Endocrine- Hypoglcemia And Neonatal Glucose Metabolism

Front 1

What glucose level will trigger autonomic responses and the sequential secretion of counterregulatory hormones?

What are the counterreg hormones?

Back 1

Glucose <67

-Glucagon, Catecholamine, GH, Cortisol, Acetylcholine

Front 2

What is the major hormone post-parandially?

What tissues are principally favored for Glucose uptake?

Back 2

Insulin (glucose disposal into tissues for storage). Major ANABOLIC hormone.

FAVORED=
Muscle (30%)*
Liver (30-50%)*
Brain (20%)

*require insulin for glucose utilization

Front 3

What is the major hormone in the post-absorptive state?

What tissues are principally favored for Glucose uptake? What about for glucose breakdown?

Back 3

Glucagon

FAVORED= Brain (insulin is not required for uptake of glucose)

Glucose PROVIDED by: Liver (80%), Kidney (20%)

Front 4

What is the first phase in the post- absorptive state? When does it begin and when does it deplete?

What happens to patients who have cirrhosis or non-functional livers?

Back 4

Glycogenolysis (in liver) *Glucagon

Starts 6hrs post meal. It depletes after 48-72 hours. Then Gluconeogenesis takes over.

80% of loss of liver leads to Hepatic hypoglycemia.

Front 5

What organs contribute to Gluconeogenesis?

Catecholamines stimulate what tissue in this phase?

Back 5

Liver and Kidney (after 72 hr fast it can contribute as much as liver!)

No glycogen. Stimulated by Catecholamines (Glucagon doesn't affect RENAL gluconeo).

Front 6

Why should you NEVER give a glucagon shot to someone with renal failure?

Back 6

It won't be useful (because glucagon triggers gluconeogenesis in the LIVER which is defective in this person). You need to give catecholamines so they can stimulate the kidney.

Front 7

What substrates are important for gluconeogenesis and where are they coming from?

Back 7

Glycerol (Adipose tissue)
Alanine, Lactate (AA from Muscle, blood cells)

Front 8

How does Adipose tissue contribute to correct the hypoglycemic state?

What is the role of muscle in correcting the hypoglycemic state?

Back 8

Adipose- makes glycerol from triacyl glycerols. Glycerol can enter gluconeogenesis or go through ketogenesis, or Kreb's cylce.

Muscle produces lactate from proteolysis but also DECREASES glucose uptake (so it can get to areas where it is important, ex: the brain)

Front 9

What is the key hormone affecting recovery from ACUTE hypoglycemia?

What is the major backup system for this hormone?

Back 9

Glucagon- important in acute hypoglycemia recovery

Epinephrine (Catecholamines)

Front 10

What are warning signs and what hormone controls them?

Back 10

Tachycardia, Tremor, Anxiety

Adrenergic symptoms triggered by Catecholamines, that alerts patient to hypoglycemic state.

Front 11

What is the effect of catecholamines on glucagon?

Back 11

Stimulates glucagon (thus glycogenolysis, gluconeogenesis, etc.)

Front 12

In conditions where cortisol is low (panhypopituitarism, sheehan syndrome, addison's disease, etc.) what is the effect on blood sugar?

Back 12

Hypoglycemia results (cortisol stimulates gluconeogenesis, lypolysis- tries to keep plasma glucose high!)

ACTH and growth hormone similarly do that.

Front 13

What is the role of Acetylcholine in the hypoglycemic response?

Back 13

It provides the warning

PARASYMP.: increases stomach motility, produces HUNGER

SYMPATHETIC: increases sweating from sympathetic nerves

Front 14

What is Whipple's triad?

Back 14

Rules for distinguishing "TRUE hypoglycemia" :

1. Sxs and signs of hypoglycemia
2. glucose <45
3. reversibility of symptoms after giving back glucose

Front 15

What might cause a person to have symptoms of hypoglycemia at a much higher glucose level?

What might cause a person to have symptoms of hypoglycemia at a much LOWER level?

Back 15

Sxs @ higher glucose level:
1. Elderly (compromised blood flow)
2. Chronic hyperglycemia (downregulate glucose transport across BBB)


Sxs @ lower glucose level:
1. Chronic hyPOglycemia (ex: insulinoma)
2. Upregulation of glucose transporter across BBB
3. Hypoglycemia unawareness

Front 16

What are some signs and symptoms of Neuroglycopenia?

Back 16

weakness, lethargy, confusion, incoordination --> eventually coma and convulsion

Front 17

Fasting hypoglycemia WITH hyperinsulinemia can be caused by a number of different things.

What are some examples?

Back 17

- Diabetes over-zealous treatment with insulin/ sulfonylurea
- Facticious (uncalled for administration of insulin)
- Insulinoma
- Meds (propranolol etc.)
- Autoimmune conditions with activating insulin antibodies

Front 18

Why would pregnancy cause a hypoglycemic state?

What about Renal insufficiency?

Back 18

Pregnancy- fetus is consuming glucose (might not need as much insulin)

Renal insufficiency: insulin doesn't get cleared and remains in circulation

Front 19

An otherwise healthy healthcare worker is found in the ER to be tachycardic, anxious and sweating. You do a blood glucose, it is low.

What is the most likely source of his presentation and what confirmatory testing would you do?

Back 19

Factitious Hypoglycemia (healthcare worker- access to meds, otherwise healthy- not diabetic)

Get Insulin, C peptide and Pro-insulin levels. All very high (indistinguishable from insulinoma). Get sulfonylurea tox screen.

Front 20

What are some meds that can cause hypoglycemia?

Back 20

Propranolol (B blocker- inhibits warning signs and gluconeogenesis as well)

ACE inhibitors (increase insulin sensitivity)

Pentamidine *lyse Beta cells

Salicylates: increase insulin secretion, inhibit hepatic glucose

Sulfonamides: act like sulfonylureas

Front 21

What is an insulinoma and if someone has one, what genetic syndrome might you want to test them for?

Back 21

Insulin secreting tumor of Pancreas (islets). Should have high insulin and low glucose. (patients may have lower threshold for hypoglycemia since they are used to hypoglycemic state).

May be part of MEN1

Front 22

What is the most reliable test for an insulinoma?

What would a person with an Insulinoma's C peptide, proinsulin, and B-hydroxybutyrate levels be?

Back 22

72 hour fast- check for increase in serum insulin (typically it should be decreased because no food).

*REMEMBER: when you suspect excess of something, suppress it!

Insulin high, C peptide high (means it's endogenously produced), proinsulin high, Ketones low (suppressed by insulin)

Front 23

Fasting Hypoglycemia WITHOUT insulinemia can be a result of what two scenarios?

Back 23

1. Hepatic tissue damage (unable to sustain gluconeogenesis, amino acids supply, etc.)

2. Nonpancreatic tumor that secretes IGF-II (mimick's insulin and increases glucose uptake by binding to receptors but isn't insulin).

Front 24

Why does alcohol consumption cause hypoglycemia?

Back 24

- It decreases gluconeogenesis
- Depeletes glycogen stores
- Causes neuroglycopenic symptoms that are difficult to distinguish from EtOH intoxication (less aware of warning signs)

Front 25

Nonfasting hypoglycemia= Reactive hypoglycemia

Explain how Postgastrectomy/bypass can cause this?

Back 25

Glucose rich food bypasses stomach and goes straight to L cells. This stimulates GLP-1 and GIP release (incretins) that stimulate Insulin release and hypoglycemia.

Front 26

What is late hypoglycemia?

Back 26

Delayed insulin rise that occurs several hours (4-5) after eating a meal. This can cause hypoglycemia in the pre-diabetic.

*usually obese pt with family history

Front 27

All of the following conditions can cause hypoglycemia (glucose <45). What would you expect the levels of Insulin, C peptide, and Proinsulin to be in the case of:

Insulinoma
Facticious
Sulfonylurea
IGFII mediated
Non-insulin

Back 27

Insulinoma: I= high, C= high, Pro= high

Facticious: I=high, C=normal/low, Pro= normal/low

Sulfonylurea: I= high, C= high, Pro= high * looks indistinguishable from insulinoma

Front 28

What does the C-peptide vs Insulin level indicate to you?

How do you distinguish a non-insulin mediated cause of hypoglycemia with a simple lab test?

Back 28

Whether the insulin source is endogenous or exogenous. Endogenous= Insulin high and so is C-peptide. Exogenous= Insulin is high, C-peptide is not.

Look for ketones (insulin suppresses ketones so if it's not insulin, ketones should be norma).

Front 29

What are the two main the treatments for hyperinsulinemia (too much insulin)?

Back 29

Diazoxide (stabilize ATP K+ channel and inhibit depolarization/ insulin secretion)

Octreotide (somatostatin analog).

Front 30

Which hyperinsulinemia medication causes hypertrichosis?

Which decreases gallbladder contractility and causes cholelithiasis?

Back 30

Hypertrich (hairy)- Diazoxide

Gallbladder sxs- Octreotide

Front 31

What is glucagon used for?

How would you treat an insulinoma? If all major treatments fail, what is your last resort?

Back 31

Glucagon- used for initial management of hypoglycemic infants

Tumor resection= 1st line for insulinoma. If all fails, use STREPTOZOCIN (severely toxic, destroys malignant B-cells).

Front 32

How does the pre-birth and post-birth environment differ for the neonate with respect to glucose?

Back 32

Constant glucose supply (in utero) --> intermittent glucose (birth + beyond)

Front 33

What changes in hormones occur at birth to keep the neonate euglycemic?

Back 33

Everything to preserve glucose:

- Catecholamines, glucagon, GH go up

-Insulin decreases

Front 34

When evaluating a neonate or infant for hypoglycemia, should you rely more on numbers of symptoms?

Back 34

Numbers (glucose <40)
This is because they have variable symptoms (some can be subtle, some profound)

ex: cyanosis, poor feeding, myoclonic jerks, subnormal temperature, sweating, etc.

Front 35

What are some risk factors for Transient neonatal hypoglycemia?

Back 35

*very common

Prematurity, small growth age, Intrauterine growth retardation, severe respiratory distress, Infant of diabetic mother (glucose passes from mom to baby)

Front 36

What would you expect the levels of cortisol, insulin, and Growth hormone to be in a child with glucose of 20?

What would you suspect if cortisol and GH were not elevated? What about if insulin was not elevated?

Back 36

Insulin- low
Cortisol- high
GH- high

*if cortisol and GH are not elevated: think about hypopit
* if insulin is not elevated: r/o insulinoma

Front 37

Diagnosis of hypoglycemia in a neonate should always involve what 3 components?

Back 37

1. detailed history
2. physical exam
3. labs

--> goal: to determine if this is endocrine or metabolic (limited substrates)

Front 38

What physical exam features might suggest a neonate has glycogen storage problems?

What about adrenal problems (low cortisol)?

Back 38

Glycogen storage- hepatosplenomegaly

Adrenal disorder- hyperpigmentation (high ACTH binds to Melanocyte receptor)

- also midline defects if you supsect pituitary developmental problem and Beckwith Wiedman Syndrome associated phenotypes.

Front 39

Inactivating mutations in the SUR1 and Kir6.2 gene can cause what syndrome in children?

Why is it good to know the genetic basis of the disease?

Back 39

Inactivate the K+ receptor in B cells (permanent closure)- can cause excess insulin release and hypoglycemia.

It helps to know gene basis because it can change treatment. These kids should meds like Diazoxide- binds channel and opens it!

Front 40

What is a treatment besides Diazoxide that can be given to children with persistent hyperinsulinemic hypoglycemia?

Back 40

Octreotide: Somatostatin analog (bids to beta cell receptors and suppress insulin secretion)

Front 41

What is the definition of Neonatal diabetes mellitus?

What are the two variants of this syndrome?

Back 41

Hyperglycemia within first month of life, lasting >2 weeks and requiring insulin.

Transient NDM
Permanent NDM

Front 42

What genetic abnormality is associated with Transient Neonatal DM?

What about Permanent Neonatal DM?

Back 42

Abnormality of Chromosome 6
-uniparental disomy, duplication, or methylation defect

Homozygous gene mutation in Pdx-1 (transcription factor involved in pancreatic formation) and IPF-1a. Complete deficiency of glucokinase.

Front 43

An activating mutation of the K+ ATP channel causes what syndrome in the neonate?

What drugs should be used to treat this?

Back 43

Neonatal Hyperglycemia. Activating mutation in Kir6.2, it's open all the time, Insulin does not get released.

Treat with Sulfonylurea.

Front 44

At the time of diagnosis, what genetic tests should be obtained for babies with hyperglycemia?

What will each test indicate if positive?

Back 44

- check chromosome 6 (if positive, it's Transient NDM)

- Kir 6.2- likely permanent
-SUR 1- likely permanent
* but, child will respond to oral meds!