Glucose metabolism disorders

Question 1

Whipples triad

Answer 1

1. Symptoms consistent with hypoglycemia
2. Low plasma glucose concentration
3. Relief of symptoms after plasma glucose is raised

Question 2

Blood Glucose ≤ 60 mg/dL

Answer 2

Symptoms of hypoglycemia begin (usually
neurogenic autonomic)

Question 3

Blood Glucose ≤ 50 mg/dL

Answer 3

Neuroglycopenia (impaired brain function) manifests

Question 4

Cause of hypoglycemia: Insulinoma

Answer 4

Pancreatic B cell tumor

Question 5

Pancreatic B cell tumor

Answer 5

Insulinoma: Patient experiences neuroglycopenic symptoms of hypoglycemia
* Confusion, blurred vision, diplopia, anxiety, convulsions
* Immediate recovery upon administration of glucose
* Blood glucose < 45 mg/dL
* Serum Insulin ≥ 6 microunit/mL

Question 6

Where are Pancreatic B cell tumors found?

Answer 6

99% found in the pancreas, 1% in ectopic pancreatic tissue

Question 7

Cause of hypoglycemia: Surreptitious administration of insulin or sulfonylureas

Answer 7

Commonly healthcare workers or those with access to a family member’s diabetic medications

Question 8

Why might Surreptitious administration of insulin or sulfonylureas occur?

Answer 8

Factitious disorder (Munchausen’s syndrome ):
Psychiatric disorder characterized by consciously simulated physical or psychological illness & need to assume a sick role for medical attention & emotional support without external incentive or reward

Question 9

Cause of hypoglycemia: Extrapancreatic tumors (rare)

Answer 9

retroperitoneal sarcomas, hepatocellular carcinomas, adrenocortical carcinomas, & miscellaneous epithelial-type tumors
Tumors are frequently large & readily palpated or visualized on CT scans or MRI

Question 10

Cause of hypoglycemia: Functional alimentary hypoglycemia

Answer 10

patient’s symptoms suggest ↑ sympathetic
activity
* Anxiety, weakness, tremor, sweating, or palpitations after meals
* Physical exam & labs are normal*
* *10% of normal patients have glucose levels < 50 mg/dL in a 4-6
hr oral glucose tolerance test

Question 11

Cause of hypoglycemia: Noninsulinoma pancreatogenous hypoglycemia syndrome

Answer 11

Rarely in patients with organic hyperinsulinism, islet cell hyperplasia is present rather than an adenoma
Patients typically have documented hyperinsulinemic hypoglycemia after meals
but not with fasting up to 72 hours

Question 12

Cause of hypoglycemia: Occult diabetes mellitus

Answer 12

Characterized by a delay in early insulin release from pancreatic B cells, resulting in initial exaggeration of hyperglycemia during a glucose tolerance test.
* In response to this hyperglycemia, an exaggerated insulin release produces a late hypoglycemia 4–5 hours after ingestion of glucose
Patients are often obese & frequently have a family history of diabetes mellitus

Question 13

Cause of hypoglycemia: Alcohol-related hypoglycemia

Answer 13

• Hepatic glycogen becomes depleted secondary to malnourishment in alcohol abusers or those unable to ingest food after an acute alcoholic
  episode followed by gastritis & vomiting.
• Exacerbated when combined with alcohol-mediated inhibition of gluconeogenesis

Question 14

Cause of hypoglycemia: Immunopathologic hypoglycemia

Answer 14

extremely rare condition in which anti-insulin
antibodies or antibodies to insulin receptors develop spontaneously

Question 15

Immunopathologic hypoglycemia antibodies

Answer 15

1 Idiopathic anti-insulin antibodies
* mechanism appears to relate to increasing dissociation of insulin from circulating pools of bound insulin, Thus causing hypoglycemia

2 Antibodies to insulin receptors
* most patients do not have hypoglycemia but rather severe insulin-resistant diabetes & acanthosis nigricans.
* However, certain anti-insulin receptor antibodies with agonist activity mimicking insulin action may develop, producing severe hypoglycemia

Question 16

Hypoglycemia medications

Answer 16

• Fluoroquinolones → especially levofloxacin (Levaquin)-acts on ATP sensitive channels in β cells
• Pentamide → antipneuocystis agent, cytotoxic to β-cells. Causes hyperinsulinemia/hypoglycemia & then insulinopenia/hyperglycemia
• Beta-adrenertic blocking agents → inhibits fatty acids & gluconeogenesis substrate release & ↓ plasma glucagon response
  Quinine → Anti-malarial drug
• Salicylates → pain reliever found in Aspirin & hundreds of other OTCs
• ACE inhibitors → ↑ sensitivity to circulating insulin by ↑ blood flow to muscle*

Question 17

Cause of Hypoglycemia: Lactic acidosis

Answer 17

Overproduction (ie tissue hypoxia), Deficient removal (ie liver failure), or both (ie circulatory collapse) causes accumulation. Normally, lactic
acid is converted to glucose in the liver & is returned to muscle cells
Sepsis → severe infection precipitates lactic acidosis → overproduction of
lactic acid

Question 18

Cause of hypoglycemia: Adrenal Insufficiency

Answer 18

• Clinical syndrome caused by failure of the adrenal cortex to synthesize & secrete adequate amounts of glucocorticoid hormones, & is characterized primarily by cortisol deficiency, with or without aldosterone deficiency.
• Addison disease
• Cortisol production is inadequate to control inflammatory response or to meet
  an elevated metabolic demand → hypoglycemia

Question 19

Neurogenic symptoms of hypoglycemia

Answer 19

• Palpitations
• Tremors
• Arousal/anxiety
• Sweating
• Hunger
• Paresthesias
• Nausea
• feelings of warmth

Question 20

Neuroglycopenic symptoms of hypoglycemia

Answer 20

• Behavioral changes
• Dizziness
• Fatigue/Drowsiness
• Difficulty speaking
• Headache
• Trouble concentrating/Confusion
• Blurred vision
• Weakness
• Seizures, loss of consciousness

Question 21

Labs for hypoglycemia

Answer 21

• Glucose
• beta-hydroxybutyrate
• Insulin & Proinsulin
• Circulating oral hypoglycemic agents (sulfonylureas & glinides)
• C-peptide
• Glucose response to glucagon, 1 mg IV
• Insulin antibodies

Question 22

Insulin antibody positivity indicates ____

Answer 22

autoimmune hypoglycemia

Question 23

absence of insulin antibody suggests _____

Answer 23

insulinoma, noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS), post-gastric bypass hypoglycemia (PGBH), or circulating oral hypoglycemic agent

Question 24

insulin < 3 microunits/mL, C-peptide < 0.2 nmol/L (0.6 ng/mL), proinsulin < 5 pmol/L indicates _____

Answer 24

IGF-mediated hypoglycemia (consider nonislet cell tumor, proceed to further dx tests based on suspected tumor type)

Question 25

beta-hydroxybutyrate ≤ 2.7 mmol/L & a post-
glucagon increase in glucose ≥ 25 mg/dL (1.4
mmol/L) Indicates _____

Answer 25

hypoglycemia is mediated
by insulin or insulin-like growth factor (IGF)

Question 26

+ oral hypoglycemic screen, or insulin > 3
microunits/mL & proinsulin < 5 pmol/L
(indicative of exogenous insulin) Suggests _____

Answer 26

factitious hypoglycemia

Question 27

nsulin ≥ 3 microunits/mL, C-peptide ≥ 0.2 nmol/L, & proinsulin ≥ 5 pmol/L Indicates _____

Answer 27

endogenous hyperinsulinism

Question 28

Noninvasive imaging techniques for suspected insulinoma (more useful if tumor size > 1 cm)

Answer 28

• transabdominal ultrasound
• magnetic resonance imaging (MRI),
• multiphase helical computed tomography (CT)
• somatostatin receptor scintigraphy
• glucagon-like peptide 1-receptor (GLP-1) scintigraphy
• positron emission tomography (PET)

Question 29

Invasive techniques for suspected insulinoma imaging

Answer 29

• pancreatic arteriography
• intra-arterial pancreatic calcium stimulation
• endoscopic pancreatic ultrasound
• intraoperative ultrasound
• transhepatic portal venous sampling

Question 30

Treatment of Medication-induced hypoglycemia

Answer 30

discontinue drug or ↓ dose

Question 31

Treatment of Insulinoma

Answer 31

surgery usually preferred, but if not feasible, frequent meals, diazoxide
(anti-insulin), or octreotide (anti GH)

Question 32

Treatment of Non-Insulinoma pancreatogenous hyperinsulinism or post-gastric bypass hypoglycemia

Answer 32

partial pancreatectomy, diazoxide, octreotide,
alpha-glucosidase inhibitors, dietary measures,
&/or intragastric glucose infusion

Question 33

Treatment for hypoglycemia: Nonislet cell tumor

Answer 33

surgical resection, radiotherapy, or
chemotherapy preferred, but if not curative,
glucocorticoid, or octreotide

Question 34

Treatment of hypoglycemia: Cortisol deficiency or growth hormone deficiency

Answer 34

hormone replacement

Question 35

Treatment of Autoimmune hypoglycemia

Answer 35

may be self-limiting, but if not consider high-dose glucocorticoids or other
immunosuppressant medication

Question 36

Treatment of Factitious hypoglycemia

Answer 36

psychiatric evaluation

Question 37

URGENT MANAGEMENT for hypoglycemia

Answer 37

Adults: IV dextrose 50% in water (D50)
Adolescents: 20-50 mL 50% solution
6 mo. – Children: IV 25% dextrose 2-4 mL/kg IV bolus then continue IV until able to eat

Question 38

Urgent Management of hypoglycemia if IV dextrose unavailable

Answer 38

Adults & children ≥ 25 kg (55.1 lbs) (aged 6-8 years: 1 mg IV, intramuscularly, subcutaneously, or intranasally as Baqsimi ® nasal powder
Children < 25 kg (55.1 lbs): 0.5 mg IV, intramuscularly, or subcutaneously
* Repeat dose, if patient does not awaken within 15 minutes
* Emergency care should be accessed for administration of IV dextrose