title: Characterization of the IGF system in 15 patients with Alström syndrome.
abstract: BACKGROUND
  Alström syndrome (ALMS) is a rare recessively inherited progressive disease (OMIM 203800). Among its diverse spectrum of clinical features are phenotypes associated with deficiencies of the GH/IGF-I axis, including short stature, obesity, insulin resistance, hypertriglyceridaemia and heart failure.
  
  
  METHODS
  To characterize the IGF system in ALMS, we evaluated a subset of 15 young adults with ALMS for hepatic, renal and thyroid function. Glycaemic and hormone measurements such as insulin, GH, FSH, LH, testosterone and 17-beta-oestradiol were clinically assessed. In addition, we measured IGF-I, IGF-II, IGF binding-protein-3 (IGFBP-3) and acid labile subunit (ALS - the subunits that constitute the main somatomedin complex in the circulation), and IGFBP-1 and IGFBP-2 (known to influence the bioavailability of the IGFs).
  
  
  RESULTS
  A significantly lower height was observed in ALMS patients compared to age-matched controls. ALMS patients were clinically obese (by weight and body mass index (BMI) standards) and leptin levels correlated with BMI. Renal and hepatic dysfunction was implicated in some patients by increased values of blood urea nitrogen (BUN) and creatinine, and transaminases, respectively. One-third of the patients presented with fasting hyperglycaemia and 80% were hyperinsulinaemic. TSH was slightly increased in 20% of patients. Baseline FSH and LH in females were within the normal range, while half of the males had abnormally low testosterone values. Male patients with hypogonadism showed significantly lower testosterone, oestrogen and ALS levels. Baseline GH values were not found to be increased. ALS and IGFBP-1 were significantly reduced and IGFBP-2 was markedly increased in ALMS patients compared to age-matched controls. The IGFs and IGFBPs were not significantly different between males and females affected with ALMS. No significant association was observed between IGFs or IGFBPs levels and weight, height, BMI, glycaemia, hyperinsulinaemia and testosterone levels. However, we found a significant association of gamma-glutamyltransferase (GGT) with IGFBP-2. IGF-I levels were significantly associated with LH in female patients.
  
  
  CONCLUSIONS
  In summary, the reduction of ALS and the increase of IGFBP-2 points to a growth hormone deficiency (GHD) condition in ALMS. However, further tests, including GH dynamics, are needed to determine whether, or to what degree disturbances in the GH/IGF axis contribute to the relatively short stature.
authors.affiliation: Medical and Surgical Sciences, University School of Medicine, Padua, Italy. pietromaffei@libero.it
authors.forename: Pietro
authors.initials: P
authors.lastname: Maffei
authors.forename: Mara
authors.initials: M
authors.lastname: Boschetti
authors.forename: Jan D
authors.initials: JD
authors.lastname: Marshall
authors.forename: Richard B
authors.initials: RB
authors.lastname: Paisey
authors.forename: Sebastian
authors.initials: S
authors.lastname: Beck
authors.forename: Eugenia
authors.initials: E
authors.lastname: Resmini
authors.forename: Gayle B
authors.initials: GB
authors.lastname: Collin
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Naggert
authors.forename: Gabriella
authors.initials: G
authors.lastname: Milan
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.forename: Francesco
authors.initials: F
authors.lastname: Minuto
authors.forename: Nicola
authors.initials: N
authors.lastname: Sicolo
authors.forename: Antonella
authors.initials: A
authors.lastname: Barreca
mesh_terms: D000328:Adult; D001766:Blindness / Q000097:blood; D001827:Body Height; D016022:Case-Control Studies; D003638:Deafness / Q000097:blood; D005260:Female; D006130:Growth Disorders / Q000097:blood*; D013006:Growth Hormone / Q000097:blood; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D007333:Insulin Resistance; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood*; D013002:Somatomedins / Q000032:analysis*; D018709:Statistics, Nonparametric; D013577:Syndrome; D013739:Testosterone / Q000097:blood
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D013002:Somatomedins; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D007986:Luteinizing Hormone; D013006:Growth Hormone