Short stature is a very common reason for consultation and concern in paediatrics. One of the causes may be neurosecretory dysfunction, characterised by obtaining a normal result in growth hormone (GH) stimulation tests, normal or high IGF-1 levels, but with abnormal nocturnal secretion test results (mean of 21 determinations); a mean ≤3 ng/mL1 is a diagnostic criterion.

Growth is a complex process involving genetic, endocrine and autocrine-paracrine factors, as well as permissive factors such as nutrition, psychosocial situation and other environmental factors.2 It is therefore a process sensitive to unfavourable conditions, making it a good indicator of health.3 GH secretion has a pulsatile pattern and is predominantly nocturnal, but it is still a largely unknown physiological and pathophysiological process in terms of the pattern of secretion and the pathways through which the different factors modify and regulate it. In the case of neurosecretory dysfunction, there is an altered nocturnal secretion pattern at the expense of a reduction in the number and amplitude of the secretion pulses.

Not all authors find a correlation between height or growth rate and spontaneous GH secretion. This topic has been studied extensively in the literature.1, 4, 5 Back in 1984, in patients with acute lymphoblastic leukaemia who had received treatment with prophylactic cranial radiotherapy, Blatt et al. found an alteration in spontaneous GH secretion and a normal response to stimulation tests, with a reduction in growth rate. This was similar to what occurred in non-irradiated patients with impaired growth, and the idea that there could be abnormalities in the neuroregulation of GH secretion was mooted.6

Short stature takes on particular importance in the population: it is the leading cause of consultation in endocrinology departments because of the associated psychological consequences. Short stature is defined as: (1) height below the 3rd percentile or −2 SD with respect to the normal curve for the same age and gender of the population to which the person belongs; (2) with a growth rate less than P25 (−1 SD) for age and gender, maintained for at least two years, regardless of current height; (3) height which, being within ±2 SD of the curve corresponding to the person's population, is below −2 SD with respect to their target height; and (4) a prediction of adult height below −2 SD with respect to the person's target height.7

Short stature is classified into two fundamental groups, idiopathic short stature and pathological short stature (primary growth or disease-related disorders, for example gastrointestinal, oncological and chronic kidney diseases, etc).8, 9 Idiopathic short stature (80% of cases) encompasses all short stature conditions in which the cause is unknown and in which the following criteria are also met: (1) normal length and weight at birth for gestational age; (2) normal body proportions; (3) absence of endocrine disease, chromosomal disease, severe psycho-affective disorders, chronic organic disease; (4) adequate nutrition; and (5) normal or slow maturation time. In other words, idiopathic short stature is a diagnosis of exclusion.10

An appropriate diagnostic approach is necessary from the initial medical consultations, with a detailed previous medical history taken, followed by a thorough physical examination. On the basis of these data, the appropriate investigations will be carried out to rule out causes of pathological short stature and, only if they are ruled out, to consider idiopathic short stature.

These investigations include GH stimulation tests, although they have limitations in terms of reproducibility, which questions their real validity as an instrument for the study of pituitary GH secretion. Despite that, they continue to be used in most countries for the diagnosis of GH deficiency and resistance. However, the value of these tests should, when appropriate, be considered in the clinical context of auxological, imaging and molecular studies.11

As has already been said, the use of GH stimulation tests continues to be a controversial issue, as no defined limits of normality have been established, and moreover they are poorly reproducible. Values considered normal are often found in patients with severe short stature and low growth rates.

The objective of this study was to evaluate the response to GH treatment in patients diagnosed with neurosecretory dysfunction, with normal GH in the stimulus test, treated until they reach adult height.