Acromegaly etiology [Neurosurgery Wiki]

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====== Acromegaly etiology ======

[[Acromegaly]] is usually caused by a pituitary [[somatotroph adenoma]]. The other main diseases causing acromegaly are ectopic GH-producing pancreatic tumors and tumors producing [[GHRH]], a hypothalamic hormone that stimulates GH secretion from the [[anterior pituitary]].
Among them are pancreatic tumors, pulmonary tumors, and hypothalamic gangliocytomas, and the endocrine mechanism stimulating GH secretion has well been documented. GHRH production or gene expression in pituitary somatotroph adenomas has been demonstrated by several investigators
((Wakabayashi I, Inokuchi K, Hasegawa O, Sugihara H, Minami S. 1992 Expression of growth hormone (GH)-releasing factor gene in GH-producing pituitary neuroendocrine tumor. J Clin Endocrinol Metab . 74:357–361.))
((Joubert (Bression) D, Benlot C, Lagoguey A, et al. 1989 Normal and growth hormone (GH)-secreting adenomatous human pituitaries release somatostatin and GH-releasing hormone. J Clin Endocrinol Metab . 68:572–577.))
((Levy A, Lightman SL. 1992 Growth hormone-releasing hormone transcripts in human pituitary neuroendocrine tumors. J Clin Endocrinol Metab . 74:1474–1476.))
((Thapar K, Kovacs K, Stefaneanu L, et al. 1997 Overexpression of the growth-hormone-releasing hormone gene in acromegaly-associated pituitary tumors. An event associated with neoplastic progression and aggressive behavior. Am J Pathol . 151:769–784.))
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The cause of acromegaly could be determined after the discovery of growth hormone (GH) and insulin-like growth factor I (IGF-I) and demonstrating an association with GH hypersecretion and elevated circulating IGF-I. 
Usually caused by [[pituitary neuroendocrine tumor]]s.

In > 95 % of cases [[GH secreting pituitary neuroendocrine tumor]].

In >75 % macroadenomas with cavernous sinus invasion and/or suprasellar extension.


A duplication event in [[GPR101]] is implicated in cases of [[gigantism]] and [[acromegaly]].

AHR gene rs2066853 polymorphism is significantly more frequent in acromegalic patients than in healthy subjects, regardless of gender, [[pituitary tumor]] size, age at diagnosis and prevalence of colonic tumours and is associated with increased disease aggresivity. Moreover, the rs4986826 variant was detected in few patients with rs2066853 polymorphism, but its role is to be cleared
((Cannavò S, Ferraù F, Ragonese M, Romeo PD, Torre ML, Puglisi S, De Menis E,
Arnaldi G, Salpietro C, Cotta OR, Albani A, Ruggeri RM, Trimarchi F. Increased
frequence of the rs2066853 variant of aryl hydrocarbon receptor gene in patients 
with acromegaly. Clin Endocrinol (Oxf). 2014 Feb 13. doi: 10.1111/cen.12424.
[Epub ahead of print] PubMed PMID: 24521362.)).

Pituitary carcinomas are exceedingly rare. Extremely infrequently acromegaly occurs as a result of ectopic secretion of growth hormone releasing hormone (GHRH) from a peripheral neuroendocrine tumour, or from excessive hypothalamic GHRH secretio. Approximately 5% of cases are associated with familial syndromes, most commonly multiple endocrine neoplasia type 1 (MEN1) syndrome, but also [[McCune-Albright syndrome]], familial acromegaly, Carney’s syndrome and Familial Isolated pituitary neuroendocrine tumor (FIPA)
((Carroll PV, Jenkins PJ. Acromegaly. In: De Groot LJ, Beck-Peccoz P, Chrousos
G, Dungan K, Grossman A, Hershman JM, Koch C, McLachlan R, New M, Rebar R, Singer
F, Vinik A, Weickert MO, editors. Endotext [Internet]. South Dartmouth (MA):
MDText.com, Inc.; 2000-. Available from
http://www.ncbi.nlm.nih.gov/books/NBK279097/
PubMed PMID: 25905322.
)).
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Co-secretion of [[growth hormone]] (GH) and [[prolactin]] (PRL) from a single [[pituitary neuroendocrine tumor]] is common. In fact, up to 25% of patients with [[acromegaly]] may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed [[prolactinoma]] is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 ([[IGF-1]]) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done
((Manuylova E, Calvi LM, Hastings C, Vates GE, Johnson MD, Cave WT Jr, Shafiq I.
Late presentation of acromegaly in medically controlled prolactinoma patients.
Endocrinol Diabetes Metab Case Rep. 2016;2016. pii: 16-0069. PubMed PMID:
27855229.
)).