Helena Gleeson

Cancer risk following growth hormone use in childhood: implications for current practice.

The therapeutic use of growth hormone (GH) has caused concern, as it is anabolic and mitogenic, and its effector hormone, insulin-like growth factor (IGF)-I is anti-apoptotic. As both hormones can cause proliferation of normal and malignant cells, the possibility that GH therapy may induce cancer, increase the risk of tumour recurrence in those previously treated for a malignancy, or increase the risk of cancer in those with a predisposition, has resulted in concerns over its use. There are theoretical and epidemiological reasons that suggest GH and IGF-I may be important in tumour formation and proliferation. Malignant tumours have been induced in animals exposed to supraphysiological doses of GH, whereas hypophysectomy appears to protect animals from carcinogen-induced neoplasms. In vitro, proliferation and transformation of normal haemopoetic and leukaemic cells occurs with supraphysiological doses of GH, but not with physiological levels. IGF, IGF binding proteins (IGFBP) and IGFBP proteases influence the proliferation of cancer cells in vitro; however, GH is probably not involved in this process. Epidemiological studies have suggested an association between levels of IGF-I and cancer, and an inverse relationship between IGFBP-3 and cancer; however, these associations have been inconsistent. A number of studies have been undertaken to determine the risk of the development of cancer in children treated with GH, either de novo, or the recurrence of cancer in those previously treated for a malignancy. Despite early concerns following a report of a cluster of cases of leukaemia in recipients of GH, there appears to be no increased risk for the development of leukaemia in those treated with GH unless there is an underlying predisposition. Even in children with a primary diagnosis of cancer, subsequent GH use does not appear to increase the risk of tumour recurrence. However, a recent follow-up of pituitary GH recipients has suggested an increase in colorectal cancer. In addition, follow-up of oncology patients has suggested an increase in second neoplasms in those who also received GH therapy. These studies emphasise the importance of continued surveillance both internationally with established databases and also nationally through single-centre studies.

Endocrine complications of neoplastic diseases in children and adolescents.

Because of the increasing population of childhood cancer survivors, there is a need to focus on the late effects of cancer therapy. After discharge by their pediatric oncologists, it is essential that patients are not lost to the health system but rather are under continued surveillance with access to the appropriate physicians. Endocrine and metabolic consequences may impact the life of the patient both soon after cancer treatment and for many years in the future. The purpose of this article is to explore the current literature in the following areas: growth hormone (GH) deficiency, gonadotropin-releasing hormone (GnRH) analogues with GH therapy in childhood, safety of GH replacement, cardiovascular risk factors, osteopenia, thyroid problems, and gonadal damage resulting in infertility.

The challenge of delivering endocrine care and successful transition to adult services in adolescents with congenital adrenal hyperplasia: experience in a single centre over 18 years

Congenital adrenal hyperplasia (CAH) has implications throughout a patients life. The challenges of organizing transition from paediatric to adult care in endocrinology are recognized.

Metabolic effects of growth hormone (GH) replacement in children and adolescents with severe isolated GH deficiency due to a GHRH receptor mutation

Background  The interpretation of the true effect of GH replacement therapy (GHRT) on metabolic status in GH deficiency (GHD) is often complicated by differing aetiologies of GHD and by the presence of additional hormone deficits.

Acquired prolactin deficiency indicates severe hypopituitarism in patients with disease of the hypothalamic–pituitary axis

objective  Prolactin deficiency has been the subject of many scientific studies, but there is a paucity of information regarding prolactin deficiency in humans. In this report, adults with disease of the hypothalamic–pituitary axis (HPA) were studied to determine the prevalence of severe acquired prolactin deficiency (APD) and the pathophysiological characteristics associated with it.

Likelihood of persistent GH deficiency into late adolescence: relationship to the presence of an ectopic or normally sited posterior pituitary gland

Objectives  The presence of an ectopic posterior pituitary gland (EPP) in childhood is associated with isolated GH deficiency (IGHD) and multiple pituitary hormone deficiency. GHD in late adolescence has been defined as a peak GH level <5 μg/l. The aim of this study was to identify the likelihood of persistent GHD in late adolescence in patients with an EPP compared with those with a normally sited posterior pituitary (NPP).

Transition in endocrinology: The challenge of maintaining continuity

Transition from child to adult status is a crucial stage in young peoples lives. It is important that young people continue to receive appropriate endocrine care throughout and following transfer from paediatric to adult services. This study examined indicators of patient loss to follow‐up at initial transfer from paediatric care to identify implications for transitional care practice and research.

DIAGNOSIS OF ENDOCRINE DISEASE: Limitations of the IGF1 generation test in children with short stature

The IGF1 generation test (IGFGT) is often used during the assessment of suspected GH insensitivity (GHI). We report the results of a survey undertaken in 2010 to determine the use of IGFGT amongst members of the European Society for Paediatric Endocrinology to evaluate suspected GHI. The literature surrounding the usefulness and limitations of IGFGT are reviewed, and recommendations provided for its use. Of 112 paediatric endocrinologists from 30 countries who responded to the survey, 91 (81%) reported that they had used the IGFGT in the previous 2 years; >10 IGFGT protocols were used. The IGFGT impacted treatment decisions for 97% of the respondents and was a prerequisite for recombinant human IGF1 treatment for 45% of respondents. From a literature review, sensitivity of the IGFGT was evaluated as 77-91% in molecularly proven cases of GHI; specificity was ≤97%, depending on the protocol. The positive predictive value of the IGFGT is likely to be low, as the frequency of normality is predictably higher than that of abnormality in GH signalling. Given the limitations of the IGFGT in the most severe cases of GHI syndrome (GHIS), the ability of the IGFGT to detect less severe GHIS is doubtful. In a pragmatic approach, the IGFGT may not be useful for the diagnosis of GHIS.

Bridging the gap: metabolic and endocrine care of patients during transition

Objective Seamless transition of endocrine patients from the paediatric to adult setting is still suboptimal, especially in patients with complex disorders, i.e., small for gestational age, Turner or Prader–Willi syndromes; Childhood Cancer Survivors, and those with childhood-onset growth hormone deficiency. Methods An expert panel meeting comprised of European paediatric and adult endocrinologists was convened to explore the current gaps in managing the healthcare of patients with endocrine diseases during transition from paediatric to adult care settings. Results While a consensus was reached that a team approach is best, discussions revealed that a ‘one size fits all’ model for transition is largely unsuccessful in these patients. They need more tailored care during adolescence to prevent complications like failure to achieve target adult height, reduced bone mineral density, morbid obesity, metabolic perturbations (obesity and body composition), inappropriate/inadequate puberty, compromised fertility, diminished quality of life and failure to adapt to the demands of adult life. Sometimes it is difficult for young people to detach emotionally from their paediatric endocrinologist and/or the abrupt change from an environment of parental responsibility to one of autonomy. Discussions about impending transition and healthcare autonomy should begin in early adolescence and continue throughout young adulthood to ensure seamless continuum of care and optimal treatment outcomes. Conclusions Even amongst a group of healthcare professionals with a great interest in improving transition services for patients with endocrine diseases, there is still much work to be done to improve the quality of healthcare for transition patients.

How to manage an adolescent girl presenting with features of polycystic ovary syndrome (PCOS); an exemplar for adolescent health care in endocrinology

Polycystic ovary syndrome (PCOS), or the potential diagnosis of PCOS, is one of the most common reasons for adolescent girls to present to endocrinology clinics. A diagnosis of PCOS has the potential to affect the young person, not only physically, but psychologically and socially. It is important we have the knowledge, skills and attitudes to work effectively with young people to address their concerns and meet their information needs. Successful engagement and management of adolescents with PCOS may have implications in adult life. In this article, the challenges of making the diagnosis of PCOS and introducing lifestyle change and the necessary skills for working with young people are discussed.