Intractable early childhood obesity as the initial sign of insulin resistant hyperinsulinism and precursor of polycystic ovary syndrome

Objective: We report that intractable early childhood obesity may be associated with severe insulin resistance syndromes (pseudo-Cushing's syndrome and pseudo-acromegaly) and precede polycystic ovary syndrome (PCOS). Study design/Results: Patient 1 had prepubertal obesity followed by early puberty and was diagnosed with pseudo-Cushing's syndrome and insulin resistance at 10.3 years. Oligomenorrhea, androgen excess, and type 2 diabetes mellitus (DM2) emerged at 13.5 years. Patient 2 developed intractable prepubertal obesity followed by atypical true sexual precocity and pseudo-Cushing's syndrome in early childhood. By 11.3 years, oligomenorrhea, androgen excess, and DM2 had appeared. Patient 3 had prepubertal overgrowth in weight and height and was diagnosed with pseudo-acromegaly, menstrual irregularity, androgen excess, and impaired glucose tolerance at 14.3 years of age. Patient 4 had prepubertal overgrowth that evolved into pseudo-acromegaly, insulin resistance, secondary amenorrhea, and androgen excess at 15.6 years. Conclusions: Intractable prepubertal obesity was recognized to culminate in early childhood pseudo-Cushing's syndrome or pseudo-acromegaly, which are manifestations of insulin-resistant hyperinsulinism, and to herald adolescent PCOS.