Primary IGF-1 Deficiency
Robert Rapaport, MD, Professor of Pediatric Endocrinology, and Director of the Comprehensive Growth Center at the Icahn School of Medicine, Mount Sinai Medical Center, New York City, discussed the differences between severe, primary IGF-1 deficiency and growth hormone (GH) deficiency in patients with short stature.
In young patients with short stature, GH deficiency is the most common cause. However, in a small subset of patients, the underlying problem is not GH deficiency but an abnormality in insulin-like growth factor-1 (IGF-1) levels. This peptide hormone was first discovered 50 years ago, and IGF-1 deficiency has been found to be caused by mutations in the GH receptor and defects in the IGF-1 gene. In patients with a specific subtype of severe, primary IGF-1 deficiency (SPIGF1D) called Laron syndrome, the specific cause is GH-receptor mutations.
Severe, primary IGF-1 deficiency is generally associated with the following patient characteristics: severe postnatal growth failure, short limb length, typical facial features (e.g., small forehead), and delays in sexual development and skeletal maturation. Crucially, affected children do not respond to a GH stimulation test.
Patients who have abnormally low GH levels can also be considered IGF-1 deficient. On the other hand, if the patient has normal GH levels, IGF-1 concentrations may still be abnormally low. According to Dr. Rapaport, patients with IGF-1 deficiency may be found to have abnormal IGF-1 levels across a spectrum from borderline low to extremely low, the latter of which represents the main feature of SPIGF1D (IGF-1 levels are 5–6 standard deviations below the mean for healthy individuals).
The only effective treatment for SPIGF1D is IGF-1 supplementation, with mecasermin, a human recombinant IGF-1 preparation. Although mecasermin is proven to increase patients’ growth velocity, patients taking the product are expected to attain “near normal” adult height only. It is given twice daily, and it does carry a risk of hypoglycemia, as IGF-1 lowers blood glucose levels. It is thus important that patients and their caregivers are well educated about avoiding this dangerous adverse effect.
Growth Hormone Deficiency
Robert Rapaport, MD, Professor of Pediatric Endocrinology, and Director of the Comprehensive Growth Center at the Icahn School of Medicine, Mount Sinai Medical Center, New York City, discusses the causes of growth hormone deficiency and its treatment. Growth failure in children is a considerable challenge for parents and pediatricians, with clinical and social stigma implications that may be avoided with early diagnosis.
The most important issue in young patients with growth failure is to detect it early, according to Dr. Rapaport. “As soon as you see a major deviation from the [expected growth chart] norm, act on it, even at age 2,” he emphasized, “because we know that best outcomes result from early detection.”
A growth failure diagnosis is delayed or underdiagnosed in minority groups; it is underdiagnosed in girls relative to boys. In most cases, children are referred to the Comprehensive Growth Center by pediatricians and primary care physicians, and it should be monitored from birth.
Growth failure in children can be caused by growth hormone (GH) deficiency, malnutrition, celiac disease, pituitary tumor (which suppresses the release of growth hormone) or a very rare genetic deletion. Once the potentially nonendocrine causes of GH deficiency are excluded, then causes related to the hypothalamus–pituitary-thyroid axis should be investigated, said Dr. Rapaport.
Growth hormone stimulation testing and low blood levels of insulin-like growth factor (IGF) and IGF-binding protein concentrations can help confirm GH deficiency as the cause. However, low IGF-1 levels can also be caused by excessively high GH levels.
In children diagnosed with GH deficiency, weekly GH injections are typically prescribed. In addition to monitoring these children for potential side effects of the GH injections, Dr. Rapoport recommended that they should undergo lab testing for IGF-1 blood concentrations every 3 to 6 months, until the bones fuse (signaling the conclusion of growth).
For more information on growth hormone deficiency and other rare endocrine disorders, visit https://checkrare.com/diseases/endocrine-disorders/