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{{Hypoglycemia}}
{{Hypoglycemia}}
{{CMG}}
{{CMG}} {{AE}} {{MAD}}
==Overview==
Laboratory investigations of hypoglycemia depend on many tests: [[plasma glucose]] is usually <55-70 mg/dL, [[Insulin|insulin,]] [[c-peptide]], [[proinsulin]], [[sulfonylurea]] screen, [[beta-hydroxybutyrate]], and 24-hour fasting [[Glucose levels low|glucose level]] are another tests that are required to establish the etiology.


==Laboratory Findings==
==Laboratory Findings==
===Defining Hypoglycemia===
===Defining Hypoglycemia===
Hypoglycemia can't be diagnosed only according to blood glucose level because it is misleading maneuver with high false positive results.The measurement should be repeated using a collection tube that contains an inhibitor of glycolysis and processing should not be delayed.
The following three characteristics should be present to diagnose hypoglycemia, which is called [[Whipple's triad]] and include:<ref name="pmid17127144">{{cite journal| author=Guettier JM, Gorden P| title=Hypoglycemia. | journal=Endocrinol Metab Clin North Am | year= 2006 | volume= 35 | issue= 4 | pages= 753-66, viii-ix | pmid=17127144 | doi=10.1016/j.ecl.2006.09.005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17127144  }}</ref>
 
So, Dependence on three characters to diagnose hypoglycemia is the accepted method. It is called Whipple's triad which includes
* Symptoms of hypoglycemia
* Symptoms of hypoglycemia
* A low plasma glucose concentration corellated with symptoms.
* A low [[plasma glucose]] concentration correlated with symptoms
* Correction of glucose level relieves symptoms.
* Correction of [[Glucose levels low|glucose level]] relieves symptoms
Strategy is to seek Whipple's triad under conditions in which hypoglycemia would be expected:
The strategy is to seek [[Whipple's triad]] under conditions in which hypoglycemia would be expected:
* If the symptoms occur in the fasting state, that evaluation should be performed during fasting.
* If symptoms occur in the [[Fasting plasma glucose|fasting state]], that evaluation should be performed during fasting.
* If there is a compelling history of postprandial symptoms, it is reasonable to seek Whipple's triad with frequent, timed plasma glucose measurements and recording of any symptoms after a mixed meal.  
* If there is a compelling history of [[postprandial]] symptoms, it is reasonable to seek [[Whipple's triad]] with frequent, timed plasma [[Blood glucose monitoring|glucose measurements]] and recording of any symptoms after a mixed meal.  
* All of the following should be measured:  
* All of the following should be measured:  
**[[Glucose]]: plasma glucose is usually <55-70 mg/dL.
**[[Insulin]]
**[[C-peptide]]
**[[Proinsulin]]
**[[Sulfonylurea]] and [[Meglitinide|meglitinide screen]]
**[[Beta-hydroxybutyrate]]<ref name="pmid15886243">{{cite journal| author=Service FJ, O'Brien PC| title=Increasing serum betahydroxybutyrate concentrations during the 72-hour fast: evidence against hyperinsulinemic hypoglycemia. | journal=J Clin Endocrinol Metab | year= 2005 | volume= 90 | issue= 8 | pages= 4555-8 | pmid=15886243 | doi=10.1210/jc.2005-0033 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15886243  }}</ref>
{| class="wikitable"
!Fasting evaluation<ref name="pmid19088155">{{cite journal| author=Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER et al.| title=Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. | journal=J Clin Endocrinol Metab | year= 2009 | volume= 94 | issue= 3 | pages= 709-28 | pmid=19088155 | doi=10.1210/jc.2008-1410 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19088155  }}</ref><ref name="pmid11095416">{{cite journal| author=Service FJ, Natt N| title=The prolonged fast. | journal=J Clin Endocrinol Metab | year= 2000 | volume= 85 | issue= 11 | pages= 3973-4 | pmid=11095416 | doi=10.1210/jcem.85.11.6934 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11095416  }}</ref>
!Mixed-meal evaluation<ref name="pmid235895422">{{cite journal| author=Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L et al.| title=Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. | journal=Diabetes Care | year= 2013 | volume= 36 | issue= 5 | pages= 1384-95 | pmid=23589542 | doi=10.2337/dc12-2480 | pmc=3631867 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23589542  }}</ref>
|-
|
* If prolonged fasting results in an episode of symptomatic hypoglycemia, [[plasma glucose]] should be measured repeatedly during fasting.
* If symptoms occur and hypoglycemia is documented, other tests mentioned above should be performed.
* If results are equivocal, patient needs another confirmatory test, such as 72-hour fast.
|
* If symptoms appear within 5 hours after meals, we should suspect postprandial hypoglycemia.<ref name="pmid105009292">{{cite journal| author=Service FJ| title=Diagnostic approach to adults with hypoglycemic disorders. | journal=Endocrinol Metab Clin North Am | year= 1999 | volume= 28 | issue= 3 | pages= 519-32, vi | pmid=10500929 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10500929  }}</ref>
* Recurrent sampling before and after meals for the following 5 hours will help diagnosis; If severe symptoms occur, blood glucose must be measured.
* If [[Whipple's triad]] is demonstrated, [[sulfonylureas]], [[Meglitinide|meglitinides]], and antibodies to insulin should also be measured.
|}


* Glucose: plasma glucose should be <55 mg/dL.
=== [[24-hour|24-hour fasting]] ===
* Insulin
* Increased release of [[glucagon]], [[epinephrine]], and [[cortisol]] are the most important factors that keep [[Blood sugar|blood glucose]] concentrations from falling during fasting.  
* C-peptide
* [[Gluconeogenesis]] is the most important factor of [[glucose]] production after a prolonged fast.<ref name="pmid8755648">{{cite journal| author=Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC| title=Contributions of gluconeogenesis to glucose production in the fasted state. | journal=J Clin Invest | year= 1996 | volume= 98 | issue= 2 | pages= 378-85 | pmid=8755648 | doi=10.1172/JCI118803 | pmc=507441 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8755648  }}</ref>  
* Proinsulin
* If insulin level is high, [[gluconeogenesis]] will be inhibited causing hypoglycemia during fasting.<ref name="pmid6876881">{{cite journal| author=Hogan MJ, Service FJ, Sharbrough FW, Gerich JE| title=Oral glucose tolerance test compared with a mixed meal in the diagnosis of reactive hypoglycemia. A caveat on stimulation. | journal=Mayo Clin Proc | year= 1983 | volume= 58 | issue= 8 | pages= 491-6 | pmid=6876881 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6876881  }}</ref>
* Sulfonylurea and meglitinide screen
* Beta-hydroxybutyrate
Fasting evaluation:
* If prolonged fasting may result in an episode of symptomatic hypoglycemia, plasma glucose should be measured repeatedly during fasting.
* If symptoms occur and hypoglycemia is documented, the other tests mentioned above should be performed.
* If the results are equivocal so patient needs another confirmatry test such as the 72-hour fast.
Mixed-meal evaluation:
* If symptoms appear within 5 hours after meals, we should suspect postprandial hypoglycemia.[2]
* Recurrent sampling before and after meals for the following 5 hours will help diagnosis; If severe symptoms occur, the samples for glucose should be analyzed.
* If Whipple's triad is demonstrated, sulfonylureas, meglitinides, and antibodies to insulin should also be measured.
24-hour fasting
* Increased release of glucagon, epinephrine and cortisol is the most important factors that keep blood glucose concentrations from falling during fasting.  
* Gluconeogenesis is the most important factor of glucose production after prolonged fast[4].
* If there is high level of insulin, gluconeogenesis will be inhibited causing hypoglycemia during fasting.
The fast is ended when:  [1,2]
* 72 hours have passed
* Plasma glucose concentration is ≤45 mg/dL
* Patient has symptoms or signs of hypoglycemia
The precise level of glucose considered low enough to define hypoglycemia is dependent on (1) the measurement method, (2) the age of the person, (3) presence or absence of effects, and (4) the purpose of the definition. While there is no disagreement as to the normal range of blood sugar, debate continues as to what degree of hypoglycemia warrants medical evaluation or treatment, or can cause harm.<ref name="Koh_1988">{{cite journal |author=Koh TH, Eyre JA, Aynsley-Green A |title=Neonatal hypoglycaemia--the controversy regarding definition |journal=Arch. Dis. Child. |volume=63 |issue=11 |pages=1386-8 |year=1988 |pmid=3202648}}</ref><ref name="Cornblath_1990">{{cite journal |author=Cornblath M, Schwartz R, Aynsley-Green A, Lloyd JK |title=Hypoglycemia in infancy: the need for a rational definition. A Ciba Foundation discussion meeting |journal=Pediatrics |volume=85 |issue=5 |pages=834-7 |year=1990 |pmid=2330247}}</ref><ref name="Cornblath_2000">{{cite journal |author=Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC |title=Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds |journal=Pediatrics |volume=105 |issue=5 |pages=1141-5 |year=2000 |pmid=10790476}}</ref>


=== Identifing the cause ===
* The fasting should be stopped in any of the following conditions: <ref name="pmid10500929">{{cite journal| author=Service FJ| title=Diagnostic approach to adults with hypoglycemic disorders. | journal=Endocrinol Metab Clin North Am | year= 1999 | volume= 28 | issue= 3 | pages= 519-32, vi | pmid=10500929 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10500929  }}</ref>
After confirmation of hypoglycemia. Physicians should have history, signs and laboratory reuslts sufficient to help them to identify the cause of hypoglycemia:
**Seventy-two hours have passed
**[[Plasma glucose]] concentration is ≤45 mg/dL
**Patient has symptoms or signs of hypoglycemia
* The precise level of [[glucose]] considered low enough to define hypoglycemia is dependent on:<ref name="Cornblath_1990">{{cite journal |author=Cornblath M, Schwartz R, Aynsley-Green A, Lloyd JK |title=Hypoglycemia in infancy: the need for a rational definition. A Ciba Foundation discussion meeting |journal=Pediatrics |volume=85 |issue=5 |pages=834-7 |year=1990 |pmid=2330247}}</ref><ref name="Cornblath_2000">{{cite journal |author=Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC |title=Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds |journal=Pediatrics |volume=105 |issue=5 |pages=1141-5 |year=2000 |pmid=10790476}}</ref>
**Measurement method
**Age
 
=== Identifying the cause ===
The following table describes the possible causes of hypoglycemia.
{| class="wikitable"
{| class="wikitable"
!
!
!Plasma insulin
!Plasma insulin<ref name="pmid17609405">{{cite journal| author=Vezzosi D, Bennet A, Fauvel J, Caron P| title=Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycaemia related to endogenous hyperinsulinism. | journal=Eur J Endocrinol | year= 2007 | volume= 157 | issue= 1 | pages= 75-83 | pmid=17609405 | doi=10.1530/EJE-07-0109 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17609405  }}</ref>
!C-peptide
!C-peptide<ref name="pmid17609405" />
!proinsulin
!proinsulin
!Sulfonylurea in plasma
!Sulfonylurea in plasma
!insulin or insulin receptor antibodies
!insulin or insulin receptor antibodies
!Postprandial symptoms
!Postprandial symptoms
!Fating symptoms
!Fasting symptoms
|-
|-
|insulinoma
|[[Insulinoma]]
|high
|High
|high
|High
|high
|High
| -
| -
| -
| -
Line 61: Line 69:
| +
| +
|-
|-
|oral hypoglycemia agent-induced
|[[Oral hypoglycemics]]<ref name="pmid9056803">{{cite journal| author=Perros P, Henderson AK, Carter DC, Toft AD| title=Lesson of the week. Are spontaneous hypoglycaemia, raised plasma insulin and C peptide concentrations, and abnormal pancreatic images enough to diagnose insulinoma? | journal=BMJ | year= 1997 | volume= 314 | issue= 7079 | pages= 496-7 | pmid=9056803 | doi= | pmc=2125998 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9056803  }}</ref>
|high
|High
|high
|High
|high
|High
| + [16]
| +  
| -
| -
| -
| -
| -
| -
|-
|-
|autoimmune hypoglycemia.
|[[Autoimmune]] hypoglycemia<ref name="pmid19440117">{{cite journal| author=Lupsa BC, Chong AY, Cochran EK, Soos MA, Semple RK, Gorden P| title=Autoimmune forms of hypoglycemia. | journal=Medicine (Baltimore) | year= 2009 | volume= 88 | issue= 3 | pages= 141-53 | pmid=19440117 | doi=10.1097/MD.0b013e3181a5b42e | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19440117  }}</ref>
|high
|High
|high
|High
|high
|High
| -
| -
| + [17]
| +  
| -
| -
| -
| -
|-
|-
|NIPHS*
|[[NIPHS]]*
|high
|High
|high
|High
|high
|High
| -
| -
| -
| -
Line 88: Line 96:
| -
| -
|-
|-
|exogenous insulin
|Exogenous [[insulin]]
|high
|High
|low
|Low
|low
|Low
| -
| -
| -
| -
Line 97: Line 105:
| -
| -
|-
|-
|nonislet cell tumors
|[[Non-islet|Non-islet cell tumors]]
|low
|Low
|low
|Low
|low
|Low
| -
| -
| -
| -
Line 106: Line 114:
| -
| -
|}
|}
<nowiki>*</nowiki>(NIPHS) noninsulinoma pancreatogenous hypoglycemia syndrome
<nowiki>*</nowiki>(NIPHS) non-insulinoma pancreatogenous hypoglycemia syndrome


=== Neonatal hypoglycemia: ===
=== Neonatal hypoglycemia: ===
Most of neonatal hypoglycemias is transient but in
Most of the neonatal hypoglycemias are transient but suspected cases as following should be investigated for metabolic diseases: 
* Hypoglycemia that requires prolonged high rates of [[dextrose]] infusion
* Persistent hypoglycemia
* [[Neurological|Neurologic]] symptoms
* History or physical findings suggestive of metabolic disease


Symptomatic patients with plasma glucose is <50 mg/dl.
==== '''What to measure?''' ====
 
* Measure plasma insulin, plasma [[C-peptide]] and [[beta-hydroxybutyrate]]
Asymptomatic patients with plasma glucose <40 mg/dl.
* [[PH|Blood pH,]] [[bicarbonate]], and [[lactate]]
* Measure plasma insulin, plasma C-peptide and beta-hydroxybutyrate.
* [[Free fatty acids]], [[Acylcarnitine hydrolase|acylcarnitine profile]], plasma free and total [[Carnitine|carnitine levels]]  
* Blood pH, bicarbonate and lactate
* Free fatty acids, acylcarnitine profile, plasma free and total carnitine levels
 
* growth hormone and cortisol.
* Urine organic acids and and serum amino acids.
Surveys of healthy children and adults show that plasma glucoses below 60 mg/dL (3.3 mM) or above 100 mg/dL (5.6 mM) are found in less than 5% of samples after an overnight fast.<ref name="Meites">{{cite book |author=Samuel Meites, editor-in-chief; contributing editors, Gregory J. Buffone... [et al.] |title=Pediatric clinical chemistry: reference (normal) values |publisher=AACC Press |location=Washington, D.C |year=1989 |pages= |isbn=0-915274-47-7 |oclc= |doi=}}</ref> In infants and young children up to 10% have been found to be below 60 mg/dL after an overnight fast. As the duration of fasting is extended, plasma glucose levels can fall further, even in healthy people. In other words, many healthy people can occasionally have glucose levels in the hypoglycemic range without symptoms or disease.


* [[Growth hormone]] and [[Cortisol]]
* [[Urine organic acids]] and [[Amino acids|serum amino acids]]
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
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Latest revision as of 14:37, 16 November 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Overview

Laboratory investigations of hypoglycemia depend on many tests: plasma glucose is usually <55-70 mg/dL, insulin, c-peptide, proinsulin, sulfonylurea screen, beta-hydroxybutyrate, and 24-hour fasting glucose level are another tests that are required to establish the etiology.

Laboratory Findings

Defining Hypoglycemia

The following three characteristics should be present to diagnose hypoglycemia, which is called Whipple's triad and include:[1]

The strategy is to seek Whipple's triad under conditions in which hypoglycemia would be expected:

Fasting evaluation[3][4] Mixed-meal evaluation[5]
  • If prolonged fasting results in an episode of symptomatic hypoglycemia, plasma glucose should be measured repeatedly during fasting.
  • If symptoms occur and hypoglycemia is documented, other tests mentioned above should be performed.
  • If results are equivocal, patient needs another confirmatory test, such as 72-hour fast.
  • If symptoms appear within 5 hours after meals, we should suspect postprandial hypoglycemia.[6]
  • Recurrent sampling before and after meals for the following 5 hours will help diagnosis; If severe symptoms occur, blood glucose must be measured.
  • If Whipple's triad is demonstrated, sulfonylureas, meglitinides, and antibodies to insulin should also be measured.

24-hour fasting

  • The fasting should be stopped in any of the following conditions: [9]
    • Seventy-two hours have passed
    • Plasma glucose concentration is ≤45 mg/dL
    • Patient has symptoms or signs of hypoglycemia
  • The precise level of glucose considered low enough to define hypoglycemia is dependent on:[10][11]
    • Measurement method
    • Age

Identifying the cause

The following table describes the possible causes of hypoglycemia.

Plasma insulin[12] C-peptide[12] proinsulin Sulfonylurea in plasma insulin or insulin receptor antibodies Postprandial symptoms Fasting symptoms
Insulinoma High High High - - - +
Oral hypoglycemics[13] High High High + - - -
Autoimmune hypoglycemia[14] High High High - + - -
NIPHS* High High High - - + -
Exogenous insulin High Low Low - - - -
Non-islet cell tumors Low Low Low - - - -

*(NIPHS) non-insulinoma pancreatogenous hypoglycemia syndrome

Neonatal hypoglycemia:

Most of the neonatal hypoglycemias are transient but suspected cases as following should be investigated for metabolic diseases:

  • Hypoglycemia that requires prolonged high rates of dextrose infusion
  • Persistent hypoglycemia
  • Neurologic symptoms
  • History or physical findings suggestive of metabolic disease

What to measure?

References

  1. ↑ Guettier JM, Gorden P (2006). "Hypoglycemia". Endocrinol Metab Clin North Am. 35 (4): 753–66, viii–ix. doi:10.1016/j.ecl.2006.09.005. PMID 17127144.
  2. ↑ Service FJ, O'Brien PC (2005). "Increasing serum betahydroxybutyrate concentrations during the 72-hour fast: evidence against hyperinsulinemic hypoglycemia". J Clin Endocrinol Metab. 90 (8): 4555–8. doi:10.1210/jc.2005-0033. PMID 15886243.
  3. ↑ Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER; et al. (2009). "Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab. 94 (3): 709–28. doi:10.1210/jc.2008-1410. PMID 19088155.
  4. ↑ Service FJ, Natt N (2000). "The prolonged fast". J Clin Endocrinol Metab. 85 (11): 3973–4. doi:10.1210/jcem.85.11.6934. PMID 11095416.
  5. ↑ 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.
  6. ↑ Service FJ (1999). "Diagnostic approach to adults with hypoglycemic disorders". Endocrinol Metab Clin North Am. 28 (3): 519–32, vi. PMID 10500929.
  7. ↑ Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC (1996). "Contributions of gluconeogenesis to glucose production in the fasted state". J Clin Invest. 98 (2): 378–85. doi:10.1172/JCI118803. PMC 507441. PMID 8755648.
  8. ↑ Hogan MJ, Service FJ, Sharbrough FW, Gerich JE (1983). "Oral glucose tolerance test compared with a mixed meal in the diagnosis of reactive hypoglycemia. A caveat on stimulation". Mayo Clin Proc. 58 (8): 491–6. PMID 6876881.
  9. ↑ Service FJ (1999). "Diagnostic approach to adults with hypoglycemic disorders". Endocrinol Metab Clin North Am. 28 (3): 519–32, vi. PMID 10500929.
  10. ↑ Cornblath M, Schwartz R, Aynsley-Green A, Lloyd JK (1990). "Hypoglycemia in infancy: the need for a rational definition. A Ciba Foundation discussion meeting". Pediatrics. 85 (5): 834–7. PMID 2330247.
  11. ↑ Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC (2000). "Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds". Pediatrics. 105 (5): 1141–5. PMID 10790476.
  12. ↑ 12.0 12.1 Vezzosi D, Bennet A, Fauvel J, Caron P (2007). "Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycaemia related to endogenous hyperinsulinism". Eur J Endocrinol. 157 (1): 75–83. doi:10.1530/EJE-07-0109. PMID 17609405.
  13. ↑ Perros P, Henderson AK, Carter DC, Toft AD (1997). "Lesson of the week. Are spontaneous hypoglycaemia, raised plasma insulin and C peptide concentrations, and abnormal pancreatic images enough to diagnose insulinoma?". BMJ. 314 (7079): 496–7. PMC 2125998. PMID 9056803.
  14. ↑ Lupsa BC, Chong AY, Cochran EK, Soos MA, Semple RK, Gorden P (2009). "Autoimmune forms of hypoglycemia". Medicine (Baltimore). 88 (3): 141–53. doi:10.1097/MD.0b013e3181a5b42e. PMID 19440117.
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