Bozzola M

Final height in girls with central precocious puberty: comparison of two different luteinizing hormone‐releasing hormone agonist treatments

In order to evaluate the effects of two long‐acting luteinizing hormone‐releasing hormone agonists on growth, bone maturation and final height in girls with central precocious puberty, we analyzed growth data from 40 girls (15 treated with buserelin intranasal spray (group A), 15 treated with triptorelin depot im every 28 days (group B) and 10 untreated (group C)). Patients in group A started treatment when chronological age (CA) was 7.7 ± 0.9 years, bone age (BA) was 10.2 ± 1.1 years and height was 131.9 ± 5.0 cm. Patients in group B started therapy when CA was 7.6 ± 0.5 years, BA 9.8 ± 1.0 years and height 133.2 ± 7.6 m. The diagnosis of untreated patients (group C) was made when CA was 7.2 ± 0.9 years, BA 9.6 ± 2.2 years and height 130.2 ± 8.6cm. Both luteinizing hormone‐releasing hormone agonists appeared to control precocious puberty. Final height in group B (160.6 ± 5.7 cm) was significantly higher than that of group A (153.2 ± 5.0 cm: p < 0.05) and group C (149.6 ± 6.3; p < 0.01), whereas the difference between groups A and C was not statistically significant. In group B a positive difference was observed between final height (160.6 ± 5.7 cm) and target height (157.6 ± 5.9 cm) (ns); on the contrary, in groups A and C, final height was lower than target height (155.5 ± 5.3 and 156.4 ± 1.3cm, respectively), but only in group C the difference was statistically significant (p < 0.01). The best results regarding final height obtained by slow‐release depot im therapy may be associated with more stable agonist blood levels during treatment.

Idiopathic short stature.

Abstract Idiopathic short stature (ISS) is a term used to describe the status of children with short stature that cannot be attributed to a specific cause. Many children diagnosed as having ISS have partial GH insensitivity, which can result from disturbances at various points of the GH-IGF-I axis. Several clinical studies on spontaneous growth in ISS showed that adult height was almost in the range of target height. GH treatment led to adult height not significantly higher than the pretreatment predicted adult height in most reports. No metabolic side effects have been observed, even when the dose was higher than in GH deficiency. Manipulation of puberty with gonadotrophin releasing hormone analogues reported by a few authors in a small number of children has shown conflicting results. Long-term psychological benefits of GH therapy for short normal children have not been demonstrated to date.

Growth hormone deficient children treated from before two years old fail to catch-up completely within five years of therapy.

We retrospectively investigated growth response to therapy of 12 patients with idiopathic growth hormone deficiency (GHD), who received GH (0.6-0.7 IU/kg/week) in daily subcutaneous injections from before 2 years of age and for a period of 60 months, in order to ascertain whether very early treatment can enable GHD children to catch-up quickly and completely their initial height deficiency. The onset of therapy was followed in all patients during the 1st year by a significant growth spurt, which persisted, even though attenuated, during the following 4 years. Height deficiency for chronological age (CA) significantly and progressively decreased during the entire study period (from -3.7 +/- 1.9 to -1.0 +/- 1.0 SDS, p < 0.0025), with a cumulative height gain of 2.7 +/- 1.6 SDS. In spite of this catch-up growth no patient attained the target percentile by the 5th year of therapy and their average height (CA) was still lower with respect to the average target height (TH) at the last check-up. Because of the significant bone age (BA) delay still persisting in most patients, a further and complete catch-up growth is likely to occur during the next years of treatment, as suggested by the finding that average height (BA) at the last examination was higher than average TH. It is concluded that: a) in spite of modern therapeutical schedules with daily GH injections and frequent adjustments of doses, GHD children, even though treated from before two years of age, fail to catch-up completely their initial height deficiency, at least by the 5th year of therapy; b) a more prolonged treatment is probably needed to allow them to attain their target percentile. This emphasizes the importance of both early diagnosis and long-lasting treatment.

Unresolved problems in optimal therapy of pubertal disorders in oncological and bone marrow transplanted patients.

Abstract Specialised clinics for the long-term follow-up of survivors from childhood cancer have developed over recent years. The problems encountered among patients who received multiple chemotherapy and radiotherapy can be challenging and require high expertise and close collaboration among different professionals (e.g. oncologists, endocrinologists, radiotherapists, psychologists). Endocrine disorders are often seen, particularly among those who received cranial radiotherapy or gonadotoxic chemotherapy; puberty can be affected and the spectrum of disorders may range from precocious or accelerated puberty to delayed, arrested or even absent pubertal development. Growth impairment can be multifactorial and growth hormone deficiency is an important but probably not the only factor involved. Many questions remain about the optimal management of this group of young patients. In the consensus guidelines that follow the overview an attempt is made to help optimise patients’ growth and puberty by suggesting practical clinical approaches to some of the most challenging issues.