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%

Bet

a C

ells

Time

Genetic predisposition

Environmental insult

Antibody positive

Diabetes

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 6 g

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 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

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

am dose

8 yo

am pm

8N 4H 4N 2H

25 x( 0.5) = 15

Am 10 U Pm 5 U

3.5 N 1.5 H7 N 3 H

am noon pm hsam

Twice Daily Insulin:NPH + R/analogue

am noon pm hsam

Three Times Daily Insulin:NPH + R/analogue

Basal-Bolus Insulin Therapy: Insulin Glargine at HS and Mealtime Lispro or Aspart

B DL HS

Insulin Glargine or Levemir

Insulin Lispro or Aspart

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;42:1151–1167.

Type 1 DM

0

1

2

3

4

5

6

7

8

24 3 8 12 18 20 24Time

Insu

lin

Correction BolusMeal Bolus

Basal

Insulin Injection Sites

Picture of lipohypertrophy

Insulin adjustment: basic principles New onset, making daily changes until stabilized Established diabetesHighs:

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 principlesTime of Day Insulin to adjust

Morning pm N

Noon am R

Supper am N

Bed pm R

am noon hspm am

R R

NN

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 10 g CHO

>20 kg 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

BG Ketones Insulin

<5 +/- Reduce N and R by 20%

5-14 +/- Give usual dose

>14 Neg to small (< 0.6)

Give 10% of TDD

>14 Moderate (++) (0.7-1.5)

Give 15% of TDD

>14 Large (3+/4+) (>1.5)

Give 20% of TDD

Insulin Dose Adjustment Guidelines for Intercurrent Illness

TDD = Total Daily Dose

Type 2 Diabetes in Children and Youth

Example: 95th Percentile Tracking Age BMI

2 yrs 19.3 4 yrs 17.8 9 yrs 21.013 yrs 25.1

For Children, BMI Changes with Age

Boys: 2 to 20 years

BMI BMI

BMI BMI

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 DiabetesNormal

Insulin resistance

Impaired Glucose Tolerance

Type 2 Diabetes

Acanthosis Nigricans

Metabolic Syndrome in Youth by BMI

0.1

6.1

28.7

50

0

5

10

15

20

25

30

35

40

45

50

<8585-95>95>97

% w

ith

Met

abo

lic

Syn

dro

me

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 ¼ overweight

Short Course

25-40% DKA

FHx T1DM in 5-10%

Predominantly white

85% overweight

Indolent course

33% ketonuria5-25% DKAFHx T2DM 74-100%

Minority youth

Thyroid Disorders

Approach to Goitre

+ve

Chronic lymphocytic

thyroiditis

-ve

Goitrogen,

Dyshormonogenesis

Thyroid Antibodies

Elevated

Hypothyroid

TSH

Goitre

Suppressed

Hyperthyroid

Normal

Euthyroid

Hypothyroidism

Hypothyroidism - TreatmentMedication: Thyroxine 75-100 mcg/m2/day

Monitor every 6 months until growth complete, then annually:

SSx hypo/hyperthyroidismGrowthSexual maturationTSH (aim for 0.25-5 mU/L)+ FT4

Recheck TSH 4-6 weeks after dose adjustment

Approach to Goitre

+ve

Chronic lymphocytic

thyroiditis

-ve

Goitrogen,

Dyshormonogenesis

Thyroid Antibodies

Elevated

Hypothyroid

+ve/-ve: Graves

Hashitoxicosis

Subacute thyroiditis

Thyroid Antibodies

Suppressed

Hyperthyroid

TSH

Goitre

Normal

Euthyroid

Graves Disease

Hashitoxicosis / Subacute thyroiditis

TSH

Time

FT4

Hyperthyroid phase Hypothyroid phase

Hyperthyroidism - ManagementMedical Management

Antithyroid medicationsMethimazole (MMI, TapazoleTM) Initial dose: 0.4-0.6 mg/kg/day q8-12hMaintenance:0.2-0.3 mg/kg/day q12-24h

Propylthiouracil (PTU)Initial Dose: 4-6 mg/kg/day q6-8hMaintenance 2-3 mg/kg/day q 12h (-24h)

PropranololIodide

Radioactive IodineSurgery

Hyperthyroidism - ManagementSide Effects of Antithyroid medications:

Mild - pruritis, rash, abdominal pain, neutropenia,

Serious - agranulocytosis, arthropathy, lupus-like syndrome, hepatitis

Hyperthyroidism - ManagementMedical 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

+ve

Chronic lymphocytic

thyroiditis

-ve

Goitrogen,

Dyshormonogenesis

Thyroid Antibodies

Elevated

Hypothyroid

+ve

Chronic lymphocytic

thyroiditis

-ve

Colloid goitre

Thyroid Antibodies

Normal

Euthyroid

+ve/-ve

Grave's disease,

Subacute thyroiditis

Thyroid Antibodies

Suppressed

Hyperthyroid

TSH

Goitre

Subclinical Hypothyroidism

Normal SubclinicalOvert

Hypothyroidism Hypothyroidism

TSH N

FT4 N N

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 over-investigation /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

Growth Velocity

Bone Age

Premature Thelarche

Estrogen

Premature Adrenarche

Androgens

Normal variant

Normal

Central

Androgens Estrogen

Peripheral

Pathological

Increased

Precocious Puberty

Approach to Precocious Puberty: Females

Premature

Thelarche

Estrogen

Premature

Adrenarche

Androgens

Normal Variant

Normal

Estrogen

+/- androgens

Central

Ovary

Adrenal

Other

Estrogen

Ovary

Adrenal

Other

Androgens

Peripheral

Pathological

Increased

Bone age, GV

Approach to Precocious Puberty: Males

Premature

Adrenarche

Androgens

Normal Variant

Normal

Testes > 4ml

Central

Testes

Adrenal

Other

Androgens

Testes

Adrenal

Other

Estrogen

Peripheral

Pathological

Increased

Bone age, GV

Delayed Puberty

Absence of secondary sexual development by age:

13 in a girl

14 in a boy

Constitutional Delay

of Growth and Puberty

Hypothalamic or

Pituitary Cause

Central

Low

Gonadal Failure

Peripheral

High

LH, FSH

Delayed Puberty

Approach to Delayed Puberty

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 don’t treat (even low dose estrogens cause

accelerated skeletal maturation)

Delayed Puberty: TreatmentHyper / 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

Growth velocity

Target Height

Familial Short Stature Constitutional Delay

Normal Variant

IUGR

Dysmorphic syndromes

Chromosomal disorders

Prenatal

Medications

Chronic disease

Endocrine

Postnatal

Proportionate Disproportionate

Pathologic

Short Stature

Idiopathic Short Stature

Chronic Disease

Endocrinopathy