Abstract
OBJECTIVE: Introduce and evaluate a new model which explains the release of brain antidiuretic hormone (ADH) independent of plasma osmolality. METHODS: Systematic review and critical analysis of the professional literature. RESULTS: Primary electronic database searches using key terms revealed 57,432 hits. Secondary searches with application of specific inclusion and exclusion criteria and manual inspection for completeness reduced the total number of studies to fourteen (N = 14). Twelve (N = 12) studies investigated human subjects in the hospital settings, and two (N = 2) studies investigated animals (rhesus monkeys and dog) under invasive experimental conditions. All fourteen studies included direct or indirect indicators of intracranial pressure (ICP), measurements of plasma ADH, and plasma osmolality or urine osmolality. Findings, in brief, reveal a stable and positive association between increased intracranial pressure (ICP) and increased ADH release, in patients with low or normal blood osmolality. Findings are reliable and reproducible across human and animal populations. CONCLUSIONS: Findings support the proposed model, which explains increase secretion of brain ADH when plasma osmolality is low or within normal limits. Mechanical pressures exerted on hypothalamic nuclei, especially paraventricular and supra-optic nuclei, as a consequence of increased intracranial pressure, produce release of ADH, independent of plasma osmolality. The mechanical pressure model explains release of ADH previously unexplained by traditional plasma osmolality models. Findings have important clinical implications for the medical and surgical management of patients.