Hormone research最新文献

Growth hormone treatment in Noonan syndrome increases growth velocity significantly during the first 2 years of treatment and, to some extent, until puberty. This increase is more pronounced if treatment is started at an early age. Treatment before the age of 5 years is not recommended due to an increased risk of malignancies. In contrast to other growth hormone-treated patients, a slight but significant further increase in height gain can be expected during pubertal growth (at least in boys). Final height improvement varies between 1 and 2 SDS in different studies. Cardiac function does not seem to be impaired during treatment. No significant adverse events have been reported.

Growth failure in Noonan syndrome is mainly postnatal of character and is dominated by slow maturation and late puberty. The postnatal early decline seems to be an intrinsic part of the syndrome. Reported adult heights are about -2 SD and are indicative of a secular trend.

The current paper introduces concise neuropsychological assessment as an essential tool for studying the contribution of cognition and behavior in the expression of genetic syndromes, like Noonan syndrome (NS). Cognitive and behavioral findings in NS show intelligence scores across a wide range, with a mildly lowered average level. Language and motor development are often delayed, but no longer dysfunctional in adulthood. Continuing mild problems in selective and sustained attention are noted, as well as suboptimal organization skills and compromised abilities to structure complex information. These problems seem to culminate in learning difficulties, requiring attention for special needs in education. It seems that a complex of psychosocial immaturity, alexithymia and amenable traits is typical of NS patients. Consequently, psychopathology or psychological problems in leading a self-serving life may often remain underreported. This is why the authors advocate the integration of the domain of social cognition and personality in NS assessment.

The hypothalamo-pituitary-adrenal axis has not been studied systematically in Noonan syndrome (NS), despite potential concerns about other aspects of hypothalamo-pituitary function. While adrenarche may be delayed in children with constitutional growth of puberty and in isolated GH deficiency, this does not generally seem to be the case in hypergonadotrophic hypogonadism due to Turner syndrome (TS) and this is (anecdotally) the usual hormonal profile in NS children and adults. Precocious or 'exaggerated' adrenarche can be associated with intrauterine growth retardation and is a forerunner of syndrome X. Although NS neonates often have 'normal' birth weights, in some it can be artificially inflated by subcutaneous edema (as in TS, where intrauterine growth retardation is characteristic). Overall, however, a controlling role for adrenarche (whether precocious or delayed) in gonadarche in NS seems unlikely. Neither normally descended testes nor normal (even if delayed) pubertal development implies normal fertility in NS men. Interactions between fetal, neonatal, childhood and pubertal testis development and gonadal axis maturation are complex. There is probably a spectrum of abnormalities in NS, but most commonly primary gonadal failure and hypergonadotrophic hypogonadism - characteristic NS molecular genetic abnormalities - may be important for normal germ cell proliferation, development and migration. The identification of different gene defects facilitates understanding of NS phenotypic diversity and provides opportunities for prospective studies on gonadal and adrenal axes in better defined populations less subject to ascertainment bias. At a clinical level, more longitudinal data are still needed with regard to the natural history of pubertal timing, its tempo of progression and the pattern of pubertal growth.

Short stature is one of the key features of Noonan syndrome (NS). Attempts have therefore been made to improve height by means of recombinant human growth hormone (rhGH) treatment. Most of these endeavors were carried out either as case studies or observational studies. The overall experience in treating NS is still rather limited, and, in general, it can be said that the NS patients who received GH treatment represent a very narrow segment. The dosages applied in both the case studies and observational studies tended to be higher than those used in the replacement therapy of GH-deficient patients, but lower than in Turner syndrome patients. The NS studies have shown that the overall height gain of patients is small (5-10 cm), and that treatment usually begins at the age of about 10 years, at a height of approximately -3.0 SDS. This small response to treatment reflects the external treatment conditions (i.e. late age at GH start, low GH dose), but may also be associated with the fact that impaired sensitivity to GH is common in NS. Both case studies and observational studies are necessary in order to obtain further evidence about the efficacy and safety of GH treatment in NS.

Background and aims: Several studies, despite using small cohorts, have shown a short-term improvement in the height velocity of short children with Noonan syndrome (NS) when treated with recombinant growth hormone (GH). However, the question is whether or not this improvement is sustained until adult height is reached. This paper reviews the few studies reporting final height data of GH treatment in individuals with NS.

Methods: Review of published papers from 4 main and several small studies with final height data after GH treatment in NS.

Results: The range of height gain to adult age varies between 0.6 and 2.0 SDS, depending on genotype, age at start of treatment, duration of treatment and which growth charts are used. The younger the age at which treatment is started, the better the result. There seems to be a correlation between growth response and genotype, with a diminished growth response when the PTPN11 mutation is present.

Conclusion: Data on the benefits of GH treatment during childhood and adolescence upon the final height are encouraging in individuals with NS. There is a substantial height gain during prepubertal years, which continues during the pubertal period, reaching a final height within the normal population in the majority of previously short individuals with NS.

Background: The clinical hallmarks of Noonan syndrome (NS) are facial dysmorphism, short stature and cardiac defects. As one of the common cardiac defects in NS is hypertrophic cardiomyopathy, there have been concerns regarding cardiac safety since the start of human growth hormone (hGH) therapy for NS.

Methods: Review of currently available data on the prevalence of cardiac defects, the theoretical effects of hGH on the heart and the results of studies on the effects of hGH on the heart.

Results: The prevalence of cardiac defects in NS is high, and the spectrum is very broad. Progression of ventricular wall thickness during hGH therapy has never been reported. There are barely any data available on children with NS and hypertrophic cardiomyopathy collected during hGH therapy. In post-marketing surveillance studies, there are no reports of adverse cardiac events related to hGH therapy.

Conclusion: The reported absence of negative effects of hGH therapy on the heart in NS and especially on ventricular wall thickness is reassuring. Still, keeping in mind the current limited experience, any effects on the heart resulting from hGH therapy should be monitored carefully in NS.

The overall risk of cancer in children with Noonan (NS), cardio-facial-cutaneous, Costello or LEOPARD syndrome is high, although no precise estimates are available. There are few data on cancer in adults with NS, but the reported numbers of malignancies in adults do not seem excessive. Juvenile myelomonocytic leukemia (JMML) is a rare aggressive leukemia in young children. A JMML-like myeloproliferative disorder has been described in about 30 neonates with NS and the PTPN11 mutation. The disorder often regresses spontaneously, but fatal complications may occur. A review of the literature indicates an increased risk of acute lymphoblastic leukemia and acute myeloid leukemia in NS. Young children with Costello syndrome have an extremely high risk of rhabdomyosarcoma, and also an increased risk of neuroblastoma and bladder carcinoma. Registry-based studies of patients with NS and related disorders diagnosed with molecular genetics and a high-quality long-term follow-up are necessary to further estimate the incidence of malignancy.