Site Search
Growth Hormone Deficiency
in Children
Growth hormone (GH) is a protein made by the pituitary gland and released into the blood in pulses.
The major way that GH promotes growth is by increasing levels of the hormone, insulin-like growth factor-1 (IGF-1), and its carrier protein, IGF binding protein-3 (IGFBP-3). GH and IGF-1 work together on the cartilage cells of the growth plate in long bones to increase bone length leading to increased height.
Growth hormone deficiency (GHD) in children is defined as growth failure associated with inadequate growth hormone production. Growth failure should be evaluated in children whose length or height remains below the normal range (i.e. <3rd percentile) or whose length or height percentile is crossing major percentile landmarks over time. Before considering growth hormone deficiency as a possible diagnosis, a child with growth failure needs to be evaluated for other conditions that can impact growth.
These include disorders with inflammation (arthritis, inflammatory bowel disease, etc.), poor nutrition (inadequate intake or malabsorption conditions such as celiac disease, etc.), other chronic conditions (kidney or liver disease, hypothyroidism, etc.) and genetic conditions that impact growth (skeletal dysplasia, familial short stature, Russell-Silver Syndrome, Turner Syndrome, etc.). Children receiving stimulant therapy for attention deficit and hyperactivity disorder may have growth impairment. However, stimulant therapy does not cause GHD. Chronic glucocorticoid therapy (inhaled or oral) can cause significant growth failure. Children with constitutional delay of growth and puberty (“late-bloomers”) can have a slow growth pattern that may be difficult to separate from GHD.
-
Testing
Screening tests for GHD in children with growth failure and no identified cause include bone age x-ray, serum IGF-1 and IGFBP-3 levels. A delayed bone age is more common in children with GHD. An IGF-1 in the low part of the normal range or below normal increases the likelihood of GHD. An MRI picture of the brain showing a small or ectopic (misplaced) pituitary gland supports a diagnosis of GHD. The gold standard for diagnosing GHD is failure to increase GH levels in a growth hormone stimulation test (GHST). A GHST is performed in children after an overnight fast by giving medications (such as insulin, clonidine, arginine, glucagon, L-Dopa, etc.) to cause release of growth hormone into the blood then drawing blood frequently. If the highest growth hormone level obtained following two separate stimuli is less than 10 ng/mL (some centers use lower cutoffs), this is diagnostic of GHD.
Diagnosis and Treatment
When a child is diagnosed with GHD, the pituitary gland is further evaluated by measuring levels of the other hormones that it makes, and by obtaining an MRI of the brain. Acquired GHD can result from damage to the pituitary gland, but often has no identifiable reason. Congenital GHD often occurs due to a genetic or a structural defect affecting the pituitary gland. Infants with GHD can have low blood sugars and may have other pituitary hormone deficiencies. GH replacement helps in maintaining normal blood sugars in infants with GHD.
Children diagnosed with GHD benefit from GH replacement therapy with improved linear growth until the growth plates fuse. rhGH therapy is traditionally given by daily subcutaneous injections. Children and their families are taught to self-inject rhGH at home. The rhGH starting dose is based upon the child’s weight and may be adjusted during therapy based upon weight gain, growth response and IGF-1 levels. Children receiving rhGH therapy should be seen by the pediatric endocrinologist every 3 to 6 months for growth monitoring and rhGH dose adjustment. The earlier a child is diagnosed with GHD, the better the final height attained. Recently, three long acting GH (LAGH) preparations received FDA-approval for once-weekly use in children with GHD. These are Skytrofa™ (lonapegsomatropin; for children > 1 year and > 11.5 kg), Sogroya™ (somapacitan; > 2.5 yrs) and Ngenla™ (somatrogon; > 3 yrs). Clinical trials have shown similar growth velocity and height gain on once-weekly LAGH injections compared to daily rhGH injections, and no significant difference in side effects. Children treated with LAGH need monitoring of their growth response and IGF-1 levels, similar to daily rhGH. Long-term follow up is needed to determine if the long–term benefits and side effects of LAGH differ from daily rhGH.
How Growth Hormone Affects the Body other than Growth
In addition to growth, GH regulates the metabolism. As calories are consumed, GH controls whether those calories are used to build bone, muscle and cartilage or stored as fat. Between meals, GH regulates the use of fat for energy. Individuals with GHD can have significant changes in body composition (decreased bone mass, lean mass and increased visceral adiposity) and elevated lipid levels. In children with growth hormone deficiency, GH replacement therapy is important to normalize metabolism. Some children with severe GHD will require rhGH replacement therapy as adults to benefit from the metabolic effects of GH.
Contributing Medical Specialists:
Heba Al-Rayess, MD
Assistant Professor
Pediatric Endocrinology
M Health Fairview Masonic Children’s Hospital
Univ. of Minnesota Medical School
Minneapolis, MinnesotaBradley S. Miller, MD, PhD
Professor and Division Director
Pediatric Endocrinology
M Health Fairview Masonic Children’s Hospital
Univ. of Minnesota Medical School
Minneapolis, MN
Medical Advisory Committee Member of The MAGIC Foundation
