Pediatric Endocrinology

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Pediatric Endocrinology

• Sarah Lawrence
• Division of Endocrinology
• CHEO

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Outline

• Growth/short stature
• Puberty precocious and delayed
• Disorders of Sex Development
• Diabetes
• Thyroid

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Short Stature
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Predicted Height
3 boys age 10 128 cm BA 8 BA 10 BA 12 Which
will be taller as an adult?
177 cm
168 cm
155 cm
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Midparental target height males
Father
Target Height
Mother
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Midparental target height females
Father
Target Height
Mother
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Endocrinopathy

• Based on this growth chart, what is the MOST
  likely cause of this boys growth failure?
• Primary hypothyroidism
• Craniopharyngioma
• Down Syndrome
• Inflammatory Bowel disease
• Scoliosis

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Chronic Disease

• Based on this growth chart, what is the MOST
  likely cause of this boys growth failure?
• Primary hypothyroidism
• Craniopharyngioma
• Down Syndrome
• Inflammatory Bowel disease
• Scoliosis

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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
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Precocious Puberty

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

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Puberty Sequence Girls
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Puberty Sequence Males
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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
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Question

• A 6 year old girl presents with pubic hair,
  axillary hair and odour and mild acne. Her
  growth is as shown. What is the MOST likely
  cause of her precocious puberty?
• Congenital adrenal hyperplasia
• Benign premature thelarche
• Benign premature adrenarche
• Adrenal tumour
• Central precocious puberty

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Question

• A 6.5 year old girl presents with a 10 month
  history of breasts and pubic hair. What is the
  MOST likely cause?
• Benign premature thelarche
• Congenital adrenal hyperplasia
• Craniopharyngioma
• Ovarian tumour
• Idiopathic central precocious puberty

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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
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Question
CAH 29/01/92

• A 5 year old boy presents with pubic hair, growth
  acceleration. He has Tanner 4 pubic hair and
  genitalia with 2 ml testes. What is the MOST
  likely diagnosis?
• Idiopathic central puberty
• Congenital adrenal hyperplasia
• Hypothalamic tumour
• Testicular tumour

x
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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
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Delayed Puberty

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

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

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

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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

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Ambiguous Genitalia (Disorders of Sex Development)
46 XY
46 XX
46 XY
46 XY
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Development of Internal and External Genitalia

• http//www.aboutkidshealth.ca/En/HowTheBodyWorks/S
  exDevelopmentAnOverview/Pages/default.aspx

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Approach to Disorders of Sex Development
Gonads palpable
No
Unilateral
Bilateral
Probable virilized female 46 XX DSD
Hypospadias
Undervirilized male 46 XY DSD
Ovotesticular DSD
Maternal
Fetal
Hormonal
Hypospadias
Mixed Gonadal
Likely CAH
Testosterone
Dysgenesis
Synthesis Defect
5-a-reductase deficiency
Androgen Insensitivity Syndrome (AIS)
Genetic syndrome
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Type 1 Diabetes
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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

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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
• Pediatrics do not need confirmatory sample on
  another day in the presence of unequivocal
  hyperglycemia and symptoms.

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Medical Encounters within 7 Days of Dx
of Patients

48
p0.0002
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Number of medical encounters
H Bui et al
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BG Targets
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HbA1c BG levels
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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

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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
• hypertonic saline, mannitol

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DKA What you need to remember

• The best way to prevent CE-DKA is to prevent DKA
• How do you prevent cerebral edema once child
  presents in DKA?
• By remembering a few guiding principles
• The younger the child, the greater the risk
• No insulin bolus
• No fluid bolus, unless in shock (max 10 cc/kg
  over 20-30 minutes)

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Complication Screening
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Type 2 Diabetes in Children and Youth
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Presentation of T1DM vs T2DM
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Acanthosis Nigricans
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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
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Metabolic Syndrome in Youth by BMI
with Metabolic Syndrome
BMI Percentile
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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

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Question

• A 13 year old boy with a BMI of 30, acanthosis
  nigricans, and a family history of Type 2
  diabetes presents with a random glucose of 15
  mmol/L, negative ketones.
• A What is the medication of first choice?
• B What is the target A1c?

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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

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Thyroid Disorders
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Approach to Goitre
Goitre
TSH
Elevated
Normal
Suppressed
Hypothyroid
Euthyroid
Hyperthyroid
Thyroid Antibodies
Thyroid Antibodies
Thyroid Antibodies
Grave's disease,
ve
-ve
ve
-ve
Chronic lymphocytic
Goitrogen,
Chronic lymphocytic
Colloid goitre
Subacute thyroiditis Toxic nodule
thyroiditis
Dyshormonogenesis
thyroiditis
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Thyroid take home points

• 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

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Thyroid take home points

• 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
• Routine monitoring q6 months while growing, q
  year once adult height

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Thyroid take home points

• Congenital hypothyroidism detected through
  newborn screening they need more intensive
  monitoring particularly in the 1st 3 years of
  life
• 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

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Questions?
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Insulin Dose Adjustment Guidelines for
Intercurrent Illness
TDD Total Daily Dose given as NovoRapid or
Humalog q4h in addition to usual insulin dose
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Constitutional Delay of Growth and Puberty