| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Eng, Charis Koziol, Deloris Quezado, Martha Sierra, Maria de La Luz Bullova, Petra Mastroyannis, Spyridon A. Stratakis, Constantine A. Rentia, Nadia Moline, Jessica Pacak, Karel Xekouki, Paraskevi Belyavskaya, Elena Lyssikatos, Charalampos Raygada, Margarita Malchoff, Carl Mastorakos, Panagiotis Giubellino, Alessio Dye, Louis Lodish, Maya Cougnoux, Antony Maher, Louis James Wassif, Christopher A. Szarek, Eva |
| Description |
Country affiliation: Slovakia Author Affiliation: Xekouki P ( Section on Endocrinology and Genetics (P.X., E.S., S.A.M., P.M., M.R., N.R., M.d.L.L.S., C.L., E.B., M.L., C.A.S.), Program on Developmental Endocrinology and Genetics, Section on Medical Neuroendocrinology (P.B., A.G.), Program in Reproductive and Adult Endocrinology, Section on Molecular Dysmorphology (C.A.W., A.C.), Program in Developmental Endocrinology and Genetics, Microscopy and Imaging Core (L.D.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Laboratory of Pathology (A.G., M.Q., K.P.), National Cancer Institute, and Biostatistics and Clinical Epidemiology Service (D.K.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892) |
| Abstract |
CONTEXT: Germline mutations in genes coding succinate dehydrogenase (SDH) subunits A, B, C, and D have been identified in familial paragangliomas (PGLs)/pheochromocytomas (PHEOs) and other tumors. We described a GH-secreting pituitary adenoma (PA) caused by SDHD mutation in a patient with familial PGLs. Additional patients with PAs and SDHx defects have since been reported. DESIGN: We studied 168 patients with unselected sporadic PA and with the association of PAs, PGLs, and/or pheochromocytomas, a condition we named the 3P association (3PAs) for SDHx germline mutations. We also studied the pituitary gland and hormonal profile of Sdhb(+/-) mice and their wild-type littermates at different ages. RESULTS: No SDHx mutations were detected among sporadic PA, whereas three of four familial cases were positive for a mutation (75%). Most of the SDHx-deficient PAs were either prolactinomas or somatotropinomas. Pituitaries of Sdhb(+/-) mice older than 12 months had an increased number mainly of prolactin-secreting cells and several ultrastructural abnormalities such as intranuclear inclusions, altered chromatin nuclear pattern, and abnormal mitochondria. Igf-1 levels of mutant mice tended to be higher across age groups, whereas Prl and Gh levels varied according to age and sex. CONCLUSION: The present study confirms the existence of a new association that we termed 3PAs. It is due mostly to germline SDHx defects, although sporadic cases of 3PAs without SDHx defects also exist. Using Sdhb(+/-) mice, we provide evidence that pituitary hyperplasia in SDHx-deficient cells may be the initial abnormality in the cascade of events leading to PA formation. |
| ISSN |
0021972X |
| e-ISSN |
19457197 |
| DOI |
10.1210/jc.2014-4297 |
| Journal |
The Journal of Clinical Endocrinology & Metabolism |
| Issue Number |
5 |
| Volume Number |
100 |
| Language |
English |
| Publisher |
Oxford University Press |
| Publisher Date |
2015-05-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Adenoma Genetics Adrenal Gland Neoplasms Paraganglioma Pheochromocytoma Pituitary Neoplasms Succinate Dehydrogenase Adolescent Animals Child, Preschool Dna Mutational Analysis Germ-line Mutation Mice Mice, Knockout Research Support, N.i.h., Extramural Research Support, N.i.h., Intramural Research Support, Non-u.s. Gov't Discipline Endocrinology Discipline Metabolism |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Endocrinology |
