Pediatric Endocrinology

1
Pediatric Endocrinology

• Sarah Lawrence
• Division of Endocrinology
• CHEO

2
Type 1 Diabetes
3
Epidemiology of Type 1

• Prevalence 0.4 of individuals lt 18 years
• Increased risk to family members
• Sibling 5
• Father with diabetes 6-8
• Mother with diabetes 2-3
• Identical twin 30-50

4
Type 1 Diabetes
Genetic predisposition
Antibody positive
Beta Cells
Diabetes
Time
Environmental insult
5
Diagnostic Criteria

• FBG gt 7.0 mmol/L OR
• Casual BG gt 11.1 with symptoms OR
• 2 hour BG in OGTT of gt 11.1

6

• INITIAL MANAGEMENT

7
New Onset DM Baseline labs

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

8
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

9
BG Targets
Age (years) Premeal target (mmol/L) HbA1c Target ()
lt 5 6-12 lt 9.0
6-12 4-10 lt 8.0
gt12 4-8 lt 7.0
10
HbA1c BG levels
11
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

12
Twice Daily InsulinNPH R/analogue
am
am
noon
pm
hs
13
Three Times Daily InsulinNPH R/analogue
am
am
noon
pm
hs
14
Basal-Bolus Insulin Therapy Insulin Glargine at
HS and Mealtime Lispro or Aspart
Insulin Glargine or Levemir
Type 1 DM
Insulin Lispro or Aspart
B
D
L
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. 19994211511167.
15
Basal
16
Insulin Injection Sites
Picture of lipohypertrophy
17
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

18
Insulin adjustment basic principles
Time of Day Insulin to adjust
Morning pm N
Noon am R
Supper am N
Bed pm R
R
R
N
N
am
noon
hs
pm
am
19
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
• lt20 kg 10 g CHO
• gt20 kg 15 g CHO

20
Hypoglycemia

• Severe hypoglycemia
• Glucagon
• lt5 years 0.5 mg
• gt 5 years 1 mg
• Minidose glucagon protocol
• Persistently low but alert and unable to manage
  orally (e.g. during illness or inadvertent
  insulin error)

21
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

22
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

23
Insulin Dose Adjustment Guidelines for
Intercurrent Illness
TDD Total Daily Dose
24
Type 2 Diabetes in Children and Youth
25
(No Transcript)
26
For Children, BMI Changes with Age
BMI
BMI
Boys 2 to 20 years
Example 95th Percentile Tracking Age
BMI 2 yrs 19.3 4 yrs 17.8 9 yrs
21.0 13 yrs 25.1
BMI
BMI
27
Genetic and Environmental Risk factors for T2DM

• Ethnicity
• Female gender
• Family history T2DM
• Intrauterine factors
• Maternal history of gestational diabetes
• Large for gestational age (gt4 kg)
• Small for gestational age (lt2.5 kg)
• Obesity
• Sedentary behaviour

28
Development of Type 2 Diabetes

• Normal
• Insulin resistance
• Impaired Glucose Tolerance
• Type 2 Diabetes

29
Acanthosis Nigricans
30
Metabolic Syndrome in Youth by BMI
with Metabolic Syndrome
BMI Percentile
31
Treatment of T2DM in Youth

• Diabetes education for the family
• Setting glycemic targets
• HbA1c lt 7.0
• Lifestyle modification
• lt10 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

32
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 ketonuria 5-25 DKA FHx T2DM 74-100 Minority youth
33
Thyroid Disorders
34
Approach to Goitre
Goitre
TSH
Elevated
Suppressed
Normal
Hypothyroid
Hyperthyroid
Euthyroid
Thyroid Antibodies
ve
-ve
Chronic lymphocytic
Goitrogen,
thyroiditis
Dyshormonogenesis
35
Hypothyroidism
36
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

37
Approach to Goitre
Goitre
TSH
Elevated
Suppressed
Normal
Hypothyroid
Hyperthyroid
Euthyroid
Thyroid Antibodies
Thyroid Antibodies
ve
-ve
ve/-ve Graves
Chronic lymphocytic
Goitrogen,
Hashitoxicosis
thyroiditis
Dyshormonogenesis
Subacute thyroiditis
38
Graves Disease
39
Hashitoxicosis / Subacute thyroiditis
Hyperthyroid phase
Hypothyroid phase
TSH
FT4
Time
40
Hyperthyroidism - Management

• Medical Management
• Antithyroid medications
• Methimazole (MMI, TapazoleTM)
• Initial dose 0.4-0.6 mg/kg/day q8-12h
• Maintenance0.2-0.3 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

41
Hyperthyroidism - Management

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

42
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

43
Approach to Goitre
Goitre
TSH
Elevated
Normal
Suppressed
Hypothyroid
Euthyroid
Hyperthyroid
Thyroid Antibodies
Thyroid Antibodies
Thyroid Antibodies
ve
-ve
ve
-ve
ve/-ve
Chronic lymphocytic
Goitrogen,
Chronic lymphocytic
Colloid goitre
Grave's disease,
thyroiditis
Dyshormonogenesis
thyroiditis
Subacute thyroiditis
44
Subclinical Hypothyroidism

• Normal Subclinical Overt
• Hypothyroidism Hypothyroidism
• TSH N
• FT4 N N

45
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

46
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 lt10mU/L often normal on repeat

47
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

48
Precocious Puberty

• Presence of secondary sexual development by age
• 8 in a girl
• 9 in a boy

49
Approach to Precocious Puberty
Precocious Puberty
Growth Velocity
Bone Age
Normal
Increased
Normal variant
Pathological
Estrogen
Androgens
Central
Peripheral
Premature Thelarche
Premature Adrenarche
Androgens
Estrogen
50
Approach to Precocious Puberty Females
Bone age, GV
Normal
Increased
Normal Variant
Pathological
Estrogen
Androgens
Central
Peripheral
Premature
Premature
Estrogen
Estrogen
Androgens
Thelarche
Adrenarche
/- androgens
Ovary
Ovary
Adrenal
Adrenal
Other
Other
51
Approach to Precocious Puberty Males
Bone age, GV
Normal
Increased
Normal Variant
Pathological
Androgens
Central
Peripheral
Premature
Testes gt 4ml
Androgens
Estrogen
Adrenarche
Testes
Testes
Adrenal
Adrenal
Other
Other
52
Delayed Puberty

• Absence of secondary sexual development by age
• 13 in a girl
• 14 in a boy

53
Approach to Delayed Puberty
Delayed Puberty
LH, FSH
Low
High
Central
Peripheral
Constitutional Delay
Hypothalamic or
Gonadal Failure
of Growth and Puberty
Pituitary Cause
54
Delayed Puberty Investigations

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

55
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)

56
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

57
Short Stature
58
Approach to Short Stature
Short Stature
Growth velocity
Target Height
Normal Variant
Pathologic
Familial Short Stature
Constitutional Delay
Proportionate
Disproportionate
Prenatal
Postnatal
Idiopathic Short Stature
IUGR
Medications
Dysmorphic syndromes
Chronic disease
Chromosomal disorders
Endocrine
59
Chronic Disease
60
Endocrinopathy