Congenital Hyperinsulinism Medication

Updated: Dec 16, 2015
  • Author: Robert S Gillespie, MD, MPH; Chief Editor: Stephen Kemp, MD, PhD  more...
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Medication Summary

Diazoxide, octreotide, and nifedipine are the primary medications used in long-term treatment of congenital hyperinsulinism (CHI), or persistent hyperinsulinemic hypoglycemia of infancy (PHHI). [22] Some authors also recommend using chlorothiazide in conjunction with diazoxide for a synergistic effect. Most of these agents have significant adverse effects, especially with long-term use. Nifedipine appears to have considerably fewer adverse effects than the others.

Patients may require continuous intravenous (IV) glucose infusion. Glucagon may also be administered emergently to maintain adequate blood glucose levels.


Glucose-Elevating Agents

Class Summary

Insulin secretion may be altered by various mechanisms. 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.

In CHI, functional abnormalities are believed to exist in the adenosine triphosphate (ATP)-sensitive potassium channels (composed of the sulfonylurea receptor [SUR gene abnormality] and the potassium channel pore protein [Kir6.2 gene abnormality]). 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 action of these calcium channels, decreasing insulin secretion.

Nifedipine is the only calcium channel blocker for which clinical trials have been performed in patients with CHI. The use of other calcium channel blockers given in liquid formulations or by alternative drug-delivery systems remains a promising area for future research. Thiazide diuretics also inhibit insulin secretion.

In CHI, chlorothiazide should be used in conjunction with diazoxide. It exerts a synergistic effect on inhibiting insulin secretion by activating a different potassium channel.

In addition to the agents described above, prompt-acting glycogenolysis is achieved with glucagon. Emergent blood glucose level elevation requires IV dextrose. Corticosteroids are rarely used for gluconeogenesis in the long term, because of their risk of toxicity.

Octreotide (Sandostatin)

Octreotide is a peptide with a pharmacologic action similar to that of somatostatin. It is a more potent inhibitor of insulin, glucagon, and growth hormone secretion than somatostatin. It elicits diverse endocrine effects, including suppression of luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH), decreased splanchnic blood flow, and inhibition of release of serotonin, gastrin, vasoactive intestinal peptide (VIP), secretin, motilin, pancreatic polypeptide, and thyroid-stimulating hormone (TSH).

Octreotide decreases gallbladder contractility and bile secretion. It is used in CHI primarily for its ability to inhibit insulin secretion.

Diazoxide (Proglycem)

Diazoxide is an antihypertensive agent that relaxes smooth muscle in the peripheral arterioles. It is related to the thiazide class of drugs but has no diuretic action. It inhibits pancreatic secretion of insulin, stimulates glucose release from the liver, and stimulates catecholamine release.


Diuretics, Thiazide

Class Summary

Some authors recommend using chlorothiazide in conjunction with diazoxide for a synergistic effect.

Chlorothiazide (Diuril)

When combined with diazoxide, chlorothiazide elicits a synergistic effect on inhibiting insulin secretion by activating a different potassium channel. It also counteracts the salt and water retention induced by diazoxide.


Cardiovascular, Other

Class Summary

Use of nifedipine in CHI is relatively new, but initial reports suggest that it is effective and extremely well tolerated.

Nifedipine (Adalat, Procardia, Nifediac, Nifedical XL)

Nifedipine, a later addition to the therapeutic armamentarium, is a calcium channel blocker that helps reduce the influx of calcium into beta cells, which is a necessary step for insulin secretion. This effect occurs with doses much lower than those traditionally used for other indications (eg, angina pectoris). Nifedipine appears to have considerably fewer adverse effects compared with other agents. [13]

Most information on adverse effects of, and interactions with, nifedipine has been obtained from studies of adults using the drug for angina pectoris at proportionately higher doses than those used in children for CHI.

A liquid formulation is not available commercially. The drug is supplied as a 10-mg liquid-in-gelcap. To measure smaller doses, the contents may be aspirated with a syringe and needle, but it is very difficult to do this accurately because of the extremely small volume of fluid in the gelcap. Extended-release (ER) formulations have also been employed in CHI.

Dextrose (Glutol, Enfamil Glucose, Similac Glucose, Glutose 15)

Dextrose is used for prompt elevation of serum glucose. It is a monosaccharide that is absorbed from the intestine and then distributed, stored, and used by the tissues. Parenterally injected dextrose is used in patients unable to sustain adequate oral intake. Direct oral absorption results in a rapid increase in blood glucose concentrations. Dextrose is effective in small doses, and no evidence indicates that it may cause toxicity. Concentrated dextrose infusions provide higher amounts of glucose and increased caloric intake in a small volume of fluid.

Glucagon (GlucaGen)

Glucagon, a polypeptide hormone, is produced by pancreatic alpha cells of the islets of Langerhans. Its effects on blood glucose are the opposite of those exerted by insulin. Glucagon elevates blood glucose levels by inhibiting glycogen synthesis and enhancing formation of glucose from noncarbohydrate sources such as proteins and fats (gluconeogenesis).

Glucagon increases hydrolysis of glycogen to glucose (glycogenolysis) in the liver, in addition to accelerating hepatic glycogenolysis and lipolysis in adipose tissue. Glucagon also increases the force of contraction in the heart and has a relaxant effect on the gastrointestinal tract.