Postmortem biochemistry and immunohistochemistry of chromogranin A as a stress marker with special regard to fatal hypothermia and hyperthermia.

Chromoganin A (CgA) is widely distributed in the secretory granules of endocrine and neuroendocrine cells and cosecreted with hormones such as catecholamines. The present study investigated postmortem serum and cerebrospinal fluid (CSF) levels of CgA in comparison with those of catecholamines, and also cellular CgA immunopositivity in the hypothalamus, adenohypophysis and adrenal medulla to assess forensic pathological significance. Serial medicolegal autopsy cases (n = 298, within 3 days postmortem) were used. Serum and CSF CgA levels were independent of the gender or age of subjects or postmortem time. The most characteristic findings were seen for fatal hypothermia (cold exposure), hyperthermia (heat stroke) and intoxication. Serum CgA levels were lower for hypothermia and intoxication than for other causes of death (p < 0.05), while CSF CgA levels were higher for hypothermia (p < 0.0001). A negative correlation was detected between serum and CSF CgA levels for hypothermia (R = 0.552, p < 0.05). Correlations between serum levels of CgA and catecholamines (adrenaline, noradrenaline and dopamine) were evident for hyperthermia (R = 0.632-0.757, p < 0.05 to <0.01), but there was no significant correlation between CgA and catecholamine levels in CSF. Cellular CgA immunopositivity in the hypothalamus, adenohypophysis and adrenal medulla varied extensively among cases in each group. However, CgA immunopositivity in hypothalamus neurons was lower for hypothermia than other causes of death including hyperthermia and intoxication. These observations suggest characteristic neuroendocrinal activation in fatal cases of hypo- and hyperthermia and also intoxication. CgA may be a useful biochemical and immunohistochemical marker for investigating these causes of death.