Diagnosis
Early diagnosis and treatment of CHI are very important in preventing any brain injury caused by hypoglycemia. Therefore, CHI should be suspected in any patient with repeated and persistent hypoglycemia. The following parameters play a major role in establishing the diagnosis of CHI:
Early diagnosis and treatment of CHI are very important in preventing any brain injury caused by hypoglycemia. Therefore, CHI should be suspected in any patient with repeated and persistent hypoglycemia. The following parameters play a major role in establishing the diagnosis of CHI:
Serum Insulin
Serum Insulin
Though the fundamental sign in diagnosis of CHI is detectable/high levels of insulin concentration in the blood at the time of hypoglycemia, the levels of insulin fluctuate widely over the time, as it is being used up for the breakdown of glucose and hence low or undetectable insulin do not always exclude the diagnosis of CHI. Therefore, it becomes difficult to establish the diagnosis of CHI if one relies only on demonstrating an elevated blood insulin concentration at the time of hypoglycemia. Other signs and chemical markers must be tested to provide clues of excess insulin action. Moreover, there is no correlation between measured serum insulin concentration and the severity of the hypoglcemia.
Though the fundamental sign in diagnosis of CHI is detectable/high levels of insulin concentration in the blood at the time of hypoglycemia, the levels of insulin fluctuate widely over the time, as it is being used up for the breakdown of glucose and hence low or undetectable insulin do not always exclude the diagnosis of CHI. Therefore, it becomes difficult to establish the diagnosis of CHI if one relies only on demonstrating an elevated blood insulin concentration at the time of hypoglycemia. Other signs and chemical markers must be tested to provide clues of excess insulin action. Moreover, there is no correlation between measured serum insulin concentration and the severity of the hypoglcemia.
Serum C-Peptide
Serum C-Peptide
A Connecting-peptide is a substance that is created when the hormone insulin is produced and released into the body. It is secreted by islet β-cells of pancreas and has a same precursor proinsulin with insulin. A proinsulin can be decomposed into one molecule of insulin and one molecule of C-peptide. This makes the molar weight of C-peptide the same as that of individual’s secreted insulin. Moreover, it is not easy for C-peptide to be degraded by the liver. Hence, C-peptide levels in the blood can also reflect the content of insulin in the body as well as the function of islet cells. In CHI, an inappropriate C-peptide concentration can be detected at the time of hypoglycemia and in some cases, serum C-peptide levels (≥0.5 ng/mL) may help confirm the diagnosis.
A Connecting-peptide is a substance that is created when the hormone insulin is produced and released into the body. It is secreted by islet β-cells of pancreas and has a same precursor proinsulin with insulin. A proinsulin can be decomposed into one molecule of insulin and one molecule of C-peptide. This makes the molar weight of C-peptide the same as that of individual’s secreted insulin. Moreover, it is not easy for C-peptide to be degraded by the liver. Hence, C-peptide levels in the blood can also reflect the content of insulin in the body as well as the function of islet cells. In CHI, an inappropriate C-peptide concentration can be detected at the time of hypoglycemia and in some cases, serum C-peptide levels (≥0.5 ng/mL) may help confirm the diagnosis.
Blood Glucose
Blood Glucose
Hypoglycemia that occurs while the newborn is on glucose infusion is strongly suggestive of CHI and an intravenous glucose infusion rate requirement of >8 mg/kg/min is diagnostic of CHI. In milder forms of CHI, it is also important to establish the duration of fasting and whether if the hypoglycemia is precipitated by meals or by exercise. Plasma glucose (always take capillary sample or free flow venous sample and not from intravenous line that is used for glucose infusion) should be taken at the time of hypoglycemia screen.
Hypoglycemia that occurs while the newborn is on glucose infusion is strongly suggestive of CHI and an intravenous glucose infusion rate requirement of >8 mg/kg/min is diagnostic of CHI. In milder forms of CHI, it is also important to establish the duration of fasting and whether if the hypoglycemia is precipitated by meals or by exercise. Plasma glucose (always take capillary sample or free flow venous sample and not from intravenous line that is used for glucose infusion) should be taken at the time of hypoglycemia screen.
Serum Ketones and Free fatty acids
Serum Ketones and Free fatty acids
The metabolic effects of high insulin concentration in the blood can also be depicted by low serum ketones and free fatty acid concentrations in the blood at the time of hypoglycemia. It is advisable to measure of point of care ketones or take these blood samples at the time of hypoglycemia screen.
The metabolic effects of high insulin concentration in the blood can also be depicted by low serum ketones and free fatty acid concentrations in the blood at the time of hypoglycemia. It is advisable to measure of point of care ketones or take these blood samples at the time of hypoglycemia screen.
Glucagon infusion
Glucagon infusion
In cases where the diagnosis of CHI is difficult, glucagon stimulation test can also be used to demonstrate the excess of insulin. Glucagon, a peptide hormone secreted by the alpha-cells of the pancreas, opposes insulin action and stimulates the release of glucose from glycogen stores of liver. A rise in blood glucose concentration by >1.5mmol/L (27mg/dl) after intramuscular or intravenous glucagon at the time of hypoglycemia is considered as positive glycemic response and is a sensitive marker of hyperinsulinism. A similar positive glycemic response can also be found after subcutaneous octreotide administration.
In cases where the diagnosis of CHI is difficult, glucagon stimulation test can also be used to demonstrate the excess of insulin. Glucagon, a peptide hormone secreted by the alpha-cells of the pancreas, opposes insulin action and stimulates the release of glucose from glycogen stores of liver. A rise in blood glucose concentration by >1.5mmol/L (27mg/dl) after intramuscular or intravenous glucagon at the time of hypoglycemia is considered as positive glycemic response and is a sensitive marker of hyperinsulinism. A similar positive glycemic response can also be found after subcutaneous octreotide administration.
It is important to note that such biochemical results are generally informative only if taken at the time of hypoglycemia called the critical sample. It is very important to discuss with the specialist before undertaking the glucagon test and diagnostic fasting test carried out in a safe setting in an experienced hospital is sometimes required to provoke hypoglycemia to collect a critical sample.
It is important to note that such biochemical results are generally informative only if taken at the time of hypoglycemia called the critical sample. It is very important to discuss with the specialist before undertaking the glucagon test and diagnostic fasting test carried out in a safe setting in an experienced hospital is sometimes required to provoke hypoglycemia to collect a critical sample.
CT SCAN
CT SCAN
Based on the genetic results, imaging may be required to differentiate between the focal and diffuse form. Currently, imaging with 18F-DOPA-PET/CT scan is undertaken to identify the location of focal lesion in the pancreas. The scan involves use of a special radioactive drug 18F-DOPA which is taken up by the pancreatic islet cells and converted into dopamine using an enzyme DOPA decarboxylase. Focal and diffuse forms of the disease show an increased activity of this enzyme and diffuse disease show a uniform uptake of 18F-DOPA throughout the whole of the pancreas, while in focal lesion the uptake of 18F-DOPA is markedly increased in a part of the pancreas as compared to the surrounding tissue around it.
Based on the genetic results, imaging may be required to differentiate between the focal and diffuse form. Currently, imaging with 18F-DOPA-PET/CT scan is undertaken to identify the location of focal lesion in the pancreas. The scan involves use of a special radioactive drug 18F-DOPA which is taken up by the pancreatic islet cells and converted into dopamine using an enzyme DOPA decarboxylase. Focal and diffuse forms of the disease show an increased activity of this enzyme and diffuse disease show a uniform uptake of 18F-DOPA throughout the whole of the pancreas, while in focal lesion the uptake of 18F-DOPA is markedly increased in a part of the pancreas as compared to the surrounding tissue around it.
Recently, there has been several studies published showing PET/CT imaging with Ga-Exendin isotope has been more effective to locate pancreatic lesion.
Recently, there has been several studies published showing PET/CT imaging with Ga-Exendin isotope has been more effective to locate pancreatic lesion.
Urgent genetic testing is extremely important in children who are either partial responsive or unresponsive to diazoxide as this will help to differentiate between focal and diffuse forms. Clinicians should arrange to send DNA samples on the child as well as mum and dad. Please discuss with us to arrange for DNA samples to be sent off and for prompt genetic results.
Urgent genetic testing is extremely important in children who are either partial responsive or unresponsive to diazoxide as this will help to differentiate between focal and diffuse forms. Clinicians should arrange to send DNA samples on the child as well as mum and dad. Please discuss with us to arrange for DNA samples to be sent off and for prompt genetic results.