Characterization of the IGF system in 15 patients with Alström syndrome.
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.
Maffei
Pietro
P
Medical and Surgical Sciences, University School of Medicine, Padua, Italy. pietromaffei@libero.it
Boschetti
Mara
M
Marshall
Jan D
JD
Paisey
Richard B
RB
Beck
Sebastian
S
Resmini
Eugenia
E
Collin
Gayle B
GB
Naggert
Jürgen K
JK
Milan
Gabriella
G
Vettor
Roberto
R
Minuto
Francesco
F
Sicolo
Nicola
N
Barreca
Antonella
A
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
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