Does Hyperthyroidism Increase Risk of Death Due to the Ingestion of Ecstasy?

Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive amphetamine derivative widely used for recreational purposes. Deaths caused by acute drug intoxication with MDMA are rare but can often involve a severe hyperthermic episode. The factors underlying the increased risk of some ecstasy users to a fatal drug reaction are not known. We present a case report of a 24-year-old woman who developed fatal hyperthermia with multi-organ complications following MDMA use and was found at autopsy to have diffuse thyroid hyperplasia (Graves' disease). An antemortem blood MDMA concentration of 0.68 mg/L was measured in a sample obtained on admission to hospital. Although a cause and effect cannot be established, as the thyroid hormone is a major regulator of thermogenesis, we suggest that hyperthyroidism predisposed the subject to ecstasy-induced hyperthermia and that a pre-existing defect affecting temperature status could be one factor in explaining some ecstasy intoxication deaths.     

Fatal hemorrhage from a periumbilical wound: Stabbing or hemorrhage from a caput medusae?

Varices are the main clinical manifestation of portal hypertension, and their bleeding is the predominant cause of mortality from this condition. Periumbilical varices are known as “caput medusae.” Reports of their bleeding are rare, with only three fatal cases described in the literature. The antemortem diagnosis is relatively simple, while the postmortem diagnosis is more complex. This paper is the first report of fatal hemorrhage from a caput medusae for which the diagnosis was made postmortem, thanks to a complete diagnostic process including scene and circumstances, medical history, and autopsy with detailed histology. The circumstantial analysis showed the presence of a large amount of blood at the scene, blood which originated from a small abdominal wound; an analysis of the subject's clinical data reported that he was affected by portal hypertension. The autopsy revealed some dilated and convoluted veins in the subcutaneous tissue of the umbilical region; a fistula between these veins and the abdominal wound was detected. The histological study confirmed the presence of periumbilical varices, one of them ruptured and connected with the overlying skin. The cause of death was attributed to a massive hemorrhage generated by a periumbilical varix in a patient affected by portal hypertension.     

Ketoacidosis and Adrenocortical Insufficiency

We herein report an autopsy case involving a 27‐year‐old Caucasian woman suffering from chronic adrenocortical insufficiency with a background of a polyendocrine disorder. Postmortem biochemistry revealed pathologically decreased aldosterone, cortisol, and dehydroepiandrosterone levels in postmortem serum from femoral blood as well as decreased cortisol and 17‐hydroxycorticosteroid in urine. Decreased vitreous sodium and increased 3‐beta‐hydroxybutyrate and C‐reactive protein concentrations were observed. The cause of death was determined to be acute adrenocortical insufficiency. Fasting ketoacidosis was postulated to have precipitated the Addisonian crisis. Traumatic causes of death and third‐party involvement were excluded. The case highlights the importance of systematically performing exhaustive postmortem biochemical investigations to formulate appropriate hypothesis regarding the pathophysiological mechanisms involved in the death process.     

Difference between in vivo and postmortem distances between anterior chest and heart surface. A combined autopsy and in vivo computerized tomography study

The distance between anterior chest surface and intrapericardial surfaces of the heart and great blood vessels was measured on 37 cases (seven with acute fatal hemopericardium) at autopsy and on 24 live persons by computerized tomography. At autopsy, the apex of the heart was always closest to the skin surface except in cases with acute fatal hemopericardium, where the heart was displaced backwards by 10-40 mm. At computerized tomography, chest-heart distances were approximately 16 mm shorter than at autopsy. Changing the position of the patient from supine to prone decreased the distances by about 10 mm. The data presented demonstrate that the topography of the heart and great vessels is changing with the position of the body in vivo and that chest-heart distance tend to increase postmortem; therefore, the depth of a stab wound in the anterior surface of the heart as measured at autopsy should be regarded as a maximal estimate of the length of the stabbing weapon actually having penetrated the tissues.     

Diabetes mellitus and hypopituitarism

A 38-year-old diabetic woman developed hyponatraemia and fatal non-ketotic coma after elective cholecystectomy. At the autopsy, it was revealed that the immediate cause of death was cerebral oedema with secondary pontine haemorrhage. The cerebral oedema was associated with severe hyponatraemia and atrophy of the endocrine organs, including the adrenal glands. Biochemical analysis of serum taken immediately before death indicated that the primary defect was pituitary insufficiency, a recognised but rare complication of diabetes.     

Sudden infant death due to asplenia syndrome

An apparently healthy 80-day-old boy died suddenly for no apparent reason. The autopsy revealed that the patient had had congenital asplenia, extensive cardiovascular anomalies, and other organ malformations, including trisegmented lungs, hypoplasia of the corpus callosum and cranial bones, a symmetrical liver, accessory hepatic tissue in the adrenal glands, malrotation of the intestine, and hypoplasia of the greater omentum.     

Incidental cardiac rhabdomyomas: a significant finding necessitating additional investigation at the time of autopsy

Cardiac rhabdomyomas are rare lesions forming part of the tuberous sclerosis complex that may be responsible for sudden death. As well as remaining clinically occult for variable periods of time, they may, along with other manifestations of tuberous sclerosis, be quite difficult to detect clinically and pathologically. A patient is described in whom multiple cardiac rhabdomyomas were an incidental finding at autopsy following fatal potassium fluoride poisoning. Other gross pathological lesions typical of tuberous sclerosis were present but were quite subtle in appearance. Awareness of the association of cardiac rhabdomyomas with tuberous sclerosis is important so that full examination of organ systems for characteristic lesions can be undertaken during the autopsy, and so that fresh and frozen tissue can be obtained at the time of dissection for further investigation.     

Postmortem methemoglobin concentrations and their significance

Small concentrations of methemoglobin are present in the blood of normal individuals. Increased concentrations of methemoglobin can be formed by the action of certain chemicals or drugs, or in individuals with specific genetic defects. There is little information available concerning the validity of postmortem methemoglobin concentration as an indicator of antemortem methemoglobinemia. We measured blood concentrations of methemoglobin in 49 autopsy specimens. We conclude that postmortem methemoglobin concentrations are not valid indicators of antemortem methemoglobinemia.     

The value of examination aids in victim identification: a retrospective study of an airplane crash in Nepal in 2002

After the crash of an airplane in Nepal in the year 2002, the dental status of the 14 European victims was examined at autopsy as well as after additional removal of the soft tissue and compared with antemortem findings which were available in 11 cases. Re-examination of all jaws showed that nine composite fillings and seven root fillings as well as one parapulpal pin could not be detected during autopsy. Because tooth-coloured restorations may be overseen even by an experienced expert, the findings underline the necessity of performing a full resection of both jaws and removal of the soft tissue. Furthermore, X-ray analysis of the jaws and the use of phosphoric acid or ultra violet radiation for recognizing tooth-coloured restorations are recommended.     

Timely antemortem and postmortem concentrations in a fatal carbamazepine overdose.

There are no published reports that include both timely antemortem and postmortem carbamazepine concentrations after massive overdose. We report a fatal overdose of carbamazepine with both timely antemortem and postmortem carbamazepine concentrations. Carbamazepine concentrations were 47.7 mcg/mL 2 h antemortem and 53 mcg/mL at 9 h postmortem. The slight rise in drug concentration may reflect continued absorption of the drug in the last 2 h before death. Postmortem carbamazepine concentrations drawn from a peripheral vessel in this patient appeared to reflect drug concentrations at the time of death.     

Functional morphology of the hypothalamo-hypophyseal-adrenal system in acute coronary failure]

Histological and morphometric studies of large-cell and small-cell hypothalamic nuclei, adenohypophysis, and adrenal cortex of patients who died from acute coronary failure revealed signs of persistent hyperfunction of small-cell nuclei of the hypothalamus, bundle and retinal adrenocortical zones, and signs of short-term hyperfunction of pituitary adenocytes. These changes indicate disorders in the hypothalamic regulation of adrenal activity.     

Post mortem determination of bromureides (author's transl)]

Concentrations of carbromal, carbromide and bromisoval are determined in blood, urine, brain, kidney and muscle taken at autopsy from 41 fatal cases after overdosage of bromureides. In addition values of total bromine in blood are presented. Contents of total bromine can only lead to the deduction that a chronical abuse of bromureides is existent or not. Concentrations of bromureides and carbromide show a wide range according to the different time between taking the drug and death particularly in cases of pure carbromal intoxications which sometimes cause death after several days. In such cases quantitative determination of carbromide, a pharmacologically active metabolite of carbromal, is the only way to prove an acute carbromal intoxication. Especially in cases of additional foreign substances death may occur in early the phase of poisoning. Bromureides decompose post mortem by putrefaction a high degree so that the condition of the cadaver is important. Brain tissue is the most usable material for examination but other organs, particularly muscle and kidney, can be analysed with success. For differential diagnosis fatal cases are presented which were not caused by drug intake.     

Postmortem serum catecholamine levels in relation to the cause of death

Catecholamines are major humoral factors and neurotransmitters that contribute to various stress responses. However, they have been considered unstable due to agony, terminal medical care and postmortem interference. The present study was a comprehensive investigation of postmortem serum levels of adrenaline (Adr), noradrenaline (Nad) and dopamine (DA) with regard to the cause of death in serial medicolegal autopsy cases (n=542) including fatalities from various traumas and diseases. There was a slight tendency toward postmortem increases of Nad and DA in cardiac blood as well as Adr and Nad in peripheral blood, a slight age-dependent decrease in Adr and DA in right heart blood, and a marked increase in serum DA due to administration during critical medical care. When these factors were taken into consideration, significantly higher cardiac blood levels were observed for Adr and Nad in injury and asphyxiation cases and for Adr in fatal methamphetamine (MA) abuse and other poisoning cases, whereas those levels were lower in fatal hypothermia. Drowning, fire fatality, acute cardiac death and cerebrovascular disease showed intermediate Adr and Nad levels. The DA level was elevated in cases of injury, hyperthermia, MA fatality and other poisoning. Topographical analyses suggested that the major sources of increased serum catecholamines in cases of injury was abdominal viscera including adrenal glands, and that in cases of asphyxiation, drowning, fire fatality, hyperthermia, MA fatality, other poisoning, acute cardiac death and cerebrovascular disease was the extremities in addition to abdominal viscera. However, there was in part a large case-to-case difference in each marker related to individual causes of death. These findings differed markedly from clinical observations and suggest that the postmortem serum catecholamine levels may reflect the magnitude of physical stress responses during the process of death in individual cases.     

Investigation of cardiac troponins in postmortem subjects: comparing antemortem and postmortem levels

The limitations of autopsy in the diagnosis of death due to ischemic heart disease are well known. In the living, a simple reliable biochemical assay for cardiac troponins is used in the diagnosis of acute myocardial ischemia. Several studies have investigated the use of biochemical assays for cardiac troponins in postmortem subjects as a means to distinguish between a cardiac and anoncardiac cause of death. All of these studies, however, rely upon assigning subjects to "cardiac" or "noncardiac" death on the basis of a postmortem examination. As postmortem examination does not always accurately distinguish between these two groups, this approach is intrinsically flawed.Our study compares antemortem and postmortem cardiac troponin levels in five subjects. The antemortem samples were retrieved from the hospital biochemistry laboratory after each subject's death. The postmortem samples for each subject were taken from different sites and at different times during the early postmortem period.Erratic results bearing little or no relation to the antemortem cardiac troponin level were obtained for all subjects. Four of the five subjects had raised antemortem troponin levels, although only one had a cardiac cause of death.From this, we conclude that postmortem blood is not a suitable substrate for standard biochemical assays of cardiac troponins, which are designed for use on serum taken from living patients. In addition, the results of our study support the view that elevated cardiac troponins are a marker of serious morbidity and are not specific for cardiac injury as the primary cause of morbidity or mortality.     

Fatal poisoning due to intravasation after oral administration of barium sulfate for contrast radiography

A fatal poisoning after oral administration of barium sulfate for contrast radiography is reported. Barium sulfate is an insoluble salt and therefore is almost nontoxic. The case described here involves a 61-year-old woman who underwent two CT scans of the digestive tract with oral administration of barium sulfate during a surgical procedure. Within several hours after the first barium swallow examination the patient presented nonspecific neurologic and cardiovascular manifestations that rapidly progressed and led to death a few days later. Laboratory findings demonstrated elevated levels of barium in the blood and cerebrospinal fluid. The most likely mechanism of poisoning was progressive intravasation of barium due to stasis of contrast material related to intestinal obstruction.     

Occult Adrenocortical Carcinoma and Unexpected Early Childhood Death

A four‐year‐old previously well boy collapsed unexpectedly and was taken immediately to hospital, where he developed seizures and cardiogenic shock with lethal, rapidly progressing multi‐organ failure. At autopsy, the height was >90th percentile and there were indications of early virilization. Internally, a friable tumor of the left adrenal gland was identified that had invaded the left renal vein and inferior vena cava. Histology revealed typical features of an adrenocortical carcinoma with aggregated trabeculae of cells containing abundant eosinophilic cytoplasm and large pleomorphic nuclei. There was strong positive cytoplasmic staining for inhibin; mitochondria were shown on electron microscopy to contain prominent electron‐dense granules. Death was due to massive pulmonary tumor embolism. Although adrenocortical carcinomas are very rare and are more commonly found in adults, the current case demonstrates that they may also occur in childhood and be responsible for unexpected death by the very unusual mechanism of tumor embolism.     

Copper-binding protein in acute copper poisoning

This paper presents a suicide case of copper sulfate ingestion. Post-mortem autopsy revealed mucous membrane necrosis of the esophagus and the stomach. Histological examination revealed centrilobular necrosis in the liver and renal insufficiency. The quantitative determination of copper, zinc and cadmium in various tissues showed that the copper concentrations in blood, liver, kidney and lung were 3.5-24-fold higher than those of the normal level, whereas zinc and cadmium concentrations were within normal range. Chromatographical patterns on Sephadex G-75 showed that most of the accumulated copper in the liver and kidney was bound to metallothionein (MT), a low molecular weight protein with high metal binding capacity which plays a role in the detoxification of heavy metals, while no copper bound to MT was found in the lung. These results suggest that the formation of Cu-induced MT in the liver and kidney occurred at the early stage in fatal acute copper poisoning.     

An Examination of the Postmortem Redistribution of Fentanyl and Interlaboratory Variability,

Fentanyl is a synthetic opioid agonist used for pain control. Often administered as a transdermal patch, it is an interesting drug for study of postmortem redistribution. We hypothesized that fentanyl concentrations would increase over time after death, as measured in blood drawn on the day prior to autopsy and in blood drawn at the time of autopsy in ten cases where fentanyl patches were identified at the scene. Concentrations were compared, and heart blood to femoral blood ratios were calculated as markers of postmortem redistribution. Fentanyl concentrations measured in peripheral blood drawn the day of autopsy (peripheral blood 2 [PB2]) were higher than those drawn the day prior to autopsy (peripheral blood 1 [PB1]) with a mean ratio (PB2/PB1) of 1.80. The ratio of heart blood concentrations (HB) to femoral blood concentrations drawn at autopsy (PB2) had a mean ratio (HB/PB2) of 1.08. Some cases had blood from the same source analyzed at two different laboratories, and concentrations of fentanyl in those samples showed inter‐ and intralaboratory differences up to 25 ng/mL. Postmortem fentanyl concentrations may be affected by antemortem factors, postmortem redistribution, and laboratory variability. Forensic pathologists must use caution in interpreting fentanyl levels as part of death investigation.     

Histologic evidence of repetitive blunt force abdominal trauma in four pediatric fatalities

In cases of acute fatal child abuse, certain injuries, including cutaneous blunt force trauma, skull fractures, subdural hematomas, intra-abdominal hemorrhage, and retinal hemorrhages are common and well described in the pediatric and forensic literature. These gross findings at autopsy, when taken into consideration with scene investigation and interviews with caregivers, may indicate both a clear manner and cause of death. In such cases, the discovery of additional pathologic changes attributable to older abusive injuries helps support a conclusion of death due to inflicted trauma. We discuss four cases of fatal child abuse in which acute blunt force abdominal trauma was the cause of death. In each of these cases, careful examination with proper sectioning and microscopy of select abdominal tissues revealed that the acute tissue trauma was superimposed on a background of older, healing injury. This older trauma was characterized by classic histologic elements of tissue repair, including fibroblast proliferation, early scar formation, increased vascularity, and hemosiderin-laden macrophages. Iron and trichrome stains were used to confirm the presence of hemosiderin and fibrosis in all four cases, but the recognition of fibroblast proliferation and a reactive vascular pattern was best seen on routine hematoxylin and eosin stains. The gross and microscopic autopsy findings, along with available investigative information, established the diagnosis of chronic physical abuse.     

Distinguishing Atherosclerotic Calcifications in Dry Bone: Implications for Forensic Identification

Atherosclerotic calcifications, as calcified atheromatous elements, are markers of cardiovascular disease. However, the literature gives little information regarding their morphological aspect, making their identification very rare in skeletonized cases. In this paper, we document the morphological, histological, and SEM aspects of atherosclerotic plaques collected from unclaimed cemeterial skeletal remains from an identified osteological collection and extracted from well‐preserved cadavers autopsied at the medico‐legal institute of Milan. Each of the three analyses provided similar results: atherosclerotic calcifications are convex‐concave plaques with a stratified structure, a pale‐yellow coloration in autopsy cases and yellow to brown when recovered in dry bone. Histologically, undecalcified and decalcified sections showed a stratified aspect formed by superimposed layers. Lastly, the SEM analysis showed a precise view of the stratified structure of the plaques in transverse section. As markers of disease, atherosclerotic calcifications can provide important antemortem information on the deceased that may be compared to antemortem data.