“Dr. Lilley, you’ll always be my favorite doctor; you helped me grow.”
These were the parting words from the last patient that I treated during my endocrinology fellowship. I had watched this young man grow from a prepubertal 17-year-old to a young man who had reached his predicted family height as I treated his delayed puberty caused by Kallmann syndrome, a problem that had been missed for years. It was the appropriate bookend for my chosen specialty.
Dr. Jessica Sparks Lilley
Watching children grow and develop into who they were meant to be is one of my favorite things about endocrinology, as well as forming meaningful relationships with families. Treating detectable deficiencies in logical and measurable ways is also extremely satisfying.
Too little testosterone? That’s a problem I can solve. Too much thyroid hormone? There’s a blocker for that! Endocrinology can be a straightforward field, and when all goes well, everyone leaves happy.
Except when they don’t.
Gatekeepers for treatment for children’s growth
“Nice to meet you. We’re here to get growth hormone.”
“We’re here because his pediatrician made us come. We’ve already decided we’re not going to put hormones into his body.”
These are common statements I hear when I first meet new patients whose parents are concerned about their children’s growth. Pediatric endocrinologists, after all, are the usual gatekeepers for this treatment.
Growth hormone (GH) often makes the news for controversial reasons – most commonly for its abuse by elite athletes hoping to exploit its anabolic effects – causing parents to have varied opinions about its possible use in their children.
Some refuse endocrinology referrals at all owing to concerns that we will push daily injections on their children. Others demand referrals for their children of average height, hoping for every perceived advantage.
GH deficiency (GHD) – a condition where the pituitary gland fails to produce enough GH – can occur because of congenital pituitary malformations; anatomic, surgical, or traumatic interruptions to the gland; or enzyme deficiencies leading to faulty production.
GHD is just one reason for poor growth, however.
Growth is one of the most important indicators of health in children. A waning growth rate may be an early symptom of serious problems. In my clinic, I’ve diagnosed severe hypothyroidism in a marathon runner, a brain tumor, celiac disease in a teenager with no gastrointestinal complaints, autoimmune hepatitis, and several other diseases needing treatment in children who show no symptoms other than poor growth.
Barriers to normal growth
Sometimes, the die is cast for children to have barriers to normal growth. Several genetic conditions can lead to poor GH production or response, and GH treatment is often necessary to approximate normal height.
These may include:
- Turner syndrome (in females who are missing an X chromosome in whole or part) should be considered in every girl with abnormally short stature; mosaic forms of the condition may be subtle and lack classic features.
- Noonan syndrome is important to detect owing to the possibility of cardiac or renal malformations that may also occur in this condition, caused by a mutation in one of the genes in the RAS-MAPK pathway.
- Russell-Silver syndrome can cause intrauterine GH restriction and has been traced to uniparental disomy of chromosome 7 or duplications, mutations, or methylation defects in chromosome 11.
- Individuals with Prader-Willi syndrome, which is characterized by low muscle tone, hyperphagia, and hypogonadism, have demonstrated dramatic benefits from GH therapy, primarily in maintaining a normal body mass index.
Children who are small for their gestational age may be GH resistant, and those who do not catch up to their growth curve by the age of 2 years may require GH treatment to reach their height potential.
GH therapy isn’t entirely benign. Rare adverse effects of overtreatment can include slipped capital femoral epiphysis (a fracture to the growth plate) and pseudotumor cerebri (idiopathic intracranial hypertension).
Overtreatment can cause acromegaly, which results in coarsened features and large hands and feet.
When is GH therapy warranted?
“Growth hormone therapy has been denied by her insurer. They want you to fill out an appeal.”
Insurance approval in the United States can be a herculean effort because GH is expensive: Out-of-pocket costs are prohibitive for most people without insurance assistance, ranging from $7,000 to $30,000 annually.
Pediatric endocrinologists aren’t in the business of cosmetic endocrinology. Treatment of idiopathic short stature has been controversial since this became an indication for GH treatment.
GH isn’t always necessary. Diagnosing the underlying cause for poor growth is the most important step.
Often, we find constitutional delay of growth and puberty, or “late bloomers.” This condition is characterized by a delayed bone age (growth plates more open than expected for age) and delayed pubertal onset. These children will often reach a normal height despite starting as some of the smallest of their peers.
However, GH plays other roles in the body than simply propelling height. Children with congenital GHD will require GH treatment to prevent hypoglycemia, especially in infancy.
GH is needed even in adults with fused growth plates for normal lipid metabolism, bone accrual, and maintaining normal muscle mass.
I have noticed marked improvements in muscle tone in many children with developmental delays who are treated with GH, and research supports cognitive benefits for certain populations.
The most common regimens for GH focus on treatment via subcutaneous injection nightly, when GH is naturally produced; sometimes, injections are given six nights out of seven to provide a break or for splitting time between households.
Newer once-weekly formulations have recently received approval, as reported by this news organization, and are coming into use.
Pediatric endocrinologists measure height and follow growth factors closely with visits every 3-6 months. GH levels are not useful outside of provocative diagnostic (stimulation) testing.
Insulinlike growth factor 1 or insulinlike growth factor binding protein levels are analyzed per Tanner stage of puberty to assess appropriate response and to make dose adjustments.
Annual standardized films of the left hand help predict progress and anticipated adult height. Treatment usually persists through puberty until growth plates are closed; if true GHD is noticed, much smaller doses are continued through adulthood.
Regardless, conversations about GH happen with your friendly local pediatric endocrinologist.
We are thrilled to help shepherd patients through their growing age to meet their potential. For more information about GH treatment for children, the MAGIC Foundation is the perfect place to start.
Dr. Lilley is director of the pediatric diabetes and lipid program, Mississippi Center for Advanced Medicine, Madison. She disclosed no relevant conflicts of interest. A version of this article first appeared on Medscape.com.