Medicine:Acromegaly

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Acromegaly is a disorder that results in excess growth of certain parts of the human body. It is caused by excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet.[1] There may also be an enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain, thickened skin, deepening of the voice, headaches, and problems with vision.[1] Complications of the disease may include type 2 diabetes, sleep apnea, and high blood pressure.[1]

Signs and symptoms

Compared with the hand of an unaffected person (left), the hand of a person with acromegaly (right) is enlarged, with fingers that are widened, thickened and stubby, and with thicker soft tissue
Mandibular overgrowth leads to prognathism, maxillary widening, teeth spacing and malocclusion
Brow ridge and forehead protrusion remaining after tumor removal and tissue swelling eliminated
  • Headaches
  • 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 resulting in a characteristic thick, deep voice and slowing of speech
  • Generalized expansion of the skull at the fontanelle
  • Pronounced brow protrusion, often with ocular distension (frontal bossing)
  • Pronounced lower jaw protrusion (prognathism) with attendant macroglossia (enlargement of the tongue) and teeth spacing
  • Hypertrichosis, hyperpigmentation and hyperhidrosis[2]: 499 
  • Skin tags
  • Carpal tunnel syndrome

Complications

Causes

Pituitary adenoma

About 98% of cases of acromegaly are due to the overproduction of growth hormone by a benign tumor of the pituitary gland called an adenoma.[9] These tumors produce excessive growth hormone and compress surrounding brain tissues as they grow larger. In some cases, they may compress the optic nerves. Expansion of the tumor may cause headaches and visual disturbances. In addition, compression of the surrounding normal pituitary tissue can alter the production of other hormones, leading to changes in menstruation and breast discharge in women and impotence in men because of reduced testosterone production.[10]

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, which are located near the pituitary. In general, younger people tend to have more aggressive tumors.[11]

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, 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 and GH oversecretion currently are the subject of intensive research.[11]

Pituitary adenomas and diffuse somatomammotroph hyperplasia may result from somatic mutations activating GNAS, which may be acquired or associated with McCune–Albright syndrome.[12][13]

Other tumors

Diagnosis

Frequent serum GH measurements in normal subjects (left panel) demonstrate that GH can fluctuate between undetectable levels most of the time interspersed with peaks of up to 30 μg/L (90 mIU/L); in acromegaly (right panel) GH hypersecretion is continuous with no undetectable levels.

Diagnosis is by measuring growth hormone after a person has consumed a glucose solution, or by measuring insulin-like growth factor I in the blood. After diagnosis, medical imaging 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 rather than acromegaly, and it is characterized by excessive height.[1]

Magnetic resonance image of a pituitary macroadenoma that caused acromegaly with compression of the optic chiasm


Differential diagnosis

Pseudoacromegaly 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.[14] Cases have been reported due to minoxidil at an unusually high dose.[15] It can also be caused by a selective post-receptor defect of insulin signalling, leading to the impairment of metabolic, but preservation of mitogenic, signaling.[16]

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 growth hormone receptor and thus impairing the effects of GH on the different tissues.

Treatment options include surgery to remove the tumor, medications, and radiation therapy. 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 analogues or GH receptor antagonists may be used. Radiation therapy may be used if neither surgery nor medications are completely effective.[1] Without treatment, life expectancy is reduced by 10 years; with treatment, life expectancy is not reduced.[17]

Medications

Somatostatin analogues

The primary medical treatment of acromegaly is to use somatostatin analogues – octreotide (Sandostatin) or lanreotide (Somatuline).

Somatostatin analogues are also sometimes used to shrink large tumors before surgery.[18]

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 gallstones, which are usually asymptomatic.[19] In some cases, octreotide treatment can cause diabetes because somatostatin and its analogues can inhibit the release of insulin. With an aggressive adenoma that is not able to be operated on, there may be a resistance to octreotide 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.[20]

Dopamine agonists

Growth hormone receptor antagonists

Paltusotine (Palsonify) was approved for medical use in the United States in September 2025.[21]

Surgery

Radiation therapy

Prognosis

Life expectancy of people with acromegaly is dependent on how early the disease is detected.[22] Life expectancy after the successful treatment of early disease is equal to that of the general population.[23] 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.[22] Upon successful surgical treatment, headaches and visual symptoms tend to resolve.[4] 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.[3] While hypertension is a complication of 40% of cases, it typically responds well to regular regimens of blood pressure medication.[3] Diabetes that occurs with acromegaly is treated with the typical medications, but successful lowering of growth hormone levels often alleviates symptoms of diabetes.[3] Hypogonadism without gonad destruction is reversible with treatment.[3] Acromegaly is associated with a slightly elevated risk of cancer.[24]

Epidemiology, history, and culture

Acromegaly affects about 6 per 100,000 people. It is most commonly diagnosed in middle age.[1] Males and females are affected with equal frequency.[25] It was first described in the medical literature by Nicolas Saucerotte in 1772.[26][27] The term is from the Greek ἄκρον (akron) meaning "extremity", and μέγα (mega) meaning "large".[1]

Notable people

  • Paul Benedict (1938–2008), American actor. Best known for portraying Harry Bentley, The Jeffersons' English next door neighbour[28]
  • Mary Ann Bevan (1874–1933), an English woman, who after developing acromegaly, toured the sideshow circuit as "the ugliest woman in the world".[29]
  • Rondo Hatton (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.[30]
  • Irwin Keyes (1952–2015), American actor. Best known for portraying Hugo Mojoloweski, George's occasional bodyguard on The Jeffersons[31]
  • Richard Kiel (1939–2014), actor, "Jaws" from two James Bond movies and Mr. Larson in Happy Gilmore[32]
  • Sultan Kösen, the world's tallest living man.[33]
  • Neil McCarthy (1932–85), British actor. Known for roles in Zulu, Time Bandits, and many British television series[34]
  • The Great Khali (Dalip Singh Rana), Indian professional wrestler, is best known for his tenure with WWE under the ring name The Great Khali. He had his pituitary tumor removed in 2012 at age 39.[35]
  • André the Giant (André Roussimoff, 1946–1993), French professional wrestler and actor, known for playing Fezzik in The Princess Bride.
  • The French Angel (Maurice Tillet, 1903–1954), Russian-born French professional wrestler, is better known by his ring name, the French Angel.[36]
  • Pío Pico, 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.[37] His remarkable recovery is likely an example of spontaneous selective pituitary tumor apoplexy.[38]
  • Tony Robbins, motivational speaker[39]
  • Antônio "Bigfoot" Silva, Brazilian kickboxer and mixed martial artist.[40][41][42]
  • Carel Struycken, Dutch actor, 2.13 m (7.0 ft), is best known for playing Lurch in The Addams Family film trilogy, The Giant in Twin Peaks, Lwaxana Troi's silent Servant Mr. Homn in Star Trek: The Next Generation, and The Moonlight Man in Gerald's Game, based on the Stephen King book.[43]
  • Big Show (Paul Wight), American professional wrestler and actor, known for his tenures in WCW, ECW, WWE, and currently, AEW.[44]
  • Matthew McGrory, (1973–2005) American actor known best for his role as Karl the Giant in the 2003 Tim Burton film Big Fish, as well as for his appearances as a member of the Wack Pack on The Howard Stern Show, where he was known as the Original Bigfoot.[45]
  • Marjon van Iwaarden, Dutch singer.[46] * Jacob Grommer (1879–1933) Belarusian mathematician. Student of David Hilbert and assistant to Albert Einstein.[47][48]

A number of notable historical figures have been, moreover, argued to have had acromegaly, despite no strict diagnosis of the condition.

  • Maximinus Thrax, Roman emperor (c. 173, reigned 235–238). Descriptions, as well as depictions, indicate acromegaly, though remains of his body are yet to be found. * Lorenzo de' Medici (1449–92) may have had acromegaly. Historical documents and portraits, as well as a later analysis of his skeleton, support the speculation.[49]
  • Pianist and composer Sergei Rachmaninoff (1873–1943), 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.[50]
  • Adam Rainer (22 February 1899 – 4 March 1950) was an Austrian man who is the only person in recorded history to have been both a dwarf and a giant. He is believed to have had acromegaly.[51]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Acromegaly". April 2012. https://www.niddk.nih.gov/health-information/health-topics/endocrine/acromegaly/Pages/fact-sheet.aspx. 
  2. ↑ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. ISBN 0-7216-2921-0. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 "A consensus on the diagnosis and treatment of acromegaly complications". Pituitary 16 (3): 294–302. September 2013. doi:10.1007/s11102-012-0420-x. PMID 22903574. 
  4. ↑ 4.0 4.1 "Surgery for acromegaly: evolution of the techniques and outcomes". Reviews in Endocrine & Metabolic Disorders 9 (1): 67–70. March 2008. doi:10.1007/s11154-007-9064-y. PMID 18228147. 
  5. ↑ "Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry". European Journal of Endocrinology 164 (6): 877–84. June 2011. doi:10.1530/EJE-10-1050. PMID 21464140. 
  6. ↑ "Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications". Hormone and Metabolic Research 35 (11–12): 712–25. 2003. doi:10.1055/s-2004-814150. PMID 14710350. 
  7. ↑ "Risk of thyroid nodular disease and thyroid cancer in patients with acromegaly—meta-analysis and systematic review". PLOS ONE 9 (2). 14 February 2014. doi:10.1371/journal.pone.0088787. PMID 24551163. Bibcode: 2014PLoSO...988787W. 
  8. ↑ "Current treatment guidelines for acromegaly". The Journal of Clinical Endocrinology and Metabolism 83 (8): 2646–52. August 1998. doi:10.1210/jcem.83.8.4995. PMID 9709926. 
  9. ↑ Harrison's Principles of Internal Medicine (19th ed.). McGraw Hill. 8 April 2015. pp. 2269–2271. ISBN 978-0-07-180215-4. 
  10. ↑ Ganapathy, M. K.; Tadi, P. (2022). Anatomy, Head and Neck, Pituitary Gland. PMID 31855373. https://www.ncbi.nlm.nih.gov/books/NBK551529/. Retrieved 27 June 2021. 
  11. ↑ 11.0 11.1 Ganapathy, M. K.; Tadi, P. (2022). Anatomy, Head and Neck, Pituitary Gland. PMID 31855373. https://www.ncbi.nlm.nih.gov/books/NBK551529/. Retrieved 27 June 2021. 
  12. ↑ "Somatic GNAS mutation causes widespread and diffuse pituitary disease in acromegalic patients with McCune–Albright syndrome". The Journal of Clinical Endocrinology and Metabolism 97 (7): 2404–13. July 2012. doi:10.1210/jc.2012-1274. PMID 22564667. 
  13. ↑ "Acromegaly and McCune–Albright syndrome". The Journal of Clinical Endocrinology and Metabolism 99 (6): 1955–69. June 2014. doi:10.1210/jc.2013-3826. PMID 24517150. 
  14. ↑ Yaqub, Abid; Yaqub, Nadia (1 September 2008). "Insulin-mediated pseudoacromegaly: a case report and review of the literature". West Virginia Medical Journal 104 (5): 12–16. Gale A201087184. PMID 18846753. 
  15. ↑ "Pseudoacromegaly induced by the long-term use of minoxidil". Journal of the American Academy of Dermatology 48 (6): 962–5. June 2003. doi:10.1067/mjd.2003.325. PMID 12789195. 
  16. ↑ "Insulin-mediated 'pseudoacromegaly'". Hormones 10 (2): 156–61. 2011. doi:10.14310/horm.2002.1306. PMID 21724541. 
  17. ↑ Ho, Ken (2011). Growth Hormone Related Diseases and Therapy: A Molecular and Physiological Perspective for the Clinician. Springer Science & Business Media. p. 400. ISBN 978-1-60761-317-6. https://books.google.com/books?id=FWmbHHL4BwsC&pg=PA400. 
  18. ↑ "Acromegaly and Gigantism". https://www.lecturio.com/concepts/acromegaly-and-gigantism/. 
  19. ↑ "Octreotide Side Effects". https://www.drugs.com/sfx/octreotide-side-effects.html. 
  20. ↑ Yamamoto, Reina; Robert Shima, Kosuke; Igawa, Hirobumi; Kaikoi, Yuka; Sasagawa, Yasuo; Hayashi, Yasuhiko; Inoshita, Naoko; Fukuoka, Hidenori et al. (2018). "Impact of preoperative pasireotide therapy on invasive octreotide-resistant acromegaly". Endocrine Journal 65 (10): 1061–1067. doi:10.1507/endocrj.ej17-0487. ISSN 0918-8959. PMID 30078825. 
  21. ↑ "Crinetics Announces FDA Approval of Palsonify (paltusotine) for the Treatment of Adults with Acromegaly" (Press release). Crinetics Pharmaceuticals. 25 September 2025. Retrieved 27 September 2025 – via GlobeNewswire.
  22. ↑ 22.0 22.1 "Clinical manifestations and diagnosis of acromegaly". International Journal of Endocrinology 2012. 2012. doi:10.1155/2012/540398. PMID 22518126. 
  23. ↑ "A Consensus Statement on acromegaly therapeutic outcomes". Nature Reviews. Endocrinology 14 (9): 552–561. September 2018. doi:10.1038/s41574-018-0058-5. PMID 30050156. 
  24. ↑ Dal, Jakob; Leisner, Michelle Z; Hermansen, Kasper; Farkas, Dóra Körmendiné; Bengtsen, Mads; Kistorp, Caroline; Nielsen, Eigil H; Andersen, Marianne et al. (1 June 2018). "Cancer Incidence in Patients With Acromegaly: A Cohort Study and Meta-Analysis of the Literature". The Journal of Clinical Endocrinology & Metabolism 103 (6): 2182–2188. doi:10.1210/jc.2017-02457. PMID 29590449. 
  25. ↑ Pack, Allan I. (2016). Sleep Apnea: Pathogenesis, Diagnosis and Treatment (2 ed.). CRC Press. p. 291. ISBN 978-1-4200-2088-5. https://books.google.com/books?id=yN_LBQAAQBAJ&pg=PA291. 
  26. ↑ Pearce, John M. S. (2003). Fragments of Neurological History. World Scientific. p. 501. ISBN 978-1-78326-110-9. https://books.google.com/books?id=2eu3CgAAQBAJ&pg=PA501. 
  27. ↑ "Nicolas Saucerotte: Acromegaly before Pierre Marie". Journal of the History of the Neurosciences 15 (3): 269–75. September 2006. doi:10.1080/09647040500471764. PMID 16887764. 
  28. ↑ Times Staff And Wire Reports (5 December 2008). "Paul Benedict dies at 70; actor from 'The Jeffersons' and 'Sesame Street'". Los Angeles Times. http://www.latimes.com/local/obituaries/la-me-benedict5-2008dec05-story.html. 
  29. ↑ "National Fairground Archive – Extracts from World's Fair, 1931–1940". 2007. http://www.nfa.dept.shef.ac.uk/history/worlds_fair/extracts/1931–1940.html#fleetwood. 
  30. ↑ Duryea, Bill (27 June 1999). "Floridian: In love with a monster". St Petersburg Times. http://www.sptimes.com/News/62799/Floridian/In_love_with_a_monste.shtml. 
  31. ↑ Dagan, Carmel (8 July 2015). "Irwin Keyes, Horror Movie Character Actor, Dies at 63". Variety. https://variety.com/2015/film/people-news/irwin-keyes-horror-dead-dies-1201536421/. 
  32. ↑ "Richard "Jaws" Kiel, Famed Bond Movie Villain, Raises Awareness Oflife-Threatening Hormone Disorder". http://www.prnewswire.com/broadcast/10119/10119_consumer.html. 
  33. ↑ "Tallest man living". https://www.guinnessworldrecords.com/world-records/tallest-man-living. 
  34. ↑ Stampede, Pete. "Neil McCarthy". The Avengers Forever. http://theavengers.tv/forever/pnote-mccarthy.htm. 
  35. ↑ Harish, Alon. "WWE Star Great Khali's Growth-Inducing Tumor Removed". ABC News. https://abcnews.go.com/Health/star-wrestler-great-khali-tumor-removed-caused-size/story?id=16874060. 
  36. ↑ Oliver, Greg. "The French Angel was more man than monster". SLAM! Wrestling. http://slam.canoe.com/Slam/Wrestling/2011/12/14/19123831.html. 
  37. ↑ "Governor Pio Pico, the monster of California...no more: lessons in neuroendocrinology". Pituitary 13 (1): 80–6. July 2008. doi:10.1007/s11102-008-0127-1. PMID 18597174. 
  38. ↑ "Pituitary tumor apoplexy: a review". Journal of Intensive Care Medicine 23 (2): 75–90. 2008. doi:10.1177/0885066607312992. PMID 18372348. 
  39. ↑ Plaskin, Glenn (13 August 2013). "Playboy Interview: Tony Robbins". Playboy. http://www.playboy.com/articles/tony-robbins-playboy-interview. 
  40. ↑ "Ex-treinador de Pezão, André Benkei explica doença do lutador e afirma: 'Ele jamais colocaria a saúde em risco'". 23 December 2013. https://extra.globo.com/esporte/mma/ex-treinador-de-pezao-andre-benkei-explica-doenca-do-lutador-afirma-ele-jamais-colocaria-saude-em-risco-11143681.html. 
  41. ↑ "TRT ban forces UFC headliner 'Bigfoot' Silva into surgery". 12 September 2014. https://mmajunkie.usatoday.com/2014/09/trt-ban-forces-ufc-headliner-bigfoot-silva-into-surgery. 
  42. ↑ "UFC title hopeful 'Bigfoot' Silva a real-life giant". https://www.usatoday.com/story/sports/ufc/2013/05/23/ufc-title-hopeful-bigfoot-silva-gigantism-ufc-160/2356405/. 
  43. ↑ McLellan, Dennis (27 December 1992). "Shedding Light on a Rare Disease: Woman Hopes O.C. Group Will Increase Awareness of Life-Threatening Effects of Excessive-Growth Illness". Los Angeles Times. https://www.latimes.com/archives/la-xpm-1992-12-27-vw-5207-story.html. 
  44. ↑ Emerson, LaTina (2 April 2011). "A giant among men". https://www.augustachronicle.com/story/entertainment/local/2011/04/02/giant-among-men/14549252007/. 
  45. ↑ "Misbehaving Pituitaries". https://www.damninteresting.com/misbehaving-pituitaries/. 
  46. ↑ "Dutch Acromegaly Patient Marjon van Iwaarden Shares Her Story". 27 May 2020. https://acromegalysupport.com/marjon-van-iwaarden-shares-her-story/. 
  47. ↑ Gutfreund, Hanoch and Jürgen Renn. The Formative Years of Relativity: The History and Meaning of Einstein's Princeton Lectures. Princeton University Press. 2017. Page 393.
  48. ↑ Denis, Brian. Einstein: A Life. John Wiley & Sons. 1997. Page 169.
  49. ↑ Lippi, Donatella; Phillipe Charlier; Paola Romagnani (May 2017). "Acromegaly in Lorenzo the Magnificent, father of the Renaissance". The Lancet 389 (10084): 2104. doi:10.1016/S0140-6736(17)31339-9. PMID 28561004. 
  50. ↑ Ramachandran, Manoj; Jeffrey K Aronson (Oct 2006). "The diagnosis of art: Rachmaninov's hand span". Journal of the Royal Society of Medicine 99 (10): 529–30. doi:10.1177/014107680609901015. PMID 17066567. 
Classification
External resources

Template:Pituitary disease



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