title: Endocrine abnormalities in patients with Fanconi anemia.
abstract: BACKGROUND
  Fanconi anemia (FA) is an inherited disorder with chromosomal instability, bone marrow failure, developmental defects, and a predisposition to cancer. Systematic and comprehensive endocrine function data in FA are limited.
  
  
  OBJECTIVE
  We studied a cohort of FA patients enrolled in the National Cancer Institute's Inherited Bone Marrow Failure Syndrome study.
  
  
  METHODS
  Retrospective review of the medical records of 45 FA patients (ages 2-49 yr), 23 of whom were intensively evaluated at the National Institutes of Health. Anthropometric measurements, GH, IGF-I, IGF binding protein-3, thyroid, gonadal hormone, lipid levels, glucose homeostasis, brain imaging, and bone mineral density were obtained in these latter patients.
  
  
  RESULTS
  Endocrine abnormalities were present in 73%, including short stature and/or GH deficiency (51%), hypothyroidism (37%), midline brain abnormalities (17%) (these patients had very short stature and 60% were GH-deficient); abnormal glucose/insulin metabolism (39%); obesity (27%); dyslipidemia (55%); and metabolic syndrome (21%). Patients with any endocrine abnormality were shorter than those without; only GH deficiency correlated significantly with short stature (P = 0.01). In addition, 65% of peripubertal or postpubertal patients had gonadal dysfunction. Ninety-two percent of the patients 18 yr or older had osteopenia or osteoporosis.
  
  
  CONCLUSIONS
  Endocrine dysfunction is widespread in children and adults with FA; we expand the FA phenotype to include early onset osteopenia/osteoporosis and lipid abnormalities. Despite the reputation of FA as a progressive, lethal disease, proper management of the full spectrum of FA-related endocrinopathy offers major opportunities to reduce morbidity and improve quality of life. Our findings emphasize the need for comprehensive endocrine and metabolic evaluation and long-term follow-up in patients with FA.
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard EPS/7024, Rockville, Maryland 20852, USA. girin@mail.nih.gov
authors.forename: Neelam
authors.initials: N
authors.lastname: Giri
authors.forename: Dalia L
authors.initials: DL
authors.lastname: Batista
authors.forename: Blanche P
authors.initials: BP
authors.lastname: Alter
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000293:Adolescent; D000328:Adult; D000365:Age Determination by Skeleton; D001827:Body Height; D001835:Body Weight; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004700:Endocrine System Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D005199:Fanconi Anemia / Q000150:complications* / Q000503:physiopathology*; D005260:Female; D018149:Glucose Intolerance / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D007018:Hypopituitarism / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D007037:Hypothyroidism / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D013963:Thyroid Hormones; D019382:Human Growth Hormone