Non-diagnosed pheochromocytoma as a cause of sudden death in a 49-year-old man: a case report with medico-legal implications

Pheochromocytomas are known to be rare causes of sudden death. A 49-year-old man with a medical history of arterial hypertension and diabetes mellitus complained about nausea and malaise in the morning. During the day his condition deteriorated. He went to the emergency department, where he was given intravenous drugs against nausea and was sent home. On the way back, his condition deteriorated dramatically so that his wife drove back to the emergency room, where he collapsed and sustained cardiac arrest; resuscitation efforts were unsuccessful. Autopsy revealed a large tumour of the left adrenal gland. The strong suspicion of pheochromocytoma was confirmed by histology, immunohistochemistry and biochemical investigations. An acute hypertensive crisis, caused by the hitherto unknown pheochromocytoma was ascertained as the cause of death. The morphological findings are presented, the difficulty to diagnose pheochromocytoma and the medico-legal implications are discussed.     

Pheochromocytoma and sudden death as a result of cerebral infarction in Turner's syndrome: report of a case

Various etiologies for hypertension in Turner's syndrome, a common feature of the disorder, are well recognized. Pheochromocytoma is not among them. A young woman with Turner's syndrome, recently diagnosed with hypertension, died suddenly and unexpectedly. A hemorrhagic cerebral infarct and an adrenal gland pheochromocytoma were found at necropsy. This is the first reported case of pheochromocytoma associated with Turner's syndrome.     

A Rare Case of Sudden Death Due to Hypotension during Cesarean Section in a Woman Suffering from Pheochromocytoma and Neurofibromatosis

Sudden death following acute hypotension due to an undiagnosed pheochromocytoma (PHEO) is a rare event. Moreover, histopathology of the myocardium in such cases is rarely reported. We present a case of a woman who died during delivery. A 37‐year‐old parturient, who was 38 weeks pregnant, suffering from neurofibromatosis underwent a cesarean section following peridural anesthesia. Acute hypotension, acute intra‐operative pulmonary edema and supraventricular paroxysmal tachyarrhythmia occurred during delivery, followed by death. The autopsy revealed the presence of a PHEO, confirmed immunohistochemically with chromogranin‐A (CgA), CD20 antibody (L26), anti‐Keratocan antibody (KER‐1) and neuron‐specific enolase (NSE), and a PHEO‐induced cardiomyopathy. The physiopathology of both stress‐induced cardiomyopathy and PHEO‐induced cardiomyopathy, as well as the role of anesthesia in provoking the death, are discussed. The association of an undiagnosed PHEO with neurofibromatosis as the cause of sudden death in pregnancy is an obstetric urgency that raises forensic pathology issues.     

Sudden death due to a paraganglioma of the organs of Zuckerkandl

A 20-year-old woman died suddenly in a hospital emergency room after presenting with nausea, vomiting, back pain, and hypertension. At autopsy, an extra-adrenal pheochromocytoma (paraganglioma) of the organs of Zuckerkandl was found, with microscopic focal myocardial necrosis similar to that described in death from adrenal pheochromocytomas. Tumors of the organs of Zuckerkandl are extremely rare; less than 100 such cases have been reported in the world's literature, and only six, including the present case, have presented as a sudden, unexpected death. The symptoms of catecholamine storm may mimic those of acute drug intoxications, leading to misdiagnosis by both clinical physicians and pathologists.     

Fournier Gangrene and Unexpected Death

Abstract: Fournier gangrene represents a rare but progressive perineal infection that may result in rapid death. A 70‐year‐old man with poorly controlled diabetes mellitus and alcohol abuse is reported who was found unexpectedly dead. He had last been contacted the night before his death. At autopsy, the most striking finding was deep necrotic ulceration of the scrotum with exposure of underlying deep muscles and testicles, with blood cultures positive for Escherichia coli. Death was, therefore, attributed to necrotic ulceration/gangrene of the perineum (Fournier gangrene) that was due to E. coli sepsis with underlying contributing factors of diabetes mellitus and alcoholism. In addition there was morbid obesity (body mass index 46.9), cirrhosis of the liver, and marked focal coronary artery atherosclerosis with significant cardiomegaly. Fournier gangrene may be an extremely aggressive condition that can result in rapid death, as was demonstrated by the rapid progression in the reported case.     

Fatal Diabetic Ketoacidosis—A Potential Complication of MDMA (Ecstasy) Use

A 19‐year‐old woman with insulin‐dependent diabetes mellitus was found dead in bed having allegedly recently taken ecstasy and consumed alcohol. At autopsy, there were microhemorrhages in the brain with subnuclear vacuolization and Armanni–Ebstein changes in renal tubules. Biochemical analyses confirmed diabetic ketoacidosis (vitreous glucose—46.5 mmol/L; β‐OH butyrate—13.86 mmol/L.). Toxicological analyses of blood showed a low level of 3,4‐methylenedioxy‐methamphetamine (MDMA) (0.01 mg/L), with acetone but no alcohol or other common drugs. Death was attributed to diabetic ketoacidosis most likely provoked by mixed MDMA/alcohol ingestion. Although the use of illicit drugs by young individuals with diabetes mellitus is being increasingly recognized, it has been noted that there is minimal information about the relationship between drug use and acute diabetic complications. Toxicological screening of cases of lethal diabetic ketoacidosis in the young may clarify lethal mechanisms in individual cases and also help to determine the extent of this problem.     

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.     

Postmortem vitreous humor beta-hydroxybutyrate: its utility for the postmortem interpretation of diabetes mellitus

Ketoacidotic coma is one of the most serious complications arising from diabetes mellitus, especially type I, and may be the cause of sudden death especially in diabetes type I. Since beta-hydroxybutyrate (beta-OHB) serum concentrations might provide more information on the severity of ketoacidosis, the aim of this study was to evaluate the concentrations of beta-OHB in vitreous humor and its correlation with other biochemical parameters during postmortem examination. We intended to ascertain the sensitivity and the specificity of these markers for diagnosing diabetes mellitus and the presence of ketoacidosis. This study involved 453 cadavers with a mean age of 57.6 years (S.D. 20.7) and a mean postmortem interval of 17.8 h (S.D. 9.6, range 2-61 h). Cases were assigned to two diagnostic groups according to the antemortem diagnosis of diabetes mellitus, based on the patients' medical records. In vitreous humor statistically significant differences were found in biochemical marker concentrations between the two diagnostic groups, the highest values being obtained in the group of subjects with a previous diagnosis of diabetes mellitus. The measurement of beta-OHB in vitreous humor may be a useful alternative to using blood during postmortem analysis. The presence of high levels of beta-OHB may help interpret the cause of death in diabetics when the autopsy result is negative.     

Determination of Human Chorionic Gonadotropin in Postmortem Samples in Ectopic Pregnancies

Increased human chorionic gonadotropin levels (HCG) can be detected in femoral blood, bile, and vitreous humor collected during autopsy of pregnant women using a standard kit designed for living patients. In the study herein, the concentrations of HCG were measured in postmortem serum, vitreous, bile, cerebrospinal, and pericardial fluids in 4 cases of fatal ectopic pregnancy and 40 controls using a quantitative electrochemiluminescence immunoassay designed for living patients. No false‐negative cases were identified in any of the analyzed samples in any of the ectopic pregnancy cases. No correlations were found between total HCG levels in postmortem serum and the other tested specimens. The results of this study would suggest that higher HCG in bile, vitreous, pericardial, and cerebrospinal fluids may confirm the existence of ectopic pregnancy and therefore identify other situations in which this hormone is increased, although gestational age cannot be reliably estimated using these values.     

Verapamil toxicity: an unusual case report and review of the literature

Verapamil blocks the rapid influx of calcium into the cardiac myocytes of the cardiac conduction system and smooth muscle of the vasculature, resulting in decreased myocardial contractility, prolonged conduction time, and vascular relaxation. A sustained-release form, verapamil SR (or ER), is available that contains higher levels of medication and requires only once-daily dosing. The majority of reported fatal cases of verapamil toxicity are due to massive, intentional overdoses. Herein, we present an unusual case of fatal verapamil SR toxicity in a 57-year-old female that resulted from accidental overdose of only 3 tablets (720 mg), as witnessed by the decedent's daughter. In spite of the low dose ingested, the postmortem cardiac blood verapamil level was clearly toxic (6000 ng/mL, or 6 mg/L). Her preexisting medical conditions included hypercholesterolemia, hypertension, iron deficiency anemia, diabetes mellitus, and associated mild chronic renal failure. Complicating factors, which likely include the decedent's preexisting renal and cardiac disease, and a review of the available literature will be discussed.     

Pregnancy-associated deaths: a 15-year retrospective study and overall review of maternal pathophysiology

Pregnancy-related death is defined by the International Classification of Diseases, Tenth Revision (ICD-10) as the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death. In the year 2000, a collaborative effort involving World Health Organization (WHO), UNICEF, and UNFPA estimated 660 maternal deaths in the United States. This averages 11 maternal deaths per 100,000 live births reported. Many pregnancy-associated deaths are not easily identified as such since the presence of a recent or current pregnancy may not be listed on the death certificate. Thus, the WHO estimates that in the United States, the maternal mortality is approximately 17/100,000 pregnancies. This is significantly higher than the goal set by the US Department of Health and Human Services in Healthy People 2010, which sets the target for maternal mortality at less than 3.3/100,000 live births. The most common causes of maternal death vary somewhat from region to region in the United States. They include pulmonary thromboembolism, amniotic fluid embolism, primary postpartum uterine hemorrhage, infection, and complications of hypertension including preeclampsia and eclampsia. Pulmonary disease, complications of anesthesia, and cardiomyopathy also are significant contributors to maternal mortality in some populations. The death of a pregnant or recently pregnant individual poses a wide scope of challenges to the forensic pathologist and investigator. The pathologist must have a broad knowledge of the physiologic and biochemical changes that occur during pregnancy, as well as the clinical and pathological manifestation of these changes. Conditions that may be "benign" in the nonpregnant individual may be lethal in the puerperal period. In addition, it should be kept in mind that deaths during pregnancy may be due to unnatural causes. Accident, homicide, and suicide must be ruled out in each case. The authors reviewed all forensic cases referred for autopsy to the Forensic Section of the Medical University of South Carolina from January 1989 through December 2003. All decedents listed as pregnant or postpartum were analyzed as to maternal age, race, past medical history, previous pregnancies and outcome, prenatal care, gestational age, fetal or neonatal outcome, location of delivery, placental findings, maternal autopsy findings, toxicology, cause of death, manner of death, and fetal or neonatal autopsy findings. The authors present this retrospective study to better determine the factors leading to maternal demise and discuss the autopsy/ancillary techniques useful in determining the cause of death in this challenging area.     

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.     

The Significance of Adrenal Hemorrhage: Undiagnosed Waterhouse‐Friderichsen Syndrome,A Case Series

A retrospective series of five cases of nontraumatic gross adrenal hemorrhage were identified in 800 consecutive forensic autopsies. All patients were males, of different ethnicities and with ages ranging from 2 to 48 years. All patients had a clinical history and autopsy findings suggestive of sepsis. Pre‐ or postmortem microbiological cultures were variably positive for Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus, and methicillin‐resistant Staphylococcus aureus. The fifth case was positive for yeast and a coagulase negative staphylococcus; contamination of this culture medium cannot be excluded. No cases had a culture positive for Neisseria meningitidis. We find that the reviewed patients with grossly or microscopically identifiable adrenal hemorrhage were otherwise healthy individuals who died suddenly as a consequence of bacterial infection. In each case, signs and symptoms compatible with premortem adrenal insufficiency were reported; in no instance was the adrenal hemorrhage clinically identified.     

Septic Ketoacidosis—A Potentially Lethal Entity with Renal Tubular Epithelial Vacuolization

Fatal ketoacidosis due to diabetes mellitus, alcoholism, and starvation may produce characteristic basal vacuolization of renal tubular epithelial cells (RTEC). Septic ketoacidosis has recently been recognized clinically as a distinct condition in which septicemia can lead to elevation of ketones and various anions unrelated to diabetes mellitus, alcoholism, or caloric deprivation. We report four lethal cases with significantly elevated vitreous ketones secondary to sepsis and/or severe localized infection in individuals with no history of diabetes mellitus, alcoholism, or starvation. Three of four cases exhibited typical basal vacuolization of RTEC. We suggest that septic ketoacidosis is an appropriate cause of death in the forensic setting where sepsis or severe localized infection is found with significant ketoacidosis (β‐hydroxybutyrate > 5 mmol/L)—in the absence of diabetes mellitus, alcoholism, starvation, or other states associated with accelerated ketogenesis. The finding of basal vacuolization of RTEC in such cases provides morphological support for the underlying metabolic derangement.     

Sex,Parity, and Scars: A Meta‐analytic Review

The ability to identify whether a female has been pregnant or has given birth has significant implications for forensic investigations and bioarcheological research. The meaning of “scars of parturition,” their causes, and their significance are a matter of contention, with a substantial literature of re‐evaluations and tests of the relationship between pelvic scarring and parity. The aim of this study was to use meta‐analytic techniques (the methodological approach) to test whether pelvic scarring, namely dorsal pubic pitting and the preauricular groove, is a predictor of parity and sex. Meta‐analyses indicated that neither dorsal pubic pitting nor the preauricular groove are predictors of parity status, while dorsal pubic pitting is a moderate predictor of sex. A weak relationship between dorsal pubic pitting and parity was identified, but this is believed to be a product of the moderate relationship with sex. This calls into question whether any causal relationship between parity and pelvic scarring exists.     

Brain amino acid abnormalities in kidney disease and diabetes mellitus

The present postmortem study examines whether specific amino acid abnormalities associated with renal diseases or diabetes mellitus in animal experiments and on clinical examination may also be found in human brain samples obtained at clinical autopsies. The material includes 12 deceased with renal insufficiency, 23 deceased with diabetes mellitus and 26 control cases with lethal cardiovascular diseases (without a history of hepatic, renal or metabolic disturbances). The autopsy and clinical records were retrospectively analyzed for age, sex, postmortem delay, cause of death, substantial preexisting diseases and histological findings. The analysis of free amino acid concentrations in human brain specimens was performed applying a Beckman amino acid analyzer. The results were evaluated using the U-test according to Mann, Willcox and Whitney. A P-value less than 0.05 was considered to be significantly different. Differences of amino acid concentrations attributable to sex, age and postmortem delay were not significant. The comparison of postmortem amino acid concentrations in the brains of patients with diabetes mellitus and controls did not reveal relevant changes. However, the patients with renal diseases, as compared to controls, showed a significant cerebral increase of urea, phenylethanolamine and gamma-aminobutyric acid. Thus, the postmortem amino acid analysis may contribute to the understanding of pathophysiological mechanisms of uremic encephalopathy and may supplement the conventional postmortem morphological diagnosis in kidney diseases by indication of functional impairment.     

Histochemical changes in the hypothalamus, hypophysis, and adrenal glands observed in ethanol poisoning

A comprehensive morphological-and-histochemical study of neuroendocrinal internals in cases of ethanol poisonings was undertaken. Actual forensic medical materials were used (62 cadavers) to make morphometry examinations of the hypothesis and adrenal glands. Besides, the distribution of alcohol dehydrogenase and acetaldehyde dehydrogenase was investigated in the mediatory differential brain sections, i.e. cerebellum, locus coeruleus, dorsal raphe nucleus, hypothalamus and adrenal glands. A differential distribution of ethanol-oxidizing enzymes as well as their changes in ethanol lethal poisoning were established; additionally, a variety of morphological signs were defined, which enable the differential diagnosis of a death reason in acute alcoholic intoxication.     

Spontaneous clostridial myonecrosis.

Spontaneous, nontraumatic clostridial myonecrosis is a rare infection with an insidious onset and usually fatal outcome. Spontaneous clostridial myonecrosis has a frequent association with colon carcinoma, leukemia, diabetes mellitus, and drug-induced immunosuppression. We present the case of a 73-year-old diabetic man who died of spontaneous Clostridium septicum myonecrosis, who had presented with fulminant gangrene of the right thigh. Clostridium septicum was cultured from the quadriceps muscle postmortem. At autopsy, in addition to the gangrene, there was a Duke's A adenocarcinoma of the cecum, which had not been diagnosed during life. When spontaneous nontraumatic clostridial myonecrosis is diagnosed at autopsy, investigation should include through exam and the obtaining of past medical history in order to elucidate predisposing factors.     

Glucose and lactate in vitreous humor compared with the determination of fructosamine for the postmortem diagnosis of diabetes mellitus

Diabetes mellitus is a chronic metabolic illness responsible for a great number of deaths. In postmortem diagnosis, because of the difficulty involved in interpreting blood glucose levels and relatively nonspecific pathologic features, biochemical markers in vitreous humor are useful. The aim of this study was to compare the results obtained for the combined determination of lactate and glucose with fructosamine levels recorded in the vitreous humor of two diagnostic groups (one diabetic and the other nondiabetic). The authors intended to ascertain the capacity of different markers measured in vitreous humor to diagnose diabetes mellitus. Fifty-one cadavers (mean age, 58.7 years; standard deviation, 17.09) were studied. The mean postmortem interval was 16.4 hours (standard deviation, 9.05). Cases were assigned to two diagnostic groups according to whether they were previously diagnosed as either diabetic or nondiabetic. Statistically significant differences for glucose, fructosamine, and the sum values of glucose and lactate were found between the two diagnostic groups. The highest levels were obtained in the group of cases with a previous diagnosis of diabetes mellitus. After the comparison of receiver operating characteristic curves, the sum values of glucose and lactate in vitreous humor is a better predictor of antemortem diabetes mellitus than the fructosamine.