Acromegaly pathophysiology: Difference between revisions
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==Genetics== | ==Genetics== | ||
*The development of acromegaly is the result of multiple genetic mutations. In pituitary adenomas, a mutation in the alpha subunit of the guanine nucleotide stimulatory protein is responsible for the excess growth hormone secretion. | |||
*The development of | |||
==Associated Conditions== | ==Associated Conditions== | ||
Patients with acromegaly may be associated with the following conditions:<ref name="pmid25356808">{{cite journal| author=Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A et al.| title=Acromegaly: an endocrine society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2014 | volume= 99 | issue= 11 | pages= 3933-51 | pmid=25356808 | doi=10.1210/jc.2014-2700 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25356808 }} </ref> | Patients with acromegaly may be associated with the following conditions:<ref name="pmid25356808">{{cite journal| author=Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A et al.| title=Acromegaly: an endocrine society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2014 | volume= 99 | issue= 11 | pages= 3933-51 | pmid=25356808 | doi=10.1210/jc.2014-2700 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25356808 }} </ref> | ||
Revision as of 15:48, 11 August 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]
Overview
Pathophysiology
Pathogenesis
- It is thought that acromegaly caused by GH secreting pituitary adenomas either microadenomas or macroadenomas. The pituitary adenoma leads to hypersecretion of the growth hormone from the somatotroph cells.
- Normally, the growth hormone is secreted and stored in the anterior pituitary gland particularly in the somatotroph cells. Growth hormone secretion is affected by several factors. Growth hormone is stimulated by ghrelin and growth hormone releasing hormone. Somatostatin inhibits the growth hormone secretion.[1]
- Insulin growth factor 1 (IGF-1) inhibits the secretion of growth hormone in two ways. IGF-1 inhibits directly the somatotroph cells or stimulates secretion the somatostatin that inhibits the GH secretion.
- Growth hormone is functioning through binding to its receptor which is a glycoprotein receptor. Binding of GH to its receptor stimulates proteins which start a process called signal transduction and transcription. Signal transduction and transcription (STAT) induces production of IGF-1 from liver, bone and pituitary gland.[2]
- The IGF-1 is responsible for the acral features of acromegaly. IGF-1 causes the rapid increase in the hand and feet size, forehead protrusion, and jaw prominence.
- The high level of IGF-1 is responsible for the following pathologic processes:
- IGF-1 is responsible for the diabetes mellitus which is common in 20% of patients with acromegaly. IGF-1 interferes with insulin on its receptor which leads to insulin resistance and glucose elevation.
- IGF-1 causes hypertrophy of the body organs like the heart (cardiomegaly) and tongue (macroglossia).
Genetics
- The development of acromegaly is the result of multiple genetic mutations. In pituitary adenomas, a mutation in the alpha subunit of the guanine nucleotide stimulatory protein is responsible for the excess growth hormone secretion.
Associated Conditions
Patients with acromegaly may be associated with the following conditions:[3]
- Multiple Endocrine Neoplasia 1 (MEN-1)
- Diabetes mellitus
- Obstructive sleep apnea
- Carpal tunnel syndrome
- Hypertension
- Osteoarthritis
References
- ↑ Dineen R, Stewart PM, Sherlock M (2016). "Acromegaly". QJM. doi:10.1093/qjmed/hcw004. PMID 26873451.
- ↑ Melmed S (2009). "Acromegaly pathogenesis and treatment". J Clin Invest. 119 (11): 3189–202. doi:10.1172/JCI39375. PMC 2769196. PMID 19884662.
- ↑ Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A; et al. (2014). "Acromegaly: an endocrine society clinical practice guideline". J Clin Endocrinol Metab. 99 (11): 3933–51. doi:10.1210/jc.2014-2700. PMID 25356808.