Pediatric Endocrinology

Sarah LawrenceDivision of EndocrinologyCHEO

Outline

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

Short Stature

Predicted Height

155 cm168 cm177 cm

3 boys age 10 128 cm

BA 8 BA 10 BA 12

Which will be taller as an adult?

Midparental [target] height: males

Mother

Father

Target Height

Midparental [target] height: females

Mother

Father

Target Height

Endocrinopathy

Based on this growth chart, what is the MOST likely cause of this boy’s growth failure?A. Primary hypothyroidismB. CraniopharyngiomaC. Down SyndromeD. Inflammatory Bowel diseaseE. Scoliosis

Chronic Disease

Based on this growth chart, what is the MOST likely cause of this boy’s growth failure?A. Primary hypothyroidismB. CraniopharyngiomaC. Down SyndromeD. Inflammatory Bowel diseaseE. Scoliosis

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

Precocious Puberty

Presence of secondary sexual development by age:

8 in a girl

9 in a boy

Puberty Sequence: Girls

Puberty Sequence: Males

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

QuestionA 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?A. Congenital adrenal hyperplasiaB. Benign premature thelarcheC. Benign premature adrenarcheD. Adrenal tumourE. Central precocious puberty

Question

A 6.5 year old girl presents with a 10 month history of breasts and pubic hair. What is the MOST likely cause?A. Benign premature thelarcheB. Congenital adrenal hyperplasiaC. CraniopharyngiomaD. Ovarian tumourE. Idiopathic central 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

x

CAH 29/01/92

QuestionA 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?

A. Idiopathic central pubertyB. Congenital adrenal hyperplasiaC. Hypothalamic tumourD. Testicular tumour

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

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

Ambiguous Genitalia (Disorders of Sex Development)

46 XY

46 XY 46 XX

46 XY

Development of Internal and External Genitalia

http://www.aboutkidshealth.ca/En/HowTheBodyWorks/SexDevelopmentAnOverview/Pages/default.aspx

Approach to Disorders of Sex Development

Maternal

Likely CAH

Fetal

Probable virilized female 46 XX DSD

No

Hypospadias

Ovotesticular DSD

Mixed Gonadal

Dysgenesis

Unilateral

Testosterone

Synthesis Defect

5-a-reductase deficiency

Androgen Insensitivity Syndrome (AIS)

Hormonal Hypospadias

Undervirilized male46 XY DSD

Bilateral

Gonads palpable

Genetic syndrome

Type 1 Diabetes

Epidemiology of Type 1

Prevalence 0.4% of individuals < 18 years

Increased risk to family membersSibling 5%Father with diabetes 6-8%Mother with diabetes 2-3%Identical twin 30-50%

Diagnostic Criteria FBG > 7.0 mmol/L OR

Casual BG > 11.1 with symptoms OR

2 hour BG in OGTT of > 11.1

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

BG Targets

Age (years) Premeal target

(mmol/L)

HbA1c Target (%)

< 5 6-12 < 8.5%

6-12 4-10 < 8.0%

>12 4-7 < 7.0%

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 hypertonic saline, mannitol

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)

Question:

An 8 yo girl is diagnosed with Type 1 diabetes. At what age should you begin screening for:

a) Microalbuminuria b) Retinopathyc) Hypothyroidismd) Hyperlipidemiae) Celiac disease

Complication Screening

Complication Who When How

Nephropathy 12 yo and DM>5 years

Annual Albumin/creatinine ratio

Retinopathy >15 yo and DM >5 years

Annual Opthalmoscopy/ fundus photography

Neuropathy Post pubertal, poor control, DM>5 years

Annual Symptoms, Sensory exam

Dyslipidemia All + targeted Age 12, 17 Fasting lipid profile

Hypertension All Twice annual BP measurement

Thyroid All Dx + q1-2y TSH, TAB

Celiac Targeted Symptoms TTG, IgA

Type 2 Diabetes in Children and Youth

Presentation of T1DM vs T2DM Type 1 Type 2

Up to ¼ overweight

Short Course

15-40% DKA

FHx T1DM in 5-10%

Predominantly white

85% overweight

Indolent course

33% ketonuria5-25% DKA

FHx T2DM 74-100%

Minority youth

Acanthosis Nigricans

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

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?

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

Thyroid Disorders

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

Grave's disease,Subacute thyroiditis

Toxic nodule

Thyroid Antibodies

Suppressed

Hyperthyroid

TSH

Goitre

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

Thyroid take home points Mild elevations of TSH should be verified

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

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

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

Thyroid take home points

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

Questions?