Overview
Definition:
Short stature (SS) is defined as a height significantly below the average for a given age and sex
Typically, it is considered when height is below the 3rd percentile or less than 2 standard deviations (SD) below the mean for age and sex
It can be a symptom of various underlying conditions, ranging from genetic and endocrine disorders to chronic diseases and psychosocial factors.
Epidemiology:
The prevalence of short stature varies, with approximately 3% of the pediatric population falling below the 3rd percentile
Growth hormone deficiency (GHD) accounts for about 15-25% of cases of idiopathic short stature
Genetic conditions like Turner syndrome (in girls) and Noonan syndrome are also significant contributors.
Clinical Significance:
Identifying and managing short stature is crucial not only for achieving optimal adult height but also for diagnosing and treating potentially serious underlying medical conditions
Early diagnosis and intervention can significantly improve a child's physical growth, psychological well-being, and long-term health outcomes
This topic is a frequent area of focus in pediatric endocrinology and is highly relevant for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Parents usually present with concerns about the child being shorter than peers
Delayed puberty may be noted
Recurrent hospitalizations for chronic illnesses might be a contributing factor
In some cases, specific dysmorphic features associated with genetic syndromes may be present
Symptoms of underlying conditions like celiac disease or hypothyroidism may also be present.
Signs:
Height below the 3rd percentile on a standardized growth chart
Disproportionate short stature (e.g., achondroplasia) versus proportionate short stature
Signs of underlying endocrine disorders: delayed puberty, hypoglycemia, or features of hypothyroidism
Dysmorphic features suggestive of genetic syndromes (e.g., webbed neck in Turner syndrome)
Signs of chronic illness: pallor, poor musculature.
Diagnostic Criteria:
Diagnosis of short stature is primarily based on serial growth measurements falling below the 3rd percentile on age- and sex-specific growth charts
Growth velocity less than 4-5 cm/year in children over 2 years old is also a significant indicator
Confirmation of GHD requires appropriate provocative testing
Genetic testing is indicated for suspected chromosomal abnormalities or specific genetic syndromes.
Diagnostic Approach
History Taking:
Detailed birth history (gestational age, birth weight/length, perinatal complications)
Detailed growth history: parental heights, previous growth measurements, onset of concerns
Nutritional history
History of chronic illnesses (renal, cardiac, gastrointestinal, hematological)
History of medications (e.g., corticosteroids)
Family history of short stature or endocrine disorders
Psychosocial history: school performance, social interactions, family stress.
Physical Examination:
Accurate measurement of height, weight, and head circumference
Plotting measurements on appropriate growth charts
Assessment of proportionality (segmental measurements: upper segment/lower segment ratio, arm span)
Examination for dysmorphic features
Evaluation for signs of chronic illness
Assessment of pubertal status using Tanner staging
Palpation of thyroid gland
Auscultation of heart and lungs.
Investigations:
Initial investigations: Complete blood count (CBC), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP) to rule out chronic inflammation/infection
Renal function tests (urea, creatinine)
Liver function tests (LFTs)
Thyroid function tests (TSH, free T4) to rule out hypothyroidism
Celiac screen (anti-TTG IgA, total IgA)
Bone age X-ray (hand-wrist radiograph) to assess skeletal maturation
Specific tests for suspected causes: karyotype for Turner syndrome, hormone levels for suspected endocrine disorders
Growth hormone (GH) provocation tests.
Differential Diagnosis:
Familial short stature
Constitutional delay of growth and puberty (CDGP)
Intrauterine growth restriction (IUGR)
Genetic syndromes (Turner syndrome, Down syndrome, Noonan syndrome, Russell-Silver syndrome)
Endocrine disorders (GHD, hypothyroidism, Cushing's syndrome, precocious puberty)
Chronic systemic diseases (malnutrition, celiac disease, chronic renal failure, chronic cardiac/pulmonary disease)
Skeletal dysplasias (achondroplasia, hypochondroplasia)
Idiopathic short stature (ISS).
Growth Hormone Testing
Indications For Testing:
Significant short stature (height < -2.0 SDS) with normal growth velocity
Height < 3rd percentile with growth velocity < 4 cm/year in children over 2 years old
Delay in pubertal onset
Suspected GHD based on clinical features (e.g., disproportionately small genitalia in boys, central obesity)
Failure to respond adequately to other therapies.
Provocative Testing Methods:
These tests stimulate GH release and measure serum GH levels at intervals
Standard protocols involve using two different stimuli, as single-test sensitivity can be low
Common stimulants include: Insulin tolerance test (ITT) - gold standard, but carries risk of hypoglycemia
Glucagon stimulation test - safer alternative, often used sequentially with ITT or for patients with contraindications to ITT
Arginine infusion test - often used in combination with other stimuli
GHRH + Arginine test - highly sensitive.
Interpretation Of Results:
Peak GH level < 7-10 ng/mL (depending on assay and stimulus) is generally considered diagnostic of GHD, especially with appropriate clinical suspicion and failure to achieve normal growth
However, interpretation should consider the entire clinical picture, bone age, and results from multiple provocative tests
IGF-1 and IGFBP-3 levels are used as screening tools and can provide supportive evidence, with low levels suggesting GHD or GH insensitivity
A normal IGF-1/IGFBP-3 level generally excludes GHD.
Indications For Growth Hormone Therapy
Growth Hormone Deficiency:
Confirmed GHD by provocative testing with low IGF-1/IGFBP-3 levels and documented significant short stature with poor growth velocity
Treatment aims to increase linear growth and achieve a near-normal adult height.
Idiopathic Short Stature:
Defined as height < -2.25 SDS with normal GH secretion and no identifiable cause
GH therapy may be considered for selected patients with significant short stature (< -2.25 SDS) and predicted adult height below a certain threshold, provided there is a demonstrated growth response.
Turner Syndrome:
GH therapy is indicated for girls with Turner syndrome to improve linear growth and achieve a taller adult height
It is typically initiated early in childhood.
Prader-willis Syndrome:
GH therapy is indicated to improve linear growth, increase muscle mass, decrease adiposity, and improve bone density in individuals with Prader-Willi syndrome.
Noonan Syndrome:
GH therapy may be beneficial for individuals with Noonan syndrome and short stature, improving linear growth and adult height.
Other Indications:
Chronic renal insufficiency (to improve growth), SGA (Small for Gestational Age) infants who fail to catch up by age 2-4 years, and short stature associated with SHOX deficiency.
Management Of Short Stature
Treatment Of Underlying Cause:
Addressing any identifiable causes is paramount
This includes treating hypothyroidism with thyroxine, managing celiac disease with a gluten-free diet, correcting nutritional deficiencies, and managing chronic systemic illnesses.
Growth Hormone Replacement Therapy:
Administered subcutaneously, typically daily, using recombinant human growth hormone (rhGH)
Dosing is usually based on body weight (e.g., 0.025-0.05 mg/kg/day) or body surface area
Treatment is continued until final adult height is achieved or growth velocity becomes negligible.
Monitoring And Follow Up:
Regular monitoring of height, weight, growth velocity, bone age, and pubertal status is essential
IGF-1 levels are monitored periodically to ensure adequate dosing and assess response
Side effects and potential complications of GH therapy (e.g., glucose intolerance, scoliosis, intracranial hypertension) must be monitored.
Nutritional Support:
Ensuring adequate caloric and protein intake is crucial to support growth, especially when considering GH therapy
Nutritional assessment and counseling may be required.
Complications
Potential Complications Of Gfd:
Failure to achieve optimal adult height
Psychological and social challenges related to being short
Potential for missed diagnosis of serious underlying conditions.
Complications Of Gh Therapy:
Glucose intolerance/diabetes mellitus (rare)
Scoliosis progression
Intracranial hypertension (pseudotumor cerebri)
Arthralgias and myalgias
Carpal tunnel syndrome
Increased risk of certain neoplasms (controversial and rare).
Prevention Strategies:
Early detection and diagnosis
Prompt treatment of underlying conditions
Careful patient selection for GH therapy
Close monitoring during GH therapy
Educating parents and patients about the management plan and potential risks.
Key Points
Exam Focus:
Definition of short stature (<-2 SD)
Growth velocity criteria (<4 cm/year)
Indications for GH provocation testing
Common GH provocative tests (ITT, Glucagon, Arginine)
Interpretation of peak GH and IGF-1 levels
Primary indications for GH therapy (GHD, ISS, Turner, PWS)
Contraindications and monitoring of GH therapy
Bone age assessment.
Clinical Pearls:
Always plot height on standardized growth charts
A normal bone age does not exclude GHD, but a significantly delayed bone age may suggest CDGP
Always consider the entire clinical context when interpreting GH stimulation tests
Low IGF-1/IGFBP-3 is a strong indicator, but not absolute proof, of GH deficiency or resistance
Short children may have serious underlying illnesses that must be ruled out before considering ISS.
Common Mistakes:
Diagnosing GHD based on a single low GH level without provocative testing
Assuming all short children need GH therapy
Not investigating for underlying systemic diseases
Inadequate monitoring of GH therapy
Over-reliance on bone age alone to diagnose growth disorders.