eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Growth Failure: Differential Diagnoses & Workup
Updated: Sep 15, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
| Achondroplasia | Short Stature |
| Constitutional Growth Delay | Silver-Russell Syndrome |
| Hypopituitarism | Skeletal Dysplasia |
| Hypothyroidism | Turner Syndrome |
| Laron Syndrome | |
| Noonan Syndrome | |
| Prader-Willi Syndrome |
Other Problems to Be Considered
Glucocorticoid excess (Cushing syndrome), endogenous and exogenous
Workup
Laboratory Studies
- 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.
- Serum electrolytes: A low bicarbonate level may indicate renal tubular acidosis, which can result in growth failure. Electrolyte levels 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.
Imaging Studies
- 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.
- Bone age determination: A radiograph of the left wrist can be compared with standards to provide an estimation of skeletal maturation. Bone age also provides a determination of growth potential (predicted adult stature may be estimated from the tables of Bayley and Pinneau).
Other Tests
- 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. 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.
More on Growth Failure |
| Overview: Growth Failure |
 Differential Diagnoses & Workup: Growth Failure |
| Treatment & Medication: Growth Failure |
| Follow-up: Growth Failure |
| Multimedia: Growth Failure |
| References |
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References
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Stabler B, Siegel PT, Clopper RR, et al. Behavior change after growth hormone treatment of children with short stature. J Pediatr. Sep 1998;133(3):366-73. [Medline].
Tanner JM. Fetus into Man: Physical Growth from Conception to Maturity. Cambridge, Mass: Harvard University Press; 1990.
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Further Reading
Keywords
slow growth velocity, short stature, growth hormone, GH, GH secretion, growth hormone–releasing hormone, GHRH, growth hormone–releasing peptide, GHRP, ghrelin, growth deficiency, GH deficiency, delayed puberty, slow growth velocity, idiopathic short stature, ISS, growth failure, familial short stature, constitutional delay, Gh deficiency, Turner syndrome, hypothyroidism, Down syndrome, cystic fibrosis, chronic renal insufficiency, juvenile rheumatoid arthritis, Hurler syndrome, intrauterine growth retardation, Noonan syndrome, Russell-Silver syndrome, skeletal dysplasia, microcephaly, cyanotic heart disease, gluten enteropathy, ulcerative colitis, Crohn disease, inflammatory bowel disease, renal tubular acidosis, dermatomyositis, psychosocial dwarfism, Prader-Willi syndrome, fetal alcohol syndrome, placental insufficiency syndrome, achondroplasia, hypochondroplasia, thyroid hormone deficiency, Laron dwarfism, Cushing syndrome, Cushing disease, androgen excess, treatment, diagnosis
