Glucocorticoid therapy suppresses abnormal secretion of big IGF‐II by non‐islet cell tumours inducing hypoglycaemia (NICTH)

Abstract

Glucocorticoid therapy has been demonstrated to consistently reverse the biochemical abnormalities caused by tumour-derived big IGF-II compared with the potentially adverse stimulatory effects of hGH treatment in causing increases in serum levels of big IGF-II.

Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment

“…15 In addition to low serum glucose levels during acute episodes, NICTH is characterized by low serum levels of insulin (often <1.44-3.60 µIU/mL [to convert to pmol/L, multiply by 6.945]) and C-peptide (often <0.3 ng/mL [to convert to nmol/L, multiply by 0.331]); low levels of growth hormone and IGF-1; normal or elevated levels of IGF-2; and an elevated IGF-2:IGF-1 ratio. 15,16 In contrast, insulinomas cause elevated insulin and C-peptide levels, and the IGF-2:IGF-1 ratio is usually within the normal range. 15 The optimal initial approach to NICTH is to treat (if possible, resect) the underlying tumor.…”

“…15 The latter, termed non-islet cell tumor hypoglycemia (NICTH), presents as recurrent or constant hypoglycemic episodes with glucose levels as low as 20 mg/dL (to convert to mmol/L, multiply by 0.0555) and typically affects elderly patients with advanced cancer. 16 Occasionally, these hypoglycemic episodes can predate the diagnosis of the underlying tumor. 15 Non-islet cell tumor hypoglycemia is usually caused by tumor cell production of IGF-2 but may also arise from tumor cell production of insulin.…”

“…4 The clinical features, associated malignancies, diagnostic studies, and treatment options of paraneoplastic endocrine syndromes are listed in Table 1. 4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20] Syndrome of InapproprIate antIdIuretIc Hormone SecretIon The syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is characterized by hypo-osmotic, euvolemic hyponatremia, affects 1% to 2% of all patients with cancer. Small cell lung cancer accounts for most of these cases, with approximately 10% to 45% of all patients with small cell lung cancer developing SIADH.…”

Glucocorticoid Therapy Ameliorated Hypoglycemia in Insulin-like Growth Factor-II-producing Solitary Fibrous Tumor

“…In patients not indicated for any of the above-mentioned therapies, however, hypoglycemia reportedly develops and becomes refractory. Glucocorticoid therapy may be useful for NICTH because it enhances gluconeogenesis and reduces the secretion of the high molecular weight form of IGF-II (6). We F i g u r e 1 .…”

“…Interestingly, five of six cases treated with glucocorticoid therapy no longer suffered from hypoglycemic attacks in spite of receiving no anti-tumor treatment (16,17). On the other hand, three of four cases treated with dextrose infusion alone had repeated hypoglycemic episodes (18) (6,13,19). In addition, glucocorticoid may inhibit the tumor growth, because IGF-II is one of the autocrine growth factors for the tumor (20).…”