Hypoglycemia is reported to be one of the manifestations of a patient with hypothalamic sarcoid infiltrates due to impaired counter-regulation of glucose. But, without hypothalamic lesion, patients with sarcoidosis would not be expected to have hypoglycemia. We recently identified a patient with an isolated sarcoidosis of the spleen who had experienced frequent fasting hypoglycemia which completely disappeared after splenectomy. During hypoglycemia, serum insulin was undetectable. Endocrinological examination revealed no abnormality. The objective was to investigate whether the patient's hypoglycemia was due to ectopic secretion of an insulin-mimetic factor by the splenic sarcoidosis. Serum insulin-like growth factor-I (IGF-I) and IGF-II were measured by RIA. Serum visfatin and free IGF-I were by ELISA. A high molecular weight form of IGF-II, termed "big" IGF-II, was identified by Western blotting. Tissue IGF-I was quantified by real time RT-PCR after RNA extraction. Before operation, total and free serum IGF-I, serum IGF-II and serum visfatin were within reference range. Big IGF-II was not detected in patient's serum extract. After operation, hypoglycemia did not recur and serum insulin returned to normal, while serum IGF-I decreased by half the preoperative level. RT-PCR revealed that mRNA level of IGF-I in the sarcoidosis tissue was about 1.8-fold greater than that in the normal spleen tissue. These data suggest that ectopic secretion of IGF-I by the splenic sarcoidosis and its direct access to the liver via the portal vein might cause fasting hypoglycemia mainly by suppressing hepatic gluconeogenesis.