title: Growth hormone and risk for cardiac tumors in Carney complex.
abstract: Carney complex (CNC) is a multiple neoplasia syndrome that is caused mostly by PRKAR1A mutations. Cardiac myxomas are the leading cause of mortality in CNC patients who, in addition, often develop growth hormone (GH) excess. We studied patients with CNC, who were observed for over a period of 20 years (1995-2015) for the development of both GH excess and cardiac myxomas. GH secretion was evaluated by standard testing; dedicated cardiovascular imaging was used to detect cardiac abnormalities. Four excised cardiac myxomas were tested for the expression of insulin-like growth factor-1 (IGF-1). A total of 99 CNC patients (97 with a PRKAR1A mutation) were included in the study with a mean age of 25.8 ± 16.6 years at presentation. Over an observed mean follow-up of 25.8 years, 60% of patients with GH excess (n = 46) developed a cardiac myxoma compared with only 36% of those without GH excess (n = 54) (P = 0.016). Overall, patients with GH excess were also more likely to have a tumor vs those with normal GH secretion (OR: 2.78, 95% CI: 1.23-6.29; P = 0.014). IGF-1 mRNA and protein were higher in CNC myxomas than in normal heart tissue. We conclude that the development of cardiac myxomas in CNC may be associated with increased GH secretion, in a manner analogous to the association between fibrous dysplasia and GH excess in McCune-Albright syndrome, a condition similar to CNC. We speculate that treatment of GH excess in patients with CNC may reduce the likelihood of cardiac myxoma formation and/or recurrence of this tumor.
authors.affiliation: National HeartLung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: W Patricia
authors.initials: WP
authors.lastname: Bandettini
authors.affiliation: National Institute of Child Health and Human Development (NICHD)NIH, Bethesda, Maryland, USA Department of PediatricsGeorgetown University Hospital, Washington, District of Columbia, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Karageorgiadis
authors.affiliation: Biostatistics and Clinical Epidemiology ServiceClinical Center, NIH, Bethesda, Maryland, USA.
authors.forename: Ninet
authors.initials: N
authors.lastname: Sinaii
authors.affiliation: National HeartLung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Rosing
authors.affiliation: National HeartLung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Vandana
authors.initials: V
authors.lastname: Sachdev
authors.affiliation: National Institute of Child Health and Human Development (NICHD)NIH, Bethesda, Maryland, USA.
authors.forename: Marie Helene
authors.initials: MH
authors.lastname: Schernthaner-Reiter
authors.affiliation: National Institute of Child Health and Human Development (NICHD)NIH, Bethesda, Maryland, USA Department of PediatricsGeorgetown University Hospital, Washington, District of Columbia, USA.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Gourgari
authors.affiliation: Department of Radiology and Imaging SciencesClinical Center, NIH, Bethesda, Maryland, USA.
authors.forename: Georgios Z
authors.initials: GZ
authors.lastname: Papadakis
authors.affiliation: National Institute of Child Health and Human Development (NICHD)NIH, Bethesda, Maryland, USA.
authors.forename: Meg F
authors.initials: MF
authors.lastname: Keil
authors.affiliation: National Institute of Child Health and Human Development (NICHD)NIH, Bethesda, Maryland, USA.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Lyssikatos
authors.affiliation: Department of Laboratory Medicine and PathologyMayo Clinic, Rochester, Minnesota, USA.
authors.forename: J Aidan
authors.initials: JA
authors.lastname: Carney
authors.affiliation: National HeartLung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Arai
authors.affiliation: National Institute of Child Health and Human Development (NICHD)NIH, Bethesda, Maryland, USA.
authors.forename: Maya
authors.initials: M
authors.lastname: Lodish
authors.affiliation: National Institute of Child Health and Human Development (NICHD)NIH, Bethesda, Maryland, USA stratakc@mail.nih.gov.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000172:Acromegaly / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000601:surgery; D000293:Adolescent; D000328:Adult; D056733:Carney Complex / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000601:surgery; D002648:Child; D005260:Female; D006338:Heart Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000601:surgery; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008297:Male; D012307:Risk Factors; D055815:Young Adult
chemical_list: C583557:IGF1 protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
keywords: acromegaly; growth hormone; insulin-like growth factor-I (IGF-I); myxoma; tumor