The blood sugar level is in dynamic equilibrium, ever changing because it is dependent upon the varying balance of supply and demand. The supply of glucose comes from three main sources: absorption of digested polysaccharides and monosaccharides from the intestinal tract, liver glycogen and, lastly, other carbon fragments derived from the glucogenic amino acids, body fat and fractions remaining from partially metabolized glucose. The first and last sources probably contribute the greater share. The crucial step in glucose metabolism appears to be the phosphorylation of glucose, a reaction catabolized by the enzyme hexokinase: Glucose + adenosine triphosphate ▪ glucose-6-phosphate + adenosine diphosphate The Coris have recently shown that this reaction is specifically inhibited by a substance obtained from the anterior lobe of the pituitary gland. This inhibiting effect is blocked by insulin and prolonged by certain adrenocortical steroids. Certain mechanisms may be suggested as operating to produce the hypoglycemia observed in various clinical disorders. Decreased absorption of glucose from the intestinal tract due to starvation or to disease of the small intestine may result in hypoglycemia, obviously because of a lowered supply. In myxedema, low blood sugar levels develop apparently because of marked slowing of the rate of passage of glucose through the intestinal mucosa. Liver glycogen is reduced not only by inadequate exogenous supply (starvation) but also from endogenous failure, as in Addison's disease; and finally by excessive utilization, as with long continued, strenuous physical effort. When the liver has been largely destroyed there may be insufficient formation and storage of glycogen. Von Gierke's disease appears to occupy a somewhat special position wherein the glycogen content of the liver is above normal but cannot be made available as glucose, hence the blood sugar values fall. In hyperinsulinism (whether due to insulin overdosage, or to endogenous overproduction by islet tumors or to other causes), the blood sugar level falls apparently because the inhibiting pituitary effect on the hexokinase reaction is blocked, at least in part, by excess insulin and the reaction is therefore accelerated. Hypoglycemia occurring in adrenal cortical insufficiency appears to be due in part to a disturbance in gluconeogenesis from certain of the amino acids. The symptomatology of hypoglycemia is diverse. In its mildest form the complaints are vague: weakness and a disinclination for physical and mental exertion. More severe episodes are characterized by congestion or pallor of the face, sweating, palpitations, hunger, thirst, tremors and anxiety. These may be followed by difficulties in speech and uncoordinated movements and finally by convulsions, paralysis and coma. The pattern of symptoms may be very different in different individuals but the characteristic train of symptoms in any one individual is apt to be recurrent. Chronic hypoglycemia of severe degree may result in damage to the central nervous system, the changes observed resembling those seen in anoxia. Edema, chromatolysis and perivascular hemorrhage, at first reversible, occur. Later there is death of nerve cells, replacement by astrocytes and loss of myelin, constituting permanent damage. Acute hypoglycemic shock is treated by intravenous administration of glucose. The response is usually prompt and dramatic. In chronic cases with irreversible damage to the central nervous system, however, the effects may be slow and disappointing. The aim of treatment in chronic, functional hypoglycemia is to supply a steady, slowly available dietary source of glucose. This is usually accomplished by small but frequent feedings of carbohydrate-rich foods. High protein diets, which cause a less marked post-prandial rise and fall in blood sugar, may be advantageous in some cases. Hypoglycemia due to islet cell adenoma or hypertrophy is amenable to surgical treatment. To avoid futile explorations, however, it is necessary to rule out “functional” hypoglycemia occurring in individuals who, for obscure reasons, have an unusually pronounced post-prandial fall in blood sugar, not due to islet tumors. To make this important differential diagnosis, too much reliance should not be placed on the glucose tolerance test; if employed, it should be borne in mind that organic hypoglycemia appears on fasting whereas the functional types show low blood sugar levels most frequently three to five hours after ingestion of glucose. The following triad is suggested as indicating exploration: (1) a repeated individual symptom pattern coming on in the fasting state; (2) a blood sugar concentration below 50 mg. per cent during an attack, or after a prolonged fast; (3) in earlier stages, relief of an acute episode by administration of glucose. When these criteria are fulfilled, careful search by the surgeon, after mobilizing the pancreas, will almost always be successful.
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Apr 18, 2023
Saul Nuñez-Castillo + 2
Open Access