Endocrine Abstracts

A 26-year-old Chinese male with autism spectrum disorder and mental retardation, was referred to start insulin therapy for uncontrolled diabetes mellitus (DM) (HbA1c: 9%; C-peptide: 1.75 ng/ml; anti-GAD AB: negative) treated with oral antidiabetic drugs since 2012.

Clinical examination revealed a tall man with overweight and truncal obesity in light of his ethnicity. We withheld facial dysmorphism with hypertelorism, scarce facial hair, and clinodactyly. He had a true gynaecomastia and acanthosis nigricans. Tanner genital stage was IV, however testicular volume was <4 ml.

Blood results showed hypergonadotropic hypogonadism (LH:14.1 U/L, FSH:25.3 U/L, testosterone: 195 ng/dl, free testosterone: 5.71 ng/dl). Additional genetic testing showed 48 XXYY karyotype.

Based on medical questionnaires, DM is described in 18% of 48 XXYY males. Following pathophysiological mechanism is proposed: low tota l and free testosterone levels are associated with truncal obesity leading to metabolic syndrome, insulin resistance and DM. Abdominal obesity and high C-peptide levels in our patient are arguments in favor of insulin resistance as possible etiological factor. Based on the pathophysiology, metformin and testosterone could be considered as therapy. Our patient was initially treated with basal-bolus insulin therapy in combination with metformin to enhance insulin sensitivity. Although in-hospital blood glucose curves were perfect, global metabolic control remained poor (HbA1c: 8.5%) due to compliance problems partially by the complexity of treatment. Therefore therapy was simplified to a combination of basal insulin and metformin. Metabolic control remained however poor. Some data suggest that testosterone treatment might improve metabolic control by increasing skeletal muscle mass and decreasing abdominal obesity. In our patient, there was however no amelioration of metabolic control after start of testosterone.

Adequate DM therapy is complicated by mental retardation seen in 48 XXYY making it difficult to use complex insulin schemes. It seems reasonable to use metformin in treatment as insulin resistance seems to play a role in the pathophysiology.