Massive ovarian enlargement (without underlying mass) is a rare finding in neonates. Ovarian enlargement has been associated with insulin-resistant states such as polycystic ovarian syndrome (PCOS) and rare congenital syndromes such as infants with leprechaunism. However, the extent, severity, and radiographic findings of ovarian growth in infants with syndromes of insulin resistance have not been fully described. We report a case of severe ovarian enlargement in an infant with congenital insulin resistance. A two-month-old born at 37 weeks via C-section with a history of intrauterine growth restriction was admitted for hyperglycemia consistent with neonatal diabetes and was subsequently diagnosed with insulin resistance syndrome (either leprechaunism or Rabson-Mendenhall syndrome) secondary to an <i>INSR</i> gene mutation. Insulin and proinsulin levels at 3 weeks of age were markedly elevated to 582.3 uIU/mL (2.0 – 19.6) and 674.3 pmol/L (≤ 18.8), respectively. An abdominal ultrasound (US) performed for abdominal distension demonstrated very enlarged ovaries containing sub-centimeter follicles. Ovarian volumes were 12.8 mL and 8.7 mL on the right and left, respectively. The mean ovarian volume for this age is 1.06 mL with a standard deviation (SD) of 0.96; this would place this patient's right and left ovaries 12.2 and 8.0 SD above the mean, respectively. CT performed at three months of age for evaluation of persistent fevers demonstrated further enlargement of the ovaries. Ovarian volumes were 106 mL and 60 mL on the right and left, which were 109 and 61 SD above the mean, respectively. A repeat US performed at four months of age showed decreasing ovarian volumes measuring 51 mL and 18 mL on the right and left, respectively (which were still 49 and 25 SD above the mean). We postulate that this case of massive ovarian enlargement in the setting of severe insulin resistance was likely due to an insulin-mediated gonadotropin-independent mechanism, as has been previously suggested in infants with leprechaunism (perhaps mediated through an intact homologous IGF-I receptor). The ovarian enlargement seen in post-pubertal females with PCOS may have a similar pathogenesis, with resultant granulosa cell proliferation with antral follicles. Ovarian cysts have also been seen in non-insulin-resistant hyperinsulinemic infants of diabetic mothers, suggesting that high circulating serum insulin may act in the trophic manner typical of gonadotropic hormones.
SPR 2020 Annual Meeting & Postgraduate Course