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* Octreotide an analog of somatostatin inhibits the secretion of insulin and glucagon.<ref name="pmid11334727">{{cite journal| author=Aparicio T, Ducreux M, Baudin E, Sabourin JC, De Baere T, Mitry E et al.| title=Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours. | journal=Eur J Cancer | year= 2001 | volume= 37 | issue= 8 | pages= 1014-9 | pmid=11334727 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11334727  }}</ref> In patients with failed diazoxide attempts.
* Octreotide an analog of somatostatin inhibits the secretion of insulin and glucagon.<ref name="pmid11334727">{{cite journal| author=Aparicio T, Ducreux M, Baudin E, Sabourin JC, De Baere T, Mitry E et al.| title=Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours. | journal=Eur J Cancer | year= 2001 | volume= 37 | issue= 8 | pages= 1014-9 | pmid=11334727 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11334727  }}</ref> In patients with failed diazoxide attempts.
* Everolimus, an inhibitor of the mammalian is option for refractory cases.
* Everolimus, an inhibitor of the mammalian is option for refractory cases.
=== Neonatal hypoglycemia: ===
Goal is to prevent neurologic complications of neonatal hypoglycemia.
Manangement differs between symptomatic and asymptomatic patients:
==== Symptomatic patients : ====
The goal is to maintain plasma glucose concentrations >70 mg/dL. 4,5
Guidelines developed by the American Academy of Pediatrics suggest aggresive treatment in these patients because of the neurodevelopmental impairment associated: 2
* Who are less than 48 hours of life with plasma glucose levels <50 mg/dL 
* Who are greater than 48 hours of life with plasma glucose levels <60 mg/dL
* Asymptomatic patients '''at risk''' for hypoglycemia or in patients in whom a low glucose concentration was identified as an incidental laboratory finding:
* Who are less than 4 hours of life with plasma glucose levels <25 to 40 mg/dL (1.4 to 2.2 mmol/L) [1].
* Who are between 4 and 24 hours of life with plasma glucose <35 to 45 mg/dL (1.9 to 2.5 mmol/L) [1].
* Who are between 24 and 48 hours of life with plasma glucose levels <45 to 50 mg/dL (2.5 to 2.8 mmol/L) [3].
* Who are greater than 48 hours of life with plasma glucose levels <60 mg/dL (3.3 mmol/L)
* In newborns with a suspected or confirmed genetic hypoglycemia disorder (such as a family history of a hypoglycemia disorder or physical exam features consistent with Beckwith-Wiedemann syndrome)
Intravenous bolus of 200 mg/kg dextrose is given over 5 m followed by the continuous administration of parenteral dextrose infusion at a rate of 6 to 8 mg/kg of dextrose per minute. [1,2]
Therapy should be initiated while awaiting laboratory confirmation of low blood glucose levels.[7]
The maximum rate of infusion for treatment is the maximum amount of fluids that neonate can deal with.
Dextrose at a concentration of 12.5 percent or less can be infused through an umbilical arterial catheter.
Patient's fluid should be monitored for volume overload or hyponatremia, diuretics may be indicated if volume overload occured.
Other interventions should be considered if the glucose infusion rate is 12 mg/kg per minute with non-responsive patients:
* Administration of glucagon should be considered patients with persistent plasma glucose <50 mg/dl. [9-12]
* 20 to 30 mcg/kg iv infusion, intramuscular or even subcutaneous to infants with persistent hypoglycemia despite parenteral glucose infusion.[11]
* A repeat dose of glucagon is given if patient didn't respond within 20 minutes of glucagon administration. Glycogen storage disorder should be suspected in these cases.
* Hydrocortisone 2 to 6 mg/kg per day for 2 days only to avoid side effects. It stimulates gluconeogenesis and decrease glucose uptake by cells.
* Diazoxide and somatostatin in patients with hyperinsulinism and pancreatectomy if patient isn't responsive.
When the glucose concentration is stabilized, oral glucose is used by tapering for 4 days but the blood glucose level should be monitored.
==== Asymptomatic patients: ====
The goal of management is to normalize patients blood glucose levels and prevent  them from becoming symptomatic:
'''Oral feeds''' 
Guidelines from the American Association of Pediatrics recommend that oral feeding should be given as quickly as possible for asymptomatic patients: 1
* Blood glucose concentrations should be measured frequently starting 20 to 30 minutes after the initial and subsequent feedings.
* Plasma glucose levels should be greater than 50 to 60 mg/dL to prevent neurological sequales. 22,23
* Infants less than 4 hours of age with plasma glucose <25 mg/dL 
* If plasma glucose concentration fails to increase, parenteral glucose is administered. If the plasma glucose increases to above 25 mg/dL, oral feedings should continue every two to three hours with preprandial measurements of plasma glucose concentration.
* Infants between 4 and 24 hours of age and with plasma glucose <35 mg/dL
* If plasma glucose level fails to increase, parenteral glucose is administered. If the plasma glucose increases to above 35 mg/dL, oral feedings should continue every two to three hours with preprandial measurements of plasma glucose concentration.
* If a patient becomes symptomatic or if plasma glucose fails to increase above 45 mg/dL after three oral feedings, then parenteral glucose should be given.
New evidence showing an association of neurodevelopmental impairment with rapid correction of hypoglycemia has led to a suggested approach of omitting the 2 ml/kg bolus of glucose and simply starting a continuous glucose infusion of 4 to 6 mg/kg/min in '''asymptomatic patients''' with a GA ≥35 weeks and at risk for hypoglycemia (maternal diabetes, large for GA, FGR, and prematurity [GA <37 weeks]) [8]


== References ==
== References ==

Revision as of 16:34, 18 July 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Medical Therapy

Asymptomatic:[1] 

  • Cases with blood glucose of ≤70 mg/dL with regular monitoring.
  • Repeating the measurement in short time.
  • Avoiding critical tasks.
  • Ingesting carbohydrates.
  • adjusting the regimen to avoid other attacks.

Symptomatic:[2]

  • Patients should have source of carbohydrates available all times.
  • 20 grams is usually sufficient to raise the blood glucose.
  • In patients taking alpha-glucosidase inhibitor (acarbose), only dextrose should be used to treat hypoglycemia becuase acarbose slowes digestion of carbohydrates.

Severe: 

  • A subcutaneous or intramuscular injection of 0.5 to 1.0 mg of glucagon will correct hypoglycemia within 15 minutes.
  • If failed this attempt or in severe cases, 25% or 50% dextrose intravenously (IV) followed by subcutaneous glucose.
  • If these measures aren't available:
  • Squeezing a glucose gel in the space between the teeth and buccal mucosa with patient head tilted on side to prevent aspiration.
  • If glucose gel isn't available, putting table sugar under the tongue may save patient.[3]
  • Hypoglycemia due to hormone deficiencies such as hypopituitarism or adrenal insufficiency usually ceases when the appropriate hormone is replaced.
  • Patients with diabetes history who has loss of consciousness and there is no method to determine nature of coma; hypoglycemi or hyperglycemia,then glucose should be given empirically. This will correct hypoglycemia and will not be particularly dangerous if blood glucose concentration is high.
  • Intranasal glucagon was effective in treating insulin-induced hypoglycemia in adults with type 1 diabetes in some studies but it is still under investigation.[4]

Postprandial hypoglycemia:

  • Frequent (every three hours) small meals or snacks.
  • Foods high in fiber, avoiding foods high in sugar.
  • Regular exercise regimen have been recommended.

Insulinoma:

Surgery is the best treatment for insulinoma and other pancreatic masses but if multiple metastases or bad general condition medical therapy is accepted:

  • Diazoxide prevents insulin secretion.[5]
  • Octreotide an analog of somatostatin inhibits the secretion of insulin and glucagon.[6] In patients with failed diazoxide attempts.
  • Everolimus, an inhibitor of the mammalian is option for refractory cases.

Neonatal hypoglycemia:

Goal is to prevent neurologic complications of neonatal hypoglycemia.

Manangement differs between symptomatic and asymptomatic patients:

Symptomatic patients :

The goal is to maintain plasma glucose concentrations >70 mg/dL. 4,5

Guidelines developed by the American Academy of Pediatrics suggest aggresive treatment in these patients because of the neurodevelopmental impairment associated: 2

  • Who are less than 48 hours of life with plasma glucose levels <50 mg/dL 
  • Who are greater than 48 hours of life with plasma glucose levels <60 mg/dL
  • Asymptomatic patients at risk for hypoglycemia or in patients in whom a low glucose concentration was identified as an incidental laboratory finding:
  • Who are less than 4 hours of life with plasma glucose levels <25 to 40 mg/dL (1.4 to 2.2 mmol/L) [1].
  • Who are between 4 and 24 hours of life with plasma glucose <35 to 45 mg/dL (1.9 to 2.5 mmol/L) [1].
  • Who are between 24 and 48 hours of life with plasma glucose levels <45 to 50 mg/dL (2.5 to 2.8 mmol/L) [3].
  • Who are greater than 48 hours of life with plasma glucose levels <60 mg/dL (3.3 mmol/L)
  • In newborns with a suspected or confirmed genetic hypoglycemia disorder (such as a family history of a hypoglycemia disorder or physical exam features consistent with Beckwith-Wiedemann syndrome)

Intravenous bolus of 200 mg/kg dextrose is given over 5 m followed by the continuous administration of parenteral dextrose infusion at a rate of 6 to 8 mg/kg of dextrose per minute. [1,2]

Therapy should be initiated while awaiting laboratory confirmation of low blood glucose levels.[7]

The maximum rate of infusion for treatment is the maximum amount of fluids that neonate can deal with.

Dextrose at a concentration of 12.5 percent or less can be infused through an umbilical arterial catheter.

Patient's fluid should be monitored for volume overload or hyponatremia, diuretics may be indicated if volume overload occured.

Other interventions should be considered if the glucose infusion rate is 12 mg/kg per minute with non-responsive patients:

  • Administration of glucagon should be considered patients with persistent plasma glucose <50 mg/dl. [9-12]
  • 20 to 30 mcg/kg iv infusion, intramuscular or even subcutaneous to infants with persistent hypoglycemia despite parenteral glucose infusion.[11]
  • A repeat dose of glucagon is given if patient didn't respond within 20 minutes of glucagon administration. Glycogen storage disorder should be suspected in these cases.
  • Hydrocortisone 2 to 6 mg/kg per day for 2 days only to avoid side effects. It stimulates gluconeogenesis and decrease glucose uptake by cells.
  • Diazoxide and somatostatin in patients with hyperinsulinism and pancreatectomy if patient isn't responsive.

When the glucose concentration is stabilized, oral glucose is used by tapering for 4 days but the blood glucose level should be monitored.

Asymptomatic patients:

The goal of management is to normalize patients blood glucose levels and prevent them from becoming symptomatic:

Oral feeds 

Guidelines from the American Association of Pediatrics recommend that oral feeding should be given as quickly as possible for asymptomatic patients: 1

  • Blood glucose concentrations should be measured frequently starting 20 to 30 minutes after the initial and subsequent feedings.
  • Plasma glucose levels should be greater than 50 to 60 mg/dL to prevent neurological sequales. 22,23
  • Infants less than 4 hours of age with plasma glucose <25 mg/dL 
  • If plasma glucose concentration fails to increase, parenteral glucose is administered. If the plasma glucose increases to above 25 mg/dL, oral feedings should continue every two to three hours with preprandial measurements of plasma glucose concentration.
  • Infants between 4 and 24 hours of age and with plasma glucose <35 mg/dL
  • If plasma glucose level fails to increase, parenteral glucose is administered. If the plasma glucose increases to above 35 mg/dL, oral feedings should continue every two to three hours with preprandial measurements of plasma glucose concentration.
  • If a patient becomes symptomatic or if plasma glucose fails to increase above 45 mg/dL after three oral feedings, then parenteral glucose should be given.

New evidence showing an association of neurodevelopmental impairment with rapid correction of hypoglycemia has led to a suggested approach of omitting the 2 ml/kg bolus of glucose and simply starting a continuous glucose infusion of 4 to 6 mg/kg/min in asymptomatic patients with a GA ≥35 weeks and at risk for hypoglycemia (maternal diabetes, large for GA, FGR, and prematurity [GA <37 weeks]) [8]

References

  1. Cryer PE (2009). "Preventing hypoglycaemia: what is the appropriate glucose alert value?". Diabetologia. 52 (1): 35–7. doi:10.1007/s00125-008-1205-7. PMID 19018509.
  2. Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L; et al. (2013). "Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society". Diabetes Care. 36 (5): 1384–95. doi:10.2337/dc12-2480. PMC 3631867. PMID 23589542.
  3. Graz B, Dicko M, Willcox ML, Lambert B, Falquet J, Forster M; et al. (2008). "Sublingual sugar for hypoglycaemia in children with severe malaria: a pilot clinical study". Malar J. 7: 242. doi:10.1186/1475-2875-7-242. PMC 2605470. PMID 19025610.
  4. Rickels MR, Ruedy KJ, Foster NC, Piché CA, Dulude H, Sherr JL; et al. (2016). "Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study". Diabetes Care. 39 (2): 264–70. doi:10.2337/dc15-1498. PMC 4722945. PMID 26681725.
  5. Hirshberg B, Cochran C, Skarulis MC, Libutti SK, Alexander HR, Wood BJ; et al. (2005). "Malignant insulinoma: spectrum of unusual clinical features". Cancer. 104 (2): 264–72. doi:10.1002/cncr.21179. PMC 4136659. PMID 15937909.
  6. Aparicio T, Ducreux M, Baudin E, Sabourin JC, De Baere T, Mitry E; et al. (2001). "Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours". Eur J Cancer. 37 (8): 1014–9. PMID 11334727.


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