Pituitary

, Volume 7, Issue 2, pp 73–82

Pituitary Pathology in Carney Complex Patients

Authors

  • Sotirios G. Stergiopoulos
    • Section on Endocrinology & Genetics (SEGEN)Developmental Endocrinology Branch (DEB), National Institute of Child Health and Human Development (NICHD)
  • Mones S. Abu-Asab
    • Laboratory of Pathology, National Cancer Institute (NCI)National Institutes of Health (NIH)
  • Maria Tsokos
    • Laboratory of Pathology, National Cancer Institute (NCI)National Institutes of Health (NIH)
    • Section on Endocrinology & Genetics (SEGEN)Developmental Endocrinology Branch (DEB), National Institute of Child Health and Human Development (NICHD)
    • D(med)Sci, Section on Endocrinology & GeneticsDEB, NICHD, NIH
Article

DOI: 10.1007/s11102-005-5348-y

Cite this article as:
Stergiopoulos, S.G., Abu-Asab, M.S., Tsokos, M. et al. Pituitary (2004) 7: 73. doi:10.1007/s11102-005-5348-y

Abstract

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.

Key Words

Carney complex pituitary tumors hyperplasia genetics PRKAR1A protein kinase A

Copyright information

© Springer Science + Business Media, Inc. 2004