ECE2011 Poster Presentations Male reproduction (19 abstracts)
Hypogonadism, insulin resistance and visceral adiposity in myotonic dystrophy
E Passeri 1, , E Bugiardini 2, , V Sansone 2, , C Fulceri 4 , E Costa 4 , B Ambrosi 1, , G Meola 2, & S Corbetta 1,
1Endocrinology and Diabetology Unit, Department Medical-Surgical Sciences, IRCCS Policlinico San Donato, San donato Milanese, Italy; 2University of Milan, Milan, Italy; 3Neurology Unit, Department Medical-Surgical Sciences, IRCCS Policlinico San Donato, San donato Milanese, Italy; 4Clinical Chemistry Laboratory, IRCCS Policlinico San Donato, San donato Milanese, Italy.
Hypogonadism occurs in myotonic dystrophy (DM) type 1 and 2, a multisystemic autosomal dominant disorder. DM patients have genetically induced insulin-resistance (IR) and visceral obesity, providing a model to study the impact of metabolic disruptions on hypogonadism. We assessed hypothalamic-pituitary-gonadal function and metabolic features in 22 DM1 and 8 DM2 males (mean±S.D., 46±11years). Hypogonadism, defined as total testosterone (T)<320 ng/dl, freeT <6.4 ng/dl and sexual dysfunction), occurred in 1/3 of patients. Response to hCG was impaired in 33% of patients. Serum Insulin-Like factor 3 (INSL3), a marker of Leydig cell function, was lower in hypogonadic than eugonadic patients as well as 31age-BMI-matched controls (0.33±0.07 vs 0.47±0.09 and 0.41±0.07 ng/ml, P=0.004) and correlated with age and freeT. LH and FSH levels were significantly higher in DM patients and 38% of eugonadic patients showed LH and FSH >95° centile of controls. Nonetheless, GnRH failed to induce a normal response in a subset of patients. Interestingly, muscle test, using MRC score, negatively correlated with LH and FSH levels (r=−0.412, P=0.032; r=0.479, P=0.011). DM patients showed an increased visceral body fat versus controls: waist/hip and body fat mass were significantly higher, hepatosteatosis, abnormal liver tests and increased epicardial fat occur in 60 and 46% of patients, respectively. IR was diagnosed in 36%, 4 had overt diabetes. FreeT levels were predicted by HOMA-IR after adjustment for age and fat mass. In conclusion, nearly 30% of DM patients showed symptomatic hypogonadism and subclinical hypogonadism is even more frequent. Leydig cells impairment is associated with INSL3 reduction and is mainly related to IR rather than visceral adiposity. Interestingly, the relationship between muscle strength and gonadotropin rise suggests that LH and FSH might be a precocious and sensitive marker of muscle degeneration in male DM patients.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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