C-type natriuretic peptide as mediator of growth in the absence of growth hormone: Unraveling the mystery of the growth without GH syndrome.

Children with craniopharyngioma exhibit a notably high incidence of normal-accelerated growth before and/or after neurosurgery/hypophysectomy despite confirmed panhypopituitarism, this constituting what is known as the growth without GH syndrome, which, to date, remains an unsolved mystery. Most cases involve suprasellar tumor extension, suggesting a factor intrinsic to tumor localization apart from neurosurgical sequelae alone. Patients need mineralocorticoid therapy post surgery, at least until GH replacement therapy is initiated, implying elevated natriuretic peptides inducing secondary mineralocorticoid deficiency. Elevated natriuretic peptides, and in particular C-type natriuretic peptide (CNP), may serve as a compensatory growth mediator in the absence of GH, acting as local regulator of endochondral ossification through natriuretic peptide receptor B (NPR-B) by promoting chondrocyte proliferation and hypertrophy, rescuing skeletal growth in GH-insensitive contexts, and as also demonstrated by the therapeutic efficacy of the CNP analog vosoritide in achondroplasia. A comprehensive research approach unraveling the role of CNP in growth may redefine our understanding of growth and management of short stature.