Medication Summary
Medications used to manage hyperinsulinism include diazoxide, octreotide, nifedipine, glucagon, growth hormone, and glucocorticoids. The choice of medications varies with the etiology and severity of hypoglycemia in individual patients.
Insulin secretion inhibiting agents
Class Summary
Insulin secretion may be altered by various mechanisms. Oral diazoxide inhibits pancreatic secretion of insulin, stimulates glucose release from the liver, and stimulates catecholamine release, which elevates blood glucose levels. Octreotide is a peptide with pharmacologic action similar to that of somatostatin, which inhibits insulin secretion. KATPs (ATP–sensitive potassium-dependent channels, composed of the SUR1 and Kir6.2) are inactive in diffuse disease. These channels initiate depolarization of the beta-cell membrane and opening of calcium channels. The resultant increase in intracellular calcium triggers insulin secretion. Calcium channel blockers block the activation of these calcium channels, decreasing insulin secretion. Nifedipine is the only calcium channel blocker that has been used for the treatment of hyperinsulinism in humans and appears to be clinically ineffective.
Diazoxide (Proglycem)
First-line treatment. PO diazoxide (Proglycem) opens KATP channels and inhibits insulin secretion. The IV preparation (Hyperstat) is not used in hyperinsulinism.
Octreotide (Sandostatin)
Somatostatin analogue, activates G-protein K channel. Hyperpolarization of beta cell results in inhibition of calcium influx and insulin release. Octreotide also used for acromegaly, carcinoid tumors, and VIPomas.
Nifedipine (Adalat, Procardia)
Blocks calcium channels and insulin release. Also used to treat hypertension and angina.
Dextrose and glucose release stimulators
Class Summary
Emergent blood glucose elevation requires intravenous dextrose. Glucagon enhances release of hepatic glycogen as glucose.
Dextrose (D-glucose)
IV glucose is used to elevate serum glucose levels promptly. PO glucose is rapidly absorbed from intestine and stored or used by the tissues. Parenterally injected dextrose is used in patients unable to sustain adequate PO intake. Direct PO absorption results in a rapid increase in blood glucose concentrations. Dextrose is effective in small doses, and no evidence exists that it may cause toxicity. Concentrated dextrose infusions provide higher amounts of glucose in a small volume of fluid but require central venous access for concentrations above 12.5% to reduce hyperosmolar damage to smaller peripheral blood vessels.
Glucagon
Stimulates hepatic glycogenolysis and gluconeogenesis.
Drugs inhibiting insulin effect
Class Summary
In refractory cases, cortisol and growth hormone have been used with variable rates of success to inhibit insulin effects. Both diminish the hypoglycemic effects of insulin. They may also enhance ketogenesis and increase the availability of alternative fuels.
Hydrocortisone (Hydrocortone, Cortef, Solu-Cortef)
Possesses glucocorticoid activity and weak mineralocorticoid effects. Causes peripheral insulin resistance, gluconeogenesis, and, with prolonged therapy, increased pancreatic release of glucagon (which promotes glycogenolysis).
Growth hormone, human (Genotropin, Humatrope, Nutropin)
Recombinant hGH. Some patients demonstrate reduced glucose requirement and improved glycemic control. Stimulates growth of linear bone, skeletal muscle, and organs. Stimulates erythropoietin, which increases red blood cell mass. Should not be considered an alternative to continuous SC glucagon, intermittent octreotide, or pancreatectomy.
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Hyperinsulinism. Mechanisms of insulin secretion.
