Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-like Growth Factor-I Deficiency
Conditions Where GH Provocative Testing is Not Required to
Diagnose GHD
GH Provocative Testing
Technical remarks:
- Very low peak GH levels on provocative testing are consistent with severe GHD, and patients with such results are expected to benefit greatly from GH treatment. However, the threshold test result that distinguishes normal from partial GHD that responds to treatment has not been well established.
- Given the substantial number of healthy, normally growing children who test below accepted limits, inadequate response to two different provocative tests is required for diagnosis of GHD. While it is possible that combining tests might yield different results from tests performed on separate days, there is no evidence against performing both tests sequentially on the same day.
- GH responses to provocative testing are blunted in obese or overweight individuals, and the peak values decrease with increasing body mass index (BMI). Unlike adults, obesity-dependent modifications to diagnostic criteria in children are undetermined.
Technical remarks:
- Best available evidence exists for boys; evidence is extrapolated to girls.
- A reasonable approach in both boys and girls would be 2 mg (1 mg for body weight
<20 kg) of β-estradiol (not ethinyl estradiol) orally on each of the two evenings preceding the test. Alternatively, boys can be primed with intramuscular testosterone (50–100 mg of a depot formulation administered 1 week before the test). - -naïve patients; it does not retroactively apply to patients already on GH treatment.
Measurement of Spontaneous GH Secretion
Treatment
Efficacy of GH Treatment for GHD
Dosing of GH Treatment for Patients With GHD
Technical remark: The PES cannot make a recommendation regarding IGF-I-based dosing because there are no published adult height data using this method. The rationale is logical, but the target IGF-I level has not been established to optimize the balance between adult height gain, potential risks, and cost.
During puberty, the PES recommends against the routine increase in GH dose to 0.7 mg/kg/week in every child with GHD.
( S , ●●○○ )Safety Issues of GH Treatment for Patients With GHD
For children considered not to be at risk, the PES recommends that counseling include information about the unknown long-term (i.e., post-treatment) risks of neoplasia still being studied.
( U , )Transitional Care After Childhood GH Treatment
GH Treatment of Patients With Idiopathic Short Stature (ISS)
IGF-I Treatment of Patients With Primary IGF-I Deficiency (PIGFD)
- Screening: auxological parameters and low IGF-I concentration.
- Causes of secondary IGF-I deficiency must be excluded, including under-nutrition, hepatic disease, and GHD.
- Circulating levels of GH-binding protein (GHBP): very low or undetectable levels suggest Laron syndrome/GHIS while normal levels are non-informative.
- IGF-I generation test and mutation analyses can be helpful but have limitations.
General Recommendations
Recommendation Grading
Overview
Title
Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-like Growth Factor-I Deficiency
Authoring Organization
Pediatric Endocrine Society
Publication Month/Year
January 1, 2017
Last Updated Month/Year
April 3, 2024
Supplemental Implementation Tools
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Document Objectives
To update the guidelines published in 2003 on the use of growth hormone (GH). Because idiopathic short stature (ISS) remains a controversial indication, and diagnostic challenges often blur the distinction between ISS, GH deficiency (GHD), and primary IGF-I deficiency (PIGFD), we focused on these three diagnoses, thereby adding recombinant IGF-I therapy to the GH guidelines for the first time.
Target Patient Population
Patients with Idiopathic short stature, GH deficiency, or primary IGF-I deficiency
Inclusion Criteria
Female, Male, Adolescent, Child, Infant
Health Care Settings
Ambulatory, Childcare center, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Counseling, Assessment and screening, Diagnosis, Management, Treatment
Diseases/Conditions (MeSH)
D013006 - Growth Hormone, D006130 - Growth Disorders, D018970 - Insulin-Like Growth Factor Binding Protein 1, D019382 - Human Growth Hormone
Keywords
growth hormone deficiency, growth hormone (GH), insulin-like growth factor-1 (IGF-1)