Endocrine Abstracts

Background: Lowe Syndrome is an X-linked recessive genetic disorder caused by OCRL gene mutations, which impair intracellular trafficking processes. Signs are multisystemic, including congenital cataracts, intellectual disability and proximal renal tubulopathy. Short stature is a common association, often attributed to chronic kidney disease through childhood. However, recent evidence suggests that the hypothalamo-pituitary-somatotroph axis may play a role.

Objectives: This case series reports three Lowe Syndrome patients with short stature and poor growth velocity at a tertiary-level centre in the United Kingdom (16yr, 18yr, and 5yr 11mo). All were diagnosed with GH deficiency or neurosecretory dysfunction through glucagon provocation tests, GH overnight profiling and/or pituitary MRI scans. All three were started on recombinant GH therapy at 15yr, 12yr 7mo and 4yr 2mo respectively (all pre-pubertal at commencement). This case series aims to analyse the efficacy of GH therapy in these patients.

Results: The first patient showed a reduced GH peak of 6.4ng/mL on provocation testing, and anterior pituitary hypoplasia on MRI. In response to GH therapy, his IGF-1 concentration doubled, puberty commenced, and growth velocity increased from 3.4 to 5.0 cm/yr. The second patient had a normal GH peak of 21.5ng/mL on provocation testing, but IGF-1 concentration was at the lower end of normal range at 106ng/ml (88-452ng/mL). He progressed well through puberty on GH therapy, with IGF-1 concentrations also doubling and growth velocity increasing from 2.8 to 4.9 cm/yr. The third patient had a normal GH peak of 11.2ng/mL on provocation tests, but undetectable IGF-1. The overnight profile was abnormal and anterior pituitary hypoplasia was identified. On GH therapy, growth velocity increased from 3.7 to 5.0 cm/yr and progression through shoes/clothes sizes hastened. However, IGF-1 levels remained low. Although these patients currently have heights <-3SDS, GH doses are still being optimized and delayed bone ages indicate further growth potential.

Conclusion: Short stature in Lowe Syndrome patients should not be presumed a consequence of renal failure alone. Aberrations of the hypothalamo-pituitary-somatotroph axis need to be considered. Recombinant GH therapy may improve linear growth, however, its impact on final height achieved is yet to be determined.