Levels of glucose-regulatory hormones in patients with non-islet cell tumor hypoglycemia: including a review of the literature

Non-islet cell tumor hypoglycemia (NICTH) is one of the causes of spontaneous hypoglycemia. The pathogenesis of NICTH is thought to be an excessive production by tumors of big insulin-like growth factor (IGF)-II. This study investigated the levels of glucose-regulatory hormones in patients with NICT...

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Published inEndocrine Journal Vol. 64; no. 7; pp. 719 - 726
Main Authors Tanimura-Inagaki, Kyoko, Nagamine, Tomoko, Fukuda, Izumi, Harada, Taro, Asai, Akira, Hizuka, Naomi, Sugihara, Hitoshi
Format Journal Article
LanguageEnglish
Published Japan The Japan Endocrine Society 01.01.2017
Japan Science and Technology Agency
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Online AccessGet full text
ISSN0918-8959
1348-4540
1348-4540
DOI10.1507/endocrj.EJ17-0072

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Abstract Non-islet cell tumor hypoglycemia (NICTH) is one of the causes of spontaneous hypoglycemia. The pathogenesis of NICTH is thought to be an excessive production by tumors of big insulin-like growth factor (IGF)-II. This study investigated the levels of glucose-regulatory hormones in patients with NICTH with high serum levels of big IGF-II (big IGF-II group) and compared these with profiles of patients with spontaneous hypoglycemia with normal IGF-II (normal IGF-II group). Circulating IRI, CPR, ACTH, cortisol, GH, and IGF-I levels measured during hypoglycemic episodes were examined retrospectively in 37 patients with big IGF-II producing NICTH and 6 hypoglycemic patients with normal IGF-II. The hormone profile data of 15 patients with NICTH from published case reports were reviewed and included in the analyses. Mean plasma glucose levels (36 vs. 29 mg/dL), serum IRI (0.53 vs. 0.37 μIU/mL), CPR (0.15 vs. 0.20 ng/mL), IGF-I SDS (-3.55 vs. -3.18 SD) and ACTH levels (27.3 vs. 33.8 pg/mL) were not significantly different between the big and normal IGF-II groups. However, mean serum GH (0.85 vs. 9.62 ng/mL) and plasma cortisol levels (16.2 vs. 34.5 μg/dL) were significantly lower in the big IGF-II group than in the normal IGF-II group (both p<0.05). In conclusion, although the magnitude of the decrease in insulin and IGF-I levels did not differ between spontaneous hypoglycemic patients caused by other etiologies, patients with NICTH tended to have low basal GH levels during hypoglycemic episodes. These differences in hormone profile may be helpful for selecting patients who require analysis of IGF-II.
AbstractList Non-islet cell tumor hypoglycemia (NICTH) is one of the causes of spontaneous hypoglycemia. The pathogenesis of NICTH is thought to be an excessive production by tumors of big insulin-like growth factor (IGF)-II. This study investigated the levels of glucose-regulatory hormones in patients with NICTH with high serum levels of big IGF-II (big IGF-II group) and compared these with profiles of patients with spontaneous hypoglycemia with normal IGF-II (normal IGF-II group). Circulating IRI, CPR, ACTH, cortisol, GH, and IGF-I levels measured during hypoglycemic episodes were examined retrospectively in 37 patients with big IGF-II producing NICTH and 6 hypoglycemic patients with normal IGF-II. The hormone profile data of 15 patients with NICTH from published case reports were reviewed and included in the analyses. Mean plasma glucose levels (36 vs. 29 mg/dL), serum IRI (0.53 vs. 0.37 μIU/mL), CPR (0.15 vs. 0.20 ng/mL), IGF-I SDS (-3.55 vs. -3.18 SD) and ACTH levels (27.3 vs. 33.8 pg/mL) were not significantly different between the big and normal IGF-II groups. However, mean serum GH (0.85 vs. 9.62 ng/mL) and plasma cortisol levels (16.2 vs. 34.5 μg/dL) were significantly lower in the big IGF-II group than in the normal IGF-II group (both p<0.05). In conclusion, although the magnitude of the decrease in insulin and IGF-I levels did not differ between spontaneous hypoglycemic patients caused by other etiologies, patients with NICTH tended to have low basal GH levels during hypoglycemic episodes. These differences in hormone profile may be helpful for selecting patients who require analysis of IGF-II.
Non-islet cell tumor hypoglycemia (NICTH) is one of the causes of spontaneous hypoglycemia. The pathogenesis of NICTH is thought to be an excessive production by tumors of big insulin-like growth factor (IGF)-II. This study investigated the levels of glucose-regulatory hormones in patients with NICTH with high serum levels of big IGF-II (big IGF-II group) and compared these with profiles of patients with spontaneous hypoglycemia with normal IGF-II (normal IGF-II group). Circulating IRI, CPR, ACTH, cortisol, GH, and IGF-I levels measured during hypoglycemic episodes were examined retrospectively in 37 patients with big IGF-II producing NICTH and 6 hypoglycemic patients with normal IGF-II. The hormone profile data of 15 patients with NICTH from published case reports were reviewed and included in the analyses. Mean plasma glucose levels (36 vs. 29 mg/dL), serum IRI (0.53 vs. 0.37 μIU/mL), CPR (0.15 vs. 0.20 ng/mL), IGF-I SDS (-3.55 vs. -3.18 SD) and ACTH levels (27.3 vs. 33.8 pg/mL) were not significantly different between the big and normal IGF-II groups. However, mean serum GH (0.85 vs. 9.62 ng/mL) and plasma cortisol levels (16.2 vs. 34.5 μg/dL) were significantly lower in the big IGF-II group than in the normal IGF-II group (both p<0.05). In conclusion, although the magnitude of the decrease in insulin and IGF-I levels did not differ between spontaneous hypoglycemic patients caused by other etiologies, patients with NICTH tended to have low basal GH levels during hypoglycemic episodes. These differences in hormone profile may be helpful for selecting patients who require analysis of IGF-II.Non-islet cell tumor hypoglycemia (NICTH) is one of the causes of spontaneous hypoglycemia. The pathogenesis of NICTH is thought to be an excessive production by tumors of big insulin-like growth factor (IGF)-II. This study investigated the levels of glucose-regulatory hormones in patients with NICTH with high serum levels of big IGF-II (big IGF-II group) and compared these with profiles of patients with spontaneous hypoglycemia with normal IGF-II (normal IGF-II group). Circulating IRI, CPR, ACTH, cortisol, GH, and IGF-I levels measured during hypoglycemic episodes were examined retrospectively in 37 patients with big IGF-II producing NICTH and 6 hypoglycemic patients with normal IGF-II. The hormone profile data of 15 patients with NICTH from published case reports were reviewed and included in the analyses. Mean plasma glucose levels (36 vs. 29 mg/dL), serum IRI (0.53 vs. 0.37 μIU/mL), CPR (0.15 vs. 0.20 ng/mL), IGF-I SDS (-3.55 vs. -3.18 SD) and ACTH levels (27.3 vs. 33.8 pg/mL) were not significantly different between the big and normal IGF-II groups. However, mean serum GH (0.85 vs. 9.62 ng/mL) and plasma cortisol levels (16.2 vs. 34.5 μg/dL) were significantly lower in the big IGF-II group than in the normal IGF-II group (both p<0.05). In conclusion, although the magnitude of the decrease in insulin and IGF-I levels did not differ between spontaneous hypoglycemic patients caused by other etiologies, patients with NICTH tended to have low basal GH levels during hypoglycemic episodes. These differences in hormone profile may be helpful for selecting patients who require analysis of IGF-II.
Author Harada, Taro
Fukuda, Izumi
Nagamine, Tomoko
Tanimura-Inagaki, Kyoko
Hizuka, Naomi
Sugihara, Hitoshi
Asai, Akira
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  organization: Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
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  organization: Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
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  organization: Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
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4. Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, et al. (2009) Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 94: 709-728.
18. Teramae S, Miyamoto H, Muguruma N, Okada Y, Goji T, et al. (2015) Insulin-like growth factor II-producing metastatic colon cancer with recurrent hypoglycemia. Clin J Gastroenterol 8: 35-40.
2. Dynkevich Y, Rother KI, Whitford I, Qureshi S, Galiveeti S, et al. (2013) Tumors, IGF-2, and hypoglycemia: insights from the clinic, the laboratory, and the historical archive. Endocr Rev 34: 798-826.
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References_xml – reference: 20. Isojima T, Shimatsu A, Yokoya S, Chihara K, Tanaka T, et al. (2012) Standardized centile curves and reference intervals of serum insulin-like growth factor-I (IGF-I) levels in a normal Japanese population using the LMS method. Endocr J 59: 771-780.
– reference: 17. Hino N, Nakagawa Y, Ikushima Y, Yoshida M, Tsuyuguchi M (2010) A case of a giant phyllodes tumor of the breast with hypoglycemia caused by high-molecular-weight insulin-like growth factor II. Breast Cancer 17: 142-145.
– reference: 22. Service FJ, Cryer PE, Vella A Hypoglycemia in adults: Clinical manifestations, definition, and causes In: UpToDate. Post TW (Ed), UpToDate, Waltham, MA. (Accessed on Dec 15, 2016, Last Update: Jun 16, 2015).
– reference: 23. Mitrakou A, Fanelli C, Veneman T, Perriello G, Calderone S, et al. (1993) Reversibility of unawareness of hypoglycemia in patients with insulinomas. N Engl J Med 329: 834-839.
– reference: 9. Tominaga N, Kawarasaki C, Kanemoto K, Yokochi A, Sugino K, et al. (2012) Recurrent solitary fibrous tumor of the pleura with malignant transformation and non-islet cell tumor-induced hypoglycemia due to paraneoplastic overexpression and secretion of high-molecular-weight insulin-like growth factor II. Intern Med 51: 3267-3272.
– reference: 24. Ron D, Powers AC, Pandian MR, Godine JE, Axelrod L (1989) Increased insulin-like growth factor II production and consequent suppression of growth hormone secretion: a dual mechanism for tumor-induced hypoglycemia. J Clin Endocrinol Metab 68: 701-706.
– reference: 16. Koizumi Y, Hiraoka A, Michitaka K, Tazuya N, Ichiryu M, et al. (2011) Severe hypoglycemia associated with insulin-like growth factor II-producing liver metastasis from gastric carcinoma treated with overnight total parenteral nutrition via a central vein catheter reserve port. Clin J Gastroenterol 4: 68-72.
– reference: 4. Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, et al. (2009) Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 94: 709-728.
– reference: 21. Fukuda I, Hizuka N, Ishikawa Y, Yasumoto K, Murakami Y, et al. (2006) Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia. Growth Horm IGF Res 16: 211-216.
– reference: 7. Inaba T, Sakai S, Nakamura H, Date M, Kure M, et al. (2014) A case of IGF-II producing NICTH that the eficacy of steroid therapy for hypoglycemia was confirmed by CGM. Tounyoubyo (Journal of the Japan diabetes society) 57: 970-
– reference: 13. Okushin K, Asaoka Y, Fukuda I, Fujiwara N, Minami T, et al. (2012) IGF-II Producing Hepatocellular Carcinoma Treated with Sorafenib: Metabolic Complications and a Foresight to Molecular Targeting Therapy to the IGF Signal. Case Rep Gastroenterol 6: 784-789.
– reference: 10. Kawashima K, Ujiie T, Jin M, Nishimura K, Miyoshi S, et al. (2009) A case of retroperitoneum soritary fibrous tumor found by hypoglicemic attack. Hinyoukika-kiyou (Acta urologica japonica) 55: 395-399 (In Japanease).
– reference: 18. Teramae S, Miyamoto H, Muguruma N, Okada Y, Goji T, et al. (2015) Insulin-like growth factor II-producing metastatic colon cancer with recurrent hypoglycemia. Clin J Gastroenterol 8: 35-40.
– reference: 19. Honma H, Takahashi Y, Matsui M, Satoh T, Fukuda I, et al. (2015) Non-Islet Cell Tumor Hypoglycemia Is Caused by Big IGF-II in a Patient with a Carcinosarcoma of the Uterus. Intern Med 54: 3165-3169.
– reference: 14. Tsunekawa T, Sato I, Sugiyama M, Shinohara Y, Yoshioka S, et al. (2012) A case of non-islet cell tumor hypoglycemia due to GIST. Nihon Naibunpitsugakkai zasshi (Folia endocrinologica japonica) 88: 379 (In Japanease).
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Snippet Non-islet cell tumor hypoglycemia (NICTH) is one of the causes of spontaneous hypoglycemia. The pathogenesis of NICTH is thought to be an excessive production...
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SubjectTerms Adrenocorticotropic hormone
Adrenocorticotropic Hormone - blood
Adult
Aged
Aged, 80 and over
Blood Glucose - analysis
C-Reactive Protein - analysis
Case reports
Cortisol
Down-Regulation
Female
Glucose
Growth hormones
Hormones
Human Growth Hormone - blood
Humans
Hydrocortisone - blood
Hypoglycemia
Hypoglycemia - etiology
Insulin
Insulin - blood
Insulin-like growth factor I
Insulin-Like Growth Factor I - analysis
Insulin-like growth factor II
Insulin-Like Growth Factor II - analysis
Insulin-Like Growth Factor II - chemistry
Insulin-like growth factors
Japan
Literature reviews
Male
Middle Aged
Molecular Weight
Neoplasms - blood
Neoplasms - physiopathology
Plasma
Reproducibility of Results
Retrospective Studies
Serum levels
Tumor
Tumors
Title Levels of glucose-regulatory hormones in patients with non-islet cell tumor hypoglycemia: including a review of the literature
URI https://www.jstage.jst.go.jp/article/endocrj/64/7/64_EJ17-0072/_article/-char/en
https://www.ncbi.nlm.nih.gov/pubmed/28529277
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https://www.proquest.com/docview/1901309212
Volume 64
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