Reversibility of Unawareness of Hypoglycemia in Patients with Insulinomas

作者：Asimina Mitrakou, Carmine Giuseppe Fanelli, Th.F. Veneman, Gabriele Perriello, Silvia Calderone, D. Platanisiotis, Anna Maria Rambotti, Sotos A. Raptis, Philip Brunetti, Philip Cryer, John E. Gerich, Geremia B. Bolli · 发表于：New England Journal of Medicine · 年份：1993 · DOI：10.1056/nejm199309163291203 · 被引用次数：226 · 研究领域：Neuroendocrine Tumor Research Advances、Pituitary Gland Disorders and Treatments、Hyperglycemia and glycemic control in critically ill and hospitalized patients

BACKGROUND: A lack of appropriate autonomic warning symptoms before the development of neuroglycopenia occurs frequently in patients with diabetes mellitus. The pathogenesis of this phenomenon is unclear, but it is associated with intensive insulin therapy, prolonged duration of diabetes, frequent episodes of hypoglycemia, and impaired glucose counterregulation. Recently, it has been proposed that repeated episodes of hypoglycemia may themselves induce the phenomenon. METHODS: To test this hypothesis and to determine whether the phenomenon is reversible, we assessed autonomic and neuroglycopenic symptoms, counterregulatory hormonal responses, and cognitive function during stepped hypoglycemic-clamp studies in 6 patients with insulinomas before and approximately six months after curative surgery and in 14 normal subjects matched for age, weight, and sex. RESULTS: Before surgery, the patients with insulinomas had lower scores than the normal subjects for autonomic symptoms (mean [+/- SD], 3.5 +/- 0.8 vs. 9.6 +/- 4.5) and neuroglycopenic symptoms (2.8 +/- 1.5 vs. 8.9 +/- 5.3). The patients also had impaired counterregulatory hormonal responses (their plasma epinephrine, norepinephrine, glucagon, growth hormone, and cortisol responses before surgery were 187 +/- 227 pg per milliliter [1.03 +/- 1.25 nmol per liter], 223 +/- 85 pg per milliliter [1.32 +/- 0.50 nmol per liter], 86 +/- 21 ng per liter, 7.4 +/- 5.2 micrograms per liter, and 12.1 +/- 1.5 micrograms per deciliter [334 +...