title: Clinical challenges in the management of isolated GH deficiency type IA in adulthood.
abstract: Isolated GH deficiency type IA (IGHDIA) is an infrequent cause of severe congenital GHD, often managed by pediatric endocrinologists, and hence few cases in adulthood have been reported. Herein, we describe the clinical status of a 56-year-old male with IGHDIA due to a 6.7 kb deletion in GH1 gene that encodes GH, located on chromosome 17. We also describe phenotypic and biochemical parameters, as well as characterization of anti-GH antibodies after a new attempt made to treat with GH. The height of the adult patient was 123 cm. He presented with type 2 diabetes mellitus, dyslipidemia, osteoporosis, and low physical and psychological performance, compatible with GHD symptomatology. Anti-GH antibodies in high titers and with binding activity (>101 IU/ml) were found 50 years after exposure to exogenous GH, and their levels increased significantly (>200 U/ml) after a 3-month course of 0.2 mg/day recombinant human GH (rhGH) treatment. Higher doses of rhGH (1 mg daily) did not overcome the blockade, and no change in undetectable IGF1 levels was observed (<25 ng/ml). IGHDIA patients need lifelong medical surveillance, focusing mainly on metabolic disturbances, bone status, cardiovascular disease, and psychological support. Multifactorial conventional therapy focusing on each issue is recommended, as anti-GH antibodies may inactivate specific treatment with exogenous GH. After consideration of potential adverse effects, rhIGF1 treatment, even theoretically indicated, has not been considered in our patient yet.
  
  
  CONCLUSIONS
  Severe isolated GHD may be caused by mutations in GH1 gene, mainly a 6.7 kb deletion.Appearance of neutralizing anti-GH antibodies upon recombinant GH treatment is a characteristic feature of IGHDIA.Recombinant human IGF1 treatment has been tested in children with IGHDIA with variable results in height and secondary adverse effects, but any occurrence in adult patients has not been reported yet.Metabolic disturbances (diabetes and hyperlipidemia) and osteoporosis should be monitored and properly treated to minimize cardiovascular disease and fracture risk.Cerebral magnetic resonance imaging should be repeated in adulthood to detect morphological abnormalities that may have developed with time, as well as pituitary hormones periodically assessed.
authors.affiliation: Department of Endocrinology Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona Pg. Vall d'Hebron 119-129, Barcelona, 08035 Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Casteràs
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig Leipzig Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kratzsch
authors.affiliation: Department of Pediatrics Andrea Prader Centre, Hospital Universitario Miguel Servet Zaragoza Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Ferrández
authors.affiliation: Department of Endocrinology Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona Pg. Vall d'Hebron 119-129, Barcelona, 08035 Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Zafón
authors.affiliation: Department of Pediatrics Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona Barcelona Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrascosa
authors.affiliation: Department of Endocrinology Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona Pg. Vall d'Hebron 119-129, Barcelona, 08035 Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Mesa