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Alström Syndrome International
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Pituitary function and IGF system in Alström SyndromePietro Maffei, Antonina Barreca, Jan D. Marshall, Richard Paisey, Sebastian Beck, Vincenzo Munno, Mara Boschetti, C. Martini1, R. Mioni, E. de Carlo1, R. Vettor, G. Federspil, Cesare Scandellari, Nicola Sicolo. e-mail: pietromaffei@libero.it Introduction: Alström Syndrome (ALMS) is a rare recessive autosomal disease. In some of the patients impairment of thyroid function, hypogonadism in males or irregular menses or amenorrhea in females and diabetes insipidus have been sporadically described. The gene responsible for the syndrome (ALMS1) has been recently localized on chromosome 2p13 and there are some data that point to a loss of ALMS1 function in the central nervous system. Although ALMS1 transcript is completely unknown it seem to be deeply involved both in metabolism and endocrine glands function. Moreover, the gene is ubiquitously expressed and has been localized in the pituitary and hypothalamus. Considering that GH-deficiency (GHD) and ALMS share some clinical and metabolic features we sought to evaluate GH and IGF-I axes in a group of ALMS patients. Methods: 26 ALMS patients (age range: 4-29 yr; 13M-13F), from all over the world, have been investigated in a single setting, during the International Alstrom Syndrome Workshop which took place in Morriburg (Canada) in August 2001. Blood sampling and anthropometric measurements have been taken in ALMS patients in the morning after overnight fasting. Anthropometric measurements included: body weight, height, BMI and waist/hip ratio (WHR). Blood samples were immediately frozen for the following investigations: kidney function (urea, creatinine); liver function (AST, ALT, GGT, bilirubin, albumin); calcium and ALP; thyroid function (FT3; FT4; TSH); cholesterol and triglycerides; glycaemia, insulin; leptin; total and free testosterone, estrogens, FSH and LH; IGF-I; IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-6, and ALS. Patients were divided in prepubertal (ALMS P1: N=13, age range 4-15 years) and young adults (ALMS A: N=13; age range 17-29 years; Pubertal Stage: P3-P5). Normal prepubertal (N P1: N=37; age range 2-14 years), obese prepubertal (O P1: N=37; age range 6-13 years) and normal young adult subjects (N A: N= 39; age range 18-35 years; ; Pubertal Stage: P4-P5) matched for gender served as controls. Results: the data demonstrated that in ALMS P1 IGF-I, IGFBP-3 and ALS were not significantly different from in N P1 and O P1, whereas ALMS A show significantly lower values than N A. Unlike N A, ALSM A did not show a significant increase of the 150 kDa complex subunits with regard to ALMS P1. Both ALMS P1 and A presented with hyperinsulinaemia (52.2±13.6 and 122.5±60.9 _IU/ml, respectively) and significantly lower IGFBP-1 and -2 concentrations in comparison with N P1 and A (Table I summarize data (Mean±SEM) of IGF system and P values). Considering all study population, in ALMS patients a significant correlation between IGF-I, IGFBP3 and ALS was normally present. However, liver and kidney function were not correlated with IGF-I, ALS or IGFBPs. Discussion: Our data suggest that an impaired GH-IGF axis in Alström may account for the impaired final height, and can be associated with overweight, central obesity and metabolic imbalance. Adult ALMS patients showed a major impairment of IGF system than prepubertal ALMS. The alterations of the IGF-I, IGFBPs and ALS appear to be unrelated to liver or kidney function. Further evaluation of GH-IGF-IGFBP system for all ALMS patients, including GH dynamic tests, will determine the cause-effect interrelationship between obesity and GH-IGF axis impairment. Table 1
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Last Modified: June 23, 2008 |
