Growth Hormone Deficiency In Survivors Research Articles

Growth hormone deficiency in adult survivors of childhood brain tumors treated with radiation.

Growth hormone deficiency (GHD) is the most common endocrine late effect in irradiated survivors of childhood brain tumors. This study aimed to determine the prevalence of GHD in adults treated with proton or photon irradiation for a brain tumor in childhood and to detect undiagnosed GHD. This study is a cross-sectional study. We investigated GHD in 5-year survivors from two health regions in Denmark treated for childhood brain tumors with cranial or craniospinal irradiation in the period 1997-2015. Medical charts were reviewed for endocrinological and other health data. Survivors without a growth hormone (GH) test at final height were invited to a GH stimulation test. Totally 41 (22 females) survivors with a median age of 21.7 years (range: 15.1-33.8 years) at follow-up and 14.8 years (range: 5.1-23.4 years) since diagnosis were included; 11 were treated with proton and 30 with photon irradiation; 18 of 21 survivors were previously found to have GHD; 16 of 20 survivors with no GH test at final height were tested, 8 (50 %) had GHD. In total, 26 of 41 patients (63%) had GHD. Insulin-like growth factor-1 (IGF-1) is associated poorly with the insulin tolerance test (ITT). This study identified a high prevalence of undiagnosed GHD in survivors with no GH test at final height. The results stress the importance of screening for GHD at final height in survivors of childhood brain tumors with prior exposure to cranial irradiation, irrespective of radiation modality and IGF-1. This cross-sectional study reports a prevalence of 63% of GHD in irradiated childhood brain tumor survivors. Furthermore, the study identified a considerable number of long-term survivors without a GH test at final height, of whom, 50% subsequently were shown to have undiagnosed GHD. Additionally, this study confirmed that a normal serum IGF-1 measurement cannot exclude the diagnosis of GHD in irradiated survivors. This illustrates the need for improvements in the diagnostic approach to GHD after reaching final height in childhood brain tumor survivors at risk of GHD. In summary, our study stresses the need for GHD testing in all adult survivors treated with cranial irradiation for a brain tumor in childhood irrespective of radiation modality.

Prevalence of childhood growth hormone deficiency in survivors of pediatric intracranial germ cell tumors.

e22526 Background: Survival rates for childhood cancer continue to rise, and there are now greater than 420,000 survivors in the United States. However, high cure rates come at the cost of short and long-term treatment-related toxicities. Endocrine disorders are among the most common late effects and are associated with poor health outcomes and lower quality of life. Survivors of pediatric intracranial germ cell tumors (iGCTs) are at high risk for endocrine disorders, particularly for growth hormone deficiency (GHD), due to their exposures to cranial radiation, chemotherapy, and brain surgery. To date, no long-term follow-up studies have explored the late effects experienced by survivors of iGCTs. Methods: Study participants were enrolled in the Germ Cell Tumor Epidemiology Study, which is a case-parent triad study conducted using the resources of the Children’s Oncology Group’s Childhood Cancer Research Network. Eligibility criteria included diagnosis with a germ cell tumor in any location at age 0-19 years in the years 2008-2015. The study population included 233 cases with a diagnosis of iGCT. We are currently following the cohort to evaluate outcomes and late effects of treatment, including medical record review to extract data on treatment characteristics and hormone deficiencies. This interim analysis includes chart review for 57 iGCT cases. Results: Of the 57 cases reviewed, there was a male predominance (73.7%) with the highest prevalence in non-Hispanic whites (80.4%). Cases of iGCTs can be subdivided into two main histologic subtypes, germinomas (36 cases) and non-germinomatous GCTs (NGGCT, 21 cases). The median age at diagnosis was 14.6 years for the germinomas and 10.5 years for NGGCTs. Data on growth hormone deficiency (GHD) was available for 42 of the 57 cases with a median follow-up of 7.4 years. Twenty-eight of the 42 cases (66.7%) had GHD; 19 in the germinoma group and 9 in the NGGCT group (p = 0.47). 17 of those with GHD were males (p = 0.10). There was no significant difference in prevalence of GHD by age of tumor diagnosis (p = 0.20). Conclusions: Survivors of iGCTs are at high risk for growth hormone deficiency. Identifying specific risk factors for developing GHD amongst these survivors can enhance the current guidelines for screening and management.

The prevalence of growth hormone deficiency in survivors of subarachnoid haemorrhage: results from a large single centre study

ObjectiveThe variation in reported prevalence of growth hormone deficiency (GHD) post subarachnoid haemorrhage (SAH) is mainly due to methodological heterogeneity. We report on the prevalence of GHD in a large cohort of patients following SAH, when dynamic and confirmatory pituitary hormone testing methods are systematically employed.DesignIn this cross-sectional study, pituitary function was assessed in 100 patients following SAH. Baseline pituitary hormonal profile measurement and glucagon stimulation testing (GST) was carried out in all patients. Isolated GHD was confirmed with an Arginine stimulation test and ACTH deficiency was confirmed with a short synacthen test.ResultsThe prevalence of hypopituitarism in our cohort was 19% and the prevalence of GHD was 14%. There was no association between GHD and the clinical or radiological severity of SAH at presentation, treatment modality, age, or occurrence of vasospasm. There were statistically significant differences in terms of Glasgow Outcome Scale (GOS; p = 0.03) between patients diagnosed with GHD and those without. Significant inverse correlations between GH peak on GST with body mass index (BMI) and waist hip ratio (WHR) was also noted (p < 0.0001 and p < 0.0001 respectively).ConclusionUsing the current testing protocol, the prevalence of GHD detected in our cohort was 14%. It is unclear if the BMI and WHR difference observed is truly due to GHD or confounded by the endocrine tests used in this protocol. There is possibly an association between the development of GHD and worse GOS score. Routine endocrine screening of all SAH survivors with dynamic tests is time consuming and may subject many patients to unnecessary side-effects. Furthermore the degree of clinical benefit derived from growth hormone replacement in this patient group, remains unclear. Increased understanding of the most appropriate testing methodology in this patient group and more importantly which SAH survivors would derive most benefit from GHD screening is required.

Recurrence of brain tumours in patients treated with growth hormone: Analysis of KIGS (Pfizer International Growth Database)

Growth hormone (GH) has been used successfully in the treatment of short stature secondary to GH deficiency in survivors of childhood brain tumours. There has been concern that GH might increase the risk of recurrence. To analyse KIGS (Pfizer International Growth Database) with respect to tumour recurrence in patients with brain tumours. Data for tumour recurrence were analysed retrospectively in 1038 patients with craniopharyngiomas, 655 with medulloblastomas, 113 with ependymomas, 297 with germinomas, and 400 with astrocytomas or gliomas. All patients had received recombinant human GH (Genotropin, Pfizer Inc.). Recurrence-free survival rates were 63% at a follow-up of 10.3 y in craniopharyngioma, 69% in 9.1 y in the glial tumours, 71% in 7.4 y in germinomas, 92% in 4.6 y in medulloblastomas and 89% in 2.5 y in ependymomas. Dose of GH and treatment modalities did not differ significantly between patients with and without recurrence. Tumour recurrence rates in surviving patients with brain tumours receiving GH treatment do not appear to be increased compared with published reports. However, longer follow-up regarding recurrences and secondary neoplasms remains essential.

Outcomes of growth hormone replacement therapy in survivors of childhood acute lymphoblastic leukemia.

Little is known about the long-term efficacy or adverse effects of growth hormone (GH) replacement therapy in survivors of childhood acute lymphoblastic leukemia (ALL) who have GH deficiency. We investigated the adult height of patients who had received GH and estimated their risk of leukemia relapse or development of a second malignancy. Of 910 patients treated for ALL at a single institution, 47 had received GH replacement therapy. The linear growth of these 47 patients was retrospectively evaluated. Their risk of leukemia relapse or second malignancy was compared with that of survivors who did not undergo GH therapy. The median height SD score at the start of GH therapy had decreased by 1.0 since the time of diagnosis of ALL. After a median duration of 4.5 years of GH therapy, adult height SD scores improved and approached height SD scores at the time of diagnosis of ALL. The median adult height for male patients was 173.2 cm (range, 157 to 191.9 cm), and for female patients, it was 158.1 cm (range, 141 to 168 cm). None of the patients developed adverse effects requiring discontinuation of GH treatment. At the 7-year and 11-year landmarks in continuous hematologic remission, there was no statistical evidence that GH therapy was associated with leukemia relapse or development of a second malignancy. This study suggests that GH replacement therapy is safe and efficacious for the correction of GH deficiency in survivors of childhood ALL.

GROWTH FAILURE AND GROWTH-HORMONE DEFICIENCY AFTER TREATMENT FOR ACUTE LYMPHOBLASTIC LEUKAEMIA

In a study of 77 children who had been treated for acute lymphoblastic leukaemia (ALL) with an LSA 2L 2 (Memorial Sloan-Kettering) chemotherapy protocol plus radiotherapy (24 Gy) as cranial prophylaxis, growth was examined 3·0-9·5 years after diagnosis. The children's growth slowed and they crossed height percentiles towards the end of or after treatment. The Z-score, which reflects the deviation of height measurements from the population mean, was used to assess height change. The mean Z-score was 0·16 at diagnosis, -0·30 2 years later, -0·71 4 years later, and -1·37 6 years later. Height for age had fallen by more than 1 standard deviation of the population mean in 32% of survivors 4 years after diagnosis and in 71% 6 years after diagnosis. Younger children and those tall for age at diagnosis were more severely affected. Growth-hormone (GH) response to standard provocation tests was measured in 46 patients; 30 had partial or complete GH deficiency. Mean pulsatile GH secretion was low in the 34 patients tested. Cranial irradiation is probably the most important causative factor in the development of GH deficiency in survivors of ALL.