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UNIVERSITY OF ILLINOIS AT CHICAGO
PEDIATRIC ENDOCRINE MANAGEMENT PROTOCOLS
Prepared by Dr. S. Pang , Dr. Ize-Ludlow ,and Dr. Shindu Kannan, and Nipapat V
Updated June –Aug /2010
Contents
I.
ADRENAL CRISIS(ALL UPDATED) ........................................................................................................... 2
II.
CALCIUM DISORDERS(UPDATE IN PROGRESS/THIS IS UNUPDATED VERSION) ..................... 6
HYPOCALCEMIA ........................................................................................................................................................ 6
HYPERCALCEMIA .................................................................................................................................................... 11
III.
GLUCOSE DISORDERS(ALL UPDATED) ................................................................................................ 14
HYPOGLYCEMIA........................................................................................................................................................ 14
DIABETES MELLITUS ............................................................................................................................................... 24
A.
Diabetic Ketoacidosis .............................................................................................................................. 24
B.
Diabetic Ketosis Only.............................................................................................................................. 30
C.
Nonketotic Hyperglycemic Hyperosmolar state--------------------------------------------------------------30
D.
Surgical Management of the Diabetic Patient ...................................................................................... 32
VI.
THYROID DISORDERS(ALL UPDATED) ................................................................................................ 33
Congenital Hypothyroidism ....................................................................................................................................... 33
Myxedema Coma ........................................................................................................................................................ 34
Hyperthyroid Storm ................................................................................................................................................... 35
Neonatal Grave's Disease (Thyrotoxicosis)............................................................................................................... 36
V. PERSITENT DYSFUNTIONAL BLEEDING IN ADOLESCENT FEMALE(NEW)------------------------38
MANAGEMENT OF SEVERE DYSFUNCTIONAL UTERINE BLEEDING(UPDATED) ................................ 388
VI. MANAGEMENT OF DIABETES INSPIDUS( IN PREPARATION)---------------------------------------Division of Pediatric Endocrinology. University of Illinois Hospital (UIH) and
Daytime UIH Office #
(312)996-1795
Evening/Weekend UIH Call Service #
(312)649-2639 –updated
Call attending who is on service (pls refer to call schedule)
I.
ADRENAL CRISIS
Emergency Management for Adrenal Insufficiency
Adrenal Crisis - Signs and symptoms:
Dehydration
Vomiting
Hypotension Lethargy
Diarrhea
Shock
Tachycardia
Fever
Adrenal crisis may be triggered by infection, trauma or surgery.
Immediately draw blood sample while starting an IV and send for stat electrolytes, glucose, pH, CO2 HCO3, BUN, CBC
and differential
In addition to the above blood sample:
- For suspected adrenal insufficiency, send blood for:
cortisol and aldosterone (3cc in red top tube)
plasma renin activity (PRA) (2.5cc chilled)
ACTH (purple top tube)
- For suspected congenital adrenal hyperplasia (CAH), send blood for:
17-hydroxyprogesterone and androgen levels (2-3 cc in red top tube)
- Do EKG.
This is a medical emergency that requires prompt recognition and treatment. It may be precipitated in the hypofunctional
adrenal cortical conditions (e.g., CAH, Addison's Disease), when patients are not yet diagnosed, are noncompliant with
therapy, or are stressed with trauma or bacterial infection or during surgery in adrenal insufficient patients. There may be
significant hyponatremia, hyperkalemia, hypoglycemia and dehydration with shock.
1. Glucocorticoid replacement: Administer hydrocortisone sodium succinate (Solu-Cortef) in a stat dose of 2.0 mg/kg IV
push or IM. One may estimate the emergency dose of hydrocortisone by IV bolus as follows: for an infant, give 25 mg;
for a small child, 50 mg; a larger child or adolescent, 100-150 mg. After the initial dose of Solu-Cortef use
hydrocortisone at 100 mg/m2/day as continuous IV infusion or q6 hours by IV bolus or IM (if an IV line cannot be
established).
For continuous IV infusion:
 In children < 2 years of age: mix 50 mg Solu-Cortef in 100 ml NS and infuse at a rate of 4 ml/hr. IV
piggyback.
 In children > 2 years of age: mix 100 mg Solu-Cortef in 100 ml NS and infuse at a rate of 4 ml/hr. IV
piggyback.
If the patient's condition does not improve or deteriorates another bolus infusion of Solu-Cortef may be given.
2. Fluid replacement:
a) In children who are severely dehydrated and hypotensive, give normal saline in 5%dextrose at 20 ml/kg over 1 hour.
This dose may be repeated if needed for 1 more hour. If in shock, give colloid 10 cc/kg over 50 - 60 minutes until
stabilized and switch to D5½NS.
b) Thereafter, administer IV fluid to correct deficit + maintenance + ongoing losses as per the degree of dehydration.
Calculate 24-hour fluid requirements as follows: Use NS or ½NS in 5-10% dextrose:
- For 10% dehydration:
Deficit:
100 ml/kg, wt./day (except adolescents & adults)
+
Maintenance: 100 ml/kg, wt. for up to 1-10 kg
50 ml/kg, wt. for up to 11-20 kg
20 ml/kg, wt. for up to >20 kg + Ongoing losses.
Administer ½ of the total fluid requirement during the first 8 hours (this includes the amount given as bolus in
the first 1-2 hours), and administer ½ over the next 16 hours.
- For children with mild (5%) or moderate (5 - <10%) dehydration: Calculate the maintenance fluid requirement
and administer 1.5 (5%) and 2 (5-10%) times maintenance respectively over 24 hours as NS or ½NS in 5-10%
dextrose, half within the first 8 hours and half in the next 16 hours.
- For children without dehydration: Administer 1.5 maintenance equally over 24 hours as ½NS in D5-10%
dextrose.
c) Do not add K to IV fluids until K level is <5 meq/L and the patient is urinating and administer only daily
maintenance K requirement.
3. Replacement of mineralocorticoids:
Pharmacologic doses of hydrocortisone and fluid/electrolyte therapy are usually sufficient for initial management
of adrenal crisis:
When the child is tolerating oral fluids, Florinef (9α- fludrocortisone) should be given orally at maintenance (0.05 0.1 mg/day) or double or triple maintenance (0.1 - 0.3 mg) if necessary until the crisis is over (make sure patients'
BP is not hypertensive either).
4. In the child with hypoglycemia:
Give IV bolus of 2-4 ml/kg of 25% dextrose. (In neonates the dose is 2 ml/kg of 10% dextrose).
Thereafter the parenteral glucose should be administered at a rate sufficient to maintain the plasma glucose level at
a range of 60-100 mg/dl
5. Hyponatremia: Calculate Na+ requirement as follows:
Deficit: (Normal serum Na+- observed serum Na+) x body weight(kg) x 0.6
Maintenance: 2-3 meq/kg/24 hours. Replace half the deficit over 8-12 hours along with the maintenance for that
period of time.
6. Hyperkalemia:
May cause cardiac arrhythmia and cardiac arrest, every patient must have an EKG and a cardiac monitor.
Periodic EKG rhythm strips should be run to detect the cardiac effects of hyperkalemia.
Management of patients with hyperkalemia:
a) If serum K+ > 6 meq/L: Kayexalate may be given by enema. Each 1 g Kayexalate will decrease the K+ level by 1
meq/L. If serum K+ is 7 meq/L give 3g of Kayexalate to reduce serum K+ to 4 meq/L. This may be repeated at 4-6
hours if necessary.
b) If serum K+ > 7 meq/L add: Sodium bicarbonate 2-3 meq/kg infusion by IV.
c) In an emergency you may use IV regular insulin with excessive glucose in IV solution but watch to avoid
hypoglycemia.
d) If the EKG shows changes related to hyperkalemia (peaked T waves, prolonged PR intervals, bradycardia,
disappearance of P waves (sinoventricular rhythm), widened QRS complex, a full blown sine wave pattern that
can lead to ventricular fibrillation and asystole) then administer 10% Ca Gluconate by IV at a rate of 0.5 cc/kg
over 10 minutes (monitor heart rate closely).
e) If all of the above fail to correct hyperkalemia, perform dialysis.
7. Do not overtreat the patient either. Overtreatment may lead to sodium and fluid overload with resulting hypertension,
hypernatremia, edema, congestive heart failure, and hypokalemia, with muscle weakness. Monitor the patient's clinical
condition, weight, input/output, blood pressure, EKG, and serum electrolytes very closely.
As the patient recovers and is able to tolerate liquids: Taper IV fluids and medications over a few days to a maintenance
glucocorticoid and Florinef replacement dose.
-3-
- Maintenance dose:
Hydrocortisone: 12.5-25 mg/m2/day in 2-3 doses.
Florinef:
0.05 - 0.2 mg/day
Management of Non-crisis Stress in Patients with Chronic Adrenal Insufficiency
1. For febrile illness:
a) Double or triple hydrocortisone dose depending on the condition of the patient.
b) If the child cannot tolerate oral therapy, as with severe vomiting or if she/he is rapidly becoming sleepy or
unconscious, the drug must be given parenterally (IV or IM). Stress dose of parenteral hydrocortisone is 50 mg in
small children and 100 mg in older children or adults one time for coverage.
c) Continue the above-stress dose for the duration of the illness.
2. For surgery:
a) Elective surgery: Give 2-3 times the evening maintenance dose of glucocorticoid orally or IM the night before
surgery.
In the morning on-call for surgery: Give Solu-Cortef or cortisone acetate 50 mg/m2/dose IM and establish an IV
line for fluid administration.
In the operating room: Give 75-100 mg/m2 by continuous IV infusion of Solu-Cortef before general anesthesia is
started, and continue throughout surgery.
Post-operatively: Give Solu-Cortef 100-150 mg/m2/day in 3-4 divided doses IV or IM.
As patient recovers, usually 1-2 days post-op, gradually taper the dose or frequency until maintenance dose is
reached. Hydrocortisone may be given orally if the patient is allowed and can tolerate oral food intake.
b) Emergency surgery: Administer hydrocortisone 50 mg IV or IM on-call to operating room for a small child and 100
mg IV or IM for larger child or adolescent, and continue same management during and post-surgery as above.
3. During trauma: Give 2-3 times maintenance dose of hydrocortisone depending on the patient's condition. If
surgery is required, follow surgical stress management.
-4-
-
In all stress conditions (febrile illness, trauma or surgery), Florinef dose generally is the same as long as
the patient is able to eat and drink well. However, if the patient vomits or is having diarrhea, the patient
must be given IV fluid therapy.
-
Reference normative data differ between the labs. Refer to the assay lab normative data.
Age
Cortisol
(μg/dL)
1-14 d
---
17d-5.75m
---
6m-7y
---
>7y
---
Tanner I
---
Tanner II-III
---
Tanner IV-V
---
For all ages
8AM level: 8-26
4PM level: 3-12
Midnight: 1-4
NORMATIVE STEROID LEVEL (Male)
SERUM
Aldo
17-OHP*
DHEA
DHEA-S
(ng/dL)
(ng/dL)
(ng/dL)
(μg/dL)
100
35-211
<10-2000
<10-200
(<10-300)
20
14-105
<10-200
<10-80
(<10-150)
60
35
14
10-79
+40
+24
+16
60
11-69
----+40
63
46
41
(7-140)
(5-154)
(7-148)
63
171
140
10-62
(30-150)
(63-457)
(56-240)
110
400
185
(25-200)
(80-800)
(80-350)
---
---
---
---
17-OHCS
(mg/d)
0-2 yr =
1.1-6.8
2-10 yr =
6.6-10.9
10-14 yr =
4.1-14.2
---
URINE
17-KS
(mg/d)
P’triol
(mg/d)
---
---
---
---
1.62
+1.2
1.62
+1.2
1.62
+1.2
2.6
+1.0
9.3
+4.4
0.06
+0.06
0.06
+0.06
0.10
+0.08
0.13
+0.05
1.11
+0.62
---
---
Age
Cortisol
(μg/dL)
1-14 d
---
17d-5.75m
---
6m-7y
---
>7y
---
Tanner I
---
Tanner II-III
---
Tanner IV-V
---
8AM level: 8-26
4PM level: 3-12
Midnight: 1-4
*Acceptable range of treated CAH:
BL: Blank
CHEA: Dehydroepiandrosterone
DHEA-S: Dehydroepiandrosterone-Sulfate
17KS: 17-Ketosteroid
For all ages
NORMATIVE STEROID LEVEL (Female)
SERUM
Aldo
17-OHP*
DHEA
DHEA-S
(ng/dL)
(ng/dL)
(ng/dL)
(μg/dL)
100
35-211
<10-2000
<10-200
(<10-300)
20
14-105
<10-200
<10-80
(<10-150)
60
43
16
10-79
+40
+38
+17
60
11-69
----+40
63
46
41
(7-140)
(5-154)
(7-148)
76
257
115
10-62
(40-182)
(51-414)
(41-211)
93
343
180
(20-260)
(72-741)
(71-340)
---
---
---
---
17-OHCS
(mg/d)
0-2 yr =
1.1-6.8
2-10 yr =
6.6-10.9
10-14 yr =
4.1-14.2
---
300-800 ng/dL
Aldo: Aldosterone
17-OHP: 17-hydroxyprogestrone
17-OHCS: 17-hydroxycorticosteroid
P’trial: Pregnanetriol
POTENCIES OF GLUCOCORTICOID PREPARATIONS
Glucocorticoid Potency
Equivalent
Steroid
(hydrocortisone)
Glucocorticoid Dose
Short-Acting
Cortisol
1.0
20
Cortisone
0.8
25
Prednisone
3.5
5
Prednisolone
4.0
5
Intermediate
Triamcinolone
5.0
4
Long-Acting
Betamethasone
25.0
0.6
Dexamethasone
30 (may be 100)
0.75
-5-
URINE
17-KS
(mg/d)
P’triol
(mg/d)
---
---
---
---
1.1
+0.03
1.1
+0.03
1.1
+0.03
2.0
+0.8
10
+5
0.06
+0.06
0.06
+0.06
0.10
+0.08
0.19
+0.4
0.69
+0.25
---
---
II. CALCIUM DISORDERS (this section is currently being updated and the below is
un-updated version as of 2010-when updated this notation will not appear)
- HYPOCALCEMIA
Definition: Total serum calcium concentration generally < 8.6 mg/dl in the presence of a normal serum albumin
concentration* or as an ionized serum calcium concentration generally < 4.5 mg/dl or as per UIH lab's normative calcium
level as of October 96 (<4.2 mg/dl).
* The total serum calcium concentration decreases approximately 0.8 mg/dl for each 1 gm/dl decrease in serum albumin
concentration.
Work-up in Hypocalcemic Patients
Neonates:
Family Hx of calcium disorder:
Pregnancy Hx: Maternal: Ca^ level, hyperparathyroidism, diabetes mellitus
Perinatal Hx: Gestational age, intra-partum events
Neonatal Hx: Check intake of high phosphorous formula such as PM 60/40 formula
Physical symptoms:
- Jitteriness, seizures, apnea, tremors
- Low Ca++ level may be associated with prematurity, birth asphyxia, congenital heart disease, infant of diabetic
mother
Work-up: Obtain blood for:
1. Ca (total and ionized), P, Mg, total protein, Cr, BUN, pH.
2. PTH level
3. VitD level (25-OH vit D)
4. Chromosomal analysis for 22 q 11 deletions to rule out DiGeorge syndrome (CATCH 22 syndrome)
5. EKG: QT internal increase in hypocalcemia, decrease in hypercalcemia
6. Chest X-ray: Thymic shadow, aortic arch position to look for DiGeorge syndrome (CATCH 22
syndrome)
Older Children
Check for:
- Chvostek's sign
- Trousseau signs (carpopedal spasm)
- Danger of laryngospasm
- Look for signs of pseudohypoparathyroidism (obesity, short stature)
Work-up: Obtain blood for:
1. Ca (total and ionized), P, Mg, total protein, A/G ratio, Cr, BUN, pH, alkaline phosphatase, SGOT,
SGPT, electrolytes.
2. T4 level
3. Cortisol level
┐to look for autoimmune
4. Anti-adrenal/parathyroid antibodies
┘endocrine failure
5. Obtain 24-hr urine for creatinine and phosphorous excretion
6. Skull X-ray or flat plate of abdomen to look for ectopic calcification
7. Ophthalmologic examination with slit lamp to look for ectopic calcification
Symptomatic Hypocalcemia (GUIDELINE)
-6-
Neonates and Older Children
- Use slow IV infusion of: 10% Ca Gluconate (1 ml = 9.3 mg of Ca++)
1-2 ml/Kg BW (up to 10 ml total/hr) in diluted solution with equal amount of DW
- For convulsion: 10% Ca gluconate (CG) IV (2 ml/Kg) very slowly (at least over 10 minutes) until seizure ends (max 1020 cc in older children)
- Maintain IV Ca at 2-3 mg Ca++/Kg/Hr = 50-70 mg Ca++/Kg/day
- Reduce IV rate by 50% over 2 days
- Do not add to IV solution containing NaHCO3 or phosphate (may cause precipitation)
- Use a freely running IV-line to avoid extravasation and tissue necrosis
- Monitor heart rate and discontinue Ca++ for bradycardia
- Serial Ca level to assess the need
- If serum Ca level does not return to normal, a coexisting Mg deficiency may be present.
If Mg level < 1.5 mg/dl Add Mg Supplement
- SEVERE: Mg sulfate 50% IM 0.2 ml/Kg q 8-12 hours
- MILD: Mg sulfate 0.2-1.2 mL/Kg/day P.O.
- Start oral Ca and vit D supplement as soon as patient tolerates oral intake.
Symptomatic/Asymptomatic/Mild Hypocalcemia (GUIDELINE)
Maintain Oral Elemental Ca
- In neonate: Ca++ 75 mg/Kg/day divided q 4-6 hours
- In older infants and children: Ca++ 50 mg/Kg/day
Ca Gluconate (9% Ca++)
10% CG 10 CC = 1 GM CG = 93 mg Ca++
1 Tab = 500 mg CG = 46 mg Ca++
- Neo-Calglucon Syrup (6.3% Ca++)
5 CC = 1.8 GM Neo-Calg =115 mg Ca++
- HYPEROSMOLAR - WATCH FOR DIARRHEA
Calcium Lactate (13% Ca++)
1 Tab = 325 mg CL = 42 mg Ca++
= 650 mg CL = 84 mg Ca++
-7-
Vitamin D Preparation:
Compound
(Trade name)
Cholecalciferol (D3)
(= Delta D)
Calciferol (D2)
(= Drisdol)
Dihydrotachysterol (DHT)
(= Hytakerol)
Calcitrol
Onset of
Action
(hrs)
Calcium Increases
Significantly
Peak Activity
(wks)
Blood Half
Life
Duration of
Biological Activity
8-24
in  2 wks
4-8
30 days
4-16 wks
8-24
in  2 wks
4-8
30 days
several months
(4-16 wks)
in a few days-1
mos.
1-2
----
1-2 wks
----
5-16 hrs
up to 20 days
in 1-4 days with
0.3 g/kg/day
<4-6
PO=1.25 cholecalciferol
(Active D3 = Rocalcitrol)
IV=If malabsorptionIV
(Calcijex)
.01-.05 g/kg/day
PRN or 3 times/wk
Short-term
onset
Calcidriol = calcifediol
------2-4
15 days
4-12 wks
(25 OH D3 = Calderol)
Extracted from references: Peds 57:729, 1976; JCEM 45:457, 1977; J of Peds 88:177, 1976; JCEM 55:238, 1982;
Harrison and Harrison, Disorders of Ca and Phosphate Metabolism in Childhood and Adolescence, 1979, p. 71.
Recommended dose of Vitamin D preparation in Infants and Children:
Compound
Cholecalciferol (Vit D3)
Calciferol
Dihydrotachysterol (DHT)
Calcitriol
= 1,25-(OH)2-D3
= 1,25-OH-cholecaeciferol
= active vit D3
=Rocaltrol
1-OH3
(synthetic analog of active Vit D3
Calcidriol (25 OH D3)
=Calderal
-8-
During Hypocalcemic Time
Adjust Dose for
Maintenance as per
Ca++ Level
---
---
0.125 mg (5,000 U) /kg/day
 Maximum 50,000 IU/day
1000-5000 IU/day
Start with high maintenance or
with higher than maintenance
dose.
0.05-0.2 mg infant/day
0.2-1.5 mg child/day
0.01-0.02 mg/kg/day
0.25 g/capsule
0.5 g/capsule
Gradual increase in dose
0.25-0.5 g/day as starting
dose or
0.03 g/kg/day
0.25-1 g/day
---
Not well established
Not well established
20 g/capsule
50 g/capsule
----
50-200 g/day
Dose
400 U/Tab or
1000 U/Tab
1.25 mg/Tab =
50,000 U
* 8,000 U/mL
0.125 mg/Tab
0.2 mg/Tab
0.4 mg/Tab
0.2 mg/5 ml
0.125 mg/capsule
0.25 mg/ml
(crystalin/mg/ml
of vegetable oil
can be prepared)
Extracted from reference: J. of Endo 91:1006, 1977; JCEM 45:456, 1977; Harrison & Harrison Disorders of Calcium
Metabolism in Childhood and Adolescence, 1979, p.71.
Aims of Treatment in Hypocalcemic Patients (Patients Receiving Vitamin D Supplement)
The primary goal is to abolish hypocalcemic symptoms and normalize Ca++ levels and avoid hypercalcemia.
Biochemical
1. To maintain serum calcium level 8.5-9.0 mg/dl. If serum calcium >10.5 mg/dl, discontinue treatment temporarily until
serum calcium level <9.5 mg/dl. ↑ fluid intake, ↓ food intake high in Ca.
2. To maintain urine calcium excretion <3 mg/kg/24h or spot urine Ca/Cr < 0.1. If >3 mg/kg/day, or spot urine Ca/Cr >
0.2, then reduce the dose to maintain lower serum calcium level without hypocalcemic symptoms.
Clinical Follow-up
1. Serial determination of serum Ca, P: pm or at least every 3 months.
2. Serial determination of urine calcium excretion: pm or at least every 6 months - 1 year.
3. Serial determination of creatinine clearance: pm or at least every 1 year.
4. Ophthalmology examination for band keratopathy and lenticular opacities (cataracts): pm or every 1 year.
NORMAL RANGE IN SERUM
GROUP
TOTAL Ca
(mg/dl)
P
(mg/dl)
Other UIHLab Other UIHLab
Other
UIHLab
Premature
7-11
8.6-10.4 5.4-10 4.5-6.5
100-400
100-400
Full-Term
7-11
8.6-10.4 3.5-8.6 4.5-6.5
100-400
100-400
Infant
9-11
8.6-10.4 4.5-6.7 4.5-6.5
100-400 ↑↑
100-400
8.8-10.5 8.6-10.4 4.5-5.5 4.5-6.5
100-400 ↑
100-400
Puberty (>10yrs.) 8.5-10.4 8.6-10.4 3.0-4.5 3-4.5
100-400 ↑↑↑
100-400
Adult(>18yrs.) 8.5-10.4 8.6-10.4 3.0-4.5 3-4.5
57-154
40-125
Childhood
-9-
ALKALINE PHOSPHATASE
N-METAPHENYL PHOSPHATE (u/L)
Laboratory Data in the Differential Diagnosis of Hypocalcemia*
25Resistance to
Hydroxyvitamin
Chronic
PseudoVitamin D
1,25Hypoparathyroidism
Hypomagnesemia
D3- 1αRenal
hypoparathyroidism
Deficiency
Dihydroxyvitamin
Hydroxylase
Disease
D3
Deficiency
Total
↓
Calcium
Ionized
↓
Calcium
Phosphorus
↑
Magnesium
N↓
Alkaline
N
phosphatase
Parathyroid
↓
hormone
25-OH-D3
N
1,25(OH)2D3
N↓
* ↓ = decreased;
↓
↓
↓
↓
↓
↓
↓
↓
↓
↓
↓
↓
↑
N
↑
↓
↓
N
↓
N
↓
N
↑
N↑
N
N
↑
↑
↑
↑
↑
↓
↑
↑
↑
↑
N
N
↓
↓N↑
N
↓
N
↑↑↑
N
↓
N
N↓
↑ = increased; N = normal
Biochemical Abnormalities in Various Types of Rickets*
Alkaline
Type of rickets
Ca++
Phosphate
HCO3PTH
Phosphatase
Nutritional
↓
↓N↑
↑
N
↑
1α-Hydroxylase deficiency
↓
↓
↑
N
↑
Calcitriol resistance
↓
↓
↑
N
↑
Familial hypophasphatemic
N
↓
↑
N
N↑
HHRH
N
↓
↑
N
↓
Tumor rickets
N
↓
↑
N
N
McCune-Albright syndrome
N
↓
↑
N
N
Uremia
↓N↑
↑
↑
↓
↑↑
Fanconi syndrome
N
↓
↑
↓
↑
Hypophosphatasia
N
↑
↓
N
N
Epiphyseal dysplasia
N
N
N
N
N
-10-
Calcifediol Calcitriol
↓
N
N
N
N
N
N
N
N
N
N
↓N↑
↓
↑
N
↑
↓N
N
↓
↓N
N
N
HYPERCALCEMIA
Definition: A child or infant can be considered to be hypercalcemic if serum total calcium concentration is >10.8 mg/L or
when ionized calcium (= Ca++) concentration is >5.6 mg/L.
To Determine Nature of Underlying Disorder
Neonatal Hypercalcemia
- Phosphate deficiency
Parenteral nutritional deficiency
Very low birth-weight infants fed human milk or (less commonly) standard formula
- Hypervitaminosis D
Excessive maternal vitamin D intake
- Hyperparathyroidism
Congenital parathyroid hyperplasia
Maternal hyperparathyroidism
Maternal and neonatal renal tubular acidosis
- Mutations in Ca++-sensing receptor gene
Neonatal, severe (primary) hyperparathyroidism
Familial, hypocalciuric hypercalcemia
- Uncertain pathophysiological mechanism
Idiopathic infantile hypercalcemia
Severe infantile hypophosphatasia
Subcutaneous fat necrosis
Blue diaper syndrome
- Chronic maternal hypercalcemia (?)
Thyrotoxicosis
Chronic thiazide diuretic, lithium therapy
Vitamin A intoxication
Causes of Hypercalcemia in Children and Older Subjects
- Hyperparathyroidism
Congenital
Autosomal recessive/dominant
Multiple endocrine neoplasia types I, IIA, (IIB)
Acquired (adenoma or hyperplasia)
Secondary (post-renal transplantation)
- Familial hypocalciuric hypercalcemia
- Hypervitaminosis D
Nutritional
Granulomatous/inflammatory diseases (sarcoidosis, leprosy, tuberculosis)
- Immobilization
- Neoplasia Secreting
Parathyroid hormone-like protein
Osteoclast activating factor(s)
- Others
Hyperproteinemia
Hypophosphatemia
Drugs (thiazides, lithium, vitamin A)
Hyperthyroidism
-11-
History:
- Age of patient, growth and developmental milestones
- Vit D and A ingestion, medications, dietary history, ingestion of milk and alkali
- History of hypothermia
- History of renal failure
- History of muscle injury, other associated disorders
- History of maternal hypoparathyroidism
- History of chronic maternal hypercalcemia: thyrotoxicosis, chronic thiazide diuretics, lithium treatment, vit A
intoxication, excessive maternal vit D intake
- Familial history
Physical examination:
- Features of patient congenital heart disease (William's syndrome)
- Subcutaneous fat necrosis
- Lymph node enlargement, hepatosplenomegaly
- Thyroid enlargement
Laboratory tests for differential diagnosis:
- Major differential test: serum PTH, serum vit D metabolites, alkaline phosphatase
- Ancillary differential tests: serum phosphorus, spot sample for urinary phosphorus, calcium excretion, and
creatinine concentration (urinary Ca/Cr >0.2 is hypercalciuria)
- Skeletal and soft tissue X-rays: bone resorption vs increased density, soft tissue ectopic calcification, osteosclerosis
- Selective tests as needed:
1. Sonogram and radionuclide studies, selective venous catheterization for differential diagnosis of primary
hyperparathyroidism vs. ectopic parathyroidism or parathyroid secreting malignancy
2. Cortisone suppression test: vit D vs. non-vit D mediated etiology
3. Abdominal sonogram for nephrocalcinosis
4. CT scan and MRI of parathyroid glands if hyperparathyroidism is proven.
Treatment of Severe and Symptomatic Hypercalcemia
Treat for symptomatic hypercalcemia or when total calcium exceeds 13 mg/dl.
1. No calcium or vitamin D ingestion
2. Increase calcium excretion
- Hydration more than 2-3 times maintenance with normal renal function. Use NS or D5½NS or 2/3 Ringers lactate.
- Na diuresis: Use Lasix 1-2 mg/kg/dose every 4-6 hours until Ca decreases to 12 mg/dl.
* Fluid balance should always be on the positive side after correcting deficit and on-going deficit.
* Replace on-going Na and K loss every 4-6 hours.
* High sodium diet promotes continued renal calcium excretion after correction of acute hypercalcemia.
3. Decrease calcium absorption
- Glucocorticoid: Cortisone 10 mg/kg/day - 300 mg/day. IV daily X3-5 days.
- Prednisone: 1-2 mg/kg/day, up to 60 mg/day.
(* Most effective in vit D toxicity, sarcoidosis, or idiopathic hypercalcemia.)
4. Inhibition of bone resorption: Most effective treatment
a) Calcitonin: 2-3 U/kg q12h IV, SC or IM. It also increases urinary excretion of calcium, and has a potent analgesic
action.
- Check calcium level q2h in the first 6 h.
- Refractory phenomenon may occur
- Mobilization ASAP
b) Bisphosphonates: (Etiodronate and Pamidronate)
- Etiodronate: 7.5 mg/kg q4h IV infusion for 3-7 days. Discontinue Tx if Ca level has fallen by 2-3 mg/dl after
-12-
1st 2-3 doses.
- Pamidronate: More potent. 14-45 mg IV infusion up to 6 days or single 24 h. infusion of 45, 60, 90 mg.
c) Mithramycin: IV bolus or 25 µg/kg BW over 4-6 hours. Can be repeated q 24-48. Extravasation can be irritating
locally and lead to cellulitis.
- Watch toxicity (nausea, anorexia, hemorrhage, liver, renal damage, proteinuria, azotemia, thrombocytopenia)
- Do not use in patients with hematological, liver, or renal disease.
- Phosphate: not recommended. May cause precipitation of Ca and P salts in the vascular system and kidneys.
Use only in severe hypercalcemia when all other measures have failed
d) Calcium Nitrate: The ultimate action is to inhibit osteoclast function.
- IV: dose = 200 mg/m2 in 1 L of fluid daily for 5 days.
- It is a nephrotoxic agent.
- Can cause associated reduction in serum phosphate concentration and hemoglobin concentration.
e) Dialysis: use in patients with renal failure.
5. Investigate etiology and removal of primary etiology.
6. Parathyroidectomy should be strongly considered for hyperparathyroidism due to progressive skeletal mineral loss and
the adverse effects of long-term hypercalcemia on the kidneys.
General Guidelines for the Management of Hypercalcemia
1. Mild hypercalcemia: Establish diagnosis, correct underlying problem.
2. Moderate hypercalcemia: Hydration and mobilization while establishing Dx and reassessment of Tx.
3. Severe Hypercalcemia: MEDICAL EMERGENCY. Draw blood for PTH, vit D metabolism, biochemical screening and
assess kidney function. Start intense medical treatment ASAP.
-13-
III. GLUCOSE DISORDERS
- HYPOGLYCEMIA
This protocol deals with cases of recurrent or persistent hypoglycemia in the pediatric age group in the form of
a decision tree (algorithm). This algorithm is meant to be an aid to the physician dealing with the hypoglycemic
child to help in choosing the appropriate laboratory studies in every step of the evaluation of the patient in
order to facilitate diagnosis and treatment.
Definition of Hypoglycemia - may be controversial
Newborn: plasma glucose level < 50 mg/dl is conventionally used for diagnosing hypoglycemia
*whole blood glucose blood glucose concentrations are 10-15% lower than plasma glucose*
Infant and child: 2 different definitions are used
1) Diagnostic level: plasma glucose < 50mg/dl
2) Therapeutic level: plasma glucose > 70mg/dl (lowest level acceptable during therapy for
hypoglycemia)
Evaluation in the Newborn
History:
- AGA, SGA, LGA
- Feeding history
- Maternal history (DB, diabetic mother, blood group incompatibility, maternal IV glucose
- Treatment, maternal medication (chlorpropamide, benzthiazide, diuretics, salicylate and/or
ethanol ingestion, eclampsia, pre-eclampsia).
Signs and symptoms:
- Apnea/tachypnea/Cyanotic episodes
- Abnormal cry/ tachypnea / hypotonia
- Lethargy/Apathy/Poor cry/Poor feeding
- Hypothermia/Hypotension
- Irritability/Tremors/Seizures
- Cardiac arrest
Physical exam:
1) Look for macrosomia ( large size) for hyperinsulinemia
2) Beckwith Wiedemann Syndrome (large tongue, umbilical hernia, macrosomia)
3) Galactosemia: Jaundice and cataracts
4) Glycogen storage disease: hepatomegaly
5) Hypopituitarism : micropenis, midline defects, cleft lip and cleft palate
Evaluation in Older Infants to Children
History:
- Perinatal history, birth weight, apgar score
- Relationship of symptoms to feeding or meals or the introduction of new foods
- Prior history of hypoglycemia episodes
- History of condition associated with hypoglycemia (e.g., diabetes mellitus)
- Family history of hypoglycemia, inborn errors, early infant deaths, reye syndrome
- Age of onset of symptoms
-14-
Toxic ingestions ( e.g., alcohol intoxication, salicylate poisening)
Relationship of symptoms to acute illness or starvation
Information about growth development
Dietary factors: dietary intake before the event, fed or fasting at the time of hypoglycemia,
symptoms after ingestion of milk product or fructose
Signs and symptoms:
- Autonomic response, primarily catecholamine-mediated
Hunger, Nausea
Sweating
Tachycardia
Feeling of anxiety/nervousness/weakness
Tremors
- Neuroglycopenia, primarily related to effects of hypoglycemia on the brain
Disordered consciousness (lethargy, tiredness, apathy, somnolence, stupor, coma)
Behavioral abnormalities (irritability, sleep disorders, anger/manic behavior, depression, confusion)
Headache
Staring spells
Seizures
Important points in physical examination:
1) Height, head circumference, weight
2) Complete neurological examination
3) Midline defects
4) Fundus examination
5) Pigmentation
6) Hepatosplenomegaly, signs of hepatic disease, e.g., jaundice
7) Size of genitalia
8) Omphalacele, Macroglossia, Visceromegaly (cardinal features of Beckwith Wiedemann Syndrome)
9) Chubby features
10) Doll’s face
11) Muscle tonus
12) Scoliosis
13) Suspected Reye Syndrome
14) Infections
15) Cataracts
-
Etiologies of Hypoglycemia by Most Common Age of Initial Occurrence
NEWBORN TO 1 YEAR
* Small for gestational age
* Premature
* Twins
* Infections/Sepsis
* Cold stress
* Infants of diabetic mothers
* Beckwith-Wiedemann
* Maternal Toxemia
* Maternal drugs, e.g. Propranolol, ß-tocolytics
* Rh incompatibility
* Exchange transfusions
* Umbilical artery malposition
* Congenital heart disease/failure
* Transient ß cell hyperinsulinism due to perinatal stress event
* Hyperinsulinism due to islet cell dysplasia (hypertrophy, adenoma)
* Congenital hyperinsulinism (peristent hyperinsulinemia of the infancy)
-15-
* Inborn errors of carbohydrate metabolism (glycogen storage diseases, galactosemia, hereditary fructose
intolerance)
* Inborn errors of fatty acid oxidation or ketogenesis +/- increase insulin level
* Cortisol and/or growth hormone deficiency (hypopituitarism, congenital adrenal hyperplasia)
* Prolonged fasting
* Carbohydrate malabsorption
* Hepatic failure
* Inborn errors of amino acid metabolism
* Inborn errors of gluconeogenesis (specific enzyme defects, galactosemia, hereditary fructose intolerance)
* Toxins: Salicylate, 1-propyl alcohol
1 YEAR TO ADOLESCENCE
* Prolonged fasting (ketotic hypoglycemia) or malnutrition Hepatic failure
* Fevers, infections
* Toxins: Salicylate, ethanol, hypoglycemic drugs
* Reye syndrome
* Cortisol and/or growth hormone deficiencies
* Islet cell adenomas
* Exogenous insulin excess (diabetes mellitus treatment, child abuse)
Etiologies of Hypoglycemia
A. Increased glucose utilization. Impaired conservation of glucose
1. Conditions of Insulin excess
a. ß cell hyperplasia: Beckwith-Wiedemann, Rh incompatibility
b. Familial hyperinsulinism ( also known as persistent hyperinsulinemia hypoglycemia of infancy or
congenital
hyperinsulism) including 3 genetic forms
- Loss of function mutation in the ß-cell plasma membrane ATP potassium channel
- Gain of function mutations of the mitochondrial enzyme glutamate dehydrogenase, also known as
hyperinsulinism-hyperammonemia
- Gain of function mutation of islet glucokinase
c. ß cell adenoma
d. Reactive hypoglycemia: umbilical artery catheter, short bowel
e. Ingestion of hypoglycemia agents: maternal or child
f. Exogenous insulin excess
2. Excessive tissue demands
A) Tumors
B) Infections
C) Cold stress
D) Exercise
3. Impaired ketogenesis/ketone utilization (Inadequate conservation of glucose)
a. Inadequate fat stores: premature, SGA, malnutrition
b. Inadequate fat mobilization: insulin excess, cortisol deficiency, growth hormone deficiency,
propranolol
c. Inadequate fatty acid oxidation
1. Carnitine deficiency (primary or secondary)
2. Decreased CPT-I activity
3. Decreased Acyl CoA dehydrogenase activity: inherited or secondary e.g., "hypoglycin" inhibition
(Jamaican vomiting sickness)
d. Inadequate ketogenesis: decreased HMG-CoA synthase/lyase activity
-16-
e. Inadequate ketone utilization: decreased ß-ketothiolase activity
B. Decreased glucose production
I. Deficiency of substrate or its mobilization
a. Glycogen: diminished stores: prematurity, SGA, neonatal stress, malnutrition, growth hormone or
cortisol deficiency
b. Glycerol: fat stores or glycerokinase deficiency
II. Defective recycling of lactate or alanine
a. Substrate deficiency: ketotic hypoglycemia
III. Disorder of glycogenolysis
Glycongen synthetase deficiency, Glucose- 6 phosphatase deficiency, Debranching enzyme,
Phospholyrase deficiency, Phosphorylase kinase
IV. Disorder of gluconeogenesis
a. Hepatic enzyme deficiency: Fructose-1,6-diphosphatase deficiency, Phosphoenolpyruvate
carboxykinase
(PEPCK) deficiency, Glucose-6-phosphatase, pyruvate
carboxkinase
b Toxins: ASA, ethanol, other alcohols
V. Other enzyme defect:
a. Galactosemia (galactose-1 -phosphate uridyl transferase
deficiency)
b. Hereditary fructose intolerance (aldolase deficiency)
VI. Hereditary disorders of ammo acid and organic acid metabolism: maple urine syrup disease,
methylmalonic
aciduria, proprionic acidemia
C. Hormone deficiencies or decreased action of hormones
1. ACTH/Cortisol: hypopituitarism, congenital adrenal hyperplasia, ACTH unresponsiveness,
Addison disease, acute steroid withdrawal
2. Growth hormone: hypopituitarism, isolated growth hormone deficiency
3. Epinephrine: propranolol administration
4. Glucagon deficiency, but well documented cases have only rarely been described
D. Hepatic failure
Work up for Hypoglycemia in the Newborn
Draw the following blood sample when hypoglycemia is present or 3-4 hours after the last feeding:
1) Draw critical blood sample for glucose, cortisol, insulin, growth hormone, acetone and if
sufficient sample, please send Free fatty acid, cortisol, T4 and TSH levels.
2) Consider evaluating pH, lactate, pyruvate and ketones if hepatomegaly is present.
3) Do urine ketone test.
4) Send urine for organic acid analysis
5) Newborn screening (errors of metabolism, include aminoacidemia, urea cycle disorders, organic
aciduria, and fatty acid oxidation disorders)
Endocrine dynamic tests such as glucagon challenge test or GH stimulation tests or ACTH provocative tests
are reserved for confirmation of suspected diagnosis.
As per the suspected diagnosis, glucagon may be used for diagnosis (Glycemic response to glucagon)
Significant rise in blood glucose more than 30 mg/dl above baseline after glucagon administration
(1mg IV), suggestive of hyperinsulinism
Treatment
Both oral and IV caloric administration should be provided simultaneously. If the child tolerates oral feeding,
-17-
oral administration of nutrients such as 5% dextrose or formula as frequent intermittent boluses or continuous
feeding should be maintained. Parenteral IV glucose treatment may be given at 6-15 mg/kg/minute and
tapered as per baby's response. Glucose infusion rate may need to increased as high as 15 to 25 mg/kg/min in
hyperinsulinemia. For the relief of acute hypoglycemic symptoms (i.e., seizures) administer 10% dextrose 2
ml/kg at a rate of 1 ml/ minute, followed by continuous parental infusion at the rate of 6-15 mg/kg/min. The
continuous parenteral glucose treatment should be continued based on the blood glucose level in the baby.
While waiting for the random or dynamic test results you may consider a trial of glucocorticoids
(Hydrocortisone 5 mg/kg/dose x 2-3 doses oral or IV), or growth hormone (0.1 mg/kg/dose 1-2 doses SQ)
Glucagon (Emergency treatment only in case of insulin induced hypoglycemia) 1 mg IM or IV but watch for
rebound hypoglycemia
Treatment for congenital hyperinsulinsim will be discussed later in this protocol
Work up for hypoglycemia in older infants and children
At the time of hypoglycemia draw a blood sample for glucose, lactate, acetoacetic acid, ß-hydroxybutyrate, free
fatty acids, insulin, growth hormone, cortisol, liver function tests and ACTH (Chilled tube). Do urine ketone test.
In patients suspected of having endogenous hyperinsulinism, measure plasma glucose, insulin, C-peptide, βhydroxybutyrate (at UIC, acetone has been used instead of β-hydroxybutyrate), and circulating oral
hypoglycemic agents during an episode of hypoglycemia.
If there is no spontaneous hypoglycemia then perform a 24 hour fasting until the child become hypoglycemic
and at the time of hypoglycemia draw a blood sample for the above tests.
Give glucagon stimulation test to check blood glucose response when hypoglycemic.
I. Presence of Ketonuria/Ketonemia: Ratio of glucose/insulin > 4
1) Cortisol > 10 mcg/dl and GH >10 ng/ml, elevated blood lactate and poor blood glucose response to
glucagon suggest:
Disorders of glycogen metabolism (specific enzyme deficiencies), galactosemia, hereditary fructose
intolerance
or
Disorders of gluconeogenesis (specific enzyme deficiencies, fructose 1,6-biphosphatase), errors in
ammo acid metabolism.
2)Cortisol < 10 mcg/dl and/or GH < 10 ng/ml. Suspect hypopituitarism and/or adrenal insufficiency
*** please note that premature newborn has limited capacity of cortisol secretion despite normal H-P-A (
hypothalamic- pituitary-adrenal ) axis therefore cortisol < 10 does not always mean cortisol deficiency ***
II. Absence of Ketonuria/Ketonemia
1) Ratio of glucose/insulin <4 ( in hypoglycemic state, any detectable insulin is inappropriate)
Cortisol > 10 mcg/dl, GH > 10 ng/ml. Lack of elevation of free fatty acids or lactate, and increase in
blood glucose by > 30 mg/dl over baseline after glucagon suggest hyperinsulinism.
Features of Hyperinsulinism in the Newborn
Glucose infusion rate >10 mg/kg/min needed to sustain normoglycemia
Large for gestational age
Mild hepatic enlargement (glycogen)
2) Glucose: insulin ratio <4 during hypoglycemia ( in hypoglycemic state, any detectable insulin is
inappropriate)
Non-ketotic hypoglycemia
Absence of ketonemia, "acetonemia" (ketonuria may be seen)
-18-
Absence of elevated free fatty acids or lactate in the blood
Rise in blood glucose >30 mg/dl above baseline 30-40 minutes after glucagon administration
Features of Hyperinsulinism in the older Children
Glucose infusion rate >5 mg/kg/min or >3 mg/kg/min in young child or adolescent respectively.
Mild hepatic enlargement (glycogen)
Glucose: insulin ratio <4 during hypoglycemia ( in hypoglycemic state, any detectable insulin is
inappropriate)
Non-ketotic hypoglycemia
Absence of ketonemia, "acetonemia" (ketonuria may be seen)
Absence of elevated free fatty acids or lactate in the blood
Rise in blood glucose >30 mg/dl above baseline 30-40 minutes after glucagon administration
2) Ratio of glucose/insulin > 4, Cortisol > 10 mcg/dl, GH >10 ng/ml, elevated free fatty acids. Do serum
camitine and urine organic acid profile.
Defects in fatty acid ß-oxidation
Carnitine deficiency
Carnitine palmitoyl transferase deficiency
Acyl CoA dehydrogenase deficiency
Other work up may be indicated as necessary:
- Radiologic imaging for congenital hyperinsulinism
1) 18F-DOPA PET scan, that is injected intravenously and concentrates in insulin cells for detection in
a PET scanner. However, 18F-DOPA is not yet FDA approved, so the test is being done under a
research protocol.
2) Pancreatic arterial calcium stimulation of insulin secretion, not to be specific as originally reported
3) CT scan, MRI, and ultrasound, have not been successful in identifying Focal KATP
hyperinsulinism
- Molecular genetic testing: 5 genes are known to be associated with familial hyperinsulinsm
1) ABCC8
2) KCNJ11
3) GLUD1
4) GCK
5) HADH
- Radiologic imaging for insulinoma
1)Selective pancreatic angiography, may be used to detect insulinoma
2) Helical or multi slice CT scan or MRI
- Tissue specimen (liver, fibroblasts, blood cells) for enzyme analysis, histology
- Toxic screen (ASA, ethanol)
- Reducing substances in the urine (galactosemia )
-19-
Clinical and Differential Diagnoses in Childhood Hypoglycemia
*Key: N — normal; 0 = absent: ↑ = low increase: ↑ ↑ = great increase; ↓ = some decrease; ↓ ↓ = marked
decrease
Serum Glycemic
Urinary
response
ketones
Hepato
to
Hypoglycemi (K) or
Condition
Uric glucagon
a
reducing
Lipid
megaly
aci
sugars
s
d Fe Faste
(S)
d
d
Normal
0
0
0
N
N ↑↑ ↑
Hyperinsulinemi Recurrent
N or
0
0
N ↑↑ ↑↑
a
severe
↓
Severe with
Ketotic
missed
K+++
0
N
N ↑ 0-↑
hypoglycemia
meals
Moderate
with
Hypopituitarism
K++
0
N
N ↑ 0-↑
missed
meals
Severe with
Adrenal
missed
K++
0
N
N ↑ 0-↑
insufficiency
meals
Enzyme
deficiency
Glucose-6Severe
K+++
++++ ↑ ↑
↑↑ 0 0
phosphatase
constant
Moderate
Debrancher
with
K++
+
N
N ↑ 0
fasting
Mild to
Phosphorylase
K++
+
N
N 0-↑ 0
moderate
Fructose-1,6Severe with
diphosphatase fasting
Galactosemia
Fructose
Intolerance
Carnitine
Deficiency
Carnitine Palmitoyl
Transferase 1
Deficiency
Acetyl CoA
Dehydrogenase
-20-
Effect of 24 – 36 h fast on plasma
Glucos Insuli Ketone Alanin Lactat
e
n
s
e
e
↓
↓
↑
↓
N
↓↓
↑↑
↓↓
N
N
↓↓
↓
↑↑
↓↓
N
↓↓
↓
↑↑
↓↓
N
↓↓
↓
↑↑
↓↓
N
↓↓
↓
↑↑
↑↑
↑↑
↓↓
↓
↑↑
↓↓
N
↓
↓
↑↑
↓↓
N
↑↑
↑↑ ↑
0
↓↓
↓
↑↑
↑↑
↑↑
0-S+++ +++
N
N
↑
0
↓
↓
↑
↓
N
After fructose 0-S+++ +++
N
N
↑
0-↑
↓
↓
↑
↓
N
Moderate to
severe
with
fasting
↓
N
↑
0
↓
↓
↓
N
N-↑
After milk or
milk
products
K++++
0
++++
0-+
Lab data in individuals with hyperinsulinemic hypoglycemia or hypoglycemia caused
by other mechanisms
Symptoms,
signs, or both
Glucose
(mg/dl)
Insulin
(µU/ml)
C-peptide
(nmol/liter)
-Hydroxybutyrate
(mmol/liter)
Glucose
increase after
glucagon
(mg/dl)
Circulating oral
hypoglycemic
agent
No
<50
<2
<0.2
2-4
<30
No
Normal
Yes
<50
>1
<0.2
<2
>30
No
Exogenous insulin
Yes
<50
>1
≥0.2
<2
>30
No
Endogenous
insulin
Yes
<50
>1
≥0.2
<2
>30
Yes
Oral
hypoglycemic
agent
Diagnostic
interpretation
Treatment of Hypoglycemia in Older Children
Use frequent oral feedings if tolerated and IV glucose of 10% dextrose to maintain blood sugar level
in the normal range. While waiting for the random or dynamic test results you may administer the
following as per suspected diagnosis:
Medication
- Glucocorticoids: HC dose: 5 mg/kg/dose x 2-3 doses/day orally or IV for suspected adrenal
insufficiency.
- Growth hormone 0.1 mg/kg/dose SQ 1-2 doses/day for suspected GH deficiency.
In all above treatments when the decision is made to stop treatment, IV fluids and medication should be
tapered and discontinued over a few days to prevent hypoglycemia, and in the case of corticosteroid
treatment, to prevent adrenal crisis.
Treatment for familial hyperinsulinism
Medication
- Diazoxide: 5-20 mg/kg/day (usually ineffective in children with KATP channels forms of
Hyperinsulinism)
- Somatostatin analog such as octreotide ( 2-10 μg/kg/day initially divided every 12 hours; increase
dosage depending upon patient response by either using a more frequent interval ( q 6-8 hr ) or larger dose
as well as the use of continuous subcutaneous injection using a portable pump greatly enhances clinical
efficacy
- Calcium chanel blocker such as Nifedipine (0.25-0.7 mg/kg/d PO divided q8h) are another alternative
therapy, but the use of calcium chanel blocker for familial hyperinsulinsm has not been evaluated in controlled
trial
- Glucagon ( Emergency treatment only in case of insulin induced hypoglycemia) 1 mg IM or IV
Dietary therapy
-
Frequent high carbohydrate meals and the ingestion of uncooked cornstarch (1-2gm/kg/dose)
-
Surgical treatment
-
Surgical exploration is warranted in children older than several weeks of age in whom
hyperinsulinism is proven and pharmacologic therapy fails to control hypoglycemia
-
Long term treatment and prognosis depend upon whether the pancreatic pathology at the time of
surgical exploration is focal or diffuse
-
Focal anomalies : selective resection is often curative
-
Diffuse lesion : require subtotal pancreatectomy, in which 95-99 percent of the pancreas is removed
SEE ALSO NEXT PAGE FOR algorithm) :
This protocol deals with cases of recurrent or persistent hypoglycemia in the
pediatric age group in the form of a decision tree (algorithm).
This algorithm is meant to be an aid to the physician dealing with the
hypoglycemic child to help in choosing the appropriate laboratory studies in
every step of the evaluation of the patient in order to facilitate diagnosis and
treatment.
-22-
This algorithm is meant to be an aid to the physician dealing with the hypoglycemic child to help in
choosing the appropriate laboratory studies in every step of the evaluation of the patient in order to
facilitate diagnosis and treatment.
-23-
DIABETES MELLITUS
A) DIABETIC KETOACIDOSIS
Diabetic Ketoacidosis is a state of hyperglycemic, hypertonic dehydration and ketotic academia .
It exists when: 1.The glucose is >200 mg/dl => 11mmol/L.
2. Ketonemia is present, ketones strongly positive at >1:2 dilution of serum and ketonuria is present.
3. The pt is acidotic (pH < 7.3 & bicarbonate < 15 meq/L for inpatient therapy).
Rapid initial evaluation is needed to confirm the diagnosis and assess the extent of metabolic abnormality. This should be
followed by starting the initial phase of treatment. Initially, treatment is very vigorous to halt and start to reverse the
metabolic disturbances, but once the situation is more controlled, over-vigorous medication can produce too rapid changes
in glucose, osmolarity and pH and possibly contribute to development of hypoglycemia and cerebral edema. Treatment
must be cautiously aggressive.
Emergency Management
I.
History:
It is especially important to note:
- usual insulin dose
- time and amount of last insulin dose
- recent blood and urine tests
- history of vomiting, sign of inter-current illness/infection
II.
Physical Examination:
- assess degree of dehydration (baseline weight, pulse, BP, skin, mucous membranes, oliguria; most diabetics in
moderate to severe ketoacidosis are 10% dehydrated)
- assess acidosis (Kussmaul breathing if present serum CO2 is likely to be <10)
- focus of infection
- assess neurologic status (mental status, neurologic exam)
III.
Initial Laboratory Assessment:
- differentiate DKA from nonketotic hyperglycemic coma
- do a bedside chemstrip. At the same time send stat blood sample to lab for: venous pH, glucose, serum
osmolarity and ketones, lytes, BUN, creatinine, calcium, phosphate and CBC with differential, urine ketones.
- for new onset diabetics, also send blood sample for insulin level or C-peptide level and islet cell antibody.
- ECG with standard limb leads and special attention to T-wave size
- other lab tests, cultures (e.g. blood, urine, sputum), x-rays, etc., if suspect precipitating cause such as infection
IV.
Treatment: This guideline is modified version from the reference recommendations based on
actual practice experience by the Pediatric Endocrine service at UIH.
This is not intended as a rigid prescription, but is offered only as a GUIDELINE. Each case should
be individually and frequently reassessed
Initial Management
I.
Fluids: Begin a flow sheet and monitor strict I &O.
Consider patient 10% dehydrated. Infuse normal saline 20 cc/kg for the first hour and calculate fluid replacement
volume (described below ) while infusing normal saline (NS). If in shock, give 10 cc/kg colloid over 50-60
minutes until stabilized.
After the first hour add 40 meq/L of K in IVF with 20 meq KCl /L and 20 meq KP04 /L provided that:
- the patient has voided urine
- there are no peaked T-waves on ECG done with standard limb leads
- serum potassium is not high or less than 6.0
-if serum phos level is not high
If serum phos level high, start w/ KCL and then switch to KCl/KP04 when phos level is not high.
-if serum K level is low, use 25 meq/L of KCl and 25 meq/L KP04 and consider use of IV K rider with 10 meq/hr x
1-4 hrs depending on the degree of hypokalemia.
II.
Insulin ( types of insulin used for IV : regular or humalog or novolog) :
DECREASE BLOOD SUGAR BY APPROXIMATELY 100 MG% EVERY HOUR.
IV insulin solution is to be made up of 50 units regular insulin in 250 cc of normal saline to yield a solution
containing 1 unit of insulin/5 cc (or 100 units in 500 cc) to be infused piggyback in IV tubing via pump or via
separate IV line via pump. Allow 50 cc to run through tubing to saturate insulin-binding sites before starting
infusion.
1. In general, for blood glucose > 500 mg% with moderate to severe acidemia (venous pH < 7.25):
a) Do not give bolus IV insulin as the fluid bolus administration during the first hour is likely to decrease
blood glucose level even without insulin.
b) Start separate IV line for insulin infusion therapy (if possible) apart from IV line for hydration.
Amount of insulin may be at 0.05-0.1 U/kg/hr depending on blood glucose level, ketosis and acidosis degree.
Example: 10 kg patient, 0.1 U x 10 = 1 unit/hr = 5 cc of insulin-saline solution/hr.
c) If blood glucose declines rapidly (> 100 mg/hr) then decrease insulin dose to 0.05 U/kg/hr, or if necessary
readjust the insulin dose.
d) When blood glucose level reaches approximately <300 and at about 250 mg%, add glucose (D5 or D10)
in IV solution while continuing and adjusting IV insulin infusion rate which will maintain blood glucose
level 100-200 mg%.
2. For blood glucose level < 500 mg% or if acidemia is mild (venous pH > 7.25) despite blood glucose level > 500
mg%, bolus insulin at 0.05 unit/kg only may be given, but it may not be necessary.
For insulin infusion:
a) If significant acidemia (venous pH < 7.25) is present despite blood glucose level < 500 mg%, then infuse
insulin dose of 0.1 U/kg/hr.
b) If acidemia is mild and blood glucose level is > 500 mg%, infuse insulin dose at 0.1 U/kg/hr.
c) If acidemia is mild, and blood glucose level is < 500 mg%, infuse insulin dose at 0.05-0.1
U/kg/hr.
In all cases, when blood glucose level reaches approximately 250 mg%, add glucose (D5 or D10) in IV
solution while continuing and adjusting IV insulin infusion rate which will maintain blood glucose level 100200 mg%.
3. Remember to:
a) Make up fresh solution q 24 hours (keep it in the refrigerator when not in use).
b) Regulate infusion with a pump. This is imperative if insulin infusion is piggy backed into other IV fluids.
Prepare separate IV for insulin.
III.
Bicarbonate:
IN GENERAL , DO NOT GIVE OR PUSH BICARBONATE-GIVING BICARBONATE HAS BEEN
REPORTED TO BE ASSOCIATED W/ A RISK FACTOR FOR WORSENING OR AIDING CEREBARAL EDEMA OR
METABOLIC ENCEPHALOPATHY IN DKA PTS.
May give only in the presence of severe acidosis (venous pH < 6.9), or if patient is hemodynamically unstable may
give bicarbonate 0.5 meq/kg diluted with equal amount of sterile water over 1-2 hours, or calculate base deficit to
-25-
correct HC03 to 14 meq/L (base deficit x 0.6 x kg) ÷ 4 = for quarter correction only or continue drip until pH 7.1
only. Example: If serum HCO3 10 meq/L and patient weight 30 kg (14-10 x 0.6 x 30 kg) ÷ 4 = 18 meq HCO3 to be infused over 1-2 hours Or
use Bicarbonate dose at 1-2 mmol/kg over 60 min.
Subsequent Management
* BRAIN HERNIATION is a life threatening and often unpredictable complication of DKA. Recent studies
indicate that some degree of cerebral edema commonly occurs during the course of DKA. Also, plasma
vasopressin is inappropriately elevated in patients with DKA. Therefore, fluid replacement should be as follows:
- MANNITOL SHOULD BE AT THE PATIENTS BEDSIDE THROUGHOUT THE FIRST 24 HOURS
OF THERAPY FOR SEVERE DKA, AND SHOULD BE GIVEN FOR CLINICAL
DETERIORATION IN MENTAL STATUS INDICATIVE OF OR SUSPICION OF CEREBRAL
EDEMA.
Monitoring:
1. Accucheck glucose level q 1 hour while on insulin infusion until patient is stable for 4
hours on unchanged insulin infusion and fluid/glucose intake, then accuchecks may be
done q 2 hours.
2. Blood glucose, electrolytes and venous pH q 2 hours initially, then q 4 hours.
3. Serum ketone dilutions q 4-6 hours initially then q 12 hours.
I.
Fluid and Electrolyte Management:
1. Calculation of Required Fluids and Electrolytes:
a) In DKA, assume a minimum of 10% dehydration, and calculate the deficit volume at 100 cc/kg of weight.
b) Maintenance daily fluid requirements:
100 cc/kg for 1st 10kg
┐
nd
50 cc/kg for 2 10 kg
├ Do not exceed total fluid 4L/m2/day
20 cc/kg for > 20 kg
┘
Example for 30 kg child
Deficit/Episode
10% dehydration
for 48 hrs replacement
Maintenance/24 and 48 hrs
Total 48 HRS
(Deficit +
Maintenance)
H2O=100 cc/kg x 30 kg
=3000 cc
100 cc/kg x 1st 10kg = 1000 cc
50 cc/kg x 2nd 10 kg = 500 cc
20 cc/kg x 3rd 10 kg = 200 cc
= 1700 cc/24 hr
= 3400 cc/48 hr
3000 cc+3400=
6400 cc/48 hr
Na+ 6 meq/kg = 180 meq
3-5 meq/kg/d = 90-150 meq/24 hr
= 135-225 meq/36 hr
= 180-300 meq/48 hr
270-330 meq/24 hr
315-405 meq/36 hr
360-480 meq/48 hr
K+ 5 meq/kg = 150 meq
1-2 meq/kg/d = 30-60 meq/24 hr
= 45-90 meq/36 hr
= 60-120 meq/48 hr
180-210 meq/24 hr
195-240 meq/30 hr
210-270 meq/48 hr
PO4 3 mM/kg = 90 mM
0.5-1 mM/kg/d = 15-30 mM/24 hr
= 22-45 mM/36 hr
= 30-60 mM/48 hr
105-120 mM/24 hr
112-135 mM/36 hr
120-150 mM/48 hr
-26-


1st hr
bolus
at 20
cc/kg
600
cc
If given
2nd hr
bolus
given at
10 cc/kg
300 cc
=
Infusion Rate
=
If no 2nd bolus:
6400 -600 cc=
5800 cc/47 hr
= 123 cc/hr
if 2nd bolus given:
6400 – 900cc=
5500cc/46 hr
=119 cc/hr
2.
Fluid replacement method after 1st hour bolus treatment:
a) For patients with significant CNS symptoms (drowsiness, sleepiness, unsatisfactory mental orientation,
hypertension, headache, etc.); to help prevent cerebral swelling, replace the required volume evenly over 46-47 hours (48 hr correction).
DO NOT replace urine loss
(* Reference: Journal of Pediatrics 1988; 113: 10-14,)
b) For patients with clear mental state and no significant CNS symptoms, replace the volume over 24-36 hr period
evenly.
3.
Electrolyte replacement:
a) For 47 hr fluid replacement following IV fluid bolus, use 1/2 rate as 0.9 NS and 1/2 infusion rate as
0.45 NS initially to avoid rapid osmolarity shift. If serum NA level is > 150 meq/L, then switch IV solution to 1/2
NS for the remaining replacement hours.
b) For 23 hr fluid replacement following IV fluid bolus, you may use ½ infusion rate as 0.9 NS and ½ infusion
rate as 0.45 NS initially. If serum Na level is > 150 meq/L, you may switch IV solution to 0.45 NS for the
remaining hours, provided NA level does not decline below 135 meq/L.
c) WHEN THE PATIENT HAS VOIDED AND THE POTASSIUM LEVEL IS not high (< 6.0 meq/L), start
40 meq potassium/L in IV solution initially. If K+ level declines < 4.0 meq/L, then increase K+ to 50 meq/L in IV
solution without delay. If phosphate is normal or low, give ½ as KCl and ½ as K 2PO4. If using phosphate, check
Calcium level, as there is a risk of hypocalcemia. Also, obtain PO4 levels before starting treatment and after
infusion at 24 and 48 hours.
However, if patient has NOT voided, but serum K+ level is < 3.5 meq/L or below normal and insulin
infusion has begun, 20-30 meq KCl/L may be given in the IVF. Check serum K + level hourly to determine
the direction of serum K+. If declining further, change it to 20meq/L KCl and 20 meq/L K2PO4. If K+ level
is moving toward 5 meq/L or above, discontinue or decrease amount of K+ in the IVF and re-check K+ level
in 1-2 hrs regardless of voiding history.
II. Insulin:
1. Continue insulin infusion, adjusting as necessary depending on the blood glucose level and the degree of acidosis.
When blood glucose is 250-300 mg% or less and there is still ketonemia, add D5-D12.5% glucose in IV. The
insulin dose may range 0.05-0.2 U/kg/hr. If blood sugar level decreases rapidly despite IV glucose, increase
glucose to D10% or D12.5 % or decrease the rate of insulin infusion, and maintain blood sugar level at 100-200
mg % until ketonemia clears.
2. When the blood glucose is < 250 mg%, venous pH is > 7.30 + HCO3 is > 15 meq/L serum ketone is negative at
dilution of < 1:2. Insulin infusion may be discontinued, subcutaneous insulin should be given at the time of
discontinuation of the insulin infusion.
3. Guideline of Subcutaneous insulin regimen is to be developed by Pediatric endocrine team : Both long acting
insulin( Lantus, Levemir or NPH) to provide basal insulin need (or this by insulin pump basal rate of short acting
-27-
insulin) and rapid/short acting insulin is used to cover carbohydrate meal dose and high blood glucose level
correction dose at meal times and or as PRN dose for non-meal time snack or for non meal time hyperglycemia.
a) For new diabetics or known diabetic with poor oral intake or on NPO: The patient needs both calories via IV .This is to
be used only as a GUIDELINE. Long-acting insulin already "on-board" must be considered, as well as other factors,
which would alter the requirement, i.e., stress, hydrocortisone administration, infection, etc. The child must be carefully
monitored, and insulin dose adjusted depending upon response. You may increase or decrease insulin dose with a
reasonably consistent glucose administration.
Review of General Principles in Management of DKA
1. The patient is insulin-deficient regardless of the blood glucose level. Therefore, ALWAYS MAINTAIN
INSULINIZATION. If the blood glucose falls too fast, decrease insulin dose or increase the IV glucose. Use D10/D12.5%
in IVF if necessary. REMEMBER THAT TO REVERSE THE METABOLIC DERANGEMENTS, THE PATIENT
NEEDS INSULIN, FLUIDS, ELECTROLYTES, AND CALORIES.
If the patient is off IV insulin he/she must be given subcutaneous regimen.
2. Clinical decisions are based on data. These include physical findings and laboratory data. Therefore, THE
PATIENT MUST BE CHECKED AT FREQUENT INTERVALS - i.e., CLOSE MONITORING OF
CHANGES IN MENTAL STATUS, VITAL SIGNS, pH, GLUCOSE, ELECTROLYTES, FLUID
BALANCE.
3. To properly integrate the data and make proper clinical decisions, AN UP-TO-THE-MINUTE FLOW SHEET
MUST BE MAINTAINED.
4. Every patient in DKA will need a lot of IV fluids, therefore, A STABLE, LARGE IV LINE IS ESSENTIAL
(not a 25g Butterfly in a tiny peripheral vein). IF A GOOD IV LINE CANNOT BE STARTED, CALL PICU
ATTENDING.
5. IV INSULIN MUST BE GIVEN VIA AN INFUSION PUMP. DO NOT ALLOW IV INSULIN TO "DRIP."
6. Always think about what you are treating while you closely follow your patient. A PROTOCOL IS A
GUIDELINE ONLY, NOT A SUBSTITUTE FOR "CEREBRATION". Each patient's DKA
management must be individualized, based on the patient's mental, physical, and biochemical findings.
7. If there are any problems, do not hesitate to call the Pediatric Endocrine Services for help.
8. SEE NEXT PAGE FOR EXAMPLE OF DIABETIC KETOACIDOSISFLOW-SHEET
References:
-J of Pediatr 1988; 113: 10-14,
-Glaser at al Risk factorsfor cerebral edema in chidren with diabetic ketoacidosis N Engl J Med 2001:344:264269
-Dunger et al European sodiety for Pediatric endocrinology/Lawson Wikins Pediatirc Endocrine society
consensus statement on diabetic ketoacidosis in children and adolescents. Pediatrics 2004: 113: e133-e140 and
Arch DisChild. 2004:89:188-194
-Wolfsdorf et al ISPAD Clinical Practise consensus Guideline 2006-2078. Pediatric Diabetes 2007,8:28-43
-Green et al failure of bicarbonate to improve outdome in severe DKA. Ann Emerg Med. 1998, 31-41-48
-28-
NAME:
HOSP. #:
DATE
DIABETIC KETOACIDOSIS
FLOW-SHEET
:
TIME (hrs)
0
CLOCK TIME
CLINICAL Vital Signs
Mental Status
Weight
INSULIN
THERAPY IV Infusion (u/hr)
(cc/hr)
SUB Q
FLUID
INTAKE
(u)
Fluid Type
IV #1
Volume
Fluid Type
IV #2
Volume
Fluid Type
Oral
Volume
FLUID
OUTPUT
Urine
Emesis
Other
LABS
Accucheck, BS
Blood Glucose
Serum Ketones
Urine Ketones
pH
Na/K
Cl/CO2
Ca/PHOS
Other
-29-
1
2
3
4
5
6
7
8
B) DIABETIC KETOSIS only
Rx of diabetic hyperglycemia with or without ketosis, but not in frank DKA, this applies to both emergency room outpatients and in hospital management:
This may not require insulin infusion and ICU, but still requires close attention, and fluid and insulin
treatment. The general approach and initial tests are the same as given for DKA.
1.
2.
3.
Fluids calculated on Maintenance and Deficit, estimate of percent dehydrated. Can take PO fluids if not vomiting.
Hydration is an essential part of therapy.
Insulin:
a) May use continuous low dose IV insulin infusion (regular insulin 0.025-0.05 unit/kg/hr), or give one initial IV
bolus regular insulin 0.05-0.1 U/kg to begin metabolic repair and give SC regular insulin dose, at the same
time which is absorbed slowly (SC insulin based on sliding scale).
b) May need to adjust, if long-acting insulin recently taken, but if hyperglycemia and ketosis are present, then by
definition, is insulin-deficient and needs short-acting insulin every 4-6 hours.
You must check Accucheck q 1 hr during or following (3 hrs) IV insulin administration.
C) NONKETOTIC HYPEROSMOLAR HYPERGLYCEMIC STATE
(Guideline for the Pediatric Patient)
This condition is characterized by severe hyperglycemia (usually > 600 mg/dl) hyperosmolarity (> 320 mOs), Arterial pH
>7.3, HCO3 > 15 meq/L, plasma ketone absent or < 1:2 dilution or beta-hydroxybutyrate 1+-0.2 mmol/L and
dehydration, stupor or coma.
Although it is usually a complication of NIDDM, it can occur in IDDM at any age if enough insulin is present to prevent
ketoacidosis, but is insufficient to control the blood sugar. This condition is rare in pediatric age patients, however, it can
occur in patients on diuretics, steroid treatment and acute illness (infection, trauma, bums, etc). Severe dehydration is
thought to be the pathogenic factor.
The principles of treatment are: (1) fluid replacement, (2) insulin to be added if fluid replacement alone for the first 2
hours does not decrease blood glucose level, and (3) treatment for underlying problem (infection, trauma, etc).
The following is our guideline for patients with non-ketotic hyperosmolar coma, and was modified from that of adult
patient management protocol.
Fluid Replacement Therapy
Too rapid a fall of plasma glucose level should be avoided in order to prevent dangerous fluid shifts, with a rapid
and marked reduction in ECF Osmolarity, fluid moves from ECF to ICF This may lead to cerebral edema.
Step 1: Do all the chemistry and hematological studies as in DKA patients.
Step 2: While waiting for lab data, initiate fluid therapy and call neurologist for a thorough neurologic examination.
First Two Hours: Fluids
- Normotensive patient - 2/3 NS or normal saline should be infused at the rate of 15-20 cc/kg/hr
- Hypotensive patient - use normal saline.
- Severe Hypotensive patient - use colloid same as in DKA.
- Insulin: none
- Calculate fluid requirement as in DKA: 10% dehydration + maintenance fluid/24 hrs.
-30-
Hour 2-24 Fluids
- If serum sodium level < 135 always use normal saline.
- If serum sodium level > 135-145 use 2/3 NS or NS
Administer 2/3 of total amount of fluid for 10% dehydration correction plus maintenance fluids evenly
distributed over the first 24 hours.
- Carefully evaluate neurological status and blood glucose levels every hour and other blood chemistry every
two hours.
- Insulin Therapy.
- At 2 hours after initiating fluid treatment, IV insulin treatment should be started if the plasma glucose level
has not decreased appreciably and is > 700 mg% (generally patients with non-ketotic hyperosmolar coma
are sensitive to insulin). Thus, use smaller dose of insulin than used in treatment of DKA, e.g. 0.03-0.05
units/kg/hr rather than the 0.1 unit/kg/hr.
- Bolus injection of insulin prior to insulin drip may or may not be needed in hyperosmolar non-ketotic coma.
If the patient has voided, potassium (KCl/K phosphate) must be added in IV fluid (20-40 meq/L of IV fluid)
as insulin infusion begins. This is the same as DKA management.
- If plasma glucose level has not decreased by 50-100 mg% two hours after insulin treatment, insulin infusion
rate should be doubled.
- When plasma glucose level is 200-300 mg%, glucose containing solution (D5NS) may be substituted for the
saline.
- Make sure IV insulin is not prematurely discontinued.
- Prior to discontinuation IV insulin administer SQ insulin 0.1-0.2 unit/kg of regular insulin at least 20-30
minutes prior to D/C IV insulin.
Step 3: During hours 2-8, evaluate the precipitating and associated conditions of the patients and other supportive
procedures.
Step 4: If the patient is alert and able to retain fluid, then gradually switch IV fluid intake to oral fluid intake. Remember
that electrolytes, phosphate and magnesium are depleted in these patients. These could be replaced orally over
the next several days.
Sliding scale, SC. Insulin should be administered at least 30 minutes prior to meal ingestion
.
Reference for adult patients: Gerich, J.E. Hyperosmolar non-ketotic coma. In: Current
Therapy in Endocrinology and Metabolism. Bardin (ed.). B.C. Decker, Philadelphia, 1988.
Reference for Pediatric patients for definition and short brief for HHS: Wolfsdorf et al
Pediatric Diabetes 2006-2007,ISPAD clinical; practice consensus guideline 2006-2007- DKA.
-31-
D) SURGERY GUIDELINES-revised based on most recent guideline as of 8/2010 by the UIH.
1. If non-emergency, schedule surgery in the morning hours and when patient is in reasonable diabetic control.
2. On day of surgery on NPO
- Fluids: use D5 electrolyte solution, for adequate hydration give maintenance to 1½ maintenance.
- Insulin:
- NO INSULIN INFUSION TO B E USED DURING SURGERY
Give 1/2 daily dose of long acting or intermediate insulin ( lantus, levemir or lente, NPH). and if high bg ,
may give one time 1/3 or ½ of short acting insulin before surgery.
- Following surgery in the recovery room, PRN short/rapid acting insulin (Novolog /Humalog) per sliding scale
every 3-4 hrs may be administered SQ to correct high blood glucose level >250 and to prevent severe
hyperglycemia and ketosis or use SC insulin infusion by insulin pump device with glucose in IVF or use IV
insulin infusion with glucose in IVF to maintain bg level<250.
3. Postoperatively after leaving recovery room:
- May need additional PRN short/rapid acting insulin to be administered SQ per sliding scale every 3-4 hrs or
SC insulin infusion by pump or IV insulin infusion with D5 NS % in IVF to achieve blood glucose level
150-200 mg/dL
- Once patient is able to eat and tolerate po, then resume usual insulin regimen but modify the dose as per po
intake
4. Management
- Electrolytes, BUN, blood glucose, pre and post-operatively, and every 2-4 hours thereafter in immediate postoperative period.
Various methods of management of diabetes during surgery may include:
1.
2.
-32-
Use of intravenous glucose with 1/2 of patient's usual morning dose of NPH, Lente, lantus with 1/3 to ½ short acting
insulin given SQ prior to surgery.
Use of intravenous glucose with the usual dose SQ NPH or Lente prior to surgery with or without prn base .sliding
scale of short acting insulin before and after surgery.
VI. THYROID DISORDERS
- CONGENITAL HYPOTHYROIDISM (CH)
Suspected CH
I. Clinically: May be present in 10-15% of hypothyroid newborns.
1. Most frequent:
a. Patient posterior fontanelle and widely opened cranial sutures.
b. Umbilical hernia.
2. Less frequent:
a. LGA babies
b. Feeding or sucking difficulties
c. Prolonged jaundice, constipation
d. Hypotonia, hoarse cry, skin mottling
II. Abnormal Newborn Screening Test Results:
1. Elevated TSH, low T4
a. Primary hypothyroidism
┬ Retest and immediate treatment with L-Thyroxine
b. Transient hypothyroidism
┘
2. Elevated TSH and normal T4: Compensated primary hypothyroidism.
3. Normal TSH, low T4
a. Transient hypothyroxinemia of the newborn: Euthyroid clinically.
b. Congenital thyroxine binding globulin deficiency: Euthyroid clinically.
c. Hypopituitary-hypothalamic hypothyroidism: Clinically suspected hypothyroidism. Suspect in newborns
with hypoglycemia, diabetes insipidus, persistent jaundice, micropenis, midline craniofacial defects, ocular
abnormalities. Investigate for panhypopituitarism.
d. Low birth weight infants.
Work-up for Suspected CH
Ultimate goal is detection and early treatment of all infants to ensure normal neurologic and somatic development.
I. If Confirmatory Testing Shows the Following:
1. Low T4, elevated TSH: Immediate replacement treatment with L-Thyroxine.
2. Low T4, normal TSH: Do TBG, T3RU. free T4 levels
a. Normal free T4, low TBG = TBG deficiency, no treatment.
Low free T4, normal TBG = possible TSH deficiency. Immediate replacement treatment with L-Thyroxine.
3. Normal T4, elevated TSH = Compensated hypothyroidism. Treat based on clinical picture. If TSH is quite high, treat
the patient with L-Thyroxine.
4. Normal T4, normal TSH
a. Normal birth weight = Transient hypothyroidism of the newborn of undetermined etiology. Follow-up the
patient's growth development on no treatment
b. History of low birth weight = Transient hypothyroidism. No treatment for a or b.
II. Bone Age: Do this only in confirmed hypothyroid cases.
III. Technician Scan or Thyroid Ultrasound: To be done either immediately or later (do not delay treatment for this).
IV. TSH blocking receptor AB: In infants born to mothers with history of autoimmune thyroid disease (can cause
transient hypothyroidism in the newborn).
-33-
Therapy
Principles of therapy should be to ensure a prompt rising of serum T4 or free T4 concentration to the upper normal range,
and suppression of serum TSH to a normal level. May begin with L-Thyroxine 10-15 µg/kg/day. Dose adjustment based
on follow-up T4 and TSH levels.
L-Thyroxine Dosage Schedule for Hypothyroidism of Infancy and Childhood
Age
Dosage (µg/kg/day) Range of Dose
Birth to 6 mo
10
25-50
6-12 mo
6-10
50-75
1 - 5 yr
5-6
75-100
6 - 12 yr
3-5
75-125
> 12 yr
2-3
100-150
MYXEDEMA COMA
Definition: The end stage of severe thyroid hormone deficiency when patients develop failure of multiple organ systems
and laps into stupor and even death.
Causes
Onset is often precipitated by additional stress:
1. Infection
2. Ingestion of sedatives or narcotics
It is very rare in children, encountered more frequently:
1. In the winter months
2. In the elderly
3. In women
4. In those with a history of goiter, autoimmune thyroid disorder or thyroid abnormality.
5. In those who have discontinued thyroid hormone treatment.
Diagnosis
Clinical:
Biochemical:
Prognosis:
Work-up:
Non-pitting edema
Hypothermia
Hypoventilation
Stupor, cardiomyopathy, convulsion
Very low serum T4 and high TSH serum levels
Depends on duration of myxedema coma. Early substitution of both general supportive treatments and
specific thyroid hormone replacement.
Serum TSH, free T4 or total T4
CBC, U/A, lytes, BUN, Cr, CK SGOT.
Blood gases, blood culture, chest X-ray, EKG
Monitoring of body temperature and BP, and serum cortisol level.
Principles of Treatment
1. Stabilization of vital body functions: airway, ventilation, circulation and temperature.
2. Hyponatremia is often present. May need to give hypertonic saline and limit the volume of water in the infusion fluid.
3. Thyroid hormone replacement: To replace thyroid hormone deficit quickly and to saturate the large binding capacity on
the thyroxine binding proteins in order to provide an effective circulating level of free T4.
- Use T4 IV only or T4 IV and T3 IV.
-34-
- Loading dose of T4: 2 µg/kg IV over 5 min., then 1.5 µg/kg daily by IV, then oral when able to eat
4. Glucocorticoid Treatment: Many patients with autoimmune thyroid diagnosis may have adrenal insufficiency, and
hydrocortisone metabolism is decreased in myxedema coma. So hydrocortisone stress dose may be given at the
beginning and repeated thereafter q 8 hrs.
HYPERTHYROID STORM
Causes
1. Withdrawal of antithyroid medications in a patient with severe hyperthyroidism.
2. Administration of radioactive iodine (short term).
3. Infection (pneumonia).
4. Surgery and anesthesia.
5. DKA and insulin reaction.
6. Vigorous palpations of the thyroid gland.
7. Trauma
8. Dental extraction.
9. Mental stress.
Clinically
Significant Fever
Cardiac: - Tachycardia (out of proportion to the fever.)
- Atrial fibrillation.
- Increased pulse pressure.
CNS:
- Altered mental status: Restlessness, severe tremors, agitation, psychosis, inability to concentrate, stupor, coma
GI:
- Nausea, vomiting, diarrhea, abdominal pain.
Other: - Pre-renal failure, hepatic failure
Lab Evaluation
- Free T4 Total T4, T3 RIA all elevated
- TSH suppressed.
- Serum lytes, renal function tests, liver function tests to manage fluid and electrolyte imbalance.
Management
This is an emergency, rare in childhood. All dosages are for adolescents - adults and dose to be adjusted for children
. Treatment should be initiated at the earliest suspicion..
1. Blockade of Thyroid Hormone Synthesis
a) Thionamides: Antithyroid drugs (in all cases)
- Methimazole=Tapazole: 30 mg every 6 hours for adolescents and 5-15 mg every 6 hours in children depending on
age.
- Use until crisis resolves.
PTU has been reported to cause infrequently but severe hepatitis in children that may be fatal and is no
longer recommended for use in children .
2. Blockade of Release of Thyroid Hormone, T4, from the Gland (in all cases)
a. Iodides: Should delay until 1-3 hours after initiation of thionamides
 NaI by IV: 0.5 mg q12 hours
 Lugol’s solution: 10 drops orally q8 hours or saturated solution of KI: 3 drops orally q8
hours
 If NaI by IV is not available and patient cannot take oral medications, use 10 drops of
-35-
Lugol’s solution added to IV fluid.
b. Lithium: 600 mg orally as initial dose then 300 mg q6 hours (in some cases).
1. Monitor serum level of lithium and keep < 1.5 meq/L
2. Do not use in heart failure, renal failure or arrhythmia.
3. Inhibition of T4 and T3 conversion:
a. Dexamethasone sodium phosphate: 2 mg IV then 2 mg orally q6 hours (in all cases).
b. The iodinated cholecystographic contrast agents (iopanoic acid and ipodate).
 They may be used as a substitute for both inorganic iodide.
 They also release inorganic iodide.
4.
Control of sympathetic and adrenal medullary effects:
a. p.o. Propranolol: 20 mg tid for adolescents, 15 mg tid for children; 10 mg tid for young children.

It also decreases peripheral T4 and T3 conversion:

If signs of heart failure occur  digitalization.
5. Control of body temperature if necessary:

Artificial cooling: Ice packs, cooling blankets

CNS blockade with IV phenothiazines and narcotic analgesic (to prevent shivering, assist in
restoring body temperature).

Chlorpromazine
25-50 mg (q4-6 hours)

Meperidine
25-50 mg
If hypothermia persists  Dantrolene 100 mg by IV
Addendum for thyrotoxicosis management using 131I therapy:
1. Set up an appointment with nuclear medicine for an uptake study on Day 1 and to receive 131I treatment on Day 2
as an outpatient.
2. Then discontinue all anti–thyroid agents for 5-7 days prior to the uptake testing date.
3. Inform the patient’s family of temporary thyrotoxic symptoms following 131I treatment and tell them that there is a
90% chance of developing permanent hypothyroidism after 131I.
4. Take precautions when treating any hyperthyroid patient with radioactive iodine as an outpatient and when there
is a child < 6 yrs old in the house.
a. If the dose of radioactive iodine is < 12 millicuries: stay away from the child in the same house for 24
hours.
b. If the dose of radioactive iodine is 12-29 millicuries: Isolation for 24 hours. Any child < 6 yrs old should
not stay in the house for 24 hours.
NEONATAL GRAVE’S DISEASE (THYROTOXICOSIS)
Occurs in 1% of infants of mothers with Graves' Disease via transplacental passage of TS Ab from the mother to the
infant.
Clinical Features
Prematurity
Goiter
Exophthalmos
Tachycardia
Hyperirritability
Congestive Heart Failure
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Jaundice
Hepatosplenomegaly
Thrombocytopenia
- Disease becomes evidently active for 5-10 days after birth if the newborn was exposed to maternal antithyroid
medication in utero.
- Mortality rate:
15-20%
- Clinical sequela:
Craniosynostosis
IQ impairment
Treatment
Very mild thyrotoxicosis:
Mild thyrotoxicosis:
Moderate thyrotoxicosis:
Severe thyrotoxicosis:
Close observation and no-specific therapy.
Tapazole=Methimazole 0.5-1 mg q 8 hrs PO
Iodide drop (Na or K): 1 drop q 8 hrs + Methimazole 1 mg q 8 hrs
Iodide 1 drop q 8 hrs
+ Methimazole 1 mg q 8 hrs
+ Propranolol 2 mg/kg/d BID to TID
- Don't use propranolol alone in neonatal hyperthyroidism due to its complication and hazard to the neonate Supportive
care includes use of oxygen, digitalis, and antibiotics if indicated.
- If large goiter is present, prevent tracheal obstruction to maintain airway.
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VII. PERSITENT DYSFUNTIONAL BLEEDING IN ADOLESCENT FEMALE
1. Administer Necon 1/35 OCP- 1 tab po t id every 8 hrs x 3 days
- 1 tab po bid every 12 hrs x 2 days
- 1 tab po per day x 1 day
2. Then start OCP (ie. Trphasil 28)
3. Do CBC baseline and then begin Ferinsol 325 mg pot id or ferrous sulfate 300 mg po daily x 1-2
months and folic acid 1 mg po daily x 1 month.
Retest CBC at 1 month and 2 months.
Medical Curettage method for severe uterine dysfunctional bleeding in adolescent
women
1. Administer Aygestin 10 mg (two 5mg tabs) PO hourly until bleeding completely stops. Begin FerInSol 325mg po tid
and folic acid 1 mg po qd continuously.
2. Then continue Aygestin 10 mg po bid x 1 month. Some spotting may occur, but this will get lighter and will stop
eventually Gyn consult and uterine ultrasound would be necessary during 1 and 2 phases
3. Discontinue Aygestin at 1 month. This will cause presumably normal amount of withdrawal bleeding.
4. Thereafter, menstrual pattern can be observed or one may go on a monthly OCP Rx or monthly Provera treatment for
5 days for regulation of menstrual cycle.
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