<p>Tumour-induced hypoglycaemia is one of the rare causes of hypoglycaemia. The most common causes include endogenous hypersecretion of insulin by the B cells of the islets of Langerhans themselves—Islet Cell Tumour Hypoglycaemia (ICTH). However, some tumours can lead to paraneoplastic hypoglycaemia by the production of substances interfering with glucose metabolism—Non-Islet Cell Tumour Hypoglycaemia (NICTH). NICTH usually occurs in patients with solid tumours of mesenchymal or epithelial origin, less frequently with haematological and neuroendocrine tumours. Diagnosis of tumour-induced hypoglycaemia is often late and challenging as it may manifest several years after diagnosis and treatment of the tumour, but on the other hand, it may also precede the diagnosis of the tumour itself.</p><p>Hypoglycaemia that is not associated with diabetes mellitus (DM) and/or its treatment is not a common clinical disorder Iglesias (Euro J Endocrinol 170:147–157, 2014), Mohammedi (Endocrinol Diabetes Metab, 2014), Groot (Endocrine-Related Cancer 14:979–993, 2007). In people without DM, hypoglycaemia is defined as a venous plasma glucose value of less than 3&#xa0;mmol/l, which is accompanied by the Whipple triad: (1) clinical signs of hypoglycaemia, (2) low plasma glucose concentration, (3) resolution of symptoms after plasma glucose correction Iglesias (Euro J Endocrinol 170:147–157, 2014), Soutelo (Arch Endocrinol Metab 61: 98–102, 2017). Cancer is a rare cause of paraneoplastic hypoglycaemia Mohammedi (Endocrinol Diabetes Metab, 2014).</p><p>Tumour-induced hypoglycaemia (TIH) is a rare cause of hypoglycaemia that can occur due to excessive or reduced insulin secretion. The pathogenic mechanisms include (1) hypersecretion of insulin by a pancreatic tumour of B cells in the islets of Langerhans—insulinoma (Islet Cell Tumour Hypoglycaemia—ICTH) or hyperplasia of B cells—nesidioblastosis (NIPHS – Non Insulinoma Pancreatogenous Hypoglycaemic Syndrome) or ectopic insulin production, (2) infiltration of the liver or adrenal glands by a tumour, and (3) production of substances that interfere with glucose metabolism in non-B cell (non-pancreatic) tumours (Non-Islet Cell Tumour Hypoglycaemia—NICTH), including antibodies against insulin receptors (e.g., in haematological malignancies). The pathogenetic mechanisms of TIH are listed in Table&#xa0;<InternalRef RefID="Tab1">1</InternalRef>. The most common cause, although rare overall, is hyperinsulinemia due to a pancreatic B cell tumour (insulinoma).<Table Float="Yes" ID="Tab1"> <Caption Language="En" xml:lang="en"> <CaptionNumber>Table&#xa0;1</CaptionNumber> <CaptionContent> <p>Pathogenetic Mechanisms and Types of Tumours Associated with TIH (adapted from 1)</p> </CaptionContent> </Caption> <tgroup cols="1"> <colspec align="left" colname="c1" colnum="1" /> <tbody> <row> <entry align="left" colname="c1"> <p><i>Insulin-secreting tumours</i></p> </entry> </row> <row> <entry align="left" colname="c1"> <p>Eutopic Tumour Insulin Pancreatic Islet: B-cell Tumour (ICTH)</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Insulinoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>Ectopic Tumour Insulin Secretion: Non-Islet-Cell Tumours (NICTH)</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Bronchial Carcinoid</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Gastrointestinal Stromal Tumour</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Squamous Cell Carcinoma of the Cervix</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Schwannoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Neurofibrosarcoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Paraganglioma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Small Cell Carcinoma of the Cervix</p> </entry> </row> <row> <entry align="left" colname="c1"> <p><i>Mechanisms other than excess tumour insulin secretion</i></p> </entry> </row> <row> <entry align="left" colname="c1"> <p>Tumour IGF2 precursors secretion (big IGF2)—“IGF2-oma”</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Leiomyosarcoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Fibrosarcoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Adrenal carcinoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Desmoplastic small round cell tumour</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Hemangiopericytoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Pheochromocytoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Renal sarcoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Uterine leiomyoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Hepatocellular carcinoma</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>Tumour somatostatin secretion “Somatostatinoma”</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Pancreatic neuroendocrine tumour</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Ovarian neuroendocrine tumour</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>Tumour IGF1 secretion “IGF1-oma”</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Large cell carcinoma of the lung</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>Tumour glucagon-like peptide 1 (GLP1) secretion “GLP1-oma”</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Ovarian neuroendocrine tumour</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Pancreatic neuroendocrine tumour</p> </entry> </row> <row> <entry align="left" colname="c1"> <p><i>Autoantibodies to insulin or its receptor “Tumour autoimmune hypoglycaemia”</i></p> </entry> </row> <row> <entry align="left" colname="c1"> <p>Other tumour-related factors</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Massive tumour burden</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Massive liver tumour infiltration</p> </entry> </row> <row> <entry align="left" colname="c1"> <p>&#xa0;Pituitary and/or adrenal glands tumour destruction</p> </entry> </row> </tbody> </tgroup> </Table></p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Tumour-Induced Hypoglycaemia: A Mini-review of Diagnostics and Treatment of This Rare Case of Hypoglycaemia

  • Ingrid Dravecká,
  • Peter Galajda,
  • Marián Mokáň

摘要

Tumour-induced hypoglycaemia is one of the rare causes of hypoglycaemia. The most common causes include endogenous hypersecretion of insulin by the B cells of the islets of Langerhans themselves—Islet Cell Tumour Hypoglycaemia (ICTH). However, some tumours can lead to paraneoplastic hypoglycaemia by the production of substances interfering with glucose metabolism—Non-Islet Cell Tumour Hypoglycaemia (NICTH). NICTH usually occurs in patients with solid tumours of mesenchymal or epithelial origin, less frequently with haematological and neuroendocrine tumours. Diagnosis of tumour-induced hypoglycaemia is often late and challenging as it may manifest several years after diagnosis and treatment of the tumour, but on the other hand, it may also precede the diagnosis of the tumour itself.

Hypoglycaemia that is not associated with diabetes mellitus (DM) and/or its treatment is not a common clinical disorder Iglesias (Euro J Endocrinol 170:147–157, 2014), Mohammedi (Endocrinol Diabetes Metab, 2014), Groot (Endocrine-Related Cancer 14:979–993, 2007). In people without DM, hypoglycaemia is defined as a venous plasma glucose value of less than 3 mmol/l, which is accompanied by the Whipple triad: (1) clinical signs of hypoglycaemia, (2) low plasma glucose concentration, (3) resolution of symptoms after plasma glucose correction Iglesias (Euro J Endocrinol 170:147–157, 2014), Soutelo (Arch Endocrinol Metab 61: 98–102, 2017). Cancer is a rare cause of paraneoplastic hypoglycaemia Mohammedi (Endocrinol Diabetes Metab, 2014).

Tumour-induced hypoglycaemia (TIH) is a rare cause of hypoglycaemia that can occur due to excessive or reduced insulin secretion. The pathogenic mechanisms include (1) hypersecretion of insulin by a pancreatic tumour of B cells in the islets of Langerhans—insulinoma (Islet Cell Tumour Hypoglycaemia—ICTH) or hyperplasia of B cells—nesidioblastosis (NIPHS – Non Insulinoma Pancreatogenous Hypoglycaemic Syndrome) or ectopic insulin production, (2) infiltration of the liver or adrenal glands by a tumour, and (3) production of substances that interfere with glucose metabolism in non-B cell (non-pancreatic) tumours (Non-Islet Cell Tumour Hypoglycaemia—NICTH), including antibodies against insulin receptors (e.g., in haematological malignancies). The pathogenetic mechanisms of TIH are listed in Table 1. The most common cause, although rare overall, is hyperinsulinemia due to a pancreatic B cell tumour (insulinoma).

Insulin-secreting tumours

Eutopic Tumour Insulin Pancreatic Islet: B-cell Tumour (ICTH)

 Insulinoma

Ectopic Tumour Insulin Secretion: Non-Islet-Cell Tumours (NICTH)

 Bronchial Carcinoid

 Gastrointestinal Stromal Tumour

 Squamous Cell Carcinoma of the Cervix

 Schwannoma

 Neurofibrosarcoma

 Paraganglioma

 Small Cell Carcinoma of the Cervix

Mechanisms other than excess tumour insulin secretion

Tumour IGF2 precursors secretion (big IGF2)—“IGF2-oma”

 Leiomyosarcoma

 Fibrosarcoma

 Adrenal carcinoma

 Desmoplastic small round cell tumour

 Hemangiopericytoma

 Pheochromocytoma

 Renal sarcoma

 Uterine leiomyoma

 Hepatocellular carcinoma

Tumour somatostatin secretion “Somatostatinoma”

 Pancreatic neuroendocrine tumour

 Ovarian neuroendocrine tumour

Tumour IGF1 secretion “IGF1-oma”

 Large cell carcinoma of the lung

Tumour glucagon-like peptide 1 (GLP1) secretion “GLP1-oma”

 Ovarian neuroendocrine tumour

 Pancreatic neuroendocrine tumour

Autoantibodies to insulin or its receptor “Tumour autoimmune hypoglycaemia”

Other tumour-related factors

 Massive tumour burden

 Massive liver tumour infiltration

 Pituitary and/or adrenal glands tumour destruction

Table 1

Pathogenetic Mechanisms and Types of Tumours Associated with TIH (adapted from 1)