Pediatric Endocrinology

Sarah Lawrence
Division of Endocrinology
CHEO

Type 1 Diabetes

Epidemiology of Type 1
Prevalence 0.4% of individuals < 18 years
Increased risk to family members

Sibling
5%
Father with diabetes 6-8%
Mother with diabetes 2-3%
Identical twin
30-50%

Type 1 Diabetes
% Beta Cells

Genetic
predisposition
Antibody
positive

Diabetes

Time
Environmental insult

Diagnostic Criteria
FBG > 7.0 mmol/L

OR

Casual BG > 11.1 with symptoms OR

2 hour BG in OGTT of > 11.1

INITIAL MANAGEMENT

New Onset DM: Baseline labs

Glucose, urea, creat, lytes, gas
Urine for glucose and ketones
TSH, thyroid antibodies

New Onset DM: Diet

1000 kcal + 100 kcal/year of age
i.e. 8 yo child = 1000 + 800 = 1800 kcal
3 meals and 3 snacks
Currently use exchange system, but changing

to carbohydrate counting
Starch 15 g
Fruit/Sugar 10 g
Dairy
6g

BG Targets
Age (years)

Premeal target
(mmol/L)

HbA1c Target (%)

<5

6-12

< 9.0%

6-12

4-10

< 8.0%

>12

4-8

< 7.0%

HbA1c & BG levels

New Onset - Insulin

Dose

25 x( 0.5) = 15

By weight: 0.5 0.75

unit/kg/day
2/3 am, 1/3 pm
2/3 N, 1/3 H
i.e. 8 yo, 25 kg

Am 10 U

7N

Pm 5 U

3H

3.5 N

1.5 H

By age

8 yo

Am N = 1 unit/year of age
AM H is 50% of this
PM dose is 50% of the
am dose

am

8N

pm

4H

4N

2H

Twice Daily Insulin:NPH + R/analogue

am

noon

pm

hs

am

Three Times Daily Insulin:NPH + R/analogue

am

noon

pm

hs

am

Basal-Bolus Insulin Therapy: Insulin Glargine at

HS and Mealtime Lispro or Aspart
Insulin Glargine or Levemir
Insulin Lispro or Aspart

Type 1 DM

HS

Time of administration
B, breakfast; L, lunch; D, dinner; HS, bedtime.
Adapted from:
1. Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002.
2. Bolli GB, et al. Diabetologia. 1999;42:11511167.

Basal

Insulin Injection Sites

Picture of lipohypertrophy

Insulin adjustment: basic principles

New onset, making daily changes until stabilized
Established diabetes

Highs:

High BG same time of day x 3 consecutive days

Increase 10% at a time

Lows:

Unexplained lows 2x/week same time of day

10-20% at a time

Insulin adjustment: basic principles

Time of Day

Insulin to adjust

Morning

pm N

Noon

am R

Supper

am N

Bed

pm R

R
N

am

noon

pm

hs

am

Hypoglycemia

Causes:
Too much exercise/activity for which you did not plan
Not enough food and/or delay in getting the
meal/snack
Too much insulin

Treatment:
<20 kg
>20 kg

10 g CHO
15 g CHO

Hypoglycemia
Severe hypoglycemia
Glucagon

<5 years 0.5 mg

> 5 years 1 mg

Minidose glucagon protocol

Persistently low but alert and unable to
manage orally (e.g. during illness or
inadvertent insulin error)

DKA: How common is it?

At diagnosis of diabetes
15-67% present with DKA
Established diabetes
1-10% of patients/year
Cerebral edema
0.4-1% of episodes of DKA
25% mortality, up to 35% with severe
neurologic deficits

Cerebral Edema in DKA

Who is at risk?
Increased risk in new onset DM, more dehydrated and
acidotic patients
?treatment factors rapid infusion of hypo-osmolar
fluids, use of bicarbonate
Treatment early intervention is key
Raise HOB, + intubate, reduce fluids
Mannitol, hypertonic saline

Insulin Dose Adjustment

Guidelines for Intercurrent Illness

TDD = Total Daily Dose

Type 2 Diabetes in
Children and Youth

For Children, BMI Changes with Age

BMI

BMI

Boys: 2 to 20 years

Example: 95th
Percentile
Tracking
Age
2 yrs
4 yrs
9 yrs
13 yrs

BMI

BMI

BMI
19.3
17.8
21.0
25.1

Genetic and Environmental Risk

factors for T2DM
Ethnicity
Female gender
Family history T2DM
Intrauterine factors

Maternal history of gestational diabetes

Large for gestational age (>4 kg)
Small for gestational age (<2.5 kg)

Obesity
Sedentary behaviour

Development of Type 2 Diabetes

Normal

Insulin resistance

Impaired Glucose Tolerance

Type 2 Diabetes

Acanthosis Nigricans

% with Metabolic Syndrome

Metabolic Syndrome in Youth by

BMI

BMI Percentile

Treatment of T2DM in Youth

Diabetes education for the family
Setting glycemic targets

HbA1c < 7.0%

Lifestyle modification
<10% achieve glycemic targets
Pharmacotherapy

Metformin has been shown to have short term efficacy

and safety in adolescents
Insulin rescue is required in those with severe
metabolic decompensation at diagnosis
e.g. DKA, A1C 9.0%, symptoms of severe
hyperglycemia, ketonuria

Presentation of T1DM vs T2DM

Type 1

Type 2

Up to overweight

85% overweight

Short Course

Indolent course

25-40% DKA
FHx T1DM in 5-10%

33% ketonuria
5-25% DKA
FHx T2DM 74-100%

Predominantly white

Minority youth

Thyroid Disorders

Approach to Goitre
Goitre

TSH

Elevated
Hypothyroid

Thyroid Antibodies

+ve
Chronic lymphocytic
thyroiditis

-ve
Goitrogen,
Dyshormonogenesis

Normal
Euthyroid

Suppressed
Hyperthyroid

Hypothyroidism

Hypothyroidism - Treatment
Medication: Thyroxine 75-100 mcg/m2/day
Monitor every 6 months until growth complete, then
annually:
SSx hypo/hyperthyroidism
Growth
Sexual maturation
TSH (aim for 0.25-5 mU/L)
+ FT4
Recheck TSH 4-6 weeks after dose adjustment

Approach to Goitre
Goitre

TSH

Elevated
Hypothyroid

Thyroid Antibodies

+ve
-ve
Chronic lymphocytic
Goitrogen,
thyroiditis
Dyshormonogenesis

Normal
Euthyroid

Suppressed
Hyperthyroid

Thyroid Antibodies

+ve/-ve: Graves
Hashitoxicosis
Subacute thyroiditis

Graves Disease

Hashitoxicosis / Subacute
thyroiditis
Hyperthyroid phase

Hypothyroid phase

TSH

FT4

Time

Hyperthyroidism - Management
Medical Management
Antithyroid medications
Methimazole (MMI, TapazoleTM)
Initial dose: 0.4-0.6 mg/kg/day q8-12h
Maintenance:0.2-0.3 mg/kg/day q12-24h
Propylthiouracil (PTU)
Initial Dose: 4-6 mg/kg/day q6-8h
Maintenance 2-3 mg/kg/day q 12h (-24h)
Propranolol
Iodide
Radioactive Iodine
Surgery

Hyperthyroidism - Management
Side Effects of Antithyroid medications:
Mild - pruritis, rash, abdominal pain, neutropenia,
Serious - agranulocytosis, arthropathy, lupus-like
syndrome, hepatitis

Hyperthyroidism - Management
Medical Management - Monitoring
Initially monitor q 4-6 weeks until T4 stabilized on
maintenance doses of MMI/PTU, then q 3-4 months.
Clinical status
T4, TSH
Generally continue treatment for 2 years then try off tx
and monitor closely for relapse

Approach to Goitre
Goitre

TSH

Elevated
Hypothyroid

Thyroid Antibodies

Normal
Euthyroid

Thyroid Antibodies

+ve
-ve
+ve
Chronic lymphocytic
Goitrogen,
Chronic lymphocytic
thyroiditis
Dyshormonogenesis
thyroiditis

-ve
Colloid goitre

Suppressed
Hyperthyroid

Thyroid Antibodies

+ve/-ve
Grave's disease,
Subacute thyroiditis

Subclinical Hypothyroidism
Normal

TSH

FT4

Subclinical
Overt
Hypothyroidism Hypothyroidism

Summary
Thyroid disorders are common in children and

adolescents

Most commonly present with goitre secondary

to autoimmune thyroiditis or a simple colloid

goitre

TSH and thyroid antibodies is usually all that is

required to establish the diagnosis

Ultrasound should be limited to those with a

palpable nodule

Summary
The normal range of TSH may be higher

in the pediatric population leading to overinvestigation /diagnosis and treatment of

thyroid disorders
Mild elevations of TSH should be verified

on repeat testing
TSH <10mU/L often normal on repeat

Summary
Natural history studies suggest a high

rate of spontaneous resolution with

autoimmune thyroid disease and thus,
repeat testing should be done before
committing to lifelong thyroid hormone
replacement

Precocious Puberty
Presence of secondary sexual development by age:
8 in a girl
9 in a boy

Approach to Precocious Puberty

Precocious Puberty
Growth Velocity
Bone Age

Normal

Increased

Normal variant

Pathological

Estrogen

Premature Thelarche

Androgens

Premature Adrenarche

Central

Peripheral

Androgens

Estrogen

Approach to Precocious Puberty: Females

Bone age, GV

Normal

Increased

Normal Variant

Pathological

Estrogen

Androgens

Central

Premature
Thelarche

Premature
Adrenarche

Estrogen
+/- androgens

Peripheral

Estrogen

Androgens

Ovary
Adrenal
Other

Ovary
Adrenal
Other

Approach to Precocious Puberty:

Males
Bone age, GV

Normal

Increased

Normal Variant

Pathological

Androgens

Central

Premature
Adrenarche

Testes > 4ml

Peripheral

Androgens

Estrogen

Testes
Adrenal
Other

Testes
Adrenal
Other

Delayed Puberty
Absence of secondary sexual development by age:

13 in a girl
14 in a boy

Approach to Delayed Puberty

Delayed Puberty

LH, FSH

Low

High

Central

Peripheral

Constitutional Delay
of Growth and Puberty

Hypothalamic or
Pituitary Cause

Gonadal Failure

Delayed Puberty: Investigations

Growth records
Bone age
LH, FSH
Sex hormone levels - not needed
Other hormones as clinically indicated (T4, TSH, GH,

Prolactin, Cortisol)

Delayed Puberty: Treatment

Constitutional Delay of Growth and Puberty
Boys:
Treat if psychologically distressed
Depot testosterone 75-100 mg IM monthly x 3

Girls:
Usually dont treat (even low dose estrogens cause
accelerated skeletal maturation)

Delayed Puberty: Treatment

Hyper / Hypogonadotropic Hypogonadism
Boys:
Testosterone intramuscular injection, transdermal patch/gel or
orally, gradually increasing to adult doses

Girls:
Start with low dose estrogen, increasing over 1-2 years, then begin
cycling with estrogen and progesterone

Short Stature

Approach to Short Stature

Short Stature
Growth velocity
Target Height

Normal Variant

Familial Short Stature

Pathologic

Constitutional Delay

Proportionate

Prenatal

Idiopathic Short
Stature

IUGR
Dysmorphic syndromes
Chromosomal disorders

Disproportionate

Postnatal

Medications
Chronic disease
Endocrine

Chronic
Disease

Endocrinopathy