Background: Insulin resistance occurs in a variety of common endocrine disorders including obesity, type 2 diabetes, polycystic ovarian syndrome, and metabolic syndrome. Additionally, rare syndromes exist that result in extreme insulin resistance. These conditions help contribute to our knowledge of the mechanisms of insulin signalling and resistance.
Objective and hypotheses: We report a case of a 12 year old female presenting to endocrinology clinic for evaluation of new onset diabetes. She was found to have extremely tall stature, acanthosis nigricans, severe hirsuitism, obesity, and acromegaloid features. We hypothesized that she had a syndrome of growth hormone excess resulting in acromegaly, tall stature, insulin resistance, and diabetes.
Method: The patient underwent non-fasting blood work as well as a 2 h oral glucose tolerance test (OGTT) measuring growth hormone and insulin. The patient and her first-degree relatives underwent whole exome sequencing.
Results: The patient had normal levels of IGF-1. However she was noted to have extremely elevated insulin level (1279 μIU/ml) postprandially. She also had evidence of biochemical hyperandrogenism with an elevated free testosterone (16 pg/ml). The patient had a bone age of 14 years. Therefore her predicted adult height was 1.83 m (+3.23 SDS). She then underwent a 2-h OGTT. After ingesting 75 g oral glucose solution, her growth hormone level was undetectable at 90 min. However, her fasting insulin level was 27.7 μIU/ml. The subsequent levels were 752, 799, 488, and 390 mIU/ml at 30, 60, 90, and 120 min respectively. Whole exome sequencing identified potential genetic causes.
Conclusion: We report a novel case of a 12 year old patient with tall stature, acromegaloid features, normal growth hormone secretion, and severe postprandial insulin resistance. This condition, insulin mediated pseudoacromegaly, is poorly represented in the medical literature. We hypothesize that this condition is caused by genetic factors. Whole exome sequencing has been performed to reveal the molecular pathogenesis underlying this condition.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology