Growth Hormone Resistance Workup

  • Author: Arlan L Rosenbloom, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Apr 18, 2012
 

Laboratory Studies

Please refer to Hyposomatotropism and Short Stature for the complete workup for growth failure.

  • GH is elevated in childhood in GHRD, but may be normal in adults; above normal response to stimulation in children and adults. See Table in Background section for other conditions
  • IGF-I and IGFBP3 are very low in GHRD. See Table in Background section for other conditions.
  • GHBP is low or absent in GHRD, except for mutations at the transmembrane region, which will result in increased GHBP. See Table in Background section for other conditions.
  • Home blood glucose monitoring may be considered for infants and young children to monitor intervention for hypoglycemia (typically frequent feeding).
  • Lipid profile is appropriate for adults with GHRD.
  • Mutational analyses should be obtained in consultation with one of the few laboratories analyzing the GH-IGF-I axis.
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Imaging Studies

  • A left hand and wrist radiograph can be used to assess osseous maturation as is done with any other growth disorder.
  • A hip radiograph series may be indicated to assess for Legg-Perthes disease (aseptic necrosis of the capital femoral epiphysis).
  • Patients being treated with rhIGF-I may need radiographic studies of upper airway due to the common adverse effect of lymphoid hyperplasia, often requiring tonsillectomy/adenoidectomy.
  • Brain imaging studies may be required because of the adverse effect of intracranial hypertension.
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Contributor Information and Disclosures
Author

Arlan L Rosenbloom, MD  Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida College of Medicine; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology

Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Florida Pediatric Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Jaime Guevara-Aguirre, MD  Founder and General Director, The Institute of Endocrinology, Metabolism and Reproduction (IEMYR), Ecuador

Jaime Guevara-Aguirre, MD is a member of the following medical societies: Endocrine Society and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Phyllis W Speiser, MD  Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London)  Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD  Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

References

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Diagram of the hypothalamic-pituitary-GH/IGF-I axis, showing mutational targets beginning with the GH-releasing hormone receptor (GHRHR), indicated in bold and italicized.
Reported patients with homozygous signal transduction and activator of translation (STAT5b) mutations.
Acid labile subunit (ALS) deficiency from mutations of the ALS gene in 15 patients. IGF-I, IGFBP3, target height, and near adult or adult height are expressed as standard deviation score (SDS). Target height is calculated as the mean parental height SDS.
Reported cases of mutations of the IGF-I receptor in 17 individuals from 7 families.
50-year-old woman with GHRD (right) and her 75-year-old mother, indicating premature aging appearance. Photos were taken at the same distance, emphasizing the small size of the subject and relative foreshortening of the facies.
10-year-old Ecuadorian girl with GHRD/Laron syndrome, who was performing at the top of the class, with her classmates.
15 Ecuadorian children with GHRD due to homozygosity for the E180 splice mutation of the GH receptor, lined up according to descending age from 15 years to 2 years, with 3 normal children standing behind age mates. Note general but not consistent statural correlation with age, most dramatic for 11-year-old boy, 4th from the left and his 8-year-old brother holding the ball who is almost the same height.
21-year-old woman and her 23-year-old brother with GHRD/Laron syndrome demonstrating variable effects on growth of the same mutation and the correlation with low levels of IGF-I in IGFBP3. Her height is 100 cm, -11.2 SDS and his height is 134 cm, -6.3 SDS, and his IGF-I level is 4 times hers and his IGFBP3 level twice hers.
Adult with GHRD standing with 3 of his fellow police officers, his affected brother, a visiting US physician (Doctor Frank Diamond) and the seated chief.
Six-month, placebo-controlled, double-blind study of rhIGF-I in 16 Ecuadorian children with GHRD, followed by 6 months open label rhIGF-I therapy of the entire group.
Treatment with rhIGF-I for 1-2 year of children with GH insensitivity. Data are from the references noted as well as package inserts.
Table. Features of GH Resistance Causes
ConditionGrowth failureGHGH binding proteinIGF-IIGFBP3
Genetic
GHRD - Recessive formsSevereElevatedAbsent-low*Very lowVery low
GHRD - Dominant negative formsMild-moderateElevatedIncreasedVery lowLow-normal
STAT5b mutationSevereElevatedNormalVery lowVery low
ALS mutationNone-moderateNormalNormalVery lowVery low
IGF-I gene mutationSevereElevatedNormalAbsent-high**Low-normal
IGF-I receptor mutationMild-moderateNormal-elevatedNormalNormal-elevatedNormal-elevated
Acquired
GH inhibiting antibodiesSevereAbsentNormalVery lowLow
MalnutritionNone-mildElevatedDecreasedVariableVariable
Diabetes mellitusNone-mildElevatedDecreasedDecreasedIncreased
Renal diseaseMild-severeNormalDecreasedNormalIncreased
Hepatic diseaseMild-severeElevatedNormal-increasedDecreasedNormal
*Increased in mutations of or near the transmembrane domain of the GH receptor



**Absent with partial IGF-I gene deletion; very high with abnormal IGF-I



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