The work-up of fasting hypoglycemia may be difficult but is crucially important because a wrong diagnosis can lead to either unnecessary pancreatectomy or a missed pancreatic tumor. We describe a patient with severe fasting hypoglycemia [22-32 mg/dl (1.2-1.8 mmol/liter) after 6 -10 h of fasting] in which the diagnosis of a secretory islet-cell tumor was obscured, rather than facilitated, by use of a new, highly specific serum insulin assay. Insulin measured by the specific assay suppressed

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... lly during fasting hypoglycemia [undetectable at < 2.0 -3.8 IU/ml (26.4 pmol/liter)], whereas insulin measured by older, less specific assays was diagnostically elevated [34, 73 IU/ml (236.1, 507.0 pmol/liter)]. Serum proin-sulin and C-peptide levels were abnormal, and further work-up revealed an islet-cell tumor that secreted predominantly proinsulin. The tumor was surgically removed, relieving the fasting hypoglycemia. We conclude that insulin levels as measured by new, highly specific insulin assays may obscure the diagnosis of a functional, proinsulin-secreting isletcell tumor. Because proinsulin cross-reacts with insulin in older insulin assays, C-peptide or proinsulin should be measured to rule out a proinsulin-secreting islet-cell tumor. Normative values for new insulin assays must be established during prolonged fasting. (J Clin Endocrinol