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Vincent Marks



Clinical presentation—discussion of the high incidence of spontaneous hypoglycaemia in elderly sick hospital inpatients, which can lead to false accusations of malicious insulin or sulphonylurea administration.

Factitious hypoglycaemia—discussion of detection of new synthetic insulin analogues.

Updated on 30 Nov 2011. The previous version of this content can be found here.
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date: 23 April 2017

Hypoglycaemia is defined as a blood glucose concentration below 3.0 mmol/litre, which is clinically important because of its effect on brain function. Much the commonest cause is excessive (in relation to intake of food and drink) administration of insulin or sulphonylurea drugs to patients known to have diabetes, but there are many rarer causes including insulinoma, toxins (alcohol), organ failure (hepatic), endocrine diseases (adrenal insufficiency, pituitary insufficiency), non-islet cell tumour hypoglycaemia, autoimmune insulin syndrome, factitious or felonious administration of insulin/sulphonylureas, and infections (malaria).

Clinical features—patients classically present either to the Emergency Department in a stuporose or comatose state with concurrent hypoglycaemia, or to outpatient services with a normal blood glucose level but a history suggesting recurrent neuroglycopenic episodes or progressive neurological/psychological dysfunction. Hypoglycaemia, often asymptomatic, develops in up to 10% of elderly patients while they are in hospital and is associated with a high mortality: there are various risk factors including bacterial infection, malnutrition, and heart, liver, or renal failure. Recognized clinical syndromes include: (1) acute neuroglycopenia—profuse sweating, anxiety/nervousness, tremor, tachycardia, hunger, and paraesthesiae, also speech and visual disturbances, unsteady gait and confusion; (2) subacute neuroglycopenia—reduction in spontaneous movements and speech, somnolence, inefficient cerebration, personality change, and amnesia of varying severity; (3) chronic neuroglycopenia—insidious changes in personality, defective memory, psychosis, or mental deterioration resembling dementia. The symptoms of acute and subacute neuroglycopenia are ephemeral but—unless aborted by restoration of normoglycaemia—can lead to stupor, coma or (in exceptional cases) death.

Diagnosis and management—hypoglycaemia is usually detected by point-of-care blood glucose determination and confirmed by formal laboratory blood glucose analysis. Treatment (in the patient unable to drink or eat safely) is with intravenous glucose 25 g (50 ml of 50% weight/volume) after (in cases where there is doubt as to the cause) blood has been withdrawn for subsequent laboratory analysis, most importantly for total insulin immunoreactivity, C-peptide, and proinsulin, and in some cases β‎-hydroxybutyrate alcohol, sulphonylureas and other hormone assays. Glucagon 1 mg may be given intramuscularly if venous access is not available.

Particular causes of hypoglycaemia

Insulinoma—insulin-secreting β‎ cell tumours are the most common endocrine neoplasm of the pancreas; most are benign and solitary, but about 10% are multiple (often as part of the MEN1 syndrome) and about 10% are malignant. Diagnosis is made by demonstrating that symptoms are caused by hypoglycaemia (typically provoked by fasting and/or rigorous exercise), relieved by intravenous glucose, and associated with inappropriately high plasma concentrations of total immunoreactive insulin, C-peptide, proinsulin, and proinsulin-like fragments with regard to the prevailing blood glucose concentration. No imaging technique is sufficiently reliable to justify dismissing a diagnosis made on sound clinical and biochemical grounds. The treatment of choice is surgical ablation. Localization by an experienced surgeon at laparotomy is remarkably (96%) successful, but can be further improved by use of intra-operative ultrasound.

Non-islet cell tumour hypoglycaemia—results from overproduction of an abnormally large form of IGF-2 or (rarely) IGF-1. Can occur with almost every histological type of malignant tumour, but least uncommonly with haemangiopericytomas, sarcomas, and primary hepatomas.

Autoimmune insulin syndrome—due to polyclonal autoantibodies to insulin that bind and sequester insulin secreted in response to a meal, and then release it after absorption is complete, producing an inappropriately high free plasma insulin level. Treatment is dietary and aimed at avoiding excessive insulin secretion in response to meals until spontaneous remission occurs, usually within a few years of onset.

Alcohol-induced hypoglycaemia—the most common cause of noniatrogenic hypoglycaemia, which typically develops within 6 to 36 h of the ingestion of moderate to large amount of alcohol (>30 g) by a fasting or malnourished subject.

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