Prolactinoma pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2], Faizan Sheraz, M.D. [3]
Overview
Prolactinoma is the most common type of pituitary adenoma. Prolactinoma may occur in approximately 30% of multiple endocrine neoplasia type 1 patients. It may also occur with Carney complex or McCune-Albright syndrome. There are a few reports of familial cases of prolactinoma unrelated to MEN 1 syndrome.[1]
Prolactinoma is also associated with various familial syndromes.[2] On gross pathology, prolactinoma is divided on the basis of size into microprolactinoma and macroprolactinoma. On microscopic histological analysis, prolactinoma has two types: sparsely granulated and densely granulated.
Pathophysiology
- Prolactinoma are monoclonal in nature. This suggests that somatic cell mutation occurs before clonal expansion of lactotrophs.[3]
- One gene involved in the pathogenesis of prolactinoma is the pituitary tumor transforming gene-1 (PTTG-1).[4][5]
- The PTTG-1 gene is related to various endocrine and non-endocrine tumors such as:
- Endocrine related tumors: pituitary, thyroid, breast, ovarian, and uterine tumors.
- Non-endocrine related tumors: central nervous system, pulmonary, and gastrointestinal tumors.
- Prolactinomas with a higher expression of the PTTG-1 gene tend to be more invasive.
- The PTTG-1 gene is related to various endocrine and non-endocrine tumors such as:
- Many prolactinomas are related to multiple endocrine neoplasia type 1.[6]
- The MEN1 gene is located on 11q13.
- The MEN1 gene is a tumor suppressor gene that follows the 'two-hit hypothesis,' which implies that both alleles that code for a particular gene must be affected before an effect manifests.
- This is due to the fact that if only one allele for the gene is damaged, the second can still produce the correct protein.
- Affected individuals carry one altered copy of the MEN1 gene and the other copy is lost due to somatic mutation.
Associated Diseases
Prolactinoma may be associated with:[1]
Genetics
Familial Pituitary adenoma|pituitary adenomas
- A pituitary adenoma may be part of a familial syndrome:[2]
| Syndrome | Gene | Gene locus | Notes |
|---|---|---|---|
| Multiple endocrine neoplasia I | MEN1 | 11q13 | Characterized by the 3 Ps: pituitary adenoma, parathyroid adenoma, pancreatic neuroendocrine tumor |
| MEN1-like syndrome | CDKN1B | 12q13 | Associated with pituitary adenoma, parathyroid adenoma, neuroendocrine tumor |
| Carney complex | PRKAR1A | 17q24 | Other findings (mnemonic NAME): nevi, atrial myxoma, myxoid neurofibroma, ephelides (freckles) |
| Familial isolated pituitary adenoma | AIP | 11q13 |
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Gross Pathology
Gross pathology of prolactinoma is as follows:[8]
- Microprolactinomas (<10mm size) are usually found in the lateral wing of pituitary gland. They are most often surrounded by well defined pseudocapsules composed of reticulin.
- Macroprolactinomas (>10mm size) differ substantially in size and behavior. Some cause sellar expansion while others invade the skull base.
- About 50% of all prolactinoma grossly invade surrounding structures.
Microscopic Pathology
- Prolactinoma are divded into two types based on microscopy:
- Sparsely granulated variant
- Densely granulated variant
References
- ↑ 1.0 1.1 Ciccarelli A, Daly AF, Beckers A (2005). "The epidemiology of prolactinomas". Pituitary. 8 (1): 3–6. doi:10.1007/s11102-005-5079-0. PMID 16411062.
- ↑ 2.0 2.1 Karhu A, Aaltonen LA (2007). "Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update". Hum Mol Genet. 16 Spec No 1: R73–9. doi:10.1093/hmg/ddm036. PMID 17613551.
- ↑ Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S (1990). "Clonal origin of pituitary adenomas". J Clin Endocrinol Metab. 71 (6): 1427–33. doi:10.1210/jcem-71-6-1427. PMID 1977759.
- ↑ Vlotides G, Eigler T, Melmed S (2007). "Pituitary tumor-transforming gene: physiology and implications for tumorigenesis". Endocr Rev. 28 (2): 165–86. doi:10.1210/er.2006-0042. PMID 17325339.
- ↑ Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD; et al. (1999). "Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas". J Clin Endocrinol Metab. 84 (2): 761–7. doi:10.1210/jcem.84.2.5432. PMID 10022450.
- ↑ Agarwal SK, Lee Burns A, Sukhodolets KE, Kennedy PA, Obungu VH, Hickman AB; et al. (2004). "Molecular pathology of the MEN1 gene". Ann N Y Acad Sci. 1014: 189–98. PMID 15153434.
- ↑ Korbonits M, Storr H, Kumar AV (2012). "Familial pituitary adenomas - who should be tested for AIP mutations?". Clin Endocrinol (Oxf). 77 (3): 351–6. doi:10.1111/j.1365-2265.2012.04445.x. PMID 22612670.
- ↑ Bigner, D. D. (2006). Russell and Rubinstein's pathology of tumors of the nervous system. London New York, NY: Hodder Arnold Distributed in the United States of America by Oxford University Press. ISBN 978-0340810071.