Approach to Approach to HypoglycemiaHypoglycemia

Diabetics and NonDiabetics and Non--DiabeticsDiabetics

IncidenceIncidence

ØØ In (DCCT), In (DCCT), 1010--3030% % of type of type 1 1 diabetics per yeardiabetics per year

ØØ Of those,Of those,1010% require % require 33rdrd party Interventionparty Intervention

ØØ In the (UKPDS),(In the (UKPDS),(3030--3535%%)of type )of type 2 2 diabetics on Insulin diabetics on Insulin require require 33rdrd party Interventionparty Intervention

CausesCauses

DrugsDrugsØØ InsulinInsulin-- most common cause,most common cause,ØØ Timing, dose,Timing, dose, typetypeØØ clearance of insulin (eg, renal failure); clearance of insulin (eg, renal failure); ØØ altered counter regulation altered counter regulation ØØ SulfonylureasSulfonylureasØØ Metformin does Metformin does notnot cause hypoglycemiacause hypoglycemiaØØ High dose salicylates, b High dose salicylates, b ––blockers, quinine,quinolonesblockers, quinine,quinolones

Renal failureRenal failure

ØØ Second gluconeogenic organSecond gluconeogenic organØØ decreased clearance of renally excreted drugs or their metabolites decreased clearance of renally excreted drugs or their metabolites

(eg, insulin, chlorpropamide, metabolite of glyburide)(eg, insulin, chlorpropamide, metabolite of glyburide)

Hepatic FailureHepatic Failure

ØØ Decreased glycogenolysis Decreased glycogenolysis ØØ Decresed gluconeogenesisDecresed gluconeogenesisØØ Large functional reserve,( Large functional reserve,( 2020% % func required to prevent func required to prevent

hypoglycemia)hypoglycemia)ØØ Genetic defects in glycometabolic pathwaysGenetic defects in glycometabolic pathwaysØØ Finally, compromised drug metabolism (tolbutamide, glyburide, Finally, compromised drug metabolism (tolbutamide, glyburide,

glipizide )glipizide )

Endocrinopathies Endocrinopathies

ØØ Adrenal (glucocorticoid)Adrenal (glucocorticoid) insufficiencyinsufficiency

ØØ Growth hormone deficiencyGrowth hormone deficiency

ØØ Glucagon deficiency Glucagon deficiency

ØØ Pituitary disease ( decreased combined corticotropin and GH Pituitary disease ( decreased combined corticotropin and GH deficiecy)deficiecy)

Poisoning Poisoning ((ethanol, propanolol,ethanol, propanolol, salicylates)salicylates)

ØØ Ethanol inhibits gluconeogenesisEthanol inhibits gluconeogenesis

ØØ EthanolEthanol--induced induced hypoglycemiahypoglycemia occurs occurs 1212--72 72 hrs after ingestionhrs after ingestion

NeoplasmNeoplasmØØ NonNon––isletislet--cell tumors cell tumors ØØ Mesenchymal tumors, Mesenchymal tumors, ØØ hepatocellular carcinoma, hepatocellular carcinoma, ØØ adrenocortical tumors, adrenocortical tumors, ØØ carcinoid tumors, carcinoid tumors, ØØ leukemia, and lymphomasleukemia, and lymphomasØØ Most of these tumors secrete IGF Most of these tumors secrete IGF ––II moleculeII moleculeØØ Some also secrete GlucagonSome also secrete Glucagon-- like peptide(GLPlike peptide(GLP--11) and Somatostatin ) and Somatostatin

Insulinoma Insulinoma ØØ Pancreatic βPancreatic β--cell tumors that secrete Insulincell tumors that secrete InsulinØØ Small,solitary, benign(Small,solitary, benign( < < 1010% % malignant)malignant)

Inability of insulinoma cells to suppress insulin secretion during low Inability of insulinoma cells to suppress insulin secretion during low levels of circulating glucose, leading to severe hypoglycemialevels of circulating glucose, leading to severe hypoglycemia

Diagnosis and Tumor LocalizationDiagnosis and Tumor LocalizationØØ Very high Insulin levelsVery high Insulin levelsØØ spiral CT,spiral CT, arteriography, ultrasonography arteriography, ultrasonography

Treatment of ChoiceTreatment of ChoiceØØ EnucleationEnucleationØØ Recurrence at Recurrence at 10 10 yrs is yrs is 66% % and and 20 20 yrs is yrs is 1010%%

Islet Hyperplasia Islet Hyperplasia

ØØ Also called nesidioblastosis or diffuse islet hyperplasiaAlso called nesidioblastosis or diffuse islet hyperplasiaor the syndrome of noninsulinoma pancreatogenous hyperinsulinismor the syndrome of noninsulinoma pancreatogenous hyperinsulinism

ØØ Represent hyperplastic processes and budding of islet cells from Represent hyperplastic processes and budding of islet cells from ducts (nesidioblastosis). Now interpreted as precursor to MEN ducts (nesidioblastosis). Now interpreted as precursor to MEN 11, , with molecular evidence.with molecular evidence.

ØØ Heterozygous knockout of the Heterozygous knockout of the MENMEN11 gene in the mouse show gene in the mouse show multiple giant hyperplastic islets that precede insulinoma. multiple giant hyperplastic islets that precede insulinoma.

ØØ Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), these Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), these infants have an identifiable genetic mutations in sulfonylurea infants have an identifiable genetic mutations in sulfonylurea receptor receptor 1 1 (SUR(SUR11) ,potassium channel Kir) ,potassium channel Kir66..22, glucokinase., glucokinase.

Autoimmune causesAutoimmune causes

ØØ AntiAnti--insulin receptor antibodyinsulin receptor antibodyØØ Rarely, Rarely, hypoglycemiahypoglycemia is caused by autoantibodies that bind the is caused by autoantibodies that bind the

insulin receptor and mimic the biologic action of insulin insulin receptor and mimic the biologic action of insulin ØØ Most patients have elevated ESR, +ve ANAMost patients have elevated ESR, +ve ANA

ØØ AntiAnti--insulin antibodyinsulin antibodyØØ autoantibodies against insulin bind free circulating plasma insulin autoantibodies against insulin bind free circulating plasma insulin

when its concentration is high and release insulin when the when its concentration is high and release insulin when the concentration of free plasma insulin drops.concentration of free plasma insulin drops.

ØØ Release of insulin at inappropriate times can cause Release of insulin at inappropriate times can cause hypoglycemiahypoglycemia..

SymptomsSymptoms

Adrenergic Symptoms Adrenergic Symptoms ØØ usually seen early with a rapid decline usually seen early with a rapid decline inin blood glucose and include blood glucose and include

tachycardia, tachypnea, vomiting, and diaphoresis tachycardia, tachypnea, vomiting, and diaphoresis

NeuroglycopenicNeuroglycopenicØØ usually associated with slower or prolonged usually associated with slower or prolonged hypoglycemia, hypoglycemia, include include

poor feeding, altered mental status, lethargy, and seizures poor feeding, altered mental status, lethargy, and seizures

Classification of HypoglycemiaClassification of Hypoglycemia

Fasting Fasting hypoglycemiahypoglycemia occurs in the postabsorptive period occurs in the postabsorptive period (ie, hours after a meal)(ie, hours after a meal)

Reactive (Reactive (postprandialpostprandial) ) hypoglycemiahypoglycemia. .

ØØ Reactive Reactive hypoglycemiahypoglycemia is controversial is controversial

ØØ low postprandial plasma glucose levels alone are not low postprandial plasma glucose levels alone are not sufficient sufficient

ØØ 1010% % to to 3030% % of normal individuals undergoing oral GTT of normal individuals undergoing oral GTT have plasma glucose <have plasma glucose <50 50 mg/Dl, with no symptoms mg/Dl, with no symptoms

ØØ Only patients with severe (eg, loss of consciousness, Only patients with severe (eg, loss of consciousness, traumatic injury or accident) attributed to postprandial traumatic injury or accident) attributed to postprandial hypoglycemiahypoglycemia require further workup. require further workup.

Dumping Syndrome/ Alimentary HypolycemiaDumping Syndrome/ Alimentary Hypolycemia

ØØ Alimentary Alimentary hypoglycemiahypoglycemia presents presents 2 2 hrs after a mealhrs after a meal

Pathophysiology Pathophysiology ØØ disruption of controlled gastric emptyingdisruption of controlled gastric emptyingØØ decreased transit time decreased transit time ØØ rapid elevation in plasma glucose that triggers rapid elevation in plasma glucose that triggers

exaggerated insulin response. exaggerated insulin response. ØØ abnormal insulin then causes a precipitous drop in blood abnormal insulin then causes a precipitous drop in blood

glucoseglucose

Pathophysiology of HypoglycemiaPathophysiology of Hypoglycemia

Responses to Hypoglycemia is our ability to suppress insulin in Responses to Hypoglycemia is our ability to suppress insulin in response to hypoglycemiaresponse to hypoglycemia

ØØ In DiabeticsIn Diabetics, , it does not occur as Insulin is supplied exogenouslyit does not occur as Insulin is supplied exogenously

ØØ Main defense is increased release of counterregulatory hormones, as Main defense is increased release of counterregulatory hormones, as Glucagon, Epinephrine, Cortisol, and Growth hormone Glucagon, Epinephrine, Cortisol, and Growth hormone

ØØ Glucagon Glucagon stimulates both glycogenolysis and gluconeogenesisstimulates both glycogenolysis and gluconeogenesis

ØØ EpinephrineEpinephrine acts via ßacts via ß--adrenergic receptors and stimulates adrenergic receptors and stimulates glycogenoalysis and gluconeogenesisglycogenoalysis and gluconeogenesis

ØØ Also acts on alphaAlso acts on alpha--22--receptors to inhibit insulin secretionreceptors to inhibit insulin secretion

ØØ Cortisol and Growth hormoneCortisol and Growth hormone contribute only after prolonged contribute only after prolonged hypoglycemia by limiting peripheral uitilization of glucose.hypoglycemia by limiting peripheral uitilization of glucose.

Counterregulatory effects of Epinephrine during Hypoglycemia

ØØ Glucagon and epinephrine secretion rises when plasma Glucagon and epinephrine secretion rises when plasma glucose concentrations fall below glucose concentrations fall below 65 65 to to 70 70 mg/dL (mg/dL (33..6 6 to to 33..9 9 mmol/L)mmol/L)

ØØ Growth hormone secretion increases when plasma Growth hormone secretion increases when plasma glucose concentrations fall below glucose concentrations fall below 60 60 to to 65 65 mg/dL (mg/dL (33..3 3 to to 33..6 6 mmol/L)mmol/L)

ØØ Cortisol secretion increases when plasma glucose Cortisol secretion increases when plasma glucose concentrations fall below concentrations fall below 60 60 mg/dL (mg/dL (33..3 3 mmol/L).mmol/L).

Hypoglycemia UnawarenessHypoglycemia Unawareness

5050% % of type of type 1 1 patients undergo diminution in their epinephrine response patients undergo diminution in their epinephrine response to hypoglycemia,to hypoglycemia,

Further patients lose the autonomic warning symptoms of hypoglycemia Further patients lose the autonomic warning symptoms of hypoglycemia and may recognize (or even fail to recognize) the condition only when and may recognize (or even fail to recognize) the condition only when somatic neurologic function becomes impaired. somatic neurologic function becomes impaired.

Usually associated with duration of diabetes and autonomic neuropathyUsually associated with duration of diabetes and autonomic neuropathy

May also occur when patients are switched to intensive insulin regimens. May also occur when patients are switched to intensive insulin regimens.

The introduction of intensified treatment regimens can lower the glucose The introduction of intensified treatment regimens can lower the glucose level that triggers epinephrine release and adrenergic symptoms.level that triggers epinephrine release and adrenergic symptoms.

The DCCT trial showed that even brief periods of antecedent The DCCT trial showed that even brief periods of antecedent hypoglycemia can suppress counterhypoglycemia can suppress counter--regulatory responses during regulatory responses during subsequent hypoglycemic episodes.subsequent hypoglycemic episodes.

DiagnosisDiagnosis

Establishing the causeEstablishing the causeØØ History (liver failure, sepsis, autoimmune disease, neoplasm, alcohol, History (liver failure, sepsis, autoimmune disease, neoplasm, alcohol,

drugs)drugs)

Establishing fasting hypoglycemiaEstablishing fasting hypoglycemiaØØ Supervised Supervised 72 72 hour fast testhour fast testØØ In hospital setting to lower risk to the patient In hospital setting to lower risk to the patient ØØ Usually hypoglycemia develops in first Usually hypoglycemia develops in first 48 48 hours of the fast in hours of the fast in 9595% of % of

casescases

7272--HOUR FASTHOUR FASTProtocolProtocol

ØDate the onset of the fast as the time of the last intake of calories

Ø Discontinue all non essential medications

ØAllow the patient to drink calorie-free and caffeine-free beverages

ØCollect blood specimens for measurement of plasma glucose, insulin, C-peptide, and proinsulin every six hours until the plasma glucose concentration is below 60 mg/dL (3.3 mmol/L) at this point, the frequency of sampling should be increased to every one to two hours.

Test end points and durationTest end points and duration

ØØ the plasma glucose concentration is ≤the plasma glucose concentration is ≤45 45 mg/dL (mg/dL (22..5 5 mmol/L) mmol/L)

ØØ the patient has symptoms or signs of hypoglycemia, the patient has symptoms or signs of hypoglycemia, ØØ 72 72 hours have elapsed, hours have elapsed, ØØ or when the plasma glucose concentration is less than or when the plasma glucose concentration is less than

55 55 mg/dL (mg/dL (3 3 mmol/L) if Whipple's triad is presentmmol/L) if Whipple's triad is presentØØ Plasma betaPlasma beta--hydroxybutyrate and sulfonylurea levels are hydroxybutyrate and sulfonylurea levels are

measuredmeasuredØØ 1 1 mg of glucagon is given intravenously and the plasma mg of glucagon is given intravenously and the plasma

glucose measured glucose measured 1010, , 2020, and , and 30 30 minutes later.minutes later.

ØØ In normal subjects, the following thresholds have been identified in In normal subjects, the following thresholds have been identified in graded glucose reductionsgraded glucose reductions

ØØ Insulin secretion decreases,(BG < Insulin secretion decreases,(BG < 8080), followed by increase in ), followed by increase in Glucagon and Epinephrine, growth hormone( BG <Glucagon and Epinephrine, growth hormone( BG <6565) and Cortisol ) and Cortisol (BG<(BG<6060)respectively )respectively

ØØ Normal subjects do not have symptomatic hypoglycemia after a Normal subjects do not have symptomatic hypoglycemia after a prolonged fast because prolonged fast because

ØØ Gluconeogenesis accounts for approximately Gluconeogenesis accounts for approximately 50 50 percent of glucose percent of glucose production after an overnight fast and for almost all glucose production after an overnight fast and for almost all glucose production after production after 42 42 hours or more of fastinghours or more of fasting

Interpretation of values after 72 hour test

ØØ ].].

Relation of Plasma Glucose and Proinsulin

Hypoglycemia Pathway

Principles of TreatmentPrinciples of Treatment

Principles of therapyPrinciples of therapy

ØØ Priority in treating hypoglycemia to maintain plasma glucose geater Priority in treating hypoglycemia to maintain plasma glucose geater than than 50 50 mg/dl, either snacks vs IV dextrosemg/dl, either snacks vs IV dextrose

ØØ The second priority is to address the underlying cause. removal or The second priority is to address the underlying cause. removal or adjustment of the offending drug, appropriate hormone replacement adjustment of the offending drug, appropriate hormone replacement for patients with deficiency, resection of the tumor in Insulioma.for patients with deficiency, resection of the tumor in Insulioma.

ØØ Patients with autoantibodies against the insulin receptor can be Patients with autoantibodies against the insulin receptor can be treated with hightreated with high--dose glucocorticoid (prednisone, dose glucocorticoid (prednisone, 60 60 mg/d) to mg/d) to prevent prevent hypoglycemiahypoglycemia

ØØ Most episodes of asymptomatic hypoglycemia and mild to moderate Most episodes of asymptomatic hypoglycemia and mild to moderate symptomatic hypoglycemia are effectively selfsymptomatic hypoglycemia are effectively self--treated by ingestion treated by ingestion of glucose tablets or carbohydrate in the form of juices, soft drinks, of glucose tablets or carbohydrate in the form of juices, soft drinks, milk, crackers, candy, or a meal.milk, crackers, candy, or a meal.

ØØ A commonly recommended dose of glucose is A commonly recommended dose of glucose is 1616--20 20 g of oral g of oral glucose.glucose.

ØØ However, the glycemic response to oral glucose is transient, usually However, the glycemic response to oral glucose is transient, usually less than less than 2 2 hours in insulinhours in insulin--induced hypoglycemiainduced hypoglycemia

ØØ Parenteral treatment is necessary when a hypoglycemic patient is Parenteral treatment is necessary when a hypoglycemic patient is unable or unwilling (because of neuroglycopenia) to take unable or unwilling (because of neuroglycopenia) to take carbohydrate orally. carbohydrate orally.

ØØ Most common Most common 1 1 amp of Damp of D5050,(?glucose),(?glucose)

ØØ Glucagon is commonly injected subcutaneously or intramuscularly Glucagon is commonly injected subcutaneously or intramuscularly standard dose, standard dose, 1 1 mg .mg .

ØØ less useful in Tless useful in T22DM than it is in TDM than it is in T11DM as stimulates insulin secretionDM as stimulates insulin secretion

ØØ Hypoglycemia related to endogenous hyperinsulinism is often curable Hypoglycemia related to endogenous hyperinsulinism is often curable by the surgical removal of an insulinoma. by the surgical removal of an insulinoma.

ØØ If this is not possible because of multiple or metastatic tumors, If this is not possible because of multiple or metastatic tumors, Diazoxide can be used, (Diazoxide can be used, (100100--800 800 mg/day) raises the plasma glucose mg/day) raises the plasma glucose concentration by suppressing insulin secretion.concentration by suppressing insulin secretion.

ØØ Side effects include hypotension,brain edema,, gastrointestinal side Side effects include hypotension,brain edema,, gastrointestinal side effects effects

ØØ Other treatments include octreotide or calcium channel antagonistsOther treatments include octreotide or calcium channel antagonists

ØØ Sort term treatment of hypoglycemia associated with nonSort term treatment of hypoglycemia associated with non––beta cell beta cell tumors involves shorttumors involves short--term measures pending effective medical, term measures pending effective medical, surgical, or radiotherapeutic treatment can be done by glucocorticoid surgical, or radiotherapeutic treatment can be done by glucocorticoid or growth hormone or growth hormone

ØØ Remissions of autoimmune hypoglycemias have been associated with Remissions of autoimmune hypoglycemias have been associated with immunosuppressive therapy, including glucocorticoids, but controlled immunosuppressive therapy, including glucocorticoids, but controlled trials are lacking. trials are lacking.

ØØ The treatment of hypoglycemia related to hepatic or renal disease, The treatment of hypoglycemia related to hepatic or renal disease, cardiac failure, or sepsis includes shortcardiac failure, or sepsis includes short--term measures and, treatment term measures and, treatment or management of the underlying disease process. or management of the underlying disease process.

Hypoglycemic ComaHypoglycemic Coma

Recovery from hypoglycemia may be delayed, because of cerebral Recovery from hypoglycemia may be delayed, because of cerebral edema. Unconsciousness lasting more than edema. Unconsciousness lasting more than 30 30 minutes after plasma minutes after plasma glucose is corrected is called posthypoglycemic coma, IV mannitol (glucose is corrected is called posthypoglycemic coma, IV mannitol (40 40 g as a g as a 2020% % solution over solution over 20 20 minutes) or glucocorticoids (e.g., minutes) or glucocorticoids (e.g., dexamethasone, dexamethasone, 10 10 mg), or both can be used along with maintenance mg), or both can be used along with maintenance of normal plasma glucose levelsof normal plasma glucose levels

CASE CASE 11 —— A A 3939--yearyear--old man was referred for evaluation of repeated episodes of old man was referred for evaluation of repeated episodes of sweating, slurred speech, and confusion during the last four years that could sweating, slurred speech, and confusion during the last four years that could be aborted by eating. On two occasions, he drove his car off the side of the be aborted by eating. On two occasions, he drove his car off the side of the road; both times he was found to be confused, his serum glucose road; both times he was found to be confused, his serum glucose concentrations ranged from concentrations ranged from 30 30 to to 40 40 mg/dL (mg/dL (11..7 7 to to 22..2 2 mmol/L), and he mmol/L), and he improved after intravenous glucose administration.improved after intravenous glucose administration.After fasting for After fasting for 12 12 hours, he began to sweat and became confused and hours, he began to sweat and became confused and combative. Serum values at that time were as follows:combative. Serum values at that time were as follows:Glucose Glucose -- 22 22 mg/dLmg/dLInsulin Insulin -- 110 110 microU/mL (microU/mL (660 660 pmol/L)pmol/L)CC--peptide peptide -- 3200 3200 pmol/L (pmol/L (00..0303--1 1 nmol/L)nmol/L)Proinsulin Proinsulin -- 800 800 pmol/L (pmol/L (22--31 31 pmol/L)pmol/L)Glucose increase after Glucose increase after glucagonglucagon -- 39 39 mg/dL (mg/dL (22..2 2 mmol/L)mmol/L)Sulfonylurea Sulfonylurea –– negativenegative

What is the nost likely Diagnosis?What is the nost likely Diagnosis?A) Surreptious Insulin useA) Surreptious Insulin useB) Antibodies to Insulin receptorB) Antibodies to Insulin receptorC) InsulinomaC) InsulinomaD) None of the aboveD) None of the above

ØØ CommentComment —— This is a classic case of insulinoma. The patient was healthy but had episodes of This is a classic case of insulinoma. The patient was healthy but had episodes of neuroglycopenia. Whipple's triad (symptoms of hypoglycemia, low serum glucose concentrations at the neuroglycopenia. Whipple's triad (symptoms of hypoglycemia, low serum glucose concentrations at the same time, and relief of symptoms by glucose administration) was satisfied. That the hypoglycemia was same time, and relief of symptoms by glucose administration) was satisfied. That the hypoglycemia was caused by endogenous insulin was confirmed by the high serum insulin, Ccaused by endogenous insulin was confirmed by the high serum insulin, C--peptide and proinsulin peptide and proinsulin concentrations, and supported by the low serum betaconcentrations, and supported by the low serum beta--hydroxybutyrate concentration and the small rise in hydroxybutyrate concentration and the small rise in serum glucose after intravenous serum glucose after intravenous glucagonglucagon administration.administration.

CASE CASE 22 —— A A 2727--yearyear--old man was referred by his local physician for evaluation of old man was referred by his local physician for evaluation of hypoglycemia found incidentally during a workhypoglycemia found incidentally during a work--up for peptic ulcer disease. up for peptic ulcer disease. Past medical history included gastric by pass surgery for morbid obesity Past medical history included gastric by pass surgery for morbid obesity 2 2 years ago. During the last four months, he had several episodes of weakness years ago. During the last four months, he had several episodes of weakness and feeling "shaky inside" late in the evening. During the night he would and feeling "shaky inside" late in the evening. During the night he would periodically drink soda. When symptomatic, reflectance meter blood glucose periodically drink soda. When symptomatic, reflectance meter blood glucose values measured by the patient using equipment purchased for his sevenvalues measured by the patient using equipment purchased for his seven--yearyear--old daughter (diagnosed with type old daughter (diagnosed with type 1 1 diabetes one year earlier) had been in the diabetes one year earlier) had been in the range of range of 40 40 to to 50 50 mg/dL (mg/dL (22..2 2 to to 22..8 8 mmol/L). Serum values after an overnight mmol/L). Serum values after an overnight fast were:fast were:Glucose Glucose -- 36 36 mg/dL (mg/dL (22..0 0 mmol/L)mmol/L)Insulin Insulin -- 140 140 microU/mL (microU/mL (840 840 pmol/L)pmol/L)CC--peptide peptide -- <<33 33 pmol/L(pmol/L(00..0303--11nmol/L)nmol/L)Proinsulin Proinsulin -- 00..9 9 pmol/L(pmol/L(22--31 31 pmol/L)pmol/L)

What is he most likely diagnosis?What is he most likely diagnosis?A)A) InsulinomaInsulinomaB)B) Insulin antibodiesInsulin antibodiesC)C) Exogenous Insulin administrationExogenous Insulin administrationD)D) Alimentary hypoglycemiaAlimentary hypoglycemia

The low serum CThe low serum C--peptide and proinsulin values indicate that the hyperinsulinemia peptide and proinsulin values indicate that the hyperinsulinemia ((140 140 microU/mL (microU/mL (840 840 pmol/L)) was due to exogenous insulin administration.pmol/L)) was due to exogenous insulin administration.

Thanks.Thanks.

ØØ CASE CASE 88 —— A A 7676--yearyear--old woman was referred for the evaluation of postprandial adrenergic old woman was referred for the evaluation of postprandial adrenergic symptoms with occasional visual changes. There was one episode of confusion while on a symptoms with occasional visual changes. There was one episode of confusion while on a telephone call to her daughter. During an episode of light headedness, sweating, weakness and telephone call to her daughter. During an episode of light headedness, sweating, weakness and irritability two hours after breakfast (which occurred while under observation), serum values were irritability two hours after breakfast (which occurred while under observation), serum values were as follows:as follows:

ØØ GlucoseGlucose 51 51 mg/dl (mg/dl (22..8 8 mmol/L) mmol/L) InsulinInsulin 66..4 4 microU/mL (microU/mL (4545..9 9 pmol/L) pmol/L) CC--peptidepeptide 22..6 6 ng/mLng/mL ((858 858 pmol/L) pmol/L) BetahydroxybutyrateBetahydroxybutyrate 00..1 1 mmol/L mmol/L Glucose increase after Glucose increase after glucagonglucagon 46 46 mg/dL (mg/dL (22..6 6 mmol/L) mmol/L) SulfonylureaSulfonylurea negative negative

ØØ A mixed meal test was performed because of the presence of postprandial symptoms A mixed meal test was performed because of the presence of postprandial symptoms accompanied by biochemical evidence of insulinaccompanied by biochemical evidence of insulin--mediated hypoglycemia. Biochemical testing mediated hypoglycemia. Biochemical testing 180 180 minutes after a mixed meal revealed the following:minutes after a mixed meal revealed the following:

ØØ GlucoseGlucose 43 43 mg/dl (mg/dl (22..4 4 mmol/L) mmol/L) InsulinInsulin 2222..0 0 microU/ml (microU/ml (157157..8 8 pmol/L) pmol/L) CC--peptidepeptide 44..7 7 ng/ml (ng/ml (1551 1551 pmol/L) pmol/L)

ØØ The biochemical tests confirmed insulinThe biochemical tests confirmed insulin--mediated hypoglycemia. The differential diagnosis mediated hypoglycemia. The differential diagnosis included noninsulinoma pancreatogenous hypoglycemia (Islet cell hypertrophy/nesidioblastosis), included noninsulinoma pancreatogenous hypoglycemia (Islet cell hypertrophy/nesidioblastosis), which is associated with postprandial hypoglycemia, insulin autoimmune hypoglycemia which is associated with postprandial hypoglycemia, insulin autoimmune hypoglycemia (postprandial or fasting hypoglycemia), or insulinoma, which more commonly presents as fasting (postprandial or fasting hypoglycemia), or insulinoma, which more commonly presents as fasting hypoglycemia. (hypoglycemia. (See "Noninsulinoma pancreatogenous hypoglycemia"See "Noninsulinoma pancreatogenous hypoglycemia" and and see "Insulinoma"see "Insulinoma").).