Endocrine Pharm

Question 1

What is the differential diagnosis for a sick, stressed infant with poor feeding and increased blood sugars?

Answer 1

Sepsis, SGA, stress response, genetic disorders, inborn errors of metabolism

Iatrogenic causes may include parenteral glucose, prematurity, IUGR, insulin resistance.

Question 2

What are common findings of neonatal diabetes?

Answer 2

Macroglossia, umbilical hernia

These findings may indicate complications associated with neonatal diabetes.

Question 3

What genetic finding was associated with the first case of neonatal diabetes?

Answer 3

Chromosome 6q24 overexpression

Question 4

What characterizes Transient Neonatal Diabetes Mellitus (TNDM)?

Answer 4

Overexpression of paternal chromosome 6q24, usually spontaneous remission in the first year

Question 5

What are common gene mutations associated with Persistent Neonatal Diabetes Mellitus (PNDM)?

Answer 5

KCNJ11, ABCC8, INS

Question 6

What is the mechanism of action of insulin?

Answer 6

Acts as an anabolic agent, promoting fuel storage by binding to receptors in muscle, fat, and liver

Question 7

What are the side effects of insulin administration?

Answer 7

Hypoglycemia, electrolyte shift (hypokalemia)

Insulin increases Na-K ATPase activity, causing potassium to shift intracellularly.

Question 8

What are the indications for insulin therapy?

Answer 8

Persistent hyperglycemia (>14 mmol/L), severe hyperglycemia (>20 mmol/L)

Question 9

What is the starting dose of insulin for neonates?

Answer 9

0.2-0.3 U/kg/day (divided hourly)

Question 10

What does the glucagon stimulation test diagnose?

Answer 10

Hyperinsulinism

Question 11

What is the mechanism of action of glucagon?

Answer 11

Binds to G protein-coupled receptors in the liver, increases cAMP, triggers glycogen catabolism

Question 12

What is the recommended initial dose for diazoxide in hyperinsulinism?

Answer 12

5-15 mg/kg/day divided BID or TID

Question 13

What is a common treatment for hypoglycemia in newborns?

Answer 13

Dextrose gel, 0.5 ml/kg

Should be administered to newborns who can tolerate oral intake.

Question 14

What is the significance of c-peptide in insulin testing?

Answer 14

More stable than insulin; provides a long-term representation of insulin secretion

Question 15

What are the types of subcutaneous insulin?

Answer 15

Short Acting: Lispro, Aspart; Long Acting: Glargine

Short acting insulins peak at 2 hours, while long acting has a duration of 24 hours.

Question 16

What factors can contribute to neonatal diabetes?

Answer 16

Genetic disorders, iatrogenic causes, stress response

Includes conditions like prematurity and insulin resistance.

Question 17

What is the role of GLUT-4 in insulin action?

Answer 17

Facilitates glucose entry into cells for energy storage

Question 18

What are the potential side effects of glucagon?

Answer 18

Nausea, vomiting, transient increase in BP/HR, potential hypokalemia

Question 19

What is the effect of insulin on fat metabolism?

Answer 19

Inhibits fat breakdown (lipolysis) and promotes fat storage

Question 20

What is the critical blood glucose level for initiating glucagon stimulation testing?

Answer 20

<2.8 mmol/L

Question 21

What is a potential risk of insulin therapy?

Answer 21

Rebound hypoglycemia after glucagon administration

Question 22

What is the structure of insulin?

Answer 22

51 amino acids, 2 chains connected by disulfide bonds

Question 23

What characterizes congenital hyperinsulinism?

Answer 23

Persistent, severe hyperinsulinism, with identifiable genetic causes in 40% of cases

Question 24

Fill in the blank: Insulin is released within _______ of a blood glucose increase.

Answer 24

5-10 minutes

Question 25

What is insulinism?

Answer 25

Persistent, severe hyperinsulinism ## Footnote Genetic causes are identifiable in 40% of children, with the majority being ABCC8/KCNJ11 mutations.

Question 26

What is the mechanism of insulin release?

Answer 26

kATP channel closes → insulin release

Question 27

What is the effect of Diazoxide on the kATP channel?

Answer 27

Opens the kATP channel ## Footnote This repolarizes the cell membrane and inhibits insulin release.

Question 28

What is the dosing recommendation for Diazoxide?

Answer 28

5-15 mg/kg/d divided BID or TID

Question 29

What side effects are associated with Diazoxide?

Answer 29

* Fluid overload * Electrolyte abnormalities * Pulmonary hypertension * Congestive heart failure * Pulmonary edema * Hyperuricemia * Neutropenia * Thrombocytopenia * Hypertrichosis

Question 30

What GIR value suggests hyperinsulinism?

Answer 30

GIR > 10

Question 31

What is a key test for evaluating hypoglycemia?

Answer 31

Glucagon stimulation test

Question 32

What are the normal serum calcium and ionized calcium levels?

Answer 32

* Serum calcium: 1.8-2.9 mmol/l * Ionized calcium: 0.9-1.3 mmol/l

Question 33

What is the treatment for symptomatic hypocalcemia?

Answer 33

IV calcium bolus

Question 34

What are the consequences of hypocalcemia?

Answer 34

* Muscle spasm * Tetany * Laryngospasm * Bronchospasm * Cardiac failure * Irritability * Seizures * Apnea

Question 35

What is the preferred form of calcium for treatment?

Answer 35

Calcium gluconate

Question 36

What are the indications for Thyroxine?

Answer 36

* Congenital hypothyroidism * NMS * Central hypothyroidism

Question 37

What is the difference between T3 and T4 in terms of activity?

Answer 37

T3 is the active thyroid hormone, while T4 is a prohormone of T3.

Question 38

What hormone reflects the body's bioavailable thyroid hormone?

Answer 38

T4

Question 39

How does T3 affect cellular actions?

Answer 39

* Increased oxygen consumption * Enhanced fatty acid oxidation * Protein synthesis * Cholesterol synthesis

Question 40

What is the dosing recommendation for Thyroxine?

Answer 40

10-15 mcg/kg/day

Question 41

What are the signs of hyperthyroidism due to over-treatment?

Answer 41

* Irritable * Poor feeding * Difficulty sleeping * Increased stool frequency * Tachycardia

Question 42

What are the key follow-up actions for Thyroxine treatment?

Answer 42

* Repeat labs 2-4 weeks * Target normal TSH if congenital hypothyroidism * Target FT4 in upper limit of normal if central hypothyroidism

Question 43

Fill in the blank: The key mechanism of action for calcium in the body is _______.

Answer 43

Vital nutrient for muscle contraction

Question 44

True or False: T4 binds more tightly to binding proteins than T3.

Answer 44

True

Question 45

What does pulse oximetry measure?

Answer 45

% of saturated hemoglobin to oxygen

Question 46

What is the optimal level of oxygenation aimed to prevent?

Answer 46

Hypoxia or hyperoxia

Question 47

What is hypoxia?

Answer 47

Occurs when oxygen supply is inadequate to meet the demands of the peripheral tissues

Question 48

List the causes of hypoxia.

Answer 48

* Inadequacy of oxygenation (passive diffusion from alveolus to pulmonary capillary) * Inadequate oxygen delivery (transport from lungs to peripheral tissues) * High oxygen consumption by the tissues

Question 49

What did the NeOProM meta-analysis find regarding target oxygen saturation?

Answer 49

Higher target range of oxygen saturation (91-95) decreases risk of death and NEC but increases ROP treatment and BPD

Question 50

What can oxygen cause due to oxidative stress?

Answer 50

Imbalance between free radicals and antioxidants in the body

Question 51

What are reactive oxygen species (ROS)?

Answer 51

Regulators of intracellular signaling pathways that modulate DNA and RNA synthesis, protein synthesis, and enzyme activation

Question 52

What are the effects of oxidative stress?

Answer 52

* Cell membrane damage * Lipid peroxidation * Protein and DNA oxidation * Apoptosis

Question 53

What is oxidative stress injury?

Answer 53

A cellular condition that occurs as a result of physiological imbalance between the level of antioxidants and oxidants in favor of oxidants

Question 54

What makes preterm brains more susceptible to free radicals?

Answer 54

* Immaturity of detoxifying enzyme systems * High lipid content * High oxygen consumption * High metabolic rate

Question 55

What role does oxidative stress play in BPD and PPHN?

Answer 55

Recognized as a critical factor

Question 56

What are targeted oxygen saturations for BPD?

Answer 56

Even in the delivery room

Question 57

What contributes to increased gut permeability in NEC?

Answer 57

Combination of NO with superoxide anion

Question 58

What happens during Phase 1 of ROP development?

Answer 58

Retinal vascularization is inhibited due to hyperoxia and loss of nutrients

Question 59

What stimulates retinal neovascularization during Phase 2 of ROP?

Answer 59

Hypoxic retina stimulating expression of EPO and VEGF

Question 60

What is Bevacizumab (Avastin) used for?

Answer 60

Treatment of stage 3+ ROP

Question 61

What is the mechanism of action of Bevacizumab?

Answer 61

Binds to and neutralizes vascular endothelial growth factor (VEGF)

Question 62

What are the side effects of Bevacizumab?

Answer 62

* Hypertension * Hypotension * Peripheral edema * Pain * Dehydration * Hyperglycemia * Proteinuria * UTI

Question 63

What is chylothorax?

Answer 63

Accumulation of lymphatic fluid in the pleural cavity

Question 64

What are the primary causes of congenital chylothorax?

Answer 64

* Trisomy * Hydrops * Congenital heart disease (CHD)

Question 65

What is the role of Octreotide?

Answer 65

Somatostatin analog used in chylothorax and other conditions

Question 66

What are the properties of Octreotide?

Answer 66

* Dosing: 1-20 mcg/kg/hr * Absorption: rapid and complete * IV bioavailability: 100%

Question 67

What are the side effects of Octreotide?

Answer 67

* Bradycardia * Abdominal pain * Fatigue * Headache * Fever

Question 68

What is Sildenafil used for?

Answer 68

Management of congenital chylothorax and pulmonary hypertension

Question 69

How does Sildenafil work?

Answer 69

Prevents degradation of cGMP by selective inhibition of phosphodiesterase-5