Seckel syndrome (SS) is described as the prototype of the primordial bird-headed type of dwarfism (Seckel 1960). It represents a spectrum of multisystem abnormalities. We present a case of SS and discuss the possible effects of IGF-1 and IGF-3 in the development of growth failure, type 2 Diabetes Mellitus (DM) and severe insulin resistance (IR).
Case: A 21-year-old female was referred to our clinic because of growth retardation and amenorrhea. At birth, she was small for gestational age, she walked at the age of 7 years. She was amenorrheic after menarch at 18-year-old. Physical examination: BP 120/80 mmHg, central obesity (15 kg, 94 cm, BMI 17 kg/m2, W/H 1.3), microcephaly, bird-headed appearance, mental retardation, acanthosis nigricans (AN). Ophthalmoscopy: non-prolipherative diabetic retinopathy. Biochemical analyses: FPG: 332 mg/dl, TG: 1046 mg/dl, T-C: 270 mg/dl, HDL-C: 22 mg/dl, elevated liver function test, HOMA-IR index: 17.7, microalbuminuria: 137 mg/d, CCr 142 ml/min. GH, IGF-1, cortisol levels were normal. IGF-3 and LH levels were elevated. Insulin tolerance test showed markedly increased GH and cortisol levels. Her bone age was higher than 18. Pelvic US: multiple anechoic cysts in ovaries and markedly increased endometrium thickness. She was diagnosed as SS with early onset type 2 DM and severe IR. To our knowledge, DM is not common in SS, only 3 cases of early unset of type 2 DM with progressive ataxia were reported by Bangstad in 1988. Insulin resistance is an important etiologic factor in the pathogenesis of DM, however, more important factor in our case is that IGF-1 resistance leading to both growth failure and IR. Despite sufficient GH, normal IGF-1 and elevated IGFBP3, the growth failure implicated an IGF-1 resistance. Moreover, AN in IR results from increased bioavailibity of IGF-1. Finally, IR constitutes an important risk for an increased risk for CVD and endometrium ca in her life.
25 - 29 Apr 2009
European Society of Endocrinology