Using growth hormone to treat short stature

What is growth hormone?

Growth hormone is a hormone that is secreted from the hypophysis (the pituitary gland), and plays several different roles in our body, in addition to helping children grow taller. Growth hormone is related to the exchange of substances in our body and its deficiency can have a negative effect on the strength of our muscles, the amount of fat tissue we have in our body, our tendency to develop low blood sugar levels, low phosphorous levels, and more.

Should we consider growth hormone treatment for anyone with short stature?

Of course not. If there is a primary cause behind the short stature (for example, Celiac), then one should attempt to treat the underlying cause. In the case of celiac, the treatment would be a gluten-free diet. Another example for an underlying cause is nutritional deficiency. In these children, the weight percentile is usually lower than the height percentile (weight is usually below the 3rd percentile), on their growth chart. In such children one should rule out an absorption disorder, and after taking a detailed medical history, a physical examination and laboratory workup as explained in the previous post, a consult with a nutritionist should be considered to find ways to improve their growth rate.

But what if you don’t find the cause of the child’s short stature? When should treatment with growth hormone be considered?

Who should be treated with growth hormone?

Not everyone can or should receive growth hormone. Treatment with growth hormone is indicated under several, specific medical situations and it is important to realize that if there is no clear medical indication, the treatment will not be offered (even though we would all obviously be happy to gain 5 cm in height).
These are FDA-approved indications for pediatric growth hormone therapy:
1. Growth hormone deficiency (either on its own or as part of a combined deficiency with other hormones that are produced by the pituitary gland).
2. Turner syndrome.
3. Chronic renal failure.
4. Prader-Willi syndrome.
5. Noonan Syndrome.
6. SHOX gene haploinsufficiency.
7. Children who were born small for gestational age (SGA) and did not catch-up by the age of 4 years.
8. Idiopathic short stature (ISS) – remember how I mentioned in my previous post that in lots of cases we don’t find a reason for the short stature? We refer to this group of children as children with idiopathic short stature. Despite this not being a formal indication in most countries, some countries allow for endocrinologists to offer treatment to children with ISS whose heights are at or below the 3rd percentile.

While the first indications on this list are clear, it is the parents of children with ISS that find themselves debating whether they want their child to get treatment. Furthermore, there are lots of families with children whose height is above the 3rd percentile who also think their child needs growth hormone.

Idiopathic short stature – who should receive treatment?

Using growth hormone to treat children with ISS is a debatable topic and sometimes it arises ethical questions as well – does every case of short stature that is at least 2 standard deviations below the average need to be treated? Maybe the differences in heights in the population is a regular variant of the norm and should not be messed with? Is growth hormone considered a cosmetic treatment, similarly to plastic surgery? Afterall, it makes sense that some people are short and small people are taller, just like people weigh differently, have different skin colour and hair colour and so on. And let’s not forget that the treatment is given through daily injections and also carries some possible side effects.

So obviously this is a complex topic…
First of all, we all know that a person’s height may have a large impact on their life, not only an aesthetic one but also one related to self-confidence, self-image, and more. We also know that within those children who have been defined as the ISS group, there are many different genetic diagnoses that we may not be aware of, and some of them will respond very well to treatment with growth hormone.

Many people will say that lots of short children were just born to short parents, and their height is simply genetic. But the fact that the parents are short does not necessarily indicate that their height is normal. Maybe if their parents were born now, they would be able to undergo a proper workup and would be entitled to receive growth hormone treatment, themselves. What I’m trying to say is that familial short stature does not necessarily rule out the need for treatment with growth hormone.

The bottom line is that for short children, who are 2 standard deviations below the average height, have an expected potential adult height that is less than 150cm if they are girls and 160cm if they are boys, where a cause for the short stature has not been found, treatment with growth hormone should be considered. I suggest sitting down for a discussion with your endocrinologist in order to talk about the advantages and disadvantages of treatment, the expected growth in height (as it is not magic and the final addition to the child’s height could be only several centimeters), the possible side effects and of course to discuss the child and family’s desires.

The question to treat gets more difficult in those children who do not meet the criteria of short stature and are above the 3rd percentile for height.

At what age can growth hormone be started?

The age of start of treatment depends on the reason behind treatment. If there is a deficiency in growth hormone or a combined deficiency with other pituitary gland hormones (cases where a provocation test will reveal absent levels and imaging will show an abnormal pituitary gland), treatment is started right after the diagnosis is made. In children who are treated because they are small for gestation age, treatment is usually started at the age of 4. In ISS, the starting age varies, it is usually around the age of 6 but it also depends on when the child first presents, the doctor’s medical considerations and the family’s personal considerations, etc.
Obviously, the improvement in height depends on when the treatment is started and the timing compared to puberty.

What is the expected response when growth hormone is started?

Growth hormone is not always a magic solution and the response to treatment and the final height depend on many different factors, for example:
 The lower the rate of growth and the lower the level of growth hormone prior to treatment – the better the response.
 The underlying reason behind treatment plays a role. For example, children with growth hormone deficiency usually respond very well to treatment. On the other hand, children with ISS, the response to treatment is not always black or white and there could be lots of different possible responses, from well responses to no response at all. Children who were born small for gestation age (either weight or height that were low for gestational age) usually respond less well compared with children who were born appropriate for gestational age.
 The age of the child – there is obviously a difference between starting treatment at the age of 5 and starting at the age of 10.
 The nutritional status – not only does nutrition have a large impact on growth, as mentioned in the previous post, but it also affects response to treatment. An imbalanced diet that does not meet the child’s metabolic needs will lead to a response that is less than expected.
 Compliance – this is another vital part. Missed days have a negative effect on treatment response.

How is growth hormone administered in practice?

Treatment is given through subcutaneous injections, once daily. Some companies have been working on better methods, such as an injection that is given once a week. But these solutions are still under development in most countries.

What type of monitoring do children who receive growth hormone need?

Monitoring during treatment is important and is carried out by both by primary care pediatricians as well as by endocrinologists every 3-4 months. During follow-up visits the physicians notes the response to treatment, the development of possible side effects, adjusts the dosing and performs blood work that is required at least once a year or as endocrinologist sees is needed.

What are the possible side effects to treatment with growth hormone?

Despite them being rare, it is still important to be familiar with possible side effects. Below are some possible side effects to treatment with growth hormone. Prior to treatment, it is important to discuss these possible side-effects and the different ways of monitoring them with your physician.

 Headache/vomiting/blurry vision – these could indicate increased intracranial hypertension that could result from excessive production of the fluid that surrounds the brain. Usually temporarily stopping treatment or reducing the dosage is helpful, but sometimes a more serious treatment is needed. In any case, these symptoms require immediate consult and treatment should not be continued without a doctor’s confirmation.
 Pain in the hip joint or knee joint and limp – these could indicate Slipped Capital Femoral Epiphysis (SCFE) or ischemia due to decreased blood flow to the hip joint (Perthes). If your child starts limping and is on growth hormone – see a doctor immediately.
 Disorders of glucose metabolism – treatment leads to a decrease in sensitivity to insulin and therefore an increase in levels of insulin. In most children, we will not see any changes to the levels of glucose in the blood, but it is still important to monitor glucose levels and hemoglobin A1C at least once a year or more depending on the physician’s discretion. This side effect is seen more commonly in children who have prior diabetes or a tendency to develop glucose intolerance (for example, Prader-Willi, Turner’s Syndrome, children who are SGA). They will usually require an increase in their anti-diabetic drug dosages.
 Gynecomastia – an increase in breast tissue in boys. It usually occurs when treatment is first started and it resolves.Read more here.
 Muscle or joint pains
 Allergic reactions – this can also occur with growth hormone just like any other medication. In such cases a different type of growth hormone can be tried.

Does treatment with growth hormone increase the prevalence of cancerous tumors in children?

The answer to this is no.
There are different myths out there about treatment with growth hormone and especially with regards to the development of tumors – as of now, there is no evidence in the medical literature that the use of growth hormone increases the risk of malignancies. Despite that, in cases where there is a known tendency for malignancy (such as in certain diagnosed genetic conditions), growth hormone is not recommended as there is not enough information about the risk of development of malignancies in these children.

How long does treatment last for?

Treatment is given up until the end of growth which occurs at a bone age of 14 in girls and 16 in boys. Also, if the rate of increase in height is below 2 cm/year, treatment is usually stopped.
The treatment is also obviously stopped if serious side effects develop or if there is no response to treatment.
It is important to mention that in cases where the treatment is stopped before a child’s growth is complete, there could be a slowing of growth and loss of the height advantage gained through treatment.

In cases of combined pituitary hormone deficiency, sometimes the treatment is continued at a lower dosage past the end of growth period, depending on the endocrinologist’s recommendation.

To summarize, the entire process of workup and diagnosis of the cause behind short stature is vital and also affects the choice of treatment. Growth hormone can be administered as a subcutaneous injection, depending on the medical indication as mentioned above. Children who receive growth hormone need to be monitored. Parents have to ensure their child receives their treatment, does not miss any days and gets the injection in different locations every day. They also have to show up to the visits and be aware of any side-effects that may develop.

Good luck!