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Hypoglycemia mediated by paraneoplastic production of Insulin like growth factor-2 from a malignant renal solitary fibrous tumor - clinical case and literature review.

Khowaja A, Johnson-Rabbett B, Bantle J, Moheet A - BMC Endocr Disord (2014)

Bottom Line: We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature.A posttranslational precursor to IGF-2 known as "big IGF" also possesses biologic activity.Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, 516 Delaware St SE, Minneapolis, MN 55455, USA. khowa002@umn.edu.

ABSTRACT

Background: Hypoglycemic episodes are infrequent in individuals without a history of diabetes mellitus or bariatric surgery. When hypoglycemia does occur in such individuals, an uncommon but important diagnosis to consider is non-islet cell tumor hypoglycemia (NICTH). We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature.

Case presentation: A 60 year old male with no relevant past medical history was referred to the endocrinology clinic with 18 month history of episodic hypoglycemic symptoms and, on one occasion was noted to have a fingerstick glucose of 36 mg/dL while having symptoms of hypoglycemia. Basic laboratory evaluation was unrevealing. Further evaluation however showed an elevated serum IGF-2 level at 2215 ng/mL (reference range 411-1248 ng/mL). Imaging demonstrated a large right suprarenal mass. A right nephrectomy with resection of the mass demonstrated a malignant solitary fibrous tumor. Post resection, the patient's IGF-2 levels normalized and hypoglycemic symptoms resolved.

Conclusion: Due to the structural and biochemical homology between IGF-2 and insulin, elevated levels of IGF-2 can result in hypoglycemia. A posttranslational precursor to IGF-2 known as "big IGF" also possesses biologic activity. Review of recent reported cases of NICTH identified widespread anatomic locations and varied pathologic diagnoses of tumors associated with paraneoplastic production of IGF-2 causing hypoglycemia. Definitive management of hypoglycemia associated with paraneoplastic production of IGF-2 consists of resection of the tumor responsible for IGF-2 production. Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause.

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Non contrast Computed Tomography (CT) of chest, abdomen and pelvis; transverse and coronal views.
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Figure 1: Non contrast Computed Tomography (CT) of chest, abdomen and pelvis; transverse and coronal views.

Mentions: Serial finger stick blood glucose monitoring during symptomatic episodes demonstrated recurrent hypoglycemia with blood glucose values of 41, 35 and 41 mg/dL. Diagnoses considered included medication induced hypoglycemia, insulinoma, chronic liver disease, pheochromocytoma and adrenal insufficiency. These diagnoses were excluded based on laboratory evaluation (Table 1).Subsequently, IGF-2 was measured and found to be 2215 ng/mL (reference range: 414 – 1248 ng/mL). Computed Tomography (CT) without contrast of chest, abdomen and pelvis showed a large right suprarenal mass measuring 14 × 17 × 16 cm, which was lobular in shape with central necrosis and calcifications (Figure 1). Technetium radionuclide bone scan did not show any metastatic disease.The patient underwent right nephrectomy and resection of the mass. Surgical pathology showed a malignant solitary fibrous tumor with spindled to epithelioid cells and focal high-grade nuclear atypia (Figure 2). The tumor cell proliferation marker Ki67 index was elevated. The tumor was positive for CD34, CD99 and Bcl-2 consistent with a diagnosis of malignant solitary fibrous tumor.


Hypoglycemia mediated by paraneoplastic production of Insulin like growth factor-2 from a malignant renal solitary fibrous tumor - clinical case and literature review.

Khowaja A, Johnson-Rabbett B, Bantle J, Moheet A - BMC Endocr Disord (2014)

Non contrast Computed Tomography (CT) of chest, abdomen and pelvis; transverse and coronal views.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4067084&req=5

Figure 1: Non contrast Computed Tomography (CT) of chest, abdomen and pelvis; transverse and coronal views.
Mentions: Serial finger stick blood glucose monitoring during symptomatic episodes demonstrated recurrent hypoglycemia with blood glucose values of 41, 35 and 41 mg/dL. Diagnoses considered included medication induced hypoglycemia, insulinoma, chronic liver disease, pheochromocytoma and adrenal insufficiency. These diagnoses were excluded based on laboratory evaluation (Table 1).Subsequently, IGF-2 was measured and found to be 2215 ng/mL (reference range: 414 – 1248 ng/mL). Computed Tomography (CT) without contrast of chest, abdomen and pelvis showed a large right suprarenal mass measuring 14 × 17 × 16 cm, which was lobular in shape with central necrosis and calcifications (Figure 1). Technetium radionuclide bone scan did not show any metastatic disease.The patient underwent right nephrectomy and resection of the mass. Surgical pathology showed a malignant solitary fibrous tumor with spindled to epithelioid cells and focal high-grade nuclear atypia (Figure 2). The tumor cell proliferation marker Ki67 index was elevated. The tumor was positive for CD34, CD99 and Bcl-2 consistent with a diagnosis of malignant solitary fibrous tumor.

Bottom Line: We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature.A posttranslational precursor to IGF-2 known as "big IGF" also possesses biologic activity.Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, 516 Delaware St SE, Minneapolis, MN 55455, USA. khowa002@umn.edu.

ABSTRACT

Background: Hypoglycemic episodes are infrequent in individuals without a history of diabetes mellitus or bariatric surgery. When hypoglycemia does occur in such individuals, an uncommon but important diagnosis to consider is non-islet cell tumor hypoglycemia (NICTH). We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature.

Case presentation: A 60 year old male with no relevant past medical history was referred to the endocrinology clinic with 18 month history of episodic hypoglycemic symptoms and, on one occasion was noted to have a fingerstick glucose of 36 mg/dL while having symptoms of hypoglycemia. Basic laboratory evaluation was unrevealing. Further evaluation however showed an elevated serum IGF-2 level at 2215 ng/mL (reference range 411-1248 ng/mL). Imaging demonstrated a large right suprarenal mass. A right nephrectomy with resection of the mass demonstrated a malignant solitary fibrous tumor. Post resection, the patient's IGF-2 levels normalized and hypoglycemic symptoms resolved.

Conclusion: Due to the structural and biochemical homology between IGF-2 and insulin, elevated levels of IGF-2 can result in hypoglycemia. A posttranslational precursor to IGF-2 known as "big IGF" also possesses biologic activity. Review of recent reported cases of NICTH identified widespread anatomic locations and varied pathologic diagnoses of tumors associated with paraneoplastic production of IGF-2 causing hypoglycemia. Definitive management of hypoglycemia associated with paraneoplastic production of IGF-2 consists of resection of the tumor responsible for IGF-2 production. Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause.

Show MeSH
Related in: MedlinePlus