Endocrinology and Metabolism Clinics of North America
SURGICAL ASPECTS OF HYPERINSULINEMIC HYPOGLYCEMIA
Section snippets
HISTORY
While still a medical student and working with the renowned mentor Virchow, Langerhans first described the pancreatic islets in 1869.25 His lack of understanding regarding the function of these cells and the importance of his discovery is evident when he states that he must “… refrain from making any hypothesis as to the nature and significance of our cells.”25 Four years after the discovery of insulin by Banting and Best, Mayo first surgically explored a patient with a malignant insulinoma.8
DIAGNOSIS
Prototypic of the servomechanical negative-feedback system of endocrine organs is the tight interaction between insulin and glucose. Surgeons who undertake explorations for insulinomas must have an understanding of the pathophysiology and diagnostic aspects of the disease to be confident of the diagnosis, especially when searching for an elusive tumor. The characteristic symptoms and the process of establishing the diagnosis are covered in depth elsewhere in this issue. This article highlights
LOCALIZATION
Localization of the insulinoma has remained the focus of attention in patients with this disease over the last 2 decades, and debate continues regarding which method is best and most cost-effective. In an attempt to facilitate preoperative discussion with the patient, including planning of the operation and relief of stress for both the surgeon and patient, the author subscribes to at least some preoperative efforts at localization (Table 2). Virtually all insulinomas are found within the
Preoperative Preparation
After the diagnosis is established and localization is completed, the patient is admitted to the hospital the evening before the operation, and 10% dextrose is infused overnight. All glucose-containing fluids are discontinued approximately 2 to 3 hours before the operation, allowing the glucose level to drift down. A limited bowel preparation and a preoperative dose of prophylactic antibiotics are optional.
Intraoperative Management
Recognizing its limitations, the author continues to monitor the glucose level at
MULTIPLE ENDOCRINE NEOPLASIA SYNDROME TYPE 1
First described by Wermer in 1963,46 the genetic origin of MEN-1 was later mapped to chromosome 11.22 Pancreatic islet cell tumors plus endocrinopathies of the parathyroid glands and the anterior pituitary comprise the classic triad of MEN-1 syndrome, transmitted as an autosomal dominant trait. Gastrin-secreting islet cell tumors are most frequently encountered in patients with MEN-1, but the dominant functioning tumor in patients aged less than 25 years is insulinoma.36
A review of the Mayo
NONINSULINOMA PANCREATOGENOUS HYPOGLYCEMIA SYNDROME
The author and his colleagues have encountered patients with dramatic and sometimes incapacitating symptoms of hypoglycemia but who experience only borderline hypoglycemia with fasting. These symptoms and biochemical proof of hypoglycemia with concomitant hyperinsulinemia occur relatively soon after meals and are seemingly provoked by food intake. Since the first report of an insulinoma at the Mayo Clinic in 1927 only 9 patients among 300 have been determined to have the condition known as
MALIGNANCY
Malignant insulinomas represent approximately 5% to 10% of all insulinomas.34 To qualify as malignant, these tumors must either invade local surrounding soft tissue or metastasize (to the liver or nodes). Cytologic changes alone, including the number of mitotic figures or the ratio of nucleus to cytoplasm,4 are not adequate to classify a tumor as malignant, and attempts to use nuclear DNA ploidy and cell cycle analysis have not proved valuable in making this distinction.15, 38 Elevated levels
SUMMARY
To make a diagnosis of insulinoma, one must consider it. Neuroglycopenic symptoms are the most prominent and convincing, and the combination of hypoglycemia and endogenous hyperinsulinemia are diagnostic of insulinoma. A glucose level of approximately 40 mg/dL with a concomitant insulin level of 6 μU/mL, a C-peptide level exceeding 200 pmol/L, and a negative screening for sulfonylurea must be documented to confirm the diagnosis. Although in the author's experience, preoperative ultrasound is
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Address reprint requests to Clive S. Grant, MD, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905
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Department of Surgery, Mayo Medical School; and the Department of Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota