

Epidemiology

Acromegaly occurs in about 3 to 5 people per million each year, and at any given time, about 50 to 60 people per million are living with the condition. According to recent research, the incidence of acromegaly is increasing. This may be due to improvements in care, especially earlier diagnosis and better treatment of complications, which decreases mortality. Those with acromegaly are typically diagnosed between the ages of 40-60 years, with 44 years being the most common age at diagnosis. On average, it takes about five years from the onset of symptoms to a diagnosis of acromegaly to be made. Acromegaly affects people of all races and occurs equally in both men and women. Females tend to be diagnosed at an older age than males, and have a longer diagnostic delay, which may be due to differences in how acromegaly presents in males and females, as women are more likely to experience nonspecific symptoms.

History, society and culture

Early history

Giants have been described throughout history, often in legends, myths and fairy tales. The first description of a giant comes from the bible. Goliath of Gath was said to be 290 cm tall and fought among the Philistines. Goliath's death at the hands of David is thought to have been due to vision problems, specifically a loss of peripheral vision, caused by a pituitary tumour pressing on the optic nerves.

Fragment of a statue of Pharaoh Akhenaten, who at one point was mistakenly believed to have acromegaly

One of the earliest proposed cases of acromegaly was the Egyptian Pharaoh Akhenaten. Akhenaten ruled in about 1358 B.C, and his acromegalic facial features have attracted the attention of many researchers. However, due to the prevalence of inbreeding at the time and similar facial features seen in those related to Akhenaten, this claim has been questioned. Maximinus Thrax, the Roman Emperor from 235–238 A.D., has also been rumoured to have acromegaly, however, there is little evidence for such claims.

Throughout the Dark Ages, there was little mention of giants; however, by the 1600s, giants became a prominent figure in society. Frederick William, who ruled Prussia from 1613 to 1640, utilized giants in combat, recruiting hundreds of soldiers above 180 cm named the “Potsdam Giants”. These giants were also recruited as bodyguards for nobility such as kings and gentry. One such bodyguard included Walter Parsons, a Staffordshire blacksmith.

Throughout the 18th century, exhibitions of giants became common, particularly in England. John Hunter, a Scottish surgeon, carried out many medical experiments related to endocrinology and displayed the skeleton of Charles Byrne, a well-known Irish giant, at the Hunter Museum. During the 19th century, giants and their skeletons were shown of during circus shows and displayed at museums; most famously was Barnum’s American Museum, which opened in New York City in 1842. Jack Earle, who had previously working in the film industry, was one of Barnum's most famous giants. Earle remained in the circus for 14 years, only once meeting anyone taller than himself, named Robert Wadlow, the tallest person ever recorded, who was 8 feet 11 inches tall.

Medical descriptions

Pierre Marie, the physician who first named acromegaly

Ancient physicians did not have the knowledge available to connect the symptoms of acromegaly to the pituitary gland. It wasn’t until the Renaissance period, when there was a rapid growth in scientific knowledge, and subsequently the 19th century, when experimental medicine began to take place, that endocrinology and knowledge about the pituitary gland grew.

The first medical description of acromegaly was most likely made by a Dutch ophthalmologist, Johannes Wier, in 1567. Throughout the 18th and 19th centuries, more descriptions of acromegaly emerged, including reports by Noel (1779), Saucerotte (1801), Gall (1810), and Magendie (1839).

Over 20 different physicians had made reports of acromegaly before acromegaly was recognized as a distinct disorder. Many different names were used to describe acromegaly before it became known as such, including “géant scrofuleux” by Jean-Louis-Marc Alibert in 1822, “prosopo-ectasia” (widening of the face) by Andre Verga in 1864, and “macrosomia” by Cesare Lombroso in 1869. The term “acromegaly” was coined in 1886 by Pierre Marie, using the Greek words άκρος (acros, edge, limb) and μεγάλος (megalos, large).

In 1886, Pierre Marie published a report about two cases of enlarged head and extremities, using the term acromegaly (otherwise known as “Marie's malady”). Marie and his intern, Souza-Leite, thought of acromegaly and gigantism as two distinct diseases, not yet having discovered the underlying pituitary gland dysfunction in the two conditions. Marie and Souza-Leite did, however, note enlargement of the pituitary gland amongst those with acromegaly in a thesis.

Pathogenetic history

The cause of acromegaly and gigantism remained controversial throughout the 19th century. In 1864, Verga published a report of an individual with acromegaly who had an enlarged sellar region. Following this, several reports were published indicating a link between the pituitary gland and acromegaly. In 1887, Oscar Minkowski of Germany found that the pituitary glands of several deceased people with acromegaly were enlarged. Four years later, Marie and Marinesco wrote a paper about an individual who was found to have a tumour on their pituitary gland on autopsy.

Throughout the late 19th century, case reports examining those with acromegaly and gigantism found connections between the two disorders. Eventually, it became clear that acromegaly and gigantism shared the same underlying cause, but differed in the age at which the disorders manifested.

Art and media

Historical accounts of acromegaly have been preserved through art, with stone figures and paintings portraying characteristic features of acromegaly. The French painter, Pierre Puget, painted the “David, vainqueur de Goliath” which features many signs of acromegaly despite it having been created over one hundred years prior to the first medical description of acromegaly. In Ancient Egypt, an artist created a stone figure of Akhenaten, a pharaoh, which displayed typical features of acromegaly.

Special populations

Geriatrics

Comorbidities and its prevalence data in elderly patients with acromegaly

Older people with acromegaly are often thought to have a milder presentation (phenotype), possibly because tumours tend to be smaller in the elderly, and they may have lower levels of GH and IGF-1 compared to younger individuals. However, both excess GH and signs of reduced pituitary function can be harder to spot in older adults, since these symptoms often overlap with normal aging. As a result, diagnosis in older individuals is often delayed.

In older patients, the OGTT isn't always possible since diabetes is more common in this age group. In such cases, checking GH levels throughout the day (a diurnal GH profile) can be an alternative. Lower GH and IGF-1 levels in elderly people with acromegaly may mirror the natural decline of these hormones with age. This drop is thought to be linked to reduced levels of GHRH from the hypothalamus and changes in sex hormone levels that occur with aging. Older people also tend to have a higher body weight than younger people, which can affect the GH response during an OGTT.

Surgery is usually the first choice of treatment for most people with acromegaly. However, in older adults, there’s more consideration about a higher risk of surgical complications due to other health issues that are more common in the elderly. Certain conditions—like narrow airways, heart problems, high blood pressure, diabetes, or cancer—can increase the chances of complications during or after surgery.

The prevalence of acromegaly in the elderly has increased and is expected to continue to grow. This rise in acromegaly cases with age is possibly due to better awareness and improved diagnostic skills among physicians.

Pregnancy

Semi-qualitative conceptual changes in GH, IGF-I and placental GH (pGH) during normal pregnancy and during pregnancy in women with acromegaly.

During a healthy pregnancy, the placenta starts producing growth hormone in the second trimester, which raises IGF-1 levels. This rise in IGF-1 normally causes the pituitary gland to reduce its GH production. The same process happens in those with acromegaly, but the tumour continues to produce GH on its own, unaffected by this feedback loop. High estrogen levels during pregnancy interfere with the liver’s ability to make IGF-1, leading to lower IGF-1 levels in pregnancy. As a result, many women with acromegaly notice an improvement in their symptoms during pregnancy.

Hormone changes during a healthy pregnancy often cause the lactotroph cells in the pituitary gland to grow. In women with acromegaly, especially those with macroadenomas, this growth can increase the risk of the tumour pressing on nearby structures, which may lead to worsening vision or severe headaches. Indications of tumour growth appear to be rare during pregnancy. Some studies have reported a higher risk of gestational diabetes mellitus, hypertension, and preeclampsia associated with acromegaly, while other studies have found that only the risk of hypertension and preeclampsia is elevated.

Clinical guidelines recommend that those with acromegaly pause acromegaly medications during pregnancy, due to the lack of information regarding the effects of these medications on fetuses.

Children

Acromegaly can only be diagnosed after the epiphyseal growth plates have fused. When there are high levels of GH before the growth plates have fused, a diagnosis of gigantism is usually made. Because of this, acromegaly is rarely diagnosed in children, however, there have been reports of acromegaly in teenagers.

See also

•  Dwarfism – Small size of an organism, caused by growth deficiency or genetic mutations
•  Isolated growth hormone deficiency – hypopituitarism characterized by abnormally low levels, absence or impaired function of growth hormone in the absence of abnormalities in other pituitary hormonesPages displaying wikidata descriptions as a fallback

Works cited

• Abdulhadi, Basma; Farmer, Charles Couch; Vaughan, T. Brooks (2022). "Mortality in acromegaly". Acromegaly. Contemporary Endocrinology. Springer International Publishing. pp. 149–160. doi:10.1007/978-3-031-16258-9_11. ISBN 978-3-031-16257-2.
• Ajmal, Adnan (2022). "Cardiovascular pathology in acromegaly". Acromegaly. Contemporary Endocrinology. Springer International Publishing. pp. 87–102. doi:10.1007/978-3-031-16258-9_7. ISBN 978-3-031-16257-2.
• Aldred, Cyril; Sandison, A. T. (1962). "The Pharaoh Akhenaten a problem in Egyptology and pathology". Bulletin of the History of Medicine. 36 (4). The Johns Hopkins University Press: 293–316. ISSN 0007-5140. JSTOR 44449183. PMID 13860217.
• Ambrosio, Maria Rosaria; Gagliardi, Irene; Chiloiro, Sabrina; Ferreira, Ana Gonçalves; Bondanelli, Marta; Giampietro, Antonella; et al. (2020). "Acromegaly in the elderly patients". Endocrine. 68 (1). Springer: 16–31. doi:10.1007/s12020-020-02206-7. ISSN 1355-008X. PMID 32060689.
• Bandeira, Diego Barata; Olivatti, Thaina Oliveira Felicio; Bolfi, Fernanda; Boguszewski, Cesar Luiz; dos Santos Nunes-Nogueira, Vania (2022). "Acromegaly and pregnancy: A systematic review and meta-analysis". Pituitary. 25 (3). Springer: 352–362. doi:10.1007/s11102-022-01208-0. ISSN 1386-341X. PMID 35098440.
• Bright, Tamis (2022). "Acromegaly and cancer". Acromegaly. Contemporary Endocrinology. Springer International Publishing. pp. 115–148. doi:10.1007/978-3-031-16258-9_10. ISBN 978-3-031-16257-2.
• Carrete, Luis R.; Aghi, Manish K. (2022). "The molecular biology and pathology of acromegaly". Acromegaly. Contemporary Endocrinology. Springer International Publishing. pp. 1–14. doi:10.1007/978-3-031-16258-9_1. ISBN 978-3-031-16257-2.
• Ceccato, Filippo; Barbot, Mattia; Lizzul, Laura; Cuccarollo, Angela; Selmin, Elisa; Merante Boschin, Isabella; et al. (2021). "Clinical presentation and management of acromegaly in elderly patients". Hormones. 20 (1). Springer: 143–150. doi:10.1007/s42000-020-00235-5. ISSN 1109-3099. PMC 7889670. PMID 32840821.
• Coopmans, Eva C.; Andela, Cornelie D.; Claessen, Kim M.J.A.; Biermasz, Nienke R. (2022). "Evaluating the impact of acromegaly on quality of life". Endocrinology and Metabolism Clinics of North America. 51 (4). Elsevier: 709–725. doi:10.1016/j.ecl.2022.04.004. ISSN 0889-8529. PMID 36244688.
• Costa, Pedro (1978). "The frontal sinuses of the remains purported to be Akhenaten". The Journal of Egyptian Archaeology. 64. JSTOR: 76–79. doi:10.2307/3856436. JSTOR 3856436.
• Crisafulli, Salvatore; Luxi, Nicoletta; Sultana, Janet; Fontana, Andrea; Spagnolo, Federica; Giuffrida, Giuseppe; et al. (2021). "Global epidemiology of acromegaly: A systematic review and meta-analysis". European Journal of Endocrinology. 185 (2). Oxford University Press: 251–263. doi:10.1530/EJE-21-0216. ISSN 0804-4643.
• Danilowicz, Karina; Sosa, Soledad (2023). "Acromegaly and cancer: An update". Archives of Medical Research. 54 (8). Elsevier: 102914. doi:10.1016/j.arcmed.2023.102914. ISSN 0188-4409. PMID 38007382.
• de Herder, Wouter W. (2009). "Acromegaly and gigantism in the medical literature. Case descriptions in the era before and the early years after the initial publication of Pierre Marie (1886)". Pituitary. 12 (3): 236–244. doi:10.1007/s11102-008-0138-y. ISSN 1386-341X. PMC 2712620. PMID 18683056.
• de Herder, Wouter W. (2016). "The history of acromegaly". Neuroendocrinology. 103 (1). Karger Publishers: 7–17. doi:10.1159/000371808. ISSN 0028-3835. PMID 25572320.
• Donegan, Diane; Stahl, Stephanie M. (2022). "Sleep-disordered breathing in acromegaly". Acromegaly. Contemporary Endocrinology. Springer International Publishing. pp. 67–85. doi:10.1007/978-3-031-16258-9_6. ISBN 978-3-031-16257-2.
• Donnelly, Deirdre E.; Morrison, Patrick J. (2014). "Hereditary gigantism-the biblical giant Goliath and his brothers". The Ulster Medical Journal. 83 (2): 86–88. ISSN 2046-4207. PMC 4113151. PMID 25075136.
• Drimmer, Fredrick (1991). "The tallest man in the world". Born different. Skylark. p. 50. ISBN 0-553-15897-X.
• Ershadinia, Nazanin; Tritos, Nicholas A. (2022). "Diagnosis and treatment of acromegaly: An update". Mayo Clinic Proceedings. 97 (2). Elsevier: 333–346. doi:10.1016/j.mayocp.2021.11.007. ISSN 0025-6196. PMID 35120696.
• Esposito, Daniela; Ragnarsson, Oskar; Johannsson, Gudmundur; Olsson, Daniel S (2021). "Incidence of benign and malignant tumors in patients with acromegaly is increased: A nationwide population-based study". The Journal of Clinical Endocrinology & Metabolism. doi:10.1210/clinem/dgab560. ISSN 0021-972X. PMID 34343297.
• Feffer, Jill B. (2022). "Musculoskeletal disorders of acromegaly". Acromegaly. Contemporary Endocrinology. Springer International Publishing. pp. 111–114. doi:10.1007/978-3-031-16258-9_9. ISBN 978-3-031-16257-2.
• Fleseriu, Maria; Langlois, Fabienne; Lim, Dawn Shao Ting; Varlamov, Elena V; Melmed, Shlomo (2022). "Acromegaly: pathogenesis, diagnosis, and management" (PDF). The Lancet Diabetes & Endocrinology. 10 (11): 804–826. doi:10.1016/S2213-8587(22)00244-3. PMID 36209758. Retrieved 2025-04-09.
• Giustina, Andrea; Barkhoudarian, Garni; Beckers, Albert; Ben-Shlomo, Anat; Biermasz, Nienke; Biller, Beverly; et al. (2020). "Multidisciplinary management of acromegaly: A consensus". Reviews in Endocrine and Metabolic Disorders. 21 (4): 667–678. doi:10.1007/s11154-020-09588-z. ISSN 1389-9155. PMC 7942783. PMID 32914330.
• Giustina, Andrea; Biermasz, Nienke; Casanueva, Felipe F.; Fleseriu, Maria; Mortini, Pietro; Strasburger, Christian; et al. (2024). "Consensus on criteria for acromegaly diagnosis and remission". Pituitary. 27 (1): 7–22. doi:10.1007/s11102-023-01360-1. ISSN 1386-341X. PMC 10837217. PMID 37923946.
• Jallad, Raquel S.; Bronstein, Marcello D. (2020). "Acromegaly in the elderly patient". Archives of Endocrinology and Metabolism. 63 (6): 638–645. doi:10.20945/2359-3997000000194. ISSN 2359-3997. PMC 10522238. PMID 31939489.
• Makri, Angeliki; Lodish, Maya (2019). "Gigantism and acromegaly". Pituitary disorders of childhood. Springer International Publishing. pp. 121–139. doi:10.1007/978-3-030-11339-1_7. ISBN 978-3-030-11338-4.
• Malenica, Maša (2024). "Gigantism and acromegaly through history". Acta Clinica Croatica. 63 (2): 384–392. doi:10.20471/acc.2024.63.02.15. PMC 11912844. PMID 40104235.
• Mammis, Antonios; Eloy, Jean Anderson; Liu, James K. (2010). "Early descriptions of acromegaly and gigantism and their historical evolution as clinical entities". Neurosurgical Focus. 29 (4). Journal of Neurosurgery Publishing Group (JNSPG): E1. doi:10.3171/2010.7.focus10160. ISSN 1092-0684. PMID 20887119.
• Marques, Pedro; Korbonits, Márta (2022). "Approach to the patient with pseudoacromegaly". The Journal of Clinical Endocrinology & Metabolism. 107 (6): 1767–1788. doi:10.1210/clinem/dgab789. ISSN 0021-972X. PMID 34792134.
• Marques, Pedro; Korbonits, Márta (2019). "Pseudoacromegaly". Frontiers in Neuroendocrinology. 52: 113–143. doi:10.1016/j.yfrne.2018.11.001. PMID 30448536.
• Marques, Pedro; Sapinho, Inês; Korbonits, Márta (2024). "Pseudoacromegaly—a challenging entity in the endocrine clinic: A systematic review". Clinical Endocrinology. 100 (6): 542–557. doi:10.1111/cen.15053. ISSN 0300-0664. PMID 38549284.
• Mbadugha, Tobechi; Ogiwara, Toshihiro; Nagm, Alhusain; Hasegawa, Takatoshi; Kamiya, Keisuke; Matsumoto, Yuki; et al. (2020). "Acromegaly in preadolescence: A case report of a 9-year-old boy with acromegaly". Surgical Neurology International. 11: 61. doi:10.25259/SNI_474_2019. ISSN 2152-7806. PMC 7193214. PMID 32363056.
• Minozzi, Simona; Pantano, Walter; di Gennaro, Francesco; Fornaciari, Gino; Catalano, Paola (2012). "Pituitary disease from the past: A rare case of gigantism in skeletal remains from the Roman imperial age". The Journal of Clinical Endocrinology & Metabolism. 97 (12): 4302–4303. doi:10.1210/jc.2012-2726. ISSN 0021-972X. PMID 23032061.
• Park, Kyeong Hye; Lee, Eun Jig; Seo, Gi Hyeon; Ku, Cheol Ryong (2020). "Risk for acromegaly-related comorbidities by sex in Korean acromegaly". The Journal of Clinical Endocrinology & Metabolism. 105 (4): e1815 – e1826. doi:10.1210/clinem/dgz317. ISSN 0021-972X.
• Pertichetti, Marta; Serioli, Simona; Belotti, Francesco; Mattavelli, Davide; Schreiber, Alberto; Cappelli, Carlo; et al. (2020). "Pituitary adenomas and neuropsychological status: A systematic literature review". Neurosurgical Review. 43 (4): 1065–1078. doi:10.1007/s10143-019-01134-z. ISSN 0344-5607. PMID 31250149.
• Perosevic, Milica; Tritos, Nicholas A. (2022). "Management of the patient with acromegaly during pregnancy". Pituitary disorders throughout the life cycle. Springer International Publishing. pp. 177–185. doi:10.1007/978-3-030-99918-6_14. ISBN 978-3-030-99917-9.
• Pivonello, Rosario; Auriemma, Renata Simona; Delli Veneri, Alessandra; Dassie, Francesca; Lorusso, Riccardina; Ragonese, Marta; et al. (2022). "Global psychological assessment with the evaluation of life and sleep quality and sexual and cognitive function in a large number of patients with acromegaly: A cross-sectional study". European Journal of Endocrinology. 187 (6): 823–845. doi:10.1530/EJE-22-0263. ISSN 0804-4643. PMC 9782455. PMID 36165745.
• Ramírez-Rentería, Claudia; Hernández-Ramírez, Laura C. (2024). "Genetic diagnosis in acromegaly and gigantism: From research to clinical practice". Best Practice & Research Clinical Endocrinology & Metabolism. 38 (3): 101892. doi:10.1016/j.beem.2024.101892. PMID 38521632.
• Risse, Guenter B. (1971). "Pharaoh Akhenaton of Ancient Egypt: Controversies among Egyptologists and physicians regarding his postulated illness". Journal of the History of Medicine and Allied Sciences. XXVI (1): 3–17. doi:10.1093/jhmas/XXVI.1.3. ISSN 0022-5045. PMID 4925839. Retrieved 2025-04-29.
• Rosendal, Christian; Arlien-Søborg, Mai Christiansen; Nielsen, Eigil Husted; Andersen, Marianne Skovsager; Feltoft, Claus Larsen; Kistorp, Caroline; et al. (2024). "The changing landscape of acromegaly – an epidemiological perspective". Reviews in Endocrine and Metabolic Disorders. 25 (4): 691–705. doi:10.1007/s11154-024-09875-z. hdl:1887/3721129. ISSN 1389-9155. PMID 38337125.
• Rowe, Allan Winter; Mortimer, Hector (1934). "Endocrine studies: Xlii. A note on acromegaly with the report of a case". Endocrinology. 18 (1): 20–32. doi:10.1210/endo-18-1-20. ISSN 0013-7227.
• Sam, Amir; Meeran, Karim; Hill, Neil (2023). "Acromegaly". Endocrinology and diabetes: Lecture notes. Wiley. pp. 96–100. doi:10.1002/9781394322015.ch15. ISBN 978-1-394-32201-5.
• Sheaves, Richard (1999). "A History of acromegaly". Pituitary. 2 (1): 7–28. doi:10.1023/A:1009913719680. PMID 11081169.
• Slagboom, Tessa N. A.; van Bunderen, Christa C.; De Vries, Ralph; Bisschop, Peter H.; Drent, Madeleine L. (2023). "Prevalence of clinical signs, symptoms and comorbidities at diagnosis of acromegaly: A systematic review in accordance with PRISMA guidelines". Pituitary. 26 (4): 319–332. doi:10.1007/s11102-023-01322-7. ISSN 1386-341X. PMC 10397145. PMID 37210433.
• Störmann, Sylvère; Cuny, Thomas (2023). "The socioeconomic burden of acromegaly". European Journal of Endocrinology. 189 (2): R1 – R10. doi:10.1093/ejendo/lvad097. ISSN 0804-4643. PMID 37536267.
• Störmann, Sylvère; Schilbach, Katharina (2025). "Promising therapies for the treatment of acromegaly". Expert Opinion on Pharmacotherapy. 26 (5): 581–594. doi:10.1080/14656566.2025.2474562. ISSN 1465-6566. PMID 40025677.
• Wass, John A.H.; Trainer, Peter J.; Korbonits, Márta (2022). "Acromegaly". Oxford textbook of endocrinology and diabetes 3e. Oxford University PressOxford. pp. 235–248. doi:10.1093/med/9780198870197.003.0026. ISBN 978-0-19-887019-7.
• Wolters, T L C; Roerink, S H P P; Sterenborg, R B T M; Wagenmakers, M A E M; Husson, O; Smit, J W A; et al. (2020). "The effect of treatment on quality of life in patients with acromegaly: A prospective study". European Journal of Endocrinology. 182 (3): 319–331. doi:10.1530/EJE-19-0732. ISSN 0804-4643. PMID 31958318.
• Xiao, Zhehao; Xiao, Pingping; Wang, Yong; Fang, Chen; Li, Yong (2023). "Risk of cancer in acromegaly patients: An updated meta-analysis and systematic review". PLOS ONE. 18 (11): e0285335. Bibcode:2023PLoSO..1885335X. doi:10.1371/journal.pone.0285335. ISSN 1932-6203. PMC 10688666. PMID 38032888.

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