Diagnosis of Severe Primary IGF-1 Deficiency

Knowing your patients’ insulin-like growth factor-1 (IGF-1) level is an important step in the diagnosis of severe primary IGF-1 deficiency (SPIGFD).³ A diagnosis of SPIGFD is made when a child’s IGF-1 concentration is a standard deviation score (SDS) of ≤ -3.0 and their growth hormone (GH) levels are within the normal range or are elevated, and their height is an SDS of ≤ -3.0.¹

IGF-1 Diagnosis

Endocrine Assessment of a Patient with Short Stature

After the general assessment of a patient with short stature (which may include a review of the patient’s growth history and medical history, physical examination, or general laboratory tests) to investigate other causes, an investigation may then be conducted to assess the growth hormone (GH)-IGF-1 axis prior to the initiation of therapy.³^,8

Possible defects in GH and IGF-1 levels^1,⁷

GH, growth hormone; IGF-1; insulin-like growth factor-1; PIGFD, primary IGF-1 deficiency; SPIGFD, severe primary IGF-1 deficiency; SDS, standard deviation score. *Defined by a height of SDS ≤ -3.0, basal IGF-1 SDS ≤ -3.0, and normal or elevated GH

Clinical Presentations of Primary IGFD

A patient with primary IGFD may exhibit a number of unique clinical features in addition to having short stature, including: ⁶^,9

Hypoglycemia
Obesity (with abdominal adiposity)
Undeveloped muscles
Midfacial hypoplasia
High-pitched voice
Osteoporosis
Small genitalia since birth
Delayed puberty

Criteria for a Diagnosis of SPIGFD

SPIGFD may be the cause of a severe impairment in growth. ¹

The diagnosis of SPIGFD is made when a patient meets the following criteria:

Height standard deviation score (SDS) ≤ -3.0
IGF-1 concentration SDS ≤ -3.0
GH is normal or elevated

SPIGFD Patients Have Height SDS of ≤ -3.0*¹

Data and formula from Centers for Disease Control and Prevention. SDS, standard deviation score. *SPIGFD is defined by a height of SDS ≤ -3.0 (shaded area), basal IGF-1 SDS ≤ -3.0, and normal or elevated GH.¹

Short Stature

The Importance of a Proper Diagnosis

Testing for severe primary IGF1 deficiency in children with short stature and suspected defect in the GH-IGF-1 axis is essential because these children have a limited time to reach their full growth potential with treatment before epiphyseal fusion. Timely diagnosis allows for the condition to be treated for a longer period prior to epiphyseal fusion.¹^,3

Proper Diagnosis

Assessment of the GH-IGF-1 Axis

Tests that may be used to help distinguish SPIGFD from GHD include:¹⁰

GH provocation (stimulation) test
Circulation levels of GH binding protein (GHBP)
IGF-1 generation test
IGF-1 mutation analyses

GH-IGF-1 Axis

Monitoring your patients during the course of treatment

In children previously diagnosed with a growth disorder and treated with GH, treatment response may vary by diagnosis, as well as by age and gender. If a child’s growth velocity is tracking below the average on an appropriate growth chart, this may be an indication that additional evaluation or re-evaluation is necessary. This evaluation may include an assessment of compliance, and whether other diagnoses, including SPIGFD, should be considered.

Monitoring

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.