Average birth weight is slightly reduced in CF and growth rate (weight and length) is reduced (in unscreened babies) in the first year of life, mainly because of impaired nutrition. Once the diagnosis is made and nutrition is improved, catch up growth usually occurs. Height velocity in early childhood is normal although CF individuals are on average 0.5 SD shorter than unaffected children. In later childhood the height deficit increases. This is mainly due to delay in puberty, with worsening lung function and the onset of CF-related diabetes contributing. Adult height is usually within the normal range for the population but reduced compared to mid-parental height.
Pituitary function (growth hormone (GH), gonadotrophins, & ACTH) is normal in CF. Chronic infection, nutritional factors and steroid treatment result in GH resistance and can also reduce GH secretion. Gonadotrophin and sex steroid secretion is normal during puberty in CF but the changes tend to be delayed compared to the normal population. Boys reach normal testicular volumes in puberty despite the majority having azoospermia.
Height (measured with a stadiometer) and weight should be recorded at every clinic visit (minimum every 3 months) and plotted on the standard growth centile charts. In children under 1 year, head circumference (OFC) should be plotted. Assess the pubertal stages in older children and adolescents:
Ask if pubic hair is present
Is there any breast development (part of chest examination)
Ask whether periods have started
Ask if pubic hair is present
Has voice broken
Who to be concerned about
The following groups may need further assessment or investigations:
anyone whose relative position in terms of height or weight is falling (they are not maintaining their centile position).
children who are very short (below 0.4th centile) even if they are maintaining their relative position.
children who seem very short for their midparental height.
delay of puberty. 98% of normal girls have started pubertal development (Tanner breast stage 2) by 13.7 years and 98% of boys have started development (testicular volume over 4 mls) by 14.2 years.
Look for factors related to CF which may impact on growth:
- nutrition - intake or malabsorption
- chronic infection
- impaired glucose tolerance or CF related diabetes
- steroid treatment
- pubertal delay
Feeding behaviour problems are common in younger children and input from clinical psychologist may be valuable. Supplemental feeds should be started early (see section 7.3). Treatment can be offered for pubertal delay.
Consider checking for non CF related causes:
- coeliac disease
- Turner syndrome (this is not always associated with clinical features and it is worth checking karyotype if a girl is very short and this has not been done before)
Consider GH deficiency if there is continuing poor height velocity with no other explanation. Investigation requires stimulation testing and other causes should be excluded before this. There have been a number of studies of the use of GH in CF patients (without GH deficiency) which have demonstrated short term anabolic benefits, but there is no evidence for increased adult height.
Patients can be discussed with Dr Bridges or Dr Alexander at any stage. We are happy to look at growth charts or assess bone ages for patients.
Referral may be helpful for the following groups:
Reduced height velocity or short stature, which does not seem to be caused by CF related problems.
Children who are so short or growing so badly that they seem to be heading for a reduced adult height. An assessment of growth may be helpful even if the clinical issues underlying this are clear and cannot be altered.
Concerns by family or child about height.
Pubertal delay. Adolescents may not express their level of concern about this very clearly so consider referral even if they do not seem very bothered. There is significant delay if there are no signs of puberty by 14 years in a girl or 15 years in a boy, although referral can be made before then if there are concerns.
High dose steroid treatment- there is little to offer in terms of treatment but an assessment of the situation can be helpful.
Bone age is a way of looking at how much growth there is still to come. There are ways of calculating adult height potential from bone age but they are not very accurate and likely to be overoptimistic in CF patients. Bone age is not likely to be helpful in children under 4 years. Assessment of bone age is operator dependent and results are more likely to be helpful if the score is assessed by someone with experience.
Pubertal delay is common in CF and is related to nutritional factors and infection. Pubertal development will occur eventually but can be very late in those with the most significant medical issues. Presentation may be with short stature or with concerns about development. There is no need to wait for an age limit before referring. Delayed puberty does not result in any benefit in terms of adult height. Delayed pubertal development has been found to contribute significantly to the psychological problems suffered by adolescents with CF.
Assessment of pubertal delay
- Height & weight.
- Tanner staging.
- Bone age if there are concerns about height.
- Gonadotrophin and sex steroid levels may be low even if the child is in already in puberty and are unhelpful.
Treatment of pubertal delay
Individuals with the most significant medical problems are the most likely to be delayed. Any nutritional problems should be addressed, and CF-related diabetes should be excluded as a contributory factor. Growth during puberty can be adversely affected by nutritional problems, infection and steroid treatment; all of which can reduce the increment in height achieved during this phase of growth. It may be appropriate to delay treatment if there is a realistic chance that medical status can be improved thus allowing growth without adverse effects. Often it is unlikely that any significant change will occur (and things might get worse), and it is then reasonable to go ahead with treatment to induce puberty even if optimum growth may not be achieved.
Potential benefits of treatment
- Psychological and social.
- Bone density - Bone density reaches a peak during puberty as a result of sex steroid action. CF patients are at increased risk of low bone density and it makes sense to optimise it at this point.
Patients should be referred to Dr Bridges or Dr Alexander. Treatment to induce puberty mimics the gradual rise in sex steroids during normal puberty and aims to complete growth and development over about 2 years. Some individuals start to develop spontaneous puberty after a few months of treatment and medication can be stopped. There is no harm in stopping treatment at any point but if spontaneous puberty does not occur, it usually makes sense to take the individual to nearly adult height and development before stopping and reassessing endogenous function. Given in these doses treatment does not have an adverse effect on adult height.
Steroid treatment for induction of puberty
Increasing doses of oral ethinyloestradiol:
- 2 or 2.5 micrograms ethinyloestradiol daily for 6 months (either 2 microgram tablets or one quarter of a 10 microgram tablet)
- 5 micrograms ethinyloestradiol daily for 6 month
- 10 micrograms ethinyloestradiol daily for 6 months
- 15 micrograms ethinyloestradiol daily for 6 months
- 20 micrograms ethinyloestradiol daily for 6 months
Adding in progesterone when 15 micrograms ethinyloestradiol is given or before this if there is any vaginal bleed, using -
levonorgestrel 30 micrograms daily or norethisterone 5mg daily for 7 days out of each 28 day cycle.
Increasing doses of intramuscular depot testosterone esters as Sustanon (250mg in 1ml)
- 50 mg IM every 4-6 weeks for 6 months
- 100 mg IM every 4 weeks for 6 months
- 100 mg IM every 3 weeks for 6 months
- 100 mg IM every 2 weeks for 6 months
There are currently no reliable data to guide pubertal induction with topical sex steroids in males or females.