Non-Islet Cell Tumor Hypoglycemia in a Patient with Uterine Carcinosarcoma

Introduction. Adrenocortical carcinomas (ACCs) are infrequently reported to present with severe hypoglycemia syndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by tumor cells. Adrenocorticotropic hormone- (ACTH) independent hypercortisolism is the norm of hormonally active ACCs, but aberrant ACTH production by tumor cells can theoretically cause ACTH-dependent hypercortisolism. The purpose of this report was to present a case of an ACC manifested with the co-occurrence of two extremely rare presentations. Case Description. We present a rare case of a 43-year-old male patient admitted with recurrent episodes of severe non-ketotic and non-insulin-mediated hypoglycemia due to IGF-II mediated disease and ACTH-dependent Cushing’s syndrome. He was diagnosed with a diffusely disseminated adrenocortical carcinoma with immunohistochemistry of tumor cells showing focal ACTH immunostain positivity. Conclusion. Non-islet cell tumor hypoglycemia and ACTH-dependent Cushing’s syndrome are extremely rare presentations of an ACC, and co-occurrence of these entities in a single patient is never reported in the literature.

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Hypoglycemia from IGF2 Overexpression Associated with Activation of Fetal Promoters and Loss of Imprinting in a Metastatic Hemangiopericytoma

Endocrine Reviews ◽

10.1210/edrv.30.4.9990 ◽

2009 ◽

Vol 30 (4) ◽

pp. 413-413

Author(s):

Elizabeth A. Lawson ◽

Xun Zhang ◽

Jonathan T. Crocker ◽

Wei-Lien Wang ◽

Anne Klibanski

Keyword(s):

Control Region ◽

Islet Cell ◽

Islet Cell Tumor ◽

Major Change ◽

Metastatic Tumor ◽

Cell Tumor ◽

Rt Pcr ◽

Loss Of Imprinting ◽

Promoter Usage ◽

Tumor Hypoglycemia

ABSTRACT Context The mechanism of IGF2 overexpression in non-islet-cell tumor hypoglycemia is not understood. Objective We investigated the imprinting control and promoter usage for IGF2 expression to identify a mechanism for increased IGF-II production in non-islet-cell tumor hypoglycemia. Patient and Methods A patient with metastatic hemangiopericytoma was studied. Tissue from the original hemangiopericytoma, metastatic tumor, and uninvolved liver was analyzed for IGF-II immunohistochemistry. IGF2, a paternally imprinted gene, shares a control region with maternally imprinted H19, a putative tumor suppressor. IGF-II and H19 mRNA expression was compared in metastatic tumor and uninvolved liver by quantitative RT-PCR. Imprinting of IGF2/H19 genes and IGF2 promoter usage in metastatic tumor was investigated by RT-PCR and sequence analysis, and the methylation pattern in the IGF2/H19 imprinting control region was analyzed. Results IGF-II protein expression was increased in metastatic tumor vs. uninvolved liver and original tumor. In the metastatic tumor, IGF-II mRNA was increased 60-fold, but H19 mRNA was comparable to uninvolved liver; loss of imprinting of IGF2, but not H19, was identified; no major change in methylation of the IGF2/H19 imprinting control regions was observed; and transcripts from four different IGF2 promoters were detected, compared to two in uninvolved liver. Conclusions IGF-2 overexpression, newly acquired in the metastatic tumor, was associated with loss of IGF2 gene imprinting and different promoter usage. The imprinting control mechanism governing the IGF2/H19 locus was intact, as evidenced by normal levels of H19, maintenance of H19 imprinting, and no major change in methylation of the imprinting control regions.

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