Growth Failure Workup

Updated: Jun 22, 2018
  • Author: Neslihan Gungor, MD; Chief Editor: Sasigarn A Bowden, MD  more...
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Workup

Laboratory Studies

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  • Thyroxine (T4) and thyroid-stimulating hormone (TSH): T4 and TSH levels are important to rule out hypothyroidism and to screen for panhypopituitarism as a cause for short stature and growth failure. As the serum total T4 assays measure both bound and unbound ("free") T4, freeT4 test is preferred for screening in most pediatric endocrine clinics.

  • Serum electrolytes, creatinine, bicarbonate, calcium, phosphate, alkaline phosphatase, albumin: A low bicarbonate level may indicate renal tubular acidosis, which can result in growth failure. Electrolyte levels and/or creatinine out of the reference range may indicate renal failure. Hypokalemic alkalosis may indicate Bartter syndrome.

  • CBC count and sedimentation rate: These tests may be helpful if inflammatory bowel disease is suspected.

  • IGF-1 and IGFBP-3: Both IGF-1 and the binding protein IGFBP-3 are growth hormone (GH) dependent. Low values suggest growth hormone deficiency. However, they are also sensitive to other factors such as nutritional state, so a low value alone is not diagnostic of growth hormone deficiency.

  • Karyotype: Girls with otherwise unexplained short stature should have karyotype determined to rule out Turner syndrome. Although Turner syndrome is diagnosed in many girls from signs present on physical examination, some girls with Turner syndrome have short stature as the only recognizable feature. In particular, girls with mosaic karyotypes or karyotypes with isochromosomes tend to exhibit fewer signs specific to Turner syndrome.

  • Celiac serology: Screening for celiac disease is considered in applicable patients. Tissue transglutaminase [tTG] immunoglobulin A [IgA] and serum total Ig A are the first line tests. Inclusion of total IgA level helps exclude a false-negative test in a patient with selective IgA deficiency. Additional (IgG based) celiac serology tests are available.

  • Additional evaluations should be considered on a case-by-case basis, if suggested by the history and physical examination. For example testing for precocious puberty, potential endocrine (such as Cushing's syndrome), skeletal or syndromic causes of short stature. Testing for SHOX gene mutations should be considered as applicable.

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Imaging Studies

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  • Bone age determination: A radiograph of the left hand and wrist can be compared with standards to provide an estimation of skeletal maturation. The most common methods used to determine skeletal age are the Greulich and Pyle Atlas and the Tanner-Whitehouse method. Bone age also provides a determination of growth potential (predicted adult stature may be estimated from the tables of Bayley and Pinneau).

  • MRI of the head: Patients who are diagnosed with growth hormone deficiency should undergo MRI of the head to rule out a brain tumor, such as a craniopharyngioma. As many as 10% of children diagnosed with a craniopharyngioma present with growth failure as the only sign. Also, approximately 15% of patients with growth hormone deficiency have an abnormality of the pituitary gland, such as an ectopic bright spot, an empty sella, or a small sella. Discovery of one of these conditions aids diagnosis of growth hormone deficiency and significantly increases the probability that such a patient requires lifelong growth hormone replacement.

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Other Tests

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  • Growth hormone response to insulin has been considered the most reliable test for growth hormone deficiency. For recognition of the diagnosis of growth hormone deficiency, many insurance companies require documenting a failure to demonstrate a growth hormone response (with a growth hormone level >10 ng/mL) to 2 provocative stimuli. Provocative stimuli include insulin-induced hypoglycemia, arginine, levodopa (L-dopa), clonidine, and glucagon.

  • Over time, the potential growth hormone supply has increased, and the peak growth hormone level considered "adequate" has increased to 10 ng/mL. In true (or classic) growth hormone deficiency, the peak growth hormone response to provocative stimuli is probably less than 5 ng/mL. Children who have classic growth hormone deficiency robustly respond to relatively small doses of growth hormone (especially during the early part of treatment), particularly in terms of growth velocity. However, many patients who have peaks in the 5-10 ng/mL range in response to growth hormone provocative agents may also respond well to growth hormone therapy. [8] In fact, no great difference in terms of response to GH is noted between this group and those whose growth hormone provocative tests are read as adequate (ie, a growth hormone peak >10 ng/mL). This latter category has been called idiopathic short stature.

  • Because of these issues, in 2003, the US Food and Drug Administration (FDA) approved growth hormone therapy for especially short children (height >2.25 standard deviations below the mean) who are not growth hormone deficient and thus fall into the category of idiopathic short stature. Also, because growth hormone testing with provocative agents uses a cut-off peak growth hormone level of 10 ng/mL, some practitioners have avoided these growth hormone provocative tests. However, the author believes that recognizing children who are severely growth hormone deficient (classic growth hormone deficiency) is valuable because these children may be more at risk for other pituitary hormone deficiencies and are much more likely to need lifelong growth hormone replacement.

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