Background: Severe insulin resistant (IR) type A is a rare inherited disorder characterized by glucose metabolism disturbances without obesity, acanthosis nigricans and hyperandrogenia due to INSR defects.
Case report: A 10-year-old girl was admitted because of skin papillomatosis and hyperpigmentations since her 7 years. She had early puberty with pubarche at 8 years and telarche at 9 years. Examination revealed normal height and weight (SDS BMI +0.49), acanthosis nigricans, clitoromegaly, no lipoatrophy, puberty stage Tanner P3B3. Laboratory tests revealed diabetes mellitus (2-hour glucose level was 11.4 mmol/l) with fasting low glucose levels (3.5 mmol/l), severe insulin resistance (hyperinsulinemic euglycemic clamp showed M-value 1.22 mg/kg/min) and hyperandrogenemism (testosterone 3.6 nmol/l, LH 3.3 U/l, FSH 4.1 U/l). Ovaries volume was 5 ml with multifollicular structure. Severe IR with signs of hyperandrogenism corresponded with INSR defects. Novel heterozygous p.E12228K mutation with uncertain pathogenicity in INSR was found. Patients father with the same mutation had multiple papillomas but normal glucose and insulin levels. Treatment with Metformin 2000 mg/day was started. After 3 months 2-hours glucose level normalized (5.7 nmol/l), the level of IR decreased (M-value 2.11 mg/kg/min). The level of testosterone remained elevated (4.89 nmol/l) and volumes of ovaries increased (11.2 and 9.1 ml).
Conclusion: Patients with acanthosis nigricans and papillomatosis should be investigated for IR. Severe IR is associated with signs of hyperandrogenia. Absence of IR in parent with the same mutation can be possibly explained by the penetrance. In our case of type A IR metformin normalized glucose metabolism but did not treat hyperandrogenism.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology