Introduction: Severe insulin resistance due to insulin receptor mutation is usually diagnosed at the neonatal period (Donohue and Rabson-Medenhall syndromes), or later in a type A insulin resistance syndrome. We report here two cases of insulin receptor mutation whose presenting signs were less noticeable.
Observation: A 13-year-old girl was referred for short stature (Height −2.5 SDS) with SGA (birth length 44.5 cm, at gestational age 41 weeks). Clinical examination was normal, pubertal stage was A2P3 S3. The glycemic nadir was 3.7 mmol/l, and GH peak was 8 ng/ml during the insulin tolerance test. All the investigations were normal, and the short stature was attributed to idiopathic SGA. At the age of 16, she was seen for acanthosis nigricans and primary amenorrhea. Pubertal stage was A4P4S4, and Ferriman score was 4. Pelvic ultrasound showed ovaries of 10 and 8 cm2. Testosterone level was 1.43 ng/ml. During OGTT, she had very high levels of fasting and insulin peak: 708 pmol/l and 52 087 pmol/l, respectively. The family history found a hyper androgenic clinic in the mother and acanthosis nigricans in the 13-year-old brother (height −1 SDS). A compound heterozygote mutation in the insulin gene was found in the index case and in the brother: exon 11 and exon 14. A 16-year-old girl (Height 156 cm, Weight 50 kg) consulted for hirsutism and secondary amenorrhea. Ferriman-Gallwey score was 7. Family history found a 13-years sister with acanthosis nigricans and hirsutism, two female cousins with PCOS, and an aunt with acanthosis nigricans. Fasting insulinemia in the girl was 1800 pmol/l. A mutation in the insulin receptor has been identified in the index case: exon 17 c.3164c>T, and molecular studies in the family are underway.
Conclusion: In short stature with SGA as well as in familial cases of PCOS, we suggest to routinely measure fasting insulinemia, as it may lead to the diagnosis of pathological insulin resistance due to insulin receptor mutation.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology