Pituitary Pathology in Carney Complex Patients
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Carney complex (CNC) is a familial multiple neoplasia syndrome with features overlapping those of McCune-Albright syndrome (MAS) and multiple endocrine neoplasia (MEN) type 1 (MEN 1). Like MAS and MEN 1 patients, patients with CNC develop growth hormone (GH)-producing pituitary tumors. Occasionally, these tumors are also prolactin-producing, but there are no isolated prolactinomas or other types of pituitary tumors. In at least some patients with CNC, the pituitary gland is characterized by hyperplastic areas; hyperplasia appears to involve somatomammotrophs only. Hyperplasia most likely precedes the formation of GH-producing adenomas in CNC, as has been suggested in MAS-related somatotropinomas, but has never been seen in MEN 1 patients. In at least one case of a patient with CNC and advanced acromegaly, a GH-producing macroadenoma showed extensive genetic changes at the chromosomal level. So far, half of the patients with CNC have germline inactivating mutations in the PRKAR1A gene; in their pituitary tumors, the normal allele of the PRKAR1A gene is lost. Loss-of-hererozygosity suggests that PRKAR1A, which codes for the regulatory subunit type 1α of the cAMP-dependent protein kinase A (PKA) may act as a tumor-suppressor gene in CNC somatomammotrophs. These data provide evidence for a PRKAR1A-induced somatomammotroph hyperpasia in the pituitary tissue of CNC patients; hyperplasia, in turn may lead to additional genetic changes at the somatic level, which then cause the formation of adenomas in some, but not all, patients.
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- Pituitary Pathology in Carney Complex Patients
Volume 7, Issue 2 , pp 73-82
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- Kluwer Academic Publishers
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- Carney complex
- pituitary tumors
- protein kinase A
- Industry Sectors
- Author Affiliations
- 1. Section on Endocrinology & Genetics (SEGEN), Developmental Endocrinology Branch (DEB), National Institute of Child Health and Human Development (NICHD), Maryland
- 2. Laboratory of Pathology, National Cancer Institute (NCI), National Institutes of Health (NIH), Maryland
- 3. D(med)Sci, Section on Endocrinology & Genetics, DEB, NICHD, NIH, Building 10, Room 10N262, 10 Center Dr. MSC1862, 20892-1862, Bethesda, Maryland