clinically healthy patient:

Diagnosis of an i n s u l i n o m a in adult patients with confirmed evidence of suspicious symptoms related to hypoglycemia has to be of prime concern in the differential diagnosis of hypoglycemia. H y p e r p l a s i a (e.g.: islet cell or beta-cell-hyperplasia, "nesidioblastosis" in adults, non-insulinoma pancreatogenic hypoglycemia-syndrome / NIPHS, focal hyperplasia) in adults is an extremely rare cause, which may pose diagnostic problems. Despite significant disabling signs due to adrenergic and / or neuroglycopenic symptoms the patients clinically appear to be healthy and do not present with pathological findings during physical inspection and investigation.

True postpandial hypoglycemia is rare and very often the diagnosis is assumed despite lack of objective data. A different entity is the adrenergic postprandial syndrome (APS), often misclassified as reactive hypoglycemia. Postprandial hypoglycemia should not be confused with the "early dumping syndrome" presenting with uncomfortable autonomic symptoms, which may occur shortly after intake of rapidly absorbed concentrated sugars and accelerated gastric emptying.

Disease / Cause	Remarks
Insulinoma	1. mostly benign insulin-secreting tumors of the pancreas 2. malignant insulinoma (10-15%) 3. insulinoma in familial multiple endocrine neoplasia type I (MEN I / menin gene) - pancreatic, parathyroid, and pituitary endocrine tumors
non-insulinoma pancreatogenic hypoglycemia-syndrome NIPHS	Islet hyperplasia, microadenomatosis ("nesidioblastosis" in adults ?)
alimentary postprandial hypoglycemia "reactive or functional" hypoglycemia	1. prototype: resection of stomach (Billroth) or 2. rapid gastric emptying after carbohydrate-rich nutrients mechanism: GLP-1 (glucagon-like-peptide 1) ? 3. insulin resistance: (i.e.early type-II diabetes with postprandial hyperglycemia, >180 mg/dl) after carbohydrates (30--90 min) and late elevated insulin response / rightward shift of insulin secretion curve 4. increased insulin sensitivity / glucagon ?
Alcohol	together with liver disease (cirrhosis) and malnutrition
Medical drugs + predisposition	see list (Drugs)
factitious hypoglycaemia	Insulin or anti-diabetic drugs (beta-cytotropic agents, i.e. sulfonylureas)
extreme physical activity	extreme athletics: marathon, triathlon, ski-longrun
mesenchymal non-islet-cell tumors	e.g. fibrosarcoma; elevated "big" IGF II levels (insulin like growth factor II)
insulin autoimmune syndrome AIS / IAIS	AIS / IAIS : autoimmune insulin syndrome assoc. with autoimmune disease 1. anti-insulin autoantibodies (in Japan / Graves' disease, lupus erythematosus, rheumatoid arthritis, insulin injections) 2.insulin receptor autoantibodies (Lupus erythematosus, scleroderma, primary biliary liver cirrhosis, ITP - purpura, Hashimoto's thyroiditis)
PHHI: familial persistent hyperinsulinemic hypoglycemia of "infancy"	diffuse nesidioblastosis / gene mutations (SUR1, Kir6.2 locus)

clinically ill patient

The underlying disease and impaired condition of the patient do not cause problems in the differential diagnosis.

Hypoxia and metabolic acidosis (lactic acidosis) lead to inhibition and attenuation of hepatic gluconeogenesis.. Efficient gluconeogenesis is essentially required for a constant blood glucose level (glucose homoeostasis). In addition, gluconeogenesis in normal kidneys contributes to glucose homoeostasis.

Disease / Cause: Internal Medicine	Remarks
severe liver failure	hepatic coma, severe hepatitis: impaired gluconeogenesis
renal insufficiency (uremia)	metabolic acidosis, retarded insulin elimination
severe cardial insufficiency (cardiomyopathy)	hypoxia with alteration of hepatic glucose metabolism , acidosis, liver congestion
sepsis	acidosis, hypoxia, liver failure, renal failure
shock, multiple organ failure	acidosis, hypoxia, liver failure, renal failure
endocrine crises	pituitary insufficiency / adrenal insufficiency / hypothyroidism: lack of ACTH, GH (growth hormone), cortisol, thyroxin
medical drugs in diseases of liver / kidneys	see list (Drugs)
extreme malnutrition	anorexia, kachexia; (malignant tumor disease, malnutrition)
bone marrow and lymph node diseases	leucemia, lymphoma, myeloma (plasmocytoma): antibodies ?
inborn errors of metabolism	glycogen storage disease, fructose intolerance, galactosemia

Source: Starke A, Saddig C. Hypoglykämien im Erwachsenenalter. In: Diabetes mellitus. Urban & Fischer, München Jena, 2. Aufl. 2000, S. 775-782 Service FJ. Hypoglycemic disorders. New Engl J Med 332, 1995, 1144-1152