title: Triple A syndrome in a patient with genetic growth hormone insensitivity: phenotypic effects of two genetic disorders.
abstract: BACKGROUND
  Primary growth hormone insensitivity (GHI) and triple A syndrome are rare autosomal recessive disorders.
  
  
  METHODS
  The patient, a 12-year-old boy from consanguineous parents, was referred for short stature at the age of 7 years (height: -5.4 SD score). He had low serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 and a blunted IGF-I response to recombinant human GH; molecular analysis of the GH receptor disclosed a homozygous A(-1)→G(-1) at the 5' pseudoexon 6Ψ splice site. Recombinant IGF-I therapy (mecasermin, Increlex®, twice daily) initiated at the age of 9 years resulted in an increase of height velocity (HV) from 4.0 to 9.5 cm/year. At the age of 10.5 years, he presented with asthenia, anorexia, weight loss, a decrease in HV and very low cortisol levels; adrenal insufficiency was confirmed and glucocorticoid therapy was initiated. Subsequent peripheral motor neuropathy, achalasia and alacrima raised the suspicion of triple A syndrome, which was confirmed by the presence of a homozygous R194X mutation in the AAAS gene.
  
  
  CONCLUSIONS
  This unusual combination of diseases, to our knowledge, has not been reported to date. Although the patient responded to recombinant IGF-I therapy for GHI, we hypothesize that the treatment could have had an inhibitory effect on 11β-hydroxysteroid dehydrogenase type 1 activity, thereby reducing the availability of cortisol and precipitating adrenal insufficiency.
authors.affiliation: Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marín
authors.forename: Paula
authors.initials: P
authors.lastname: Casano-Sancho
authors.forename: Nancy
authors.initials: N
authors.lastname: Villarreal-Peña
authors.forename: Giorgia
authors.initials: G
authors.lastname: Sebastiani
authors.forename: Sergio
authors.initials: S
authors.lastname: Pinillos
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez-Dueñas
authors.forename: Vivian
authors.initials: V
authors.lastname: Hwa
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
mesh_terms: D000309:Adrenal Insufficiency / Q000150:complications* / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D004931:Esophageal Achalasia / Q000150:complications* / Q000235:genetics; D006801:Humans; D046150:Laron Syndrome / Q000150:complications* / Q000235:genetics; D008297:Male; D010375:Pedigree