Pituitary pathology in Carney complex patients.
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 1alpha 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.
Stergiopoulos
Sotirios G
SG
Section on Endocrinology & Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, USA.
Abu-Asab
Mones S
MS
Tsokos
Maria
M
Stratakis
Constantine A
CA
D000172:Acromegaly / Q000473:pathology; D000328:Adult; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000473:pathology*; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000473:pathology* / Q000648:ultrastructure; D010902:Pituitary Gland / Q000473:pathology* / Q000648:ultrastructure; D010911:Pituitary Neoplasms / Q000473:pathology* / Q000648:ultrastructure
D019382:Human Growth Hormone