Medical Treatment Of Insulinomas Diet

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Acute episodes of hypoglycemia are reversed with carbohydrate. Patients frequently learn this practice for themselves before the diagnosis is made and snack frequently. This often results in weight gain. More severe attacks, including coma, require intravenous glucose administration. Many patients with hyperinsulinism find that they do better on a highprotein diet, as do patients with reactive hypo-glycemia. This has added appeal in that the total carbohydrate and fat intake can be decreased, as well as total daily calories.

Diazoxide

The most commonly used and effective drug for the management of hyperinsulinism with hypoglycemia is diazoxide. It is currently primarily used for its diabetogenic action in the treatment of hyperinsulinism. The dose of diazoxide ranges from 300 to 800 mg daily in patients with hyperinsulinism. Diazoxide inhibits insulin secretion by a direct action on beta cells and also by stimulating epinephrine release, which itself further inhibits insulin release.

There are unpleasant effects of diazoxide, the most prominent being fluid retention, gastrointestinal irritation, hypertrichosis, and agranulocytosis. Fluid retention can usually be corrected by thiazide diuretics. Despite these associated conditions, dia-zoxide is usually tolerated by most patients and has been helpful both for preoperative management of these patients and for long-term therapy in patients with insulinoma who have unresectable tumors or who are unwilling to undergo surgery. In our medical center, a small number of patients with insulinoma have been successfully managed on diazoxide for over 5 years.

Unfortunately, about 40% of patients either fail to respond to diazoxide treatment or have clinical sequelae that compel them to discontinue its use. Seven of 41 patients at our medical center failed to respond to diazoxide.5 Fourteen of these 41 patients had complications (palpitations [13], edema [5], nausea [2], gastrointestinal discomfort [2], and elevated uric acid [2]). Five of these patients had symptoms or complications that were so severe that they discontinued their diazoxide. Thus, diazoxide was successful in only 29 of our 41 patients.5 This response to the diazoxide treatment is comparable with that reported by other medical centers.18

Somatostatin Analogues

Somatostatin, a naturally occurring peptide widely distributed in the body, inhibits the release of growth hormone. Somatostatin analogues have been used for various types of endocrine tumors with considerable success. Somatostatin has been used effectively to reverse hyperinsulinism in metastatic islet cell carcinoma in some patients.19 However, the experience with octreotide in the treatment of insulinomas is limited, and many patients fail to respond. In our experience, octreotide scans were positive in fewer than 30% of patients with insulinomas. Rarely, octreotide may exacerbate the hypoglycemia.20

Other Therapy

The effectiveness of chemotherapy against malignant insulinomas is limited despite the introduction of several experimental drugs. Regimens using streptozocin in combination with 5-fluorouracil and doxorubicin have been used in the past and continue to be acceptable chemotherapies for unre-sectable insulinomas despite their side effects. Streptozocin is an antibiotic isolated from Strepto-myces achromogenes, which is highly toxic to pancreatic beta cells. Streptozocin controls hypo-glycemic symptoms in approximately two-thirds of patients with metastatic islet cell carcinoma and also causes a measurable reduction in tumor size in about 50%.21 It appears to prolong survival.22 However, these benefits are achieved at the cost of significant toxicity, including liver and renal toxicity, which develops in approximately two-thirds of patients.22 Other drugs under investigation include calcium channel blockers and interferon-a; these agents are primarily experimental. Hepatic artery chemoembolization, radiofrequency ablation, and debulking have been tried with some success to control the hypoglycemia.

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