Growth hormone: panacea or punishment for short stature?

Learning to live with being short is more important for short normal children

After the nutrition dependent phase of fetal and infant growth has ended (towards the latter part of the first year of life) growth hormone secretion becomes the predominant controller of the rate of human growth.1 Almost any child given growth hormone in sufficient doses will grow more quickly, and dose-response curves for human growth hormone treatment have been with us for some years.2

Although much has been written about the predictors of response to treatment, only final height really matters. The French study reported on page 708 by Coste et al is important because it is concerned solely with that end point.3 As the authors make clear, their study has all the merits (large numbers) and demerits (different data collection staff, reporting errors, different laboratories) of a register based study, but it shows clearly that those patients treated earliest do best—and this is the most important message. Not for a long time has it been believed that growth hormone treatment would restore a normal height to patients unless it were started at a time when there was no growth deficit. The paper is also important because it points out that the treatment of short normal patients in the mistaken (“compassionate”) belief that treatment could improve final height is a cruel illusion and an expensive mistake.

So who does need growth hormone? The short answer is those who are deficient of it, but the argument about how to define cut off values for a continuously distributed variable like growth hormone secretion has occupied thousands of journal pages. Such values are as illusory as those for obesity or hypertension. When a child is deficient in growth hormone his or her growth rate falls as the infancy curve of growth comes to its end,4 and, without growth hormone, a low growth rate leads to extremely short final stature. The earlier growth hormone is introduced, the better will be the result because treatment only enables the height prediction prevailing at the start of treatment to be realised.5 Any difference between that value and the genetically determined target is not redeemable. Thus, for an affected child to attain a height normal for the family, treatment has to start early and continue throughout childhood. This is why children who acquire growth hormone deficiency later in childhood, when they have already achieved some normal growth, have a better final height than those with growth hormone deficiency recognised by short stature at 3 years of age.

When pituitary growth hormone was withdrawn in 1985 and replaced with the synthetic preparation, clinicians had an opportunity to test a product whose supply was limited only by cost on many other patients with short stature. The results of treatment in patients with these so called wider indications are still debated, but the size and the length of the French study indicate how long we may have to wait for definitive conclusions. Growth hormone clearly has a place in managing short stature in Turner syndrome, renal failure, dysmorphic syndromes, and some skeletal dysplasias, but, because final heights are what matter, trials of treatment in these conditions should still be restricted to centres where long term results can be collated and monitored. The system for central reporting available in France is not universal.

Although many doctors and parents attest to the unhappiness, loss of quality of life, and educational disadvantage of short children, these are not generally identifiable in the community; nor is the functioning of adults who were short as children disadvantaged.6 Even in a clinic population, we could not identify sufficiently hard psychological end points to test the hypothesis that the increase in growth rate which growth hormone treatment will achieve in short children would be beneficial.7 In other words, it is much more important for a short child to acquire coping skills than to buy inches through pharmacological means. The many reports quoted by Coste et al attest to a socially unimportant, even if statistically significant, increase in final height in short children treated with growth hormone. Doctors pressurised into prescribing growth hormone may care to contemplate the aggregation of risk factors for coronary heart disease and the problems of stigmatising otherwise normal children. Growth hormone is contraindicated for normal short children because it is expensive and does little to increase adult stature.