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Abstract

Background/Aims: Acromegaly is frequently accompanied with impaired glucose tolerance (IGT) and diabetes mellitus (DM). It remains unclear which factors determine the abnormal glucose tolerance status in acromegaly. In addition, diverse actions of GH and IGF-I in regulating glucose metabolism in acromegaly have not yet been well elucidated. The aim of this study was to investigate the factors associated with abnormal glucose tolerance in acromegaly. Subjects and Study Design: We conducted a retrospective cross-sectional study that included 48 patients with active acromegaly. The subjects were divided into two groups by the results of 75 g OGTT: normal glucose tolerance (NGT) group (n = 19) and IGT+DM group (n = 29). Results: Systolic blood pressure (SBP) was significantly higher in the IGT+DM than in the NGT group. Homeostasis model assessment of β-cell function (HOMA-β) was significantly decreased in the IGT+DM group compared with the NGT group. Although serum GH or IGF-I levels were not different between the two groups, the IGF-I/GH ratio in the IGT+DM group was significantly lower than that in the NGT group. Conclusions: We have shown that a low serum IGF-I/GH ratio was associated with abnormal glucose tolerance in acromegaly. We propose that the IGF-I/GH ratio is a useful marker to understand the metabolic status in acromegaly.

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Abstract. Von Hippel-Lindau (VHL) disease (VHLD) is a hereditary autosomal dominant syndrome that causes various benign and malignant tumors. VHLD is caused by mutations in the VHL tumor suppressor gene. Here, we report a mutation in the VHL gene in a Japanese family with VHLD type 2A, characterized by pheochromocytoma (PHE), and hemangioblastomas (HAB) in both the retina and thoracic spinal cord but without renal cell carcinoma (RCC). We identified a heterozygous A to G point mutation at the second base of codon 131 of the VHL protein (pVHL). This mutation was predicted to convert codon 131 from asparagine to serine (N131S). Although most mutations in VHLD type 2A have been detected in the α domain of pVHL, the present mutated amino acid was located at the region encoding the β domain of pVHL. Previous patients with the N131K or N131T mutation in pVHL developed VHLD type 2B with RCC or VHLD type 1 without PHE, respectively. We also identified somatic loss of heterozygosity (LOH) at chromosome 3p25-26 in the adrenal tumor of the patient. The results of our study suggest that not only the location of mutation but also the altered amino acid may be critical for determining the clinical phenotype of VHLD. LOH was associated with the development of PHE in a patient with the N131S mutation in pVHL.