Postmortem biochemistry and immunohistochemistry of adrenocorticotropic hormone with special regard to fatal hypothermia

https://doi.org/10.1016/j.forsciint.2008.04.023Get rights and content

Abstract

Adrenocorticotropic hormone (ACTH) is involved in systemic reactions to stress. The aim of the present study was a comprehensive analysis of serum and cerebrospinal fluid (CSF) levels of ACTH, and the pituitary immunohistochemistry with special regard to fatal hypothermia in routine forensic autopsy cases (n = 162: 5–97 years of age; 114 males and 48 females; 4 h to 3 days postmortem, median, 19.2 h). The ACTH concentrations were independent of the postmortem time, gender, or age of the subjects. The serum ACTH level was similar to the clinical reference value for sharp instrument injury, fire fatality, and hypothermia, but was lower in other groups including hyperthermia, in particular for asphyxia and poisoning. The CSF level was usually much higher than the serum level, but was significantly lower for hypothermia and hyperthermia than in other groups (p < 0.01). The rate of ACTH-immunopositivity in the anterior pituitary was low in cases of fatal hypothermia and hyperthermia, while it was high in cases of blunt injury, fire fatality, and acute ischemic heart disease. These observations showed that ACTH levels in the serum and CSF depended on the cause of death. The serum level was maintained despite a low CSF level and pituitary immunopositivity for fatal hypothermia, while the serum and CSF levels as well as pituitary immunopositivity were decreased for hyperthermia.

Introduction

Pituitary adrenocorticotropic hormone (ACTH) is involved in systemic reactions to stress [1], [2], [3], [4], [5]. Previous studies showed that exposure to cold air attenuated the increase in ACTH and β-endorphine concentrations in response to high-intensity exercise and drug administration [6]. These findings suggest that ACTH can be used as a marker of fatal hypothermia. A diagnosis of “death due to hypothermia” is usually based on “classical signs” including frost-erythema and Wischnewski's ulcers, in consideration of circumstantial evidence and excluding other causes of death. Pathological signs may be found in about 2/3 of cases. However, a positive diagnosis may be difficult in other cases. For additional evidence of fatal hypothermia, there have been several studies on fatty vacuoles in the renal tubule epithelium and cardiomyocytes [7], [8], [9] and changes in the endocrine system [10]. Experimental studies showed an increase in ACTH in cold-stressed rats [11] and in healthy human volunteers [12]. However, there appears to have been no published data for postmortem ACTH levels with regard to the cause of death. The present study was performed to comprehensively examine ACTH concentrations in serial autopsy cases with special regard to fatal hypothermia.

Section snippets

Materials

Serial forensic autopsies (n = 162, 4–85.5 h postmortem) at our institute were examined. The cases involved 114 males and 48 females, between 5 years and 97 years (median, 62 years) of age. Blood from the right cardiac chamber and cerebrospinal fluid (CSF) from the basilar subarachnoid cisterna were collected using syringes. The blood samples were immediately centrifuged to separate sera. The specimens were stored at −20 °C until use and centrifuged before analysis.

The causes of death were

Relationship to gender, age, survival and postmortem period

There were no gender-related or age-dependent differences in serum and CSF ACTH levels. The relationships of serum and CSF ACTH concentrations to the postmortem period (estimated time of blood and CSF sampling after death) were insignificant for any case or individual causes of death. Although there was no correlation between serum ACTH and survival period in any groups, CSF ACTH showed a moderate positive correlation with the survival period for poisoning (R = 0.777, p < 0.01) and a high negative

Discussion

In the present study, serum and CSF ACTH levels and pituitary ACTH immunopositivity differed among the causes of death without any postmortem time-dependency, usually showing a much higher CSF level than serum level except for hypothermia and hyperthermia. The postmortem serum ACTH level was similar to the clinical reference value and even higher for sharp instrument injury, fire fatality and hypothermia, but was lower in most of the other cases. However, distinct differences between fire

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