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.

Study Design and Patients: 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.