eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Short Stature: Differential Diagnoses & Workup
Updated: Aug 4, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Causes of growth failure in children (partial list)
- GI
- Protein or caloric deprivation
- Inflammatory bowel disease -Crohn disease, ulcerative colitis
- Cystic fibrosis (CF)
- Sprue (gluten intolerance)
- Protein-losing enteropathy
- Endocrine
- Hypothyroidism
- Primary - Hashimoto thyroiditis, Pendred syndrome
- Secondary - Thyrotropin (thyroid-stimulating hormone [TSH]) deficiency
- Tertiary - Thyrotropin-releasing hormone (TRH) deficiency
- Other - Iatrogenic or environmental radioablation, neoplasm
- Growth hormone deficiency (GHD) complete absence or insufficiency (partial absence)
- Neurosecretory GHD
- Panhypopituitarism (combined anterior pituitary hormone deficiencies)
- Growth hormone-releasing hormone (GHRH) deficiency
- Poorly controlled type 1 diabetes mellitus - Mauriac syndrome
- Chronic hypernatremia - Hypothalamic adipsia, poorly controlled diabetes insipidus
- Hypercortisolism - Iatrogenic glucocorticoid administration, or Cushing syndrome
- Hypocortisolism -DAX1 gene mutation, autoimmune adrenalitis (Addison disease); (Note that adrenocorticotropic hormone deficiency alone has been associated with tall stature; short stature results from hypocortisolism only in persons with salt wasting.)
Normal variant short stature (also called familial short stature)
- Genetic (known defect)
- Down syndrome (trisomy 21)
- Silver-Russell syndrome
- Hypochondroplasia
- SHOX gene mutations
- Turner syndrome
- Leri-Weill dyschondrosteosis
- Growth hormone (GH) receptor gene mutations (Laron syndrome)
- IGF1 gene mutation
- IGF1R gene mutation
- PROP1 gene mutations
- POU1F1 gene mutations
- GHRH gene mutations
- GH gene mutations
- Insulin receptor gene mutations (leprechaunism)
- Genetic (unknown defect)
- Silver-Russell syndrome
- Shwachman-Diamond syndrome
- Pulmonic
- CF
- Severe asthma
- Chronic obstructive pulmonary disease
- Restrictive lung disease
- Cardiac
- Hypoxemia
- Congestive heart failure
- Low cardiac output states
- Precocious puberty
- Renal
- Chronic renal insufficiency
- Renal failure
- Renal tubular acidosis
- Psychosocial dwarfism
- Chronic neglect
- Starvation
Workup
Laboratory Studies
- Laboratory studies used to assess the major causes of short stature in children include the following:
- 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.
- 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).
- Measuring 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.
- Measurement of serum levels of insulinlike growth factor-I (IGF-I), formerly named somatomedin C, and IGF binding protein-3 (IGFBP-3)
- Other useful tests include the following:
- CBC count for hematologic disease
- Wintrobe sedimentation rate for inflammatory bowel disease
- 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.)
- 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.
- 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.
- Serum transferrin and prealbumin concentrations for undernutrition
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:
- 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.
- Alternate GH secretagogues used successfully in combination as 2 serial tests include arginine, levodopa, propranolol with glucagon, exercise, clonidine, or epinephrine.
- Perform all GH provocative testing under the supervision of a pediatric endocrinologist.
- Please refer to Hyposomatotropism for further details of these tests.
More on Short Stature |
| Overview: Short Stature |
 Differential Diagnoses & Workup: Short Stature |
| Treatment & Medication: Short Stature |
| Follow-up: Short Stature |
| Multimedia: Short Stature |
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References
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Further Reading
Keywords
short stature, short height, familial short stature, genetic short stature, constitutional delay of growth, constitutional growth delay, growth failure, GF, growth pattern, longitudinal growth assessment, chronic short stature, undernutrition genetic disorders, Bayley-Pinneau table, Tanner-Goldstein-Whitehouse table, premature closure of the epiphysial growth plates, growth hormone deficiency, GHD, Turner syndrome, TS, Ullrich-Turner syndrome, eating disorders, malabsorption, polyuria, polydipsia, upper-to-lower segment ratio, US/LS, Hashimoto thyroiditis, pseudohypoparathyroidism, Albright hereditary osteodystrophy, ulcerative stomatitis, Crohn disease, ulcerative colitis, Down syndrome, trisomy 21, insulinlike growth factor, IGF, IGF binding protein, IGFBP, Lerí-Weill dyschondrosteosis, SHOX, treatment, diagnosis
