Although low concentrations of blood glucose were recognized as a concomitant of some disease states in the nineteenth century,<sup>100 Wauchope G.M. Hypoglycemia Q J Med 1933 ;  2 : 117-125

Cliccare qui per andare alla sezione Riferimenti</sup> it was not until insulin became available for the treatment of diabetes mellitus in the early 1920s that symptoms similar to those arising from overtreatment of diabetes mellitus were observed in nondiabetic persons. This observation led to the postulation of a new disease entity called hyperinsulinemia.<sup>34 Harris S. Hyperinsulinism and dysinsulinism JAMA 1924 ;  83 : 729-733

Cliccare qui per andare alla sezione Riferimenti</sup> Support for the existence of hyperinsulinism was provided from the identification of a malignant pancreatic islet cell tumor in 1926 in a patient who had episodes of severe hypoglycemia.<sup>104 Wilder R.M., Allan R.N., Power M.H. , e al. Carcinoma of the islands of the pancreas: Hyperinsulinism and hypoglycemia JAMA 1927 ;  89 : 348-355

Cliccare qui per andare alla sezione Riferimenti</sup> Following the death of the patient, postmortem extracts of tissue metastatic to the liver were noted to cause marked hypoglycemia when injected into rabbits. The first surgical cure of hyperinsulinism was reported by Howland and co-workers<sup>42 Howland G., Campbell W.R., Maltby E.J. , e al. Dysinsulinism: Convulsions and coma due to islet cell tumor of pancreas, with operation and cure JAMA 1929 ;  93 : 674

Cliccare qui per andare alla sezione Riferimenti</sup> in 1929 following the successful removal of an insulinoma from a hypoglycemic patient. Consequent to the development of a radioimmunoassay for insulin,<sup>106 Yalow R.S., Berson S.A. Immunoassay of endogenous plasma insulin in man J Clin Invest 1960 ;  39 : 1157  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> hyperinsulinism was confirmed as the pathophysiologic basis for hypoglycemia caused by insulinoma. Elucidation of the biochemistry of glucose metabolism and hormonal control of glucose counterregulation in the latter part of this century has permitted the identification of other non–insulin-mediated causes of hypoglycemia.

In the two decades after the identification of insulinoma as the cause of hypoglycemia, the focus in patients with hypoglycemia was the pancreas.<sup>102 Whipple A.O. The surgical therapy of hyperinsulinism J Int Chir 1938 ;  3 : 237-276

Cliccare qui per andare alla sezione Riferimenti</sup> It was recognized that food deprivation provoked hypoglycemia. Consequently, the prolonged (72-hour) fast evolved as the chief diagnostic test when the measurement of blood glucose during a spontaneous episode of hypoglycemia was not feasible. In addition, patients with hyperinsulinism were noted characteristically to experience symptoms of the neuroglycopenic type.