Understanding SPIGFD

Severe insulin-like growth factor-1 deficiency (SPIGFD) is distinct from growth hormone deficiency (GHD)2. On this page you can read about the relationship between insulin-like growth factor (IGF)-1 and growth hormone (GH) in controlling growth in children and how SPIGFD develops.

IGF-1 is an Essential Hormone for Growth

IGF-1 is a 70-amino acid peptide hormone and growth factor considered one of the most important hormonal regulators of postnatal growth. 2,3 The major regulator of circulating IGF-1 is growth hormone (GH). 3

Growth

The GH-IGF-1 Relationship

GH is secreted from the pituitary gland and binds to the GH receptor (GHR) in many tissues, including the growth plate and the liver. 2,4

Although GH has direct effects at the growth plate, its major growth-promoting action is mediated through the GHR in the liver, which stimulates the production of IGF-1. 4

IGF-1 is released from the liver into the peripheral tissues, where it has a direct impact on linear bone growth and bone remodeling.

The Role of GH and IGF-1 to Promote Growth 2,4 6

Growth function

GH, growth hormone; IGF-1; insulin-like growth factor. GH activates GHR in the liver to stimulate IGF-1 production and release; Circulating IGF-1 promotes normal growth.2,5

GH-IGF-1 Relationship

Primary IGF-1 Deficiency Leads to Growth Failure

Deficiency in IGF-1 may lead to short stature in children and adolescents.6 Primary IGFD is characterized by abnormally low levels of IGF-1 in the presence of normal or elevated GH levels. 2,7

Normal growth becomes disrupted due to the inability of IGF-1 to mediate the growth-promoting activity of GH. 2, 7

Disruption of Growth in Primary IGF-1 Deficiency 2,4

Primary IGFD

GH, growth hormone; IGF-1; insulin-like growth factor-1; IGFD, IGF-1 deficiency. Primary IGFD is defined by low IGF-1 concentrations despite the presence of normal or elevated GH concentrations. GH is unable to activate the GHR in the liver or the GHR signaling is defective. IGF-1 is not stimulated and growth rate is affected. 1,2

IGF-1 Deficiency

When does Primary IGFD Become Severe Primary IGFD?

After ruling out other diseases and inadequate nutrition, growth failure caused by SPIGFD is defined by:1

  • height standard deviation score (SDS) ≤ -3.0
  • basal IGF-1 SDS ≤ -3.0
  • normal or elevated GH.

IGFD becomes SPIGFD

What Causes SPIGFD?

SPIGFD arises from a deficiency of either the production or peripheral action of IGF-1 on linear growth. 6

These defects may arise from a number of causes, including: 1,2,6

  • GHR gene mutations or deletions
  • GHR abnormalities
  • Post-GHR signaling pathway defects
  • Bioinactive IGF-1
  • Primary defects of synthesis and action of IGF-1

How Deficiency in IGF-1 Levels Develop

GH, growth hormone; GHR, growth hormone receptor; IGF-1; insulin-like growth factor-1; IGFD, IGF-1 deficiency.

What Causes SPIGFD?

Important Safety Information and Indication

Contraindications 

  • Hypersensitivity to mecasermin (rhIGF-1), any of the inactive ingredients in INCRELEX®, or who have experienced a severe hypersensitivity to INCRELEX®. Allergic reactions have been reported, including anaphylaxis requiring hospitalization.
  • Intravenous Administration.
  • Closed Epiphyses.
  • Malignant Neoplasia in pediatric patients with malignant neoplasia or a history of malignancy.

Warnings and Precautions

  • Hypoglycemia: INCRELEX® should be administered 20 minutes before or after a meal or snack and should not be administered when the meal or snack is omitted. Glucose monitoring and INCRELEX® dose titration are recommended until a well-tolerated dose is established and as medically indicated.
  • Intracranial Hypertension: Funduscopic examination is recommended at the initiation of and periodically during the course of therapy.
  • Lymphoid Tissue Hypertrophy: Patients should have periodic examinations to rule out potential complications.
  • Slipped Capital Femoral Epiphysis: Carefully evaluate any pediatric patient with the onset of a limp or hip/knee pain during INCRELEX® therapy.
  • Progression of Scoliosis: Patients with a history of scoliosis, treated with INCRELEX®, should be monitored.
  • Malignant Neoplasia: There have been postmarketing reports of malignant neoplasia in pediatric patients who received treatment with INCRELEX®. The tumors were observed more frequently in patients who received INCRELEX® at higher than recommended doses or at doses that produced serum IGF-1 levels above the normal reference ranges for age and sex. Monitor all patients receiving INCRELEX® carefully for development of neoplasms. If malignant neoplasia develops, discontinue INCRELEX® treatment.
  • Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preserved Solution: Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and infants treated with benzyl alcohol-preserved drugs. Use of INCRELEX® in infants is not recommended.

Adverse Reactions

Common adverse reactions include hypoglycemia, local and systemic hypersensitivity, and tonsillar hypertrophy.

Indication

INCRELEX® (mecasermin) is indicated for the treatment of growth failure in pediatric patients aged 2 years and older with severe primary IGF-1 deficiency* (IGFD), or with hormone (GH) gene deletion who have developed neutralizing antibodies to GH.1

Limitations of use: INCRELEX® is not a substitute to GH for approved GH indications. INCRELEX® is not indicated for use in patients with secondary forms of IGFD, such as GH deficiency, malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory steroids.1

*Severe primary IGF-1 deficiency (IGFD) is defined by height standard deviation score ≤ -3.0 and basal IGF-1 standard deviation score ≤ -3.0 and normal or elevated GH.

© 2020 Ipsen Biopharmaceuticals, Inc. All rights reserved. November 2020 INC-US-001014

Are you a healthcare provider?

This site is intended for U.S. healthcare professionals only. By clicking Yes, you attest that you are a healthcare professional licensed in the U.S.

 

Yes

No