What is the evaluation approach for a patient with short stature?

From the Guidelines

A short stature workup should begin with a comprehensive history and physical examination, focusing on growth patterns, family heights, and timing of puberty, as recommended by recent guidelines 1. The initial evaluation should include an assessment of growth velocity, which is ideally measured by reviewing previous growth points or by remeasurement over a 4-6 month interval 1. Key components of the workup include:

• Initial laboratory testing: complete blood count, comprehensive metabolic panel, thyroid function tests (TSH, free T4), IGF-1, IGFBP-3, celiac screening, inflammatory markers (ESR, CRP), and a bone age X-ray
• Consideration of karyotype for girls to evaluate for Turner syndrome
• Growth hormone stimulation testing if IGF-1 levels are low or if growth velocity is significantly decreased despite normal screening labs
• Genetic testing for conditions like Noonan syndrome, SHOX deficiency, or other genetic causes of short stature
• Nutritional assessment and evaluation for chronic diseases that may affect growth (inflammatory bowel disease, renal disease, etc.) The workup should be tailored to the child's specific presentation, with referral to a pediatric endocrinologist if growth velocity is below the 3rd percentile, height is significantly discordant from family heights, or if there are concerning findings on initial evaluation 1. Early diagnosis is crucial as growth hormone therapy is most effective when started early, ideally before puberty when growth plates are still open, and recent updates in clinical practice recommendations support this approach 1.

From the FDA Drug Label

Idiopathic Short Stature (ISS) - Nutropin AQ is indicated for the treatment of ISS, also called non-GHD short stature, defined by height SDS ≤ –2. 25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in pediatric patients whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means

• The workup for short stature should include a diagnostic evaluation to exclude other causes associated with short stature that should be observed or treated by other means.
• Key components of the workup are not explicitly stated in the label, but it is implied that the evaluation should assess for conditions such as hypothyroidism, under-nutrition, and advanced bone age.
• The label also mentions the importance of evaluating for antibodies to recombinant human GH (rhGH) in patients who fail to respond to treatment 2.

From the Research

Short Stature Workup

• Short stature is defined as a height that is greater than or equal to 2 standard deviations (SDS) below the mean height for reference children comparable for sex and age 3
• The possible causes of short stature could be divided into three groups: primary growth disorders, secondary growth disorders, and idiopathic short stature 3
• A detailed evaluation of a child with growth impairment should include an accurate history, a standardized physical examination, general and specific laboratory evaluations, radiologic investigations, and genetic testing 3

Diagnostic Approach

• Growth monitoring is a fundamental approach to evaluate a child's health and identify pathological deviations 3
• Height and weight measurements, calculation of height velocity over time are main instruments to discover pathological deviations 3
• The diagnosis of growth hormone deficiency (GHD) requires a careful evaluation of clinical history, physical examination, and appropriate interpretation of longitudinal growth 4

Treatment Options

• Growth hormone treatment is recommended when GHD is confirmed 4
• Treatment is effective and safe, but requires daily injections during many years, which can affect adherence 4
• Recombinant human growth hormone (rhGH) treatment is indicated to hasten growth/increase height in some cases of worrisome growth 5

Screening for Endocrinopathy

• Short stature can be a useful screening test for endocrinopathy in slipped capital femoral epiphysis 6
• Patients who are on or below the tenth percentile for height at the time of presentation should be screened for a possible endocrine abnormality using measurement of thyroid-stimulating hormone and free thyroxine as a preliminary screening test 6