Primary IGF-1 Deficiency

Primary IGF-1 Deficiency

What is Primary IGF-1 Deficency

Children with short stature may have low levels of the hormones associated with normal growth. Children with low levels of growth hormone (GH) are said to have growth hormone deficiency (GHD) and this results in growth failure (see the Growth Hormone Deficiency & MPHD page). GHD leads to low levels of insulin-like growth factor-1 (IGF-1), a hormone made primarily in the liver. IGF-1 regulates the growth-promoting effects of GH by acting on ‘target’ body tissues such as the growth plates of the bones.

Some children have growth failure, despite normal or even high levels of GH. In some of these children we find abnormally low levels of IGF-1 and this condition is called Primary Insulin-like Growth Factor Deficiency (PIGFD). Here the term ‘primary’ means that no secondary cause of low IGF-1 levels (e.g. a chronic medical illness) can be identified

 

Why does it occur?

Severe primary IGF-1 deficiency (SPIGFD) is a medical term used when IGF-1 levels are extremely low or undetectable in the blood. The classical (most well recognised) form of SPIGFD is a genetic condition called Laron syndrome. Patients with Laron syndrome have an abnormal growth hormone receptor (GHR) which does not function properly. The GHR is vital for normal growth, as it recognises and binds GH, triggering release of IGF-1 and stimulating growth in the individual cells of the body. In Laron, the abnormal GHR makes patients resistant to the effects of GH and as a result, the IGF-1 levels are low or undetectable. A number of other genetic abnormalities in the GH – IGF-1 pathway are known to cause SPIGFD and short stature.

How is PIGF-1 Deficiency diagnosed?

A diagnosis of Primary Insulin-like Growth Factor Deficiency (IGFD) is made by identifying:

  • Growth failure or short stature
  • Normal growth hormone production
  • Low levels of IGF-1
  • No other underlying disease or causes of poor growth e.g. chronic diseases, poor nutrition

When all of these criteria are met, a doctor may diagnose PIGFD. PIGFD may be divided into moderate and severe forms based on how short the child is and how low the IGF-1 levels are relative to other children of the same age. As some children with PIGFD have an underlying abnormality in their genes, genetic testing is sometimes offered as part of the initial investigations.

Common Characteristics

The primary symptom of PIGFD is short stature at below ‘normal’ levels. Additionally a child with PIGFD may suffer from tiredness and a lack of energy. The short stature will make them appear younger than their peers but it will not impact on their intellectual abilities.

Treatment & Support

In the UK, PIGFD can now be treated with Increlex, a recombinant (man-made) form of IGF-1. This is also called mecasermin. It has the same chemical structure and acts in the same way as naturally produced IGF-1. Increlex is used to treat children who have growth problems due to low levels of IGF-1 in their blood. Growth hormone therapy is not useful in PIGFD because GH levels are normal, and the body is resistant to the effects of GH. Increlex is given as an injection just under the skin (subcutaneous), twice each day. It must be given shortly before or just after a meal. This is because it has effects similar to insulin and can reduce the blood sugar levels.

In order to fulfil the criteria for Increlex treatment in the UK, children must be aged 2-18 years and have severe primary IGF-1 deficiency (SPIGFD). In the UK, this is defined as height <-3 standard deviation scores (SDS) below the mean, serum IGF-1 <2.5th centile and normal GH production.

Please consider calling our helpline for support and advise, we can also help put you in touch with other families with the same condition. We also have members of our Facebook Group who may be able to help you.

Personal Stories

We hope to add personal experiences and stories from people affected by IGF-1 Deficiency soon.

Further Reading/Downloads

Increlex patient and physician leaflets can be downloaded here

The BSPED supported guideline ‘Recombinant IGF-1 Therapy in Children with
Severe Primary IGF-1 Deficiency (SPIGFD)’ can be accessed here:

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