Growth Hormone Therapy Benefits Pituitary Stalk Interruption Syndrome Patients with Short Stature: A Retrospective Study of 75 Han Chinese

Objective. We aim to investigate the long-term benefits of growth hormone (GH) therapy in short stature adolescents and adults with pituitary stalk interruption syndrome (PSIS), which would be beneficial for future clinical applications. Design and Methods. In this study, initial height, final height, total height gain, and GH treatment history were retrospectively investigated in 75 Chinese PSIS patients. We compared height gain between the GH treated cohort and untreated cohort and explored the impact of different GH therapy duration on height gain. Results. For GH treated patients, their final height (SDS) increased from -1.99±1.91 (−6.93~2.80) at bone age (BA) of 11.2 (5.0~17.0) years to -1.47±1.64 (−7.82~1.05) at BA of 16.6 (8.0~18.0) years (P=0.016). And GH treated patients had more height gain than the untreated patients (P<0.05). There was a significant difference between the different GH therapy duration groups (P=0.001): GH 0 versus GH 3, P=0.000; GH 1 versus GH 3, P=0.028; GH 2 versus GH 3, P=0.044. Conclusion. Adult Chinese PSIS patients with short stature benefited the most from at least 12 months of GH therapy. Although patient diagnosis age was lagged behind in the developing countries, GH treatment was still effective for them and resulted in a higher final height and more height gain

Alterações neurorradiológicas em pacientes com deficiência de hormônio de crescimento.

Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Departamento de Pediatria

Effect of growth hormone therapy on Taiwanese children with growth hormone deficiency

Background/PurposeHuman growth hormone (GH) has been successfully used in children with GH deficiency (GHD). However, there are few published data on the effect of GH in Taiwanese children with GHD.MethodsWe performed a retrospective cohort study to identify factors influencing the effect of GH therapy on ethnic Chinese children with GHD in Taiwan. Idiopathic GHD can be classified into isolated GHD (IGHD) and multiple pituitary hormone deficiency (MPHD). The study looked at the effect of GH on the auxological, biochemical, and imaging parameters of 51 patients (13 girls and 38 boys) in three different diagnostic groups: MPHD (n = 12), IGHD (n = 8), and transient GHD (TGHD; n = 31). TGHD is defined as a GH peak >10 μg/L in re-evaluation by two GH stimulation tests approximately 6 months after discontinuation of GH therapy.ResultsThe height velocity for first-year GH therapy was 7.61 ± 1.46, 8.14 ± 1.92, and 9.99 ± 2.75 cm/y in the TGHD, IGHD, and MPHD groups, respectively. After post hoc comparison, the MPHD group had a significantly accelerated height velocity in the first year compared to the TGHD group. Correlation analysis showed that a change in height standard deviation score (SDS) in the first year had a significant negative correlation with the following variables: peak GH (r = −0.52, p < 0.001), pretreatment height SDS (r = −0.49, p < 0.001), and height-target height (Ht-TH) SDS (r = −0.49, p < 0.001). Change in height SDS in the first 2 years had a significantly negative correlation with peak GH (r = −0.51, p < 0.001), insulin-like growth factor-1 SDS (r = −0.35, p = 0.022), height SDS (r = −0.60, p < 0.001), difference between bone age and chronological age (r = −0.46, p = 0.001), and Ht-TH SDS (r = −0.50, p = 0.001). After using multiple linear regression, the pretreatment GH peak value was found to be significantly associated with height increments after 1 year of GH treatment (B = −0.07, p = 0.014).ConclusionThe administration of GH to children with GHD results in a pronounced acceleration in linear growth during the first year of treatment, especially in those with MPHD. The diagnosis of GHD requires comprehensive auxological, biochemical, and brain magnetic resonance imaging assessment. We also suggest that patients with GHD, specifically IGHD, must undergo a re-evaluation of GH secretion after completion of GH therapy

The Growth Hormone Deficiency (GHD) Reversal Trial: effect on final height of discontinuation versus continuation of growth hormone treatment in pubertal children with isolated GHD—a non-inferiority Randomised Controlled Trial (RCT)

Background: Growth hormone deficiency (GHD) is the commonest endocrine cause of short stature and may occur in isolation (I-GHD) or combined with other pituitary hormone deficiencies. Around 500 children are diagnosed with GHD every year in the UK, of whom 75% have I-GHD. Growth hormone (GH) therapy improves growth in children with GHD, with the goal of achieving a normal final height (FH). GH therapy is given as daily injections until adult FH is reached. However, in many children with I-GHD their condition reverses, with a normal peak GH detected in 64–82% when re-tested at FH. Therefore, at some point between diagnosis and FH, I-GHD must have reversed, possibly due to increase in sex hormones during puberty. Despite increasing evidence for frequent I-GHD reversal, daily GH injections are traditionally continued until FH is achieved. // Methods/design: Evidence suggests that I-GHD children who re-test normal in early puberty reach a FH comparable to that of children without GHD. The GHD Reversal study will include 138 children from routine endocrine clinics in twelve UK and five Austrian centres with I-GHD (original peak GH < 6.7 mcg/L) whose deficiency has reversed on early re-testing. Children will be randomised to either continue or discontinue GH therapy. This phase III, international, multicentre, open-label, randomised controlled, non-inferiority trial (including an internal pilot study) will assess whether children with early I-GHD reversal who stop GH therapy achieve non-inferior near FH SDS (primary outcome; inferiority margin 0.55 SD), target height (TH) minus near FH, HRQoL, bone health index and lipid profiles (secondary outcomes) than those continuing GH. In addition, the study will assess cost-effectiveness of GH discontinuation in the early retesting scenario. // Discussion: If this study shows that a significant proportion of children with presumed I-GHD reversal generate enough GH naturally in puberty to achieve a near FH within the target range, then this new care pathway would rapidly improve national/international practice. An assumed 50% reversal rate would provide potential UK health service cost savings of £1.8–4.6 million (€2.05–5.24 million)/year in drug costs alone. This new care pathway would also prevent children from having unnecessary daily GH injections and consequent exposure to potential adverse effects. // Trial registration: EudraCT number: 2020-001006-3

Growth Hormone Deficiency: Diagnosis and Therapy in Children

Short stature has been defined as a height below the 2 standard deviation for age, sex and ethnicity. Growth hormone deficiency (GHD) represents a condition characterized by reduced GH secretion, isolated or associated with other pituitary hormone deficiencies. In a child with short stature and growth deceleration, after the exclusion of other causes of growth failure, the diagnosis of GHD has to be confirmed by measurement of GH secretion after at least two stimulation tests. Patients with GHD should be treated with rhGH as soon as possible, to obtain normalization of growth and normal final height. The catch-up growth in response to rhGH therapy is maximal during the first years and could be affected by many variables, such as birth-weight, age and height at start of treatment and of puberty, and duration of treatment. Overall, rhGH is believed to be safe and significant side-effects in children are very rare, including benign intracranial hypertension, hyperglycaemia, arthralgia and myalgia. Patients with childhood onset GHD are usually retested in late adolescence to confirm the GHD persistence and to continue of GH therapy. In conclusion, the present chapter provides useful and updated information about the diagnosis, treatment and follow-up of children with GHD

Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review

Objective To systematically determine the impact of growth hormone therapy on adult height of children with idiopathic short stature. Design Systematic review. Data sources Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from retrieved articles of randomised and non-randomised controlled trials from 1985 to April 2010. Data extraction Height in adulthood (standard deviation score) and overall gain in height (SD score) from baseline measurement in childhood. Study selection Randomised and non-randomised controlled trials with height measurements for adults. Inclusion criteria were initial short stature (defined as height >2 SD score below the mean), peak growth hormone responses >10 μg/L, prepubertal stage, no previous growth hormone therapy, and no comorbid conditions that would impair growth. Adult height was considered achieved when growth rate was Results Three randomised controlled trials (115 children) met the inclusion criteria. The adult height of the growth hormone treated children exceeded that of the controls by 0.65 SD score (about 4 cm). The mean height gain in treated children was 1.2 SD score compared with 0.34 SD score in untreated children. A slight difference of about 1.2 cm in adult height was observed between the two growth hormone dose regimens. In the seven non-randomised controlled trials the adult height of the growth hormone treated group exceeded that of the controls by 0.45 SD score (about 3 cm). Conclusions Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults, although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed. The individual response to therapy is highly variable, and additional studies are needed to identify the responders

Tratamento da baixa estatura idiopática : experiência da unidade de endocrinologia pediátrica

Orientadora: Profª. Drª. Rosana Marques PereiraMonografia (especialização) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Curso de Especialização em Endocrinologia PediátricaInclui referênciasResumo : Objective: To evaluate the efficacy of treatment of children and adolescents with idiopathic short stature (ISS) attended at a Public University Hospital in Brazil. Patients and methods: Review of 134 charts of patients with indication for recombinant growth hormone (GHr) between May 2007 and May 2017 and collection of the following data: sex, chronological age, weight and length at birth, pubertal stage, Z-score of target stature (TS), GH peak with clonidine and/or insulin hypoglycemia, prescribed GHr dose, adjuvant treatment, duration of treatment, final stature (FS) Z-score. Stature Z-score and Z-score of the final stature prevision (FSP) were obtained pre-treatment and annually. Results: 65 patients fulfilled the ISS criteria; 33 were on treatment (> 12 months) and 10 reached FS. IGF-1 was normal in 92.3% and all had one or both of the responsive stimulus tests (peak > 5.0 ng/mL). The Z-score of stature at the 1st, 2nd, 3rd, 4th (p <0.01) and 5th (p = 0.01) years of treatment were higher than the Z-score of initial stature. The FSP Z-score at the 1st, 2nd, 3rd (p <0.01) and 4th years (p = 0.01) of treatment was higher than the Z-score of the initial FSP. All patients who achieved FS used adjuvant treatment. The FS Z-score was not different from the TS Z-score (p = 0.24). Stature gain ranged from 0.9 to 7.9 cm. Conclusion: The treatment of children with ISS is safe and effective, but with great variability of response. Its administration should be individualized considering psychosocial benefits, adverse effects and costs

Advances in differential diagnosis and management of growth hormone deficiency in children

Growth hormone (GH) deficiency (GHD) in children is defined as impaired production of GH by the pituitary gland that results in growth failure. This disease might be congenital or acquired, and occurs in isolation or in the setting of multiple pituitary hormone deficiency. Isolated GHD has an estimated prevalence of 1 patient per 4000–10,000 live births and can be due to multiple causes, some of which are yet to be determined. Establishing the correct diagnosis remains key in children with short stature, as initiating treatment with recombinant human GH can help them attain their genetically determined adult height. During the past two decades, our understanding of the benefits of continuing GH therapy throughout the transition period from childhood to adulthood has increased. Improvements in transitional care will help alleviate the consequent physical and psychological problems that can arise from adult GHD, although the consequences of a lack of hormone replacement are less severe in adults than in children. In this Review, we discuss the differential diagnosis in children with GHD, including details of clinical presentation, neuroimaging and genetic testing. Furthermore, we highlight advances and issues in the management of GHD, including details of transitional care