The Low-Down on anEvidence-Based Approachto Short Stature

The Low-Down on anEvidence-Based Approachto Short Stature

AKASH SINHAMBBS, MD/PHD, MRCPCH, FRCPCPAEDIATRIC ENDOCRINOLOGIST/ PAEDIATRICIANABBOTSFORD2015

Disclosures

I have none to declare

Introduction Important in all areas of medicine dealing with children Perceived or real impairment of growth Referred due to physical, psychological or social difficulties In most it is a variation of normal physiology rather than a

pathological cause However all need logical process of assessment

Important in all areas of medicine dealing with children Perceived or real impairment of growth Referred due to physical, psychological or social difficulties In most it is a variation of normal physiology rather than a

pathological cause However all need logical process of assessment

Background

Phases of growth

Prenatal Genetics Maternal size Maternal health Nutritional supply

Postnatal

Predominantly interested in postnatal growth Different influences

Prenatal Genetics Maternal size Maternal health Nutritional supply

Postnatal

Predominantly interested in postnatal growth Different influences

Example of prenatal influencesInfant of a diabetic mother Congenital hypothyroidism

FASCongenital infection

Phases of growth

Prenatal

Postnatal Genetics

Parental size

Nutrition

Health

Hormones

Prenatal

Postnatal Genetics

Parental size

Nutrition

Health

Hormones

Phases of linear growth

Growthhormone

Sex steroids

Height velocity curves Individual height curves

Nutrition

Growthhormone

Early wobble

Finding your centile

Pubertal growth♀: Growth spurt 2 yearsbefore boys, at start of clinicalpuberty

Peak height velocity ~12 years

Followed by menarche

Peak height velocity ~8 cm/yr

♂: Growth spurt when pubertyalready well established(testicular volume 10-12 mls)

Peak height velocity ~14 years

Peak height velocity ~10cm/yr

♀: Growth spurt 2 yearsbefore boys, at start of clinicalpuberty

Peak height velocity ~12 years

Followed by menarche

Peak height velocity ~8 cm/yr

♂: Growth spurt when pubertyalready well established(testicular volume 10-12 mls)

Peak height velocity ~14 years

Peak height velocity ~10cm/yr

♂>♀ height by ~13-13.5 cm

Causes of short stature

Causes of short stature

Familial(short parents)

Delayed pubertyBony dysplasias

Nurture

SGA

ChronicillnessChromosomes

Syndromes

Hormones

Familial short stature

Familial(short parents)

CalculateMidParentalheight

Boy: Father + [Mother+13cm]/2+/- 8.5cm

Girl: [Father-13cm]/2+ Mother+/- 8.5cm

Constitutional delay of growthand puberty

Familial(short parents)

Delayed puberty

Small for gestational age

Familial(short parents)

Delayed puberty

SGA

85% show‘catch-up’growth..

the rest staysmall

85% show‘catch-up’growth..

the rest staysmall =15%

Chronic illness

Familial(short parents)

Delayed pubertyDelayed puberty

Chronicillness

SGA

Chromosomes

Familial(short parents)

Delayed pubertyDelayed puberty

Chronicillness

SGA

Chromosomes

SHOX gene

DownsDownsSyndromeSyndrome

Syndromes

Familial(short parents)

Delayed puberty

Chronicillness

SGA

Chromosomes

Syndromes

PraderPrader WilliWilliSyndromeSyndrome

NoonanNoonanSyndromeSyndrome

SilverSilverRussellRussell

SyndromeSyndrome

Bony dysplasias

Familial(short parents)

Bonydysplasias

Delayed puberty

Chronicillness

SGA

Chromosomes

Syndromes

Bonydysplasias

Nurture

Familial(short parents)

Bonydysplasias

Nurture

Delayed puberty

Chronicillness

SGA

Chromsomes

Syndromes

Bonydysplasias

Hormones

Familial(short parents)

Delayed pubertyBony dysplasias

Nurture

SGA

ChronicillnessChromosomes

Syndromes

Hormones

Endocrine disorders

Growth hormone insufficiency

Pseudohypoparathyroidism

Hypothyroidism

Cushing’s syndrome

GH resistance (Laron syndrome)

Growth hormone insufficiency

Pseudohypoparathyroidism

Hypothyroidism

Cushing’s syndrome

GH resistance (Laron syndrome)

** Height/weight comparison **

Causes GH insufficiency

GeneticGH-1 or GHRH receptor mutations Pit-1, Prop-1 mutations

CongenitalGHRH deficiency (~80%, isolated GH deficiency) Structural defects: SOD, holoprosencephaly, agenesis

of corpus callosum Intrauterine infections

AcquiredCNS tumours: cranio, germinoma, optic glioma LCH, inflammatory disease Head injury, cranial irradiation

GeneticGH-1 or GHRH receptor mutations Pit-1, Prop-1 mutations

CongenitalGHRH deficiency (~80%, isolated GH deficiency) Structural defects: SOD, holoprosencephaly, agenesis

of corpus callosum Intrauterine infections

AcquiredCNS tumours: cranio, germinoma, optic glioma LCH, inflammatory disease Head injury, cranial irradiation

Diagnosis GH deficiency Diagnosis not easy! Auxological data:

Short with height below parental target Subnormal height velocity

Dysmorphic features-mid facial crowding and central adiposity Biochemical data:

Isolated GH level no use IGF-1 occasionally helpful GH stimulation tests

Glucagon

Insulin tolerance test

Radiological data: Abnormal MRI pituitary gland

Diagnosis not easy! Auxological data:

Short with height below parental target Subnormal height velocity

Dysmorphic features-mid facial crowding and central adiposity Biochemical data:

Isolated GH level no use IGF-1 occasionally helpful GH stimulation tests

Glucagon

Insulin tolerance test

Radiological data: Abnormal MRI pituitary gland

Baseline investigations

Accurate history, examination and auxologicaldata most important

Baseline investigations

Accurate history, examination and auxologicaldata most important

Baseline investigations

Accurate history, examination and auxologicaldata most important

If required:CBC, ESR/CRP Lytes,BUN, creatinine, bicarbonateCalcium, phosphate, PTH, liver enzymesCoeliac screen Karyotype (girls) TFTs, prolactin, IGF-1 Bone age

? Genetics opinion if dysmorphic /disproportionate

Accurate history, examination and auxologicaldata most important

If required:CBC, ESR/CRP Lytes,BUN, creatinine, bicarbonateCalcium, phosphate, PTH, liver enzymesCoeliac screen Karyotype (girls) TFTs, prolactin, IGF-1 Bone age

? Genetics opinion if dysmorphic /disproportionate

1 2

12

1 2

Twin 2

Twin 1

Twin 2

2

1

Summary The shorter the child, the more

probability of a pathology

Summary The shorter the child, the more

probability of a pathology The further away from the

parental target height, the moreprobability of a pathology

The most useful tool is a GROWTHCHART

The shorter the child, the moreprobability of a pathology

The further away from theparental target height, the moreprobability of a pathology

The most useful tool is a GROWTHCHART

Summary The shorter the child, the more

probability of a pathology The further away from the

parental target height, the moreprobability of a pathology

The most useful tool is a GROWTHCHART

Children with GHD are not slimand do not have a well-definedmusculature

The short, heavy child is morelikely to have pathology than arelatively tall, heavy child

The shorter the child, the moreprobability of a pathology

The further away from theparental target height, the moreprobability of a pathology

The most useful tool is a GROWTHCHART

Children with GHD are not slimand do not have a well-definedmusculature

The short, heavy child is morelikely to have pathology than arelatively tall, heavy child