Necrosis of the pancreas in the haemolytic uraemic syndrome.

Abstract

SUMMARY A case of haemolytic uraemic syndrome in a three year old boy is described. The clinical course was complicated by hyperglycaemia, and biochemical assay of plasma showed an almost total lack of pancreatic insulin. Extensive necrosis of the exocrine and endocrine pancreas was found at necropsy. The possible pathological physiology of this complication and its prognostic importance are discussed.The haemolytic uraemic syndrome is a multi-system disease. Small vessel necrosis has been found in most organs, including the islet cells of the pancreas.'-3 Recently, Upadhaya et al described three patients who developed severe hyperglycaemia during haemolytic uraemic syndrome following diazoxide administration.4 We describe a case of haemolytic uraemic syndrome in a patient who did not receive diazoxide but who developed severe hyperglycaemia associated with extensive destruction of pancreatic tissue. Case reportA 3 year old boy was admitted to hospital with an eight day history of diarrhoea and vomiting, with three days of bloody stools, and a five day history of abdominal pain. He had been treated with a standard glucose and electrolyte solution. On admission he was anuric, and prerenal failure was diagnosed.He was treated with volume expansion and, subsequently, antibiotics following bacteriological culture of blood, stool, and urine (all negative). He remained anuric and was transferred to Sheffield Children's Hospital for further management of his renal failure. Examination showed an alert, orientated boy who was mildly oedematous. His blood pressure was 130/90 mm Hg and a grade 1/6 systolic ejection murmur was audible at the left sternal edge. His abdomen was distended but not tender and contained free fluid. No masses were palpable, and the bowel sounds were reduced. Rectal examination was unremarkable. The remainder of the examination was normal.

Diabetes During Diarrhea-Associated Hemolytic Uremic Syndrome

“…The mechanism may instead be the direct result of HUS with thrombotic microangiopathy of the pancreatic microvasculature. Pancreatic necrosis was present in four of five children with diabetes who had autopsies (25,27,28); two of these children demonstrated extensive thrombosis of pancreatic arterides (25,28). That several patients had concomitant exocrine pancreatic dysfunction also suggests a vascular mechanism.…”

“…Pancreatic autoantibodies, including islet cell, insulin, GAD, and insulinoma-associated protein 2 antibodies, were measured in five patients and found to be negative in all; methods used to measure these antibodies were not described (14,29 -31,33). These five patients, as well as two additional subjects, were reported to have some measure of impaired insulin secretion (low endogenous insulin levels [14,25,28,31], low basal C-peptide levels [29], impaired response to Sustacal challenge [30], or abnormal first-phase insulin response to intravenous glucose [33]). Long-term outcome was reported for 44 of 49 children.…”

“…Some have proposed that it is related to the initiation of peritoneal dialysis with glucose solutions or to the use of medications such as glucocorticoids or diazoxide. This is unlikely, as the hyperglycemic effects of diazoxide are transient (46); some patients never received glucocorticoids (18,19,25,26,28,30,31), diazoxide (18,19,25,26, 29 -31,33), or peritoneal dialysis (20,30); and one patient developed diabetes before peritoneal dialysis was instituted (18). It is possible that the children may have had "stress hyperglycemia" rather than true diabetes (47).…”

“…The mechanism of insulin deficiency does not appear to be immune, as pancreatic autoantibodies were negative in all five patients studied (14,29 -31,33). A viral etiology producing both diabetes and DϩHUS is also unlikely, as viral studies were negative in one patient (31), viral particles were absent at autopsy in two patients (27,28), and the pathogenesis of DϩHUS is not viral but related to Shiga toxin-producing bacteria (3). Given that absolute insulin deficiency is not silent, it is unlikely that diabetes predated DϩHUS in all patients.…”

Hyperglycemia in Diarrhea-Associated Hemolytic-Uremic Syndrome

“…Hyperglycemia might develop in patients with diar rhea-associated hemolytic-uremic syndrome (D + HUS) and is a serious complication [1][2][3][4][5][6][7][8][9][10][11][12], Previous reports of this complication have included either isolated patients or reports including only 2-4 patients. We initiated this study to identify the clinical features present in 8 patients with D + HUS who developed hyperglycemia and also to identify any risk factors that might have contributed to the development of hyperglycemia in these patients.…”