Format

Send to:

Choose Destination

Somatotroph adenoma(PITA1)

MedGen UID:
91097
Concept ID:
C0346302
Neoplastic Process
Synonyms: ACROMEGALY DUE TO PITUITARY ADENOMA 1; AIP-Related Familial Isolated Pituitary Adenomas; ISOLATED FAMILIAL SOMATOTROPINOMA; PITA1; PITUITARY ADENOMA 1, MULTIPLE TYPES; Pituitary adenoma, growth hormone-secreting; Pituitary tumor, growth hormone-secreting, somatic; SOMATOTROPHINOMA, FAMILIAL
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Somatic mutation
MedGen UID:
107465
Concept ID:
C0544886
Cell or Molecular Dysfunction
Sources: HPO, OMIM
Any mutation with an origin in cells that are not destined to become gametes. As a consequence, such mutations are not transmitted to progeny, though they will be transmitted during any mitosis within the individual. Somatic mutations may contribute to a broad variety of pathologies including cancer.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
Somatic mutation (HPO, OMIM)
SNOMED CT: Somatotroph adenoma (254957009); Growth hormone-secreting pituitary adenoma (254957009)
 
Genes (locations): AIP (11q13.2); GNAS (20q13.32)
OMIM®: 102200

Definition

AIP-related isolated familial pituitary adenoma (AIP-related FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and non-functioning pituitary adenomas (NFPA). Rarely TSH- or ACTH-secreting adenomas (thyrotropinoma and corticotropinoma) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-related FIPA is around 20-24 years (age range: 6-66 years). [from GTR]

Additional descriptions

From GeneReviews
AIP-related isolated familial pituitary adenoma (AIP-related FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and non-functioning pituitary adenomas (NFPA). Rarely TSH- or ACTH-secreting adenomas (thyrotropinoma and corticotropinoma) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-related FIPA is around 20-24 years (age range: 6-66 years).  https://www.ncbi.nlm.nih.gov/books/NBK97965
From OMIM
Mutations in the AIP gene have been found predominantly in growth hormone (GH)-secreting adenomas, but have also been found in adrenocorticotropic hormone (ACTH)-secreting, thyroid hormone (TSH)-secreting, and prolactin (PRL)-secreting pituitary tumors. Pituitary adenomas are benign monoclonal neoplasms of the anterior pituitary gland, accounting for approximately 15% of intracranial tumors. Growth hormone (139250)-secreting adenomas, also known as somatotropinomas, which clinically result in acromegaly, comprise about 20% of all pituitary tumors and are the second most common hormone-secreting pituitary tumor after prolactin (176760)-secreting tumors, which account for 40 to 45% of pituitary tumors. ACTH-secreting tumors, which result in Cushing disease, and thyrotropin (TSHB; 188540)-secreting tumors are much less common. Nonsecreting pituitary tumors, which account for about 33%, can cause symptoms due to local compressive effects of tumor growth (Vierimaa et al., 2006; Georgitsi et al., 2007; Horvath and Stratakis, 2008). Acromegaly is characterized by coarse facial features, protruding jaw, and enlarged extremities (Vierimaa et al., 2006). Familial isolated somatotropinoma (FIS) is defined as the occurrence of at least 2 cases of acromegaly or gigantism in a family that does not exhibit features of other endocrine syndromes. FIS patients tend to have onset about 4 to 10 years earlier than patients with sporadic disease (Gadelha et al., 1999; Horvath and Stratakis, 2008). Cushing disease is characterized by central obesity, moon facies, diabetes, 'buffalo hump,' hypertension, fatigue, easy bruising, depression, and reproductive disorders. Cushing disease is associated with increased morbidity and mortality, mainly due to cardiovascular or cerebrovascular disease and infections (summary by Perez-Rivas et al., 2015). Familial isolated pituitary adenoma (FIPA) and pituitary adenoma predisposition (PAP) are terms referring to families in which 2 or more individuals develop pituitary tumors. Within a family, tumor types can be heterogeneous, with members of the same family having GH-secreting, prolactin-secreting, ACTH-secreting, or nonsecreting adenomas; in contrast, some families are homogeneous with regard to tumor type. Familial isolated somatotropinoma refers specifically to GH-secreting tumors and is usually associated with an acromegaly phenotype. Thus, FIS is a subset of FIPA or PAP (Toledo et al., 2007). Schlechte (2003) discussed prolactinoma in general terms as a clinical, diagnostic, and therapeutic problem. Genetic Heterogeneity of Pituitary Adenomas Also see pituitary adenoma-2 (PITA2; 300943), caused by mutation in the GPR101 gene (300393); pituitary adenoma-3 (PITA3; 617686), caused by somatic activating mutations in the GNAS1 gene (139320); pituitary adenoma-4 (PITA4; 219090), caused by somatic mutation in the USP8 gene (603158); and pituitary adenoma-5 (PITA5; 617540), caused by mutation in the CDH23 gene (605516). Patients with the chromosome Xq26.3 microduplication syndrome (300942) have growth hormone-secreting adenomas. Familial acromegaly can also occur in association with multiple endocrine neoplasia type I (MEN1; 131100), Carney complex (CNC1; 160980), and the McCune-Albright syndrome (174800). Rostomyan et al. (2015) performed a retrospective analysis of 208 patients with pituitary gigantism due to pituitary adenoma or hyperplasia. Most patients (78.4%) were male, and the median onset of rapid growth was 13 years of age for boys and 11 years for girls. Of the 143 patients who consented to genetic testing, 29% had AIP mutations, and microduplication at Xq26.3 (XLAG; 300942) was present in 2 familial isolated pituitary adenoma kindreds and in 10 sporadic patients. Rostomyan et al. (2015) noted that no genetic etiology was identified in more than 50% of the cases, and that the genetically unexplained cases showed more aggressive disease in terms of invasion, hormone levels, and lower control rates.  http://www.omim.org/entry/102200

Clinical features

Growth hormone excess
MedGen UID:
1304
Concept ID:
C0001206
Disease or Syndrome
A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80)
Hyperprolactinemia
MedGen UID:
5698
Concept ID:
C0020514
Disease or Syndrome
Hyperprolactinemia unrelated to pregnancy occurs in approximately 0.1 to 0.3% of the general population and may result in infertility, hypogonadism, and galactorrhea. Such nonphysiologic hyperprolactinemia is caused mainly by drugs or by tumors in the anterior pituitary gland, primarily prolactinomas (see 102200). However, 10 to 60% of patients with hyperprolactinemia who undergo MRI have normal findings (summary by Newey et al., 2013).
Pituitary adenoma
MedGen UID:
45933
Concept ID:
C0032000
Neoplastic Process
A benign epithelial tumor derived from intrinsic cells of the adenohypophysis.
Prolactinoma, familial
MedGen UID:
10936
Concept ID:
C0033375
Neoplastic Process
AIP-related isolated familial pituitary adenoma (AIP-related FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and non-functioning pituitary adenomas (NFPA). Rarely TSH- or ACTH-secreting adenomas (thyrotropinoma and corticotropinoma) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-related FIPA is around 20-24 years (age range: 6-66 years).
Menstrual irregularities
MedGen UID:
56379
Concept ID:
C0156404
Finding
Deviations from the normal process; e.g. delayed, difficult, profuse, scanty, unusual bleeding, etc.
Increased serum insulin-like growth factor 1
MedGen UID:
390982
Concept ID:
C2676198
Finding
An elevated level of insulin-like growth factor 1 (IGF1) in the blood circulation.
Pituitary growth hormone cell adenoma
MedGen UID:
866320
Concept ID:
C4018860
Neoplastic Process
A type of pituitary adenoma that produces grwoth hormone.
Pituitary adenoma
MedGen UID:
45933
Concept ID:
C0032000
Neoplastic Process
A benign epithelial tumor derived from intrinsic cells of the adenohypophysis.
Prolactinoma, familial
MedGen UID:
10936
Concept ID:
C0033375
Neoplastic Process
AIP-related isolated familial pituitary adenoma (AIP-related FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and non-functioning pituitary adenomas (NFPA). Rarely TSH- or ACTH-secreting adenomas (thyrotropinoma and corticotropinoma) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-related FIPA is around 20-24 years (age range: 6-66 years).
Pituitary growth hormone cell adenoma
MedGen UID:
866320
Concept ID:
C4018860
Neoplastic Process
A type of pituitary adenoma that produces grwoth hormone.
Hypertension
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
Blood pressure that is abnormally high.
Left ventricular hypertrophy
MedGen UID:
57442
Concept ID:
C0149721
Disease or Syndrome
Enlargement of the LEFT VENTRICLE of the heart. This increase in ventricular mass is attributed to sustained abnormal pressure or volume loads and is a contributor to cardiovascular morbidity and mortality.
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A disease of the heart muscle or myocardium proper. Cardiomyopathies may be classified as either primary or secondary, on the basis of etiology, or on the pathophysiology of the lesion: hypertrophic, dilated, or restrictive.
Growth hormone excess
MedGen UID:
1304
Concept ID:
C0001206
Disease or Syndrome
A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80)
Hyperprolactinemia
MedGen UID:
5698
Concept ID:
C0020514
Disease or Syndrome
Hyperprolactinemia unrelated to pregnancy occurs in approximately 0.1 to 0.3% of the general population and may result in infertility, hypogonadism, and galactorrhea. Such nonphysiologic hyperprolactinemia is caused mainly by drugs or by tumors in the anterior pituitary gland, primarily prolactinomas (see 102200). However, 10 to 60% of patients with hyperprolactinemia who undergo MRI have normal findings (summary by Newey et al., 2013).
Pituitary adenoma
MedGen UID:
45933
Concept ID:
C0032000
Neoplastic Process
A benign epithelial tumor derived from intrinsic cells of the adenohypophysis.
Prolactinoma, familial
MedGen UID:
10936
Concept ID:
C0033375
Neoplastic Process
AIP-related isolated familial pituitary adenoma (AIP-related FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and non-functioning pituitary adenomas (NFPA). Rarely TSH- or ACTH-secreting adenomas (thyrotropinoma and corticotropinoma) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-related FIPA is around 20-24 years (age range: 6-66 years).
Pituitary growth hormone cell adenoma
MedGen UID:
866320
Concept ID:
C4018860
Neoplastic Process
A type of pituitary adenoma that produces grwoth hormone.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Growth hormone excess
MedGen UID:
1304
Concept ID:
C0001206
Disease or Syndrome
A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80)
Hyperprolactinemia
MedGen UID:
5698
Concept ID:
C0020514
Disease or Syndrome
Hyperprolactinemia unrelated to pregnancy occurs in approximately 0.1 to 0.3% of the general population and may result in infertility, hypogonadism, and galactorrhea. Such nonphysiologic hyperprolactinemia is caused mainly by drugs or by tumors in the anterior pituitary gland, primarily prolactinomas (see 102200). However, 10 to 60% of patients with hyperprolactinemia who undergo MRI have normal findings (summary by Newey et al., 2013).
Pituitary adenoma
MedGen UID:
45933
Concept ID:
C0032000
Neoplastic Process
A benign epithelial tumor derived from intrinsic cells of the adenohypophysis.
Prolactinoma, familial
MedGen UID:
10936
Concept ID:
C0033375
Neoplastic Process
AIP-related isolated familial pituitary adenoma (AIP-related FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and non-functioning pituitary adenomas (NFPA). Rarely TSH- or ACTH-secreting adenomas (thyrotropinoma and corticotropinoma) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-related FIPA is around 20-24 years (age range: 6-66 years).
Menstrual irregularities
MedGen UID:
56379
Concept ID:
C0156404
Finding
Deviations from the normal process; e.g. delayed, difficult, profuse, scanty, unusual bleeding, etc.
Increased serum insulin-like growth factor 1
MedGen UID:
390982
Concept ID:
C2676198
Finding
An elevated level of insulin-like growth factor 1 (IGF1) in the blood circulation.
Pituitary growth hormone cell adenoma
MedGen UID:
866320
Concept ID:
C4018860
Neoplastic Process
A type of pituitary adenoma that produces grwoth hormone.
Galactorrhea
MedGen UID:
777088
Concept ID:
C3665358
Disease or Syndrome
Excessive or inappropriate LACTATION in females or males, and not necessarily related to PREGNANCY. Galactorrhea can occur either unilaterally or bilaterally, and be profuse or sparse. Its most common cause is HYPERPROLACTINEMIA.
Galactorrhea
MedGen UID:
777088
Concept ID:
C3665358
Disease or Syndrome
Excessive or inappropriate LACTATION in females or males, and not necessarily related to PREGNANCY. Galactorrhea can occur either unilaterally or bilaterally, and be profuse or sparse. Its most common cause is HYPERPROLACTINEMIA.

Recent clinical studies

Etiology

Aljabri KS, Bokhari SA, Assiri FY, Alshareef MA, Khan PM
Ann Saudi Med 2016 Sep-Oct;36(5):341-345. doi: 10.5144/0256-4947.2016.341. PMID: 27710986
Shanik MH
Endocr Pract 2016 Feb;22(2):210-9. Epub 2015 Oct 5 doi: 10.4158/EP15825.RA. PMID: 26437214
van der Pas R, Feelders RA, Gatto F, de Bruin C, Pereira AM, van Koetsveld PM, Sprij-Mooij DM, Waaijers AM, Dogan F, Schulz S, Kros JM, Lamberts SW, Hofland LJ
J Clin Endocrinol Metab 2013 Dec;98(12):E1880-90. Epub 2013 Sep 30 doi: 10.1210/jc.2013-1987. PMID: 24081741
Larkin S, Reddy R, Karavitaki N, Cudlip S, Wass J, Ansorge O
Eur J Endocrinol 2013 Apr;168(4):491-9. Epub 2013 Mar 15 doi: 10.1530/EJE-12-0864. PMID: 23288882
Bhayana S, Booth GL, Asa SL, Kovacs K, Ezzat S
J Clin Endocrinol Metab 2005 Nov;90(11):6290-5. Epub 2005 Aug 23 doi: 10.1210/jc.2005-0998. PMID: 16118335

Diagnosis

Bhayana S, Booth GL, Asa SL, Kovacs K, Ezzat S
J Clin Endocrinol Metab 2005 Nov;90(11):6290-5. Epub 2005 Aug 23 doi: 10.1210/jc.2005-0998. PMID: 16118335
Saveanu A, Lavaque E, Gunz G, Barlier A, Kim S, Taylor JE, Culler MD, Enjalbert A, Jaquet P
J Clin Endocrinol Metab 2002 Dec;87(12):5545-52. doi: 10.1210/jc.2002-020934. PMID: 12466351
Syro LV, Horvath E, Kovacs K
J Endocrinol Invest 2000 Jan;23(1):37-41. doi: 10.1007/BF03343674. PMID: 10698050
Matsuno A, Sanno N, Tahara S, Teramoto A, Osamura RY, Wada H, Murakami M, Tanaka H, Nagashima T
Endocr J 1999 Mar;46 Suppl:S81-4. PMID: 12054127
Matsuno A, Katakami H, Sanno N, Ogino Y, Osamura RY, Matsukura S, Shimizu N, Nagashima T
J Clin Endocrinol Metab 1999 Sep;84(9):3241-7. doi: 10.1210/jcem.84.9.6008. PMID: 10487694

Therapy

Zhou C, Jiao Y, Wang R, Ren SG, Wawrowsky K, Melmed S
J Clin Invest 2015 Apr;125(4):1692-702. Epub 2015 Mar 16 doi: 10.1172/JCI78173. PMID: 25774503Free PMC Article
Glynn N, Agha A
Endocr Pract 2013 Jul-Aug;19(4):e88-91. doi: 10.4158/EP13036.CR. PMID: 23512395
Bhayana S, Booth GL, Asa SL, Kovacs K, Ezzat S
J Clin Endocrinol Metab 2005 Nov;90(11):6290-5. Epub 2005 Aug 23 doi: 10.1210/jc.2005-0998. PMID: 16118335
Rickels MR, Snyder PJ
Pituitary 2004;7(2):107-10. doi: 10.1007/s11102-005-5353-1. PMID: 15761660
Sauer J, Renner U, Hopfner U, Lange M, Müller A, Strasburger CJ, Pagotto U, Arzt E, Stalla GK
J Clin Endocrinol Metab 1998 Jul;83(7):2429-34. doi: 10.1210/jcem.83.7.4963. PMID: 9661623

Prognosis

Peng H, Fan J, Wu J, Lang J, Wang J, Liu H, Zhao S, Liao J
Cell Physiol Biochem 2013;31(2-3):379-88. Epub 2013 Mar 8 doi: 10.1159/000343375. PMID: 23548416
Glynn N, Agha A
Endocr Pract 2013 Jul-Aug;19(4):e88-91. doi: 10.4158/EP13036.CR. PMID: 23512395
Buchfelder M, Weigel D, Droste M, Mann K, Saller B, Brübach K, Stalla GK, Bidlingmaier M, Strasburger CJ; Investigators of German Pegvisomant Observational Study.
Eur J Endocrinol 2009 Jul;161(1):27-35. Epub 2009 May 1 doi: 10.1530/EJE-08-0910. PMID: 19411302
Bhayana S, Booth GL, Asa SL, Kovacs K, Ezzat S
J Clin Endocrinol Metab 2005 Nov;90(11):6290-5. Epub 2005 Aug 23 doi: 10.1210/jc.2005-0998. PMID: 16118335
Zargar AH, Laway BA, Masoodi SR, Salahuddin M, Ganie MA, Bhat MH, Wani AI, Bashir MI
Saudi Med J 2004 Oct;25(10):1428-32. PMID: 15494816

Clinical prediction guides

Nishizawa H, Fukuoka H, Iguchi G, Inoshita N, Yamada S, Takahashi Y
Exp Clin Endocrinol Diabetes 2013 May;121(5):295-9. Epub 2013 May 14 doi: 10.1055/s-0032-1331697. PMID: 23674160
Peng H, Liu H, Zhao S, Wu J, Fan J, Liao J
PLoS One 2013;8(3):e59024. Epub 2013 Mar 28 doi: 10.1371/journal.pone.0059024. PMID: 23555615Free PMC Article
Bhayana S, Booth GL, Asa SL, Kovacs K, Ezzat S
J Clin Endocrinol Metab 2005 Nov;90(11):6290-5. Epub 2005 Aug 23 doi: 10.1210/jc.2005-0998. PMID: 16118335
Rickels MR, Snyder PJ
Pituitary 2004;7(2):107-10. doi: 10.1007/s11102-005-5353-1. PMID: 15761660
Sauer J, Renner U, Hopfner U, Lange M, Müller A, Strasburger CJ, Pagotto U, Arzt E, Stalla GK
J Clin Endocrinol Metab 1998 Jul;83(7):2429-34. doi: 10.1210/jcem.83.7.4963. PMID: 9661623

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center