Laboratory Studies
Laboratory studies used to assess the major causes of short stature in children include the following:
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Measurement of serum levels of insulinlike growth factor-I (IGF-I), formerly named somatomedin C, and IGF binding protein-3 (IGFBP-3)
These are useful tests for growth hormone deficiency (GHD), except in pubertal patients and those with history of a brain tumor.
Patients with certain CNS neoplasms may have normal serum growth factor levels despite having GHD, particularly during puberty.
Consider provocative tests of pituitary function in any patient with normal thyroid function suspected to be GH deficient.
Interpret a low serum IGF-I concentration cautiously because poor nutrition is associated with low serum IGF-I concentration.
The serum IGFBP-3 concentration has greater specificity than serum IGF-I concentration in the diagnosis of GHD.
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Karyotype by G-banding
The 45,X pattern defines patients with Ullrich-Turner syndrome.
Because 10% of patients with Ullrich-Turner syndrome possess a mosaic karyotype (eg, 45,X; 46,XX), counting at least 30 cells reduces the possibility of failing to identify a patient with mosaic Turner syndrome (TS).
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Measurement of serum levels of GH
Beyond the first months of life, endogenous GH is secreted in a pulsatile fashion. These intermittent peaks are greatest after exercise, after meals (as blood glucose levels decrease), and during deep sleep. Therefore, measuring a single random serum GH value is of no use in the evaluation of the short child. Beyond the neonatal period, values obtained during the daytime are unlikely to be detectable.
Although a random serum GH value of more than 10 mg/dL generally excludes GHD, a random low serum GH concentration does not confirm the diagnosis of GHD.
Other useful tests include the following:
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CBC count for hematologic disease
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Wintrobe sedimentation rate for inflammatory bowel disease
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Antiendomysial immunoglobulin A (IgA) and immunoglobulin G (IgG), transglutaminase IgG, and antigliadin IgG titers for sprue (gluten enteropathy) (Antiendomysial IgA titers are more sensitive, and IgG titers are more specific.)
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Serum total thyroxine (total T4) and thyrotropin (TSH) levels to test for hypothyroidism
Determination of serum free T4 concentration is necessary in patients in whom TSH deficiency, TRH deficiency, or thyroxine-binding globulin (TBG) deficiency is suspected.
Directly assay free T4 levels using equilibrium dialysis.
Many reference laboratories report a value termed the free thyroxine index, which is calculated by multiplying the total T4 by an internal standard; however, if free T4 assessment is needed, measure it directly.
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Sweat chloride testing to exclude cystic fibrosis (CF): Consider this test in patients who are short and have a history of meconium ileus or pulmonary symptoms.
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Serum transferrin and prealbumin concentrations for undernutrition
Murray et al estimated that through the use of genetic studies, such as copy number variant analysis, targeted gene panels, and whole-exome sequencing, a molecular diagnosis could be derived for 25-40% of children initially diagnosed with idiopathic short stature. [10]
Imaging Studies
Perform anteroposterior radiography of left hand and wrist to assess bone age (see image below).
Bone age comparison between an 8-year-old boy (left) and a 14-year-old adolescent boy (right).
Chondrodysplasia of the distal radial epiphysis (Madelung deformity) suggests Lerí-Weill dyschondrosteosis.
Perform renal and cardiac ultrasonography in all patients with Ullrich-Turner syndrome. The most commonly associated anomalies include horseshoe kidney and bicuspid aortic valve.
Other Tests
Perform hearing tests in all patients with Ullrich-Turner syndrome. Use Bayley-Pinneau or Tanner-Goldstein-Whitehouse methods. These methods are often used to predict final adult height and become more accurate with advancing bone age.
Within 5 years of epiphyseal closure, the predicted height may fall within ±5 cm of the final adult height, with 95% confidence. The Bayley-Pinneau method can be used with a bone age as young as 6 years; however, the prediction is less accurate at the younger ages.
Procedures
Several provocative tests have been developed for the evaluation of suspected GHD, including the following:
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Insulin-induced hypoglycemia is the most powerful stimulus for GH secretion; however, this test also carries the greatest potential for harm and is the only GH provocative test that has been associated with fatalities.
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Alternate GH secretagogues used successfully in combination as 2 serial tests include arginine, levodopa, propranolol with glucagon, exercise, clonidine, or epinephrine.
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Peak GH level is higher if the patient has been recently exposed to sex steroids, but controversy among pediatric endocrinologists persists regarding the use of sex steroid priming prior to stimulation testing.
Perform all GH provocative testing under the supervision of a pediatric endocrinologist. Please refer to Hyposomatotropism for further details of these tests.
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Proper use of a wall-mounted stadiometer.
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Comparison of the growth patterns between idiopathic short stature and constitutional growth delay.
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Bone age comparison between an 8-year-old boy (left) and a 14-year-old adolescent boy (right).
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Growth chart for Turner syndrome. Note that the upper limit overlaps the range for girls of normal height.
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A single, central, maxillary incisor reflects a defect in midline facial development.
