eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Growth Failure: Treatment & Medication
Updated: Sep 15, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Treatment is directed at the cause of the growth failure. If the child is diagnosed with hypothyroidism, treatment is thyroid hormone replacement. Likewise, if the child is diagnosed with growth hormone (GH) deficiency, the treatment is growth hormone replacement therapy. In 2003, the FDA approved the use of growth hormone for children who are not growth hormone deficient but who are at least 2.25 standard deviations below the mean for height, who are unlikely to have an adult height above -2 standard deviations, and who have no explanation for their short stature. This disorder has been termed idiopathic short stature.
Consultations
Although a primary care physician often initiates the workup, the child is usually referred to an endocrinologist for a more detailed investigation of possible causes for growth failure.
Medication
Growth hormone (GH) is approved by the FDA for treatment of growth failure caused by the following: growth hormone deficiency, Turner syndrome, chronic renal insufficiency, intrauterine growth failure with postnatal growth failure, Prader-Willi syndrome, and idiopathic short stature.
Growth Hormone
These agents are used for physiologic replacement of growth hormone deficiency and are used pharmacologically as a growth-promoting agent in patients with Turner syndrome, chronic renal insufficiency, intrauterine growth failure, Prader-Willi syndrome, or idiopathic short stature.
Somatropin (Humatrope, Nutropin AQ, Genotropin, Norditropin, Omnitrope, Saizen, Tev-Tropin, Zorbtive)
Recombinant DNA origin GH. In children whose epiphyses are not yet fused, GH therapy usually results in a significant increase in growth velocity (averaging 10-11 cm/y during the first year of therapy in GH deficiency and 7-9 cm/y during the first year in other disorders). Response wanes each year, but growth velocity continues to be faster than pretreatment rates.
Adult
0.05-0.1 mg/kg/wk SC, generally administered in divided doses as a daily SC injection; one sixth to one fourth of the childhood dose
Pediatric
0.18-0.375 mg/kg/wk SC divided into 6-7 injections; FDA has approved doses as high as 0.7 mg/kg/wk during puberty
Excessive glucocorticoid therapy inhibits the growth-promoting effect
Documented hypersensitivity; acute critical illness due to complication following open heart or abdominal surgery or multiple accidental traumas; acute respiratory failure; closed epiphyses; active neoplasia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
GH therapy in patients with functioning renal allografts is not indicated; insulin dose may require adjustment in patients with diabetes mellitus when GH therapy is initiated; progression of scoliosis can occur in patients who experience rapid growth; discontinue use if neoplasia develops
Androgen
Oxandrolone, along with growth hormone, has been used in Turner syndrome to potentiate the growth-promoting effect of growth hormone.
Oxandrolone acetate (Oxandrin)
Synthetic testosterone derivative. A weak androgen that cannot be aromatized to estrogen.
Adult
2.5 mg PO bid/qid
Pediatric
0.1 mg/kg PO qd
May inhibit the metabolism of PO hypoglycemic agents
Documented hypersensitivity; known or suspected carcinoma of the prostate or breast; carcinoma of the breast in females with hypercalcemia; nephrosis; hypercalcemia
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Women should look for signs of virilization; may increase edema with concomitant administration of glucocorticoid or ACTH; may decrease levels of T4-binding globulin, resulting in decrease total T4 serum levels but normal free T4 levels
Boxed warning: Known to cause peliosis hepatitis (associated with life-threatening liver failure or intra-abdominal hemorrhage), liver cell tumors (benign and malignant), and blood lipid changes
Insulinlike growth factor
IGF-I (mecasermin) has been approved by the FDA for primary severe IGF-I deficiency. Some children with idiopathic short stature may have a degree of growth hormone insensitivity; these children may benefit from treatment with IGF-I. Clinical studies are presently in progress to determine whether this hypothesis is correct.
Mecasermin (Increlex)
Recombinant human IGF-1 indicated for long-term treatment of growth failure in children with severe (ie, basal IGF-1 and height SD scores <-3, normal or elevated GH level) primary IGF-1 deficiency (primary IGFD). IGF-1 is essential for normal growth of children's bones, cartilage, and organs by stimulating glucose, fatty acids, and amino acid uptake into tissues. IGF-1 is the principal hormone for statural growth and directly mediates GH effect. Primary IGFD is characterized by lack of IGF-1 production despite normal or elevated GH levels.
Adult
Contraindicated
Pediatric
<2 years: Not established
>2 years: 0.04-0.08 mg/kg SC bid initially with meal or snack; if tolerated after 1 wk, may increase by 0.04 mg/kg/dose, not to exceed 0.12 mg/kg bid
Individualize dose and adjust downward if hypoglycemia occurs
Data limited; caution with coadministration of other drugs that alter blood glucose levels
Documented hypersensitivity; closed epiphyses; active or suspected neoplasia; IV administration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include hypoglycemia, lipohypertrophy, and tonsillar hypertrophy; contains benzyl alcohol (associated with neurotoxicity in neonates); must be administered with meal or snack to avoid hypoglycemic effect (preprandial glucose monitoring recommended); similar to GH administration, intracranial hypertension with papilledema may develop and cause visual changes, headache, nausea, or vomiting; rapid growth may cause slipped capital femoral epiphysis and scoliosis progression; protein substance administration may cause local or systemic reaction (eg, flushing, hypotension/hypertension, rash, dyspnea)
Gonadotropin Releasing Hormone Analog
Gonadotropin-releasing hormone analog has been occasionally used to try to slow the onset and progression of puberty, thus resulting in a longer time for growth. Studies have demonstrated a small, but statistically significant, increase in predicted adult height. The effect seems to be greater if early puberty is is interrupted with this therapy. Part of the problem of using this therapy is that children who are experiencing short stature are troubled by being different, and delaying puberty beyond a normal point is also making them different from their peers.
Leuprolide acetate (Lupron)
Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels.
Adult
3.75 mg IM every mo
Pediatric
Administer as in adults; only administered postmenarche
None reported
Documented hypersensitivity; undiagnosed vaginal bleeding, and spinal cord compression
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Urinary tract obstruction, tumor flare, and bone pain may occur; monitor patients for weakness and paresthesias
Aromatase Inhibitor
Maturation of the skeleton has been shown to be the result of estrogen in both boys and girls. Studies have shown that inhibiting conversion of androgen to estrogen for a period of 3 years may result in increases in adult height prediction by as much as 3 inches or more. Actual adult height data are pending, although these data are just beginning to appear.
Letrozole (Femara)
Letrozole is an aromatase inhibitor, which interferes with the conversion of androgen to estrogen.
Adult
2.5 mg PO qd
Pediatric
Not established; limited data suggest administering as in adults
Strong inhibitor of CYP450 2A6, moderate inhibitor of CYP450 2C19; increases the effects of CYP2A6 substrates (eg, dexmedetomidine, ifosfamide); coadministration with tamoxifen reduces letrozole plasma levels by 38%
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in impaired liver function, impaired renal function, seizure disorder, cardiac or pulmonary disease; may cause vasomotor symptoms, dizziness, fatigue, or loss of bone density; patients should be cautioned before operating machinery or driving
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
[Guideline] New York State Department of Health. Growth, body composition, and metabolism. New York (NY): New York State Department of Health; 2007 Nov. [Full Text].
Lindsay R, Feldkamp M, Harris D. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. Jul 1994;125(1):29-35. [Medline].
Lacey KA, Parkin JM. Causes of short stature. A community study of children in Newcastle upon Tyne. Lancet. Jan 12 1974;1(7846):42-5. [Medline].
Carrel AL, Allen DB. Effects of growth hormone on body composition and bone metabolism. Endocrine. Apr 2000;12(2):163-72. [Medline].
Grimberg A, Kutikov JK, Cucchiara AJ. Sex differences in patients referred for evaluation of poor growth. J Pediatr. Feb 2005;146(2):212-6. [Medline].
Hindmarsh PC, Brook CG. Short stature and growth hormone deficiency. Clin Endocrinol (Oxf). Aug 1995;43(2):133-42. [Medline].
Hintz RL. Growth hormone treatment of idiopathic short stature. Horm Res. 1996;46(4-5):208-14. [Medline].
Hintz RL. Disorders of growth. In: Brunwald E, Fauci AS, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 13th ed. New York, NY: McGraw-Hill Medical Publishing Division; 1994.
Horner JM, Thorsson AV, Hintz RL. Growth deceleration patterns in children with constitutional short stature: an aid to diagnosis. Pediatrics. Oct 1978;62(4):529-34. [Medline].
Kojima M, Hosoda H, Date Y. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. Dec 9 1999;402(6762):656-60. [Medline].
Kojima M, Hosoda H, Matsuo H. Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab. Apr 2001;12(3):118-22. [Medline].
Stabler B, Clopper RR, Siegel PT, et al. Academic achievement and psychological adjustment in short children. The National Cooperative Growth Study. J Dev Behav Pediatr. Feb 1994;15(1):1-6. [Medline].
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.
Tanner JM. Normal growth and techniques of growth assessment. Clin Endocrinol Metab. Aug 1986;15(3):411-51. [Medline].
Zemel B. The recognition and treatment of growth disorders - a 50-year retrospective. Ann Hum Biol. Sep-Oct 2009;36(5):496-510. [Medline].
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
