Hypoglycemia laboratory findings: Difference between revisions
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{{CMG}} {{AE}} {{MAD}} | {{CMG}} {{AE}} {{MAD}} | ||
==Overview== | ==Overview== | ||
Laboratory investigations of hypoglycemia | Laboratory investigations of hypoglycemia depend on many tests: plasma glucose should be <55 mg/dL, insulin, c-peptide, proinsulin, sulfonylurea screen, beta-hydroxybutyrate, 24-hour fasting and identifying the cause after that. | ||
==Laboratory Findings== | ==Laboratory Findings== | ||
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* A low plasma glucose concentration correlated with symptoms. | * A low plasma glucose concentration correlated with symptoms. | ||
* Correction of glucose level relieves symptoms. | * Correction of glucose level relieves symptoms. | ||
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 the symptoms occur in the 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 glucose measurements and recording of any symptoms after a mixed meal. | ||
| Line 24: | Line 24: | ||
* Sulfonylurea and meglitinide screen | * Sulfonylurea and meglitinide screen | ||
* Beta-hydroxybutyrate | * Beta-hydroxybutyrate | ||
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> | {| 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> | |||
!Mixed-meal evaluation | |||
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* If prolonged fasting may result in an episode of symptomatic hypoglycemia, plasma glucose should be measured repeatedly during fasting. | * 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 symptoms occur and hypoglycemia is documented, the other tests mentioned above should be performed. | ||
* If the results are equivocal so patient needs another confirmatory test such as the 72-hour fast. | * If the results are equivocal so the patient needs another confirmatory test such as the 72-hour fast. | ||
|<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 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> | * 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, the samples for glucose should be analyzed. | * 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. | * If Whipple's triad is demonstrated, sulfonylureas, meglitinides, and antibodies to insulin should also be measured. | ||
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24-hour fasting | 24-hour fasting | ||
* Increased release of glucagon, epinephrine and cortisol is the most important factors that keep blood glucose concentrations from falling during fasting. | * Increased release of glucagon, epinephrine and cortisol is the most important factors that keep blood glucose concentrations from falling during fasting. | ||
Revision as of 16:26, 27 July 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 should be <55 mg/dL, insulin, c-peptide, proinsulin, sulfonylurea screen, beta-hydroxybutyrate, 24-hour fasting and identifying the cause after that.
Laboratory Findings
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.
So, Dependence on three characters to diagnose hypoglycemia is the accepted method. It is called Whipple's triad which includes
- Symptoms of hypoglycemia
- A low plasma glucose concentration correlated with symptoms.
- Correction of glucose level relieves symptoms.
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 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.
- All of the following should be measured:
- Glucose: plasma glucose should be <55 mg/dL.
- Insulin
- C-peptide
- Proinsulin
- Sulfonylurea and meglitinide screen
- Beta-hydroxybutyrate
| Fasting evaluation:[1] | Mixed-meal evaluation |
|---|---|
|
[2]
|
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: [5]
- 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:[6][7]
- Measurement method
- Age of the person
- Presence or absence of effects
- The purpose of the definition.
Identifing the cause
After confirmation of hypoglycemia. Physicians should have history, signs and laboratory reuslts sufficient to help them to identify the cause of hypoglycemia:
| Plasma insulin | C-peptide | proinsulin | Sulfonylurea in plasma | insulin or insulin receptor antibodies | Postprandial symptoms | Fating symptoms | |
|---|---|---|---|---|---|---|---|
| insulinoma | high | high | high | - | - | - | + |
| oral hypoglycemia agent-induced | high | high | high | + [8] | - | - | - |
| autoimmune hypoglycemia. | high | high | high | - | + [9] | - | - |
| NIPHS* | high | high | high | - | - | + | - |
| exogenous insulin | high | low | low | - | - | - | - |
| nonislet cell tumors | low | low | low | - | - | - | - |
*(NIPHS) noninsulinoma pancreatogenous hypoglycemia syndrome
Neonatal hypoglycemia:
Most of 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 metablic disease
What to measure?
- Measure plasma insulin, plasma C-peptide and beta-hydroxybutyrate.
- Blood pH, bicarbonate, and lactate
- Free fatty acids, acylcarnitine profile, plasma free and total carnitine levels
- growth hormone and cortisol.
- Urine organic acids and serum amino acids.
Surveys of healthy children and adults show that plasma glucoses below 60 mg/dL or above 100 mg/dL are found in less than 5% of samples after an overnight fast.[10]
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.
References
- ↑ 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.
- ↑ 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.
- ↑ Service FJ (1999). "Diagnostic approach to adults with hypoglycemic disorders". Endocrinol Metab Clin North Am. 28 (3): 519–32, vi. PMID 10500929.
- ↑ 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.
- ↑ Service FJ (1999). "Diagnostic approach to adults with hypoglycemic disorders". Endocrinol Metab Clin North Am. 28 (3): 519–32, vi. PMID 10500929.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Samuel Meites, editor-in-chief; contributing editors, Gregory J. Buffone... [et al.] (1989). Pediatric clinical chemistry: reference (normal) values. Washington, D.C: AACC Press. ISBN 0-915274-47-7.