Short Stature

A detailed review

By

Saptharishi L G

Napoleon Bonaparte

Definition

Failure To Thrive Vs Short Stature

FTT – primarily poor weight gain in infants & young children

FTT – linear growth may be secondarily affected

SS – primarily subnormal linear growth thru’out childhood & adolescence

Approach

Approach to a child presenting to OPD with complaints of short stature

IDIOPATHIC short stature

DEFN ‘heterogeneous state that encompasses individuals

of short stature, including those of FSS, for which there is currently No recognized cause’

‘condition in which the height of an individual is > 2 SD score (SDS) below the corresponding mean height for a given age, sex, and population group without evidence of systemic, endocrine, nutritional, or chromosomal abnormalities’

Steps in assessment

Accurate ht measurement

Assessment of body proportions

Assessment of height velocity

Compare with population norms

Compare with genetic potential

Sexual Maturity Rating

Calculation Of Genetic Potential

Underlying conceptGrowth until 2 yrs : 66% drift across centiles2 yr onwards : ‘Growth Channels’

Mid Parental Height

Estimated Target Height

Target Height Range

Practical demonstration

Bone age

Aka skeletal age

Two internationally accepted methodsGruelich – Pyle atlas methodTanner & Whitehouse (TW2) method

Underlying concept – further growth potential

Usefulness in short stature

Recent Korean study comparing bone age in FSS Vs CDGP

CAUSES OF SHORT STATURE

Familial short statureComes from a short but otherwise normal family

One or both parents (and usually few other family members) 1.5 to 2 SD below mean ht

Growth channel is low but parallels normal curve

If GV is low or stature is extremely low out of keeping with the family pattern, Suspect other problems

NORMAL bone age IMPLICATION

FSS contd…

Etiology:Not clearClassified under ISSSubtle disorders of GH or its receptors- beyond

sensitivity of tests ??Neuro-secretory dysfunction : abnormal release

pattern but normal response to testing

ManagementCounselling & Reassurance

Constitutional delay in growth & adolescence

Aka CDGP, CDGD

Also considered a normal variant

Delayed onset of puberty & delayed growth spurt

H/o delayed puberty/ growth spurt in one or both parents (or other family members)

The final stature of that family member is NORMAL

CDGA contd..

Delayed bone age ‘Room for growth’

Subtle dysregulation of GH secretion?

DDx – Chronic illness, Panhypopituitarism

Differentiated by GnRH testing / LH assay

MANAGEMENT:Reassurance & CounsellingRole of short course of low-dose sex steroidsRole of GH therapy

Endocrine causes

GH deficiencyCongenital – with midline defects, with pituitary

agenesis, genetic defectsAcquired – Tumors, LCH, Infxns, trauma,

hydrocephalus, autoimmune, psycho-social, radiation

Laron dwarfism

Hypothyroidism

Glucocorticoid excess – endo and exogenous

DM / DI /Hypophosphatemic rickets

GH deficiency

Severe GHD : 1 in 4000Truncal obesity with ‘fat marbling’ / MICROPENISCrowding of mid-facial features with cherubic faciesHigh pitched voice / poor musculature / adiposityDelayed puberty Inadequate response on stimultn test (<7 mU/L)

Partial GHD : 7 -15 mU/L reponse on testing

Disorder of hypothalamic release of GHRH

GHD contd..

Any case of GHD, Neuro-imaging (MRI)Midline defects – septo-optic dysplasia, absent

septum pellucidumAny compressive lesions / tumors / hydrocephalus

NOTE : GH biosynthesis affected in primary hypothyroidism and celiac diseae

NOTE : GH testing – only in an euthyroid individual

Management : GH 15 -21 U (5-7mg/sq m/wk) in daily SC divided doses.

Larger doses (10 mg/sq m/wk) Turner’s and CRF

Placebo effect of GH – considerable (latest studies)

GH provocation testing

Screening – post exercise / 3- 4 hr post prandial / 1 hr after sleep onset

Pharmacological – Clonidine / ITT /arginine / glucagon

Miscellaneous – Physiologic sleep studies / urinary GH

Insulin Hypoglycemia Tolerance Testing85 % Normal children > 15 mU/L after 30 -60 minPotentially dangerous – expert endocrinologist

Role of Urinary GH testing – non invasive but how useful?

Hypothyroidism

Congenital or acquired (IDD/auto-immune)

Impaired linear growth + Goitre + Relative obesity

O/E : Bradycardia, dry hair/skin, delayed reflexes

Classical history of dry skin / constipation / cold intolerance not frequent in children

BONE age – significant delay

Rx – Thyroxine replacement

Corticosteroid excess

Endogenous – Cushing syndrome / cushing disease / adrenal tumor

Mostly exogenous – in our settings (Chooran) / prescribed steroids

Cotinues to gain wt at a rapid rate despite a fall in ht velocity (compare with exogenous obesity)

24 hr urine sample for cortisol testing

Treat primary cause

Disproportionate Short stature

Innate failure of bone or cartilage to grow normally

Usually inherited (AD) with clear-cut family history

NOTE : In these children, Bone age NOT reliable

Achondroplasia / Hypochondroplasia Characteristic radiologic findings with Increased US/LS

ratio Progressive deceleration of growth in infancy Humerus & femur – particularly short 125 cm /131 cm – final stature

Other osteochondrodysplasias

Chromosomal disordersTurner syndrome

SHOX gene (also plays role in ISS)SS + ovarian failureCharacteristic features of TurnersHigh dose GH therapySeparate growth charts

Prader Willi – uniparental disomy

Down syndrome – independent of hypothyroidism

Russel- Silver (primordial dwarfism)

Bloom / Williams / Fetal alcohol / Fanconi / LMB

Emotional deprivation

Aka deprivation dwarfism / psychosocial dwarfism

Two types – with food deprivation / Pure emotional

Height age < weight age

May mimic hypopituitarism- abnormal GH response to testing

Rapidly normalizes after initiating therapy

When to suspect ? History – typical . Good social history required ‘Frozen watchfulness’ & lack of emotional bonding Munchhausen by proxy

Nutritional

MOST common cause in INDIA

Chronic PEM / Under nutrition

Cause – poverty

Weight age < Height age

3 day diet record – prospective

Dietary management as per protocol

Chronic diseases

Why short stature ?? Poor appetite / poor intake – IBD / renal dysfunction Poor absorption – Malabsorption syn., Celiac disease Medications used – Bronchial asthma Chronic acidosis - RTA Secondary endocrine dysfunction

Typical history

SS may be the presenting feature of a chronic disease esp IBD, celiac disease and renal dysfunction

Rx– primary disease ; GH therapy in CRF

HOW TO INVESTIGATE A CHILD WITH SHORT STATURE ??

RED FLAGS in short stature

Height > 2-2.5 SD below mean for age

Subnormal growth velocity

Abnormal body proportions

Abnormal Height : weight ratio

Dysmorphic features

Goitre

Abnormal CNS & eye findings

GROWTHHORMONE

Role & Issues

Role of Growth Hormone

Placebo effect of GH

What is the response to GH ? >90% children with GHD achieve adult ht within their

target range ht Response in CRF & Turner’s is also prominent

Side effects of GH therapy Glucose intolerance, Hyperinsulinism, hyperlipidemia,

Hypertension, Type II DM, Benign intracranial hypertension

When to avoid GH ? Chromosome fragility syndromes

UPCOMING CONCEPTS>>>

Actually how advantageous is tall stature ??

How to identify ideal ht for a person ?

Are there any benefits of ‘pushing a child into normalcy’ ?

Psychosocial benefits of Tall stature

Pitfalls of the concept of GENETIC POTENTIAL

Child –also inherits an ‘environment’

Possibility of an unrecognized & untreated growth disorder in parents

GH deficiency / skeletal dysplasia / pseudohypoparathyroidism must be excluded