scholarly journals Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

Pituitary ◽  
2021 ◽  
Author(s):  
Margaret C. S. Boguszewski ◽  
Adriane A. Cardoso-Demartini ◽  
Cesar Luiz Boguszewski ◽  
Wassim Chemaitilly ◽  
Claire E. Higham ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Clinical Practice ◽  
Brain Tumors ◽  
Cancer Recurrence ◽  
Childhood Cancer Survivors ◽  
Multicenter Studies ◽  
Gh Treatment ◽  
Secondary Neoplasms ◽  
Gh Replacement

AbstractIndividuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.

scholarly journals Incidence of second neoplasm in childhood cancer survivors treated with GH: an analysis of GeNeSIS and HypoCCS

2013 ◽  
Vol 168 (4) ◽  
pp. 565-573 ◽  
Author(s):  
Whitney W Woodmansee ◽  
Alan G Zimmermann ◽  
Christopher J Child ◽  
Qi Rong ◽  
Eva Marie Erfurth ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Observational Studies ◽  
Childhood Cancer Survivors ◽  
Second Neoplasm ◽  
Primary Malignancy ◽  
Gh Treatment ◽  
Gh Replacement ◽  
Increased Risk

ObjectiveChildhood cancer survivors are commonly treated with GH for GH deficiency that develops either as a result of primary malignancy or its treatment. One study – the Childhood Cancer Survivor Study (CCSS) – demonstrated increased risk of second neoplasm (SN) in GH-treated childhood cancer survivors compared with non-GH treated, after adjusting for key risk factors. We assessed the incidence of SN in GH-treated childhood cancer survivors in outpatient observational studies of GH replacement.DesignRetrospective analysis of two prospective cohort studies that collected data on safety of GH replacement as prescribed in clinical practice.MethodsChildhood cancer survivors enrolled in Eli Lilly and Company's pediatric (Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)) and adult (Hypopituitary Control and Complications Study (HypoCCS)) observational studies of GH treatment were assessed for incidence of SN.ResultsThe percentage of childhood cancer survivors treated with GH who developed a SN was 3.8% in pediatric GeNeSIS participants and 6.0% in adult HypoCCS participants. The estimated cumulative incidence of SN at 5 years of follow-up in these studies was 6.2 and 4.8% respectively.ConclusionsThe incidence of SN in GeNeSIS and HypoCCS GH-treated participants is similar to the published literature and is thus consistent with increased risk of SN in childhood cancer survivors treated with GH. As follow-up times were relatively short (<3 years), longer observation is recommended. Nevertheless, clinicians should be alerted to the possibility of increased risk of SN in childhood cancer survivors treated with GH and continue chronic surveillance.

scholarly journals Pregnancy outcomes in women receiving growth hormone replacement therapy enrolled in the NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web-Enabled Research (ANSWER) Program

Pituitary ◽  
2021 ◽  
Author(s):  
Beverly M. K. Biller ◽  
Charlotte Höybye ◽  
Paul Carroll ◽  
Murray B. Gordon ◽  
Anna Camilla Birkegård ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Outcome Study ◽  
Real World Data ◽  
Multicenter Studies ◽  
Clinical Trial Registration ◽  
Normal Delivery ◽  
Growth Hormone Replacement Therapy ◽  
Gh Replacement

Abstract Purpose Data on the safety of growth hormone (GH) replacement therapy during pregnancy are limited. We report a combined analysis of data from pregnant women treated with GH while enrolled in two non-interventional, multicenter studies: NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web-Enabled Research (ANSWER) Program. Methods Pregnancy data were pooled from NordiNet® IOS and the ANSWER Program. Data were collected during routine clinic visits by participating physicians using a web-based system. Patients exposed to GH replacement therapy during pregnancy were included in the analysis. Results The study population included 40 female patients with typical causes of adult GH deficiency (GHD). Overall, there were 54 pregnancies. Of these, 47 were exposed to GH between conception and delivery. In 48.9% of pregnancies exposed to GH, the dose was > 0.6 mg/day. GH was continued past conception and then stopped during the first, second, and third trimester, in 27.7%, 17.0%, and 2.1% of pregnancies, respectively. In 29.8%, GH was continued throughout pregnancy, with an unchanged dose in most cases. Of the 47 GH-exposed pregnancies, 37 (78.7%) progressed to normal delivery. There were three adverse events reported in two pregnancies. Conclusion These real-world data suggest that there were no new safety signals related to GH exposure in women with GHD during pregnancy. These results are consistent with findings from previous studies reporting data in pregnancies exposed to GH at conception or throughout pregnancy. This observational study in additional pregnancies provides further evidence that GH exposure does not adversely affect pregnancy outcome. Clinical trial registration: ClinicalTrials.gov NCT00960128 (date of registration: August 13, 2009) and NCT01009905 (date of registration: November 5, 2009).

Issues in the Transition From Childhood to Adult Growth Hormone Therapy

PEDIATRICS ◽  
1999 ◽  
Vol 104 (Supplement_5) ◽  
pp. 1004-1010
Author(s):  
David B. Allen
Keyword(s):  
Growth Hormone ◽  
Replacement Therapy ◽  
Blood Lipid ◽  
Hormone Deficiency ◽  
Late Adolescent ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Beneficial Effects ◽  
Gh Replacement ◽  
Adult Growth

The consequences of severe growth hormone deficiency (GHD) in adults and the beneficial effects of GH replacement therapy are clear. However, the majority of children who have a diagnosis of GHD and who are treated with GH do not have permanent GHD and will not require treatment during adulthood. Several issues must be considered in selecting candidates for adult GH treatment and transitioning their care from pediatrics to adult medicine. Counseling about possible lifelong treatment should focus on children with panhypopituitarism and those with severe isolated GHD that is associated with central nervous system abnormalities. When to terminate growth-promoting GH therapy should be guided by balancing the high cost of late-adolescent treatment with the attainment of reasonable statural goals. Retesting for GH secretion is appropriate for all candidates for adult GH therapy; the GH axis can be tested within weeks after the cessation of treatment, but confirming an emerging adult GHD state with body composition, blood lipid, and quality-of-life assessments may require 1 year or more of observation. Selecting patients for lifelong adult GH replacement therapy will present diagnostic, therapeutic, and ethical problems similar to those in treating childhood GHD. The experience and expertise of pediatric endocrinologists in diagnosing and treating GHD should be offered and used in identifying and transitioning appropriate patients to adult GH therapy.

scholarly journals Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors

2018 ◽  
Vol 36 (28) ◽  
pp. 2854-2862 ◽  
Author(s):  
Ralph E. Vatner ◽  
Andrzej Niemierko ◽  
Madhusmita Misra ◽  
Elizabeth A. Weyman ◽  
Claire P. Goebel ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Young Adults ◽  
Young Adult ◽  
Thyroid Hormone ◽  
Radiation Dose ◽  
Brain Tumors ◽  
Adrenocorticotropic Hormone ◽  
Hormone Deficiency ◽  
Children And Young Adults

Purpose There are sparse data defining the dose response of radiation therapy (RT) to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. We examined the correlation between RT dose to these structures and development of endocrine dysfunction in this population. Materials and Methods Dosimetric and clinical data were collected from children and young adults (< 26 years of age) with brain tumors treated with proton RT on three prospective studies (2003 to 2016). Deficiencies of growth hormone (GH), thyroid hormone, adrenocorticotropic hormone, and gonadotropins were determined clinically and serologically. Incidence of deficiency was estimated using the Kaplan-Meier method. Multivariate models were constructed accounting for radiation dose and age. Results Of 222 patients in the study, 189 were evaluable by actuarial analysis, with a median follow-up of 4.4 years (range, 0.1 to 13.3 years), with 31 patients (14%) excluded from actuarial analysis for having baseline hormone deficiency and two patients (0.9%) because of lack of follow-up. One hundred thirty patients (68.8%) with medulloblastoma were treated with craniospinal irradiation (CSI) and boost; most of the remaining patients (n = 56) received involved field RT, most commonly for ependymoma (13.8%; n = 26) and low-grade glioma (7.4%; n = 14). The 4-year actuarial rate of any hormone deficiency, growth hormone, thyroid hormone, adrenocorticotropic hormone, and gonadotropin deficiencies were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. Age at start of RT, time interval since treatment, and median dose to the combined hypothalamus and pituitary were correlated with increased incidence of deficiency. Conclusion Median hypothalamic and pituitary radiation dose, younger age, and longer follow-up time were associated with increased rates of endocrinopathy in children and young adults treated with radiotherapy for brain tumors.

scholarly journals Change in baseline characteristics over 20 years of adults with growth hormone (GH) deficiency on GH replacement therapy

2019 ◽  
Vol 181 (6) ◽  
pp. 629-638 ◽  
Author(s):  
Charlotte Höybye ◽  
Pia Burman ◽  
Ulla Feldt-Rasmussen ◽  
Judith Hey-Hadavi ◽  
Ferah Aydin ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Replacement Therapy ◽  
Gh Deficiency ◽  
Fasting Blood Glucose ◽  
Standard Deviation Score ◽  
Pituitary Hormone ◽  
Adult Onset ◽  
Gh Treatment ◽  
Gh Replacement ◽  
Baseline Characteristics

Objective Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) have indicated a shift in patient characteristics at diagnosis. The objective of this study was to compare baseline characteristics of patients diagnosed with adult-onset GHD naive to GH replacement during three study periods (1994–1999 (P1), 2000–2004 (P2), and 2005–2012 (P3)) using the KIMS (Pfizer’s International Metabolic) database. Methods Data were retrieved for a total of 6069 patients with adult-onset GHD from six countries (Belgium, Germany, Netherlands, Spain, Sweden, and UK): P1 (n = 1705), P2 (n = 2397), and P3 (n = 1967). Results The proportions of patients with pituitary/hypothalamic tumors and patients with multiple pituitary hormone deficiencies decreased per entry year period, while the proportions with hypertension and diabetes increased. The lag time from diagnosis of pituitary disease to start of GH treatment decreased by 2.9 years over the entry year periods. IGF-1 increased by 0.1 standard deviation score per entry year period. Maximum GH following various stimulation tests, BMI, and waist circumference increased. The use of radiotherapy, glucocorticoid replacement doses, and the proportion of women >50 years on estrogen replacement therapy decreased. The effects of 1 year of GH replacement were similar over the entry year periods despite changes in the patients’ baseline characteristics. An expected increase in fasting blood glucose was seen after 1 year of GH treatment. Conclusions The degree of confirmed GHD became less pronounced and more patients with co-morbidities and diabetes were considered for GH replacement therapy, possibly reflecting increased knowledge and confidence in GH therapy gained with time.

Long-term effects of growth hormone (GH) replacement therapy on the body composition of adults with GH deficiency: A 60-month follow-up

2001 ◽  
Vol 11 ◽  
pp. S127
Author(s):  
A. Troendle ◽  
E. Fontana ◽  
V. Giusti ◽  
F. Gomez ◽  
R.C. Gaillard
Keyword(s):  
Growth Hormone ◽  
Body Composition ◽  
Replacement Therapy ◽  
Gh Deficiency ◽  
The Body ◽  
Long Term Effects ◽  
Gh Replacement

scholarly journals Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study

2015 ◽  
Vol 172 (6) ◽  
pp. 779-790 ◽  
Author(s):  
Christopher J Child ◽  
Daniel Conroy ◽  
Alan G Zimmermann ◽  
Whitney W Woodmansee ◽  
Eva Marie Erfurth ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Childhood Cancer Survivors ◽  
Colorectal Cancers ◽  
Intracranial Tumour ◽  
Recurrence Rates ◽  
Gh Treatment ◽  
Second Neoplasms ◽  
Increased Risk ◽  
Propensity Score Adjustment

ObjectiveSpeculation remains that GH treatment is associated with increased neoplasia risk. Studies in GH-treated childhood cancer survivors suggested higher rates of second neoplasms, while cancer risk data for GH-treated and untreated hypopituitary adults have been variable. We present primary cancer risk data from the Hypopituitary Control and Complications Study (HypoCCS) with a focus on specific cancers, and assessment of recurrence rates for pituitary adenomas (PA) and craniopharyngiomas (CP).DesignIncident neoplasms during HypoCCS were evaluated in 8418 GH-treated vs 1268 untreated patients for primary malignancies, 3668 GH-treated vs 720 untreated patients with PA history, and 956 GH-treated vs 102 untreated patients with CP history.MethodsUsing population cancer rates, standardised incidence ratios (SIRs) were calculated for all primary cancers, breast, prostate, and colorectal cancers. Neoplasm rates in GH-treated vs untreated patients were analysed after propensity score adjustment of baseline treatment group imbalances.ResultsDuring mean follow-up of 4.8 years, 225 primary cancers were identified in GH-treated patients, with SIR of 0.82 (95% CI 0.71–0.93). SIRs (95% CI) for GH-treated patients were 0.59 (0.36–0.90) for breast, 0.80 (0.57–1.10) for prostate, and 0.62 (0.38–0.96) for colorectal cancers. Cancer risk was not statistically different between GH-treated and untreated patients (relative risk (RR)=1.00 (95% CI 0.70–1.41), P=0.98). Adjusted RR for recurrence was 0.91 (0.68–1.22), P=0.53 for PA and 1.32 (0.53–3.31), P=0.55 for CP.ConclusionsThere was no increased risk for all-site cancers: breast, prostate or colorectal primary cancers in GH-treated patients during HypoCCS. GH treatment did not increase the risk of PA and CP recurrences.

scholarly journals The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up

2021 ◽  
pp. S61-S68
Author(s):  
P. Vaňuga ◽  
M. Kužma ◽  
D. Stojkovičová ◽  
J. Smaha ◽  
P. Jackuliak ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Growth Hormone ◽  
Trabecular Bone ◽  
Replacement Therapy ◽  
Bone Mineral ◽  
Trabecular Bone Score ◽  
Mineral Density ◽  
Gh Replacement

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

scholarly journals SUN-348 Growth Hormone Replacement in Adults During 8 Years Leads to Sustained Increase in Bone Mineral Density

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Juraj Payer ◽  
Martin Kužma ◽  
Daša Stojkovičová ◽  
Juraj Smaha ◽  
Peter Jackuliak ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Growth Hormone ◽  
Bone Mass ◽  
Bone Turnover ◽  
Single Center ◽  
Mineral Density ◽  
Gh Replacement ◽  
Turnover Markers

Abstract Introduction: Adult growth hormone deficiency (AGHD) is associated with lower bone mass and likely with increased risk of fragility fractures. GH replacement leads to increase in bone mineral density (BMD).However, only few studies longer than 2 years exist. Aim: To assess long-term effect of recombinant GH replacement on BMD and bone turnover markers duringperiod of 8 years. Patients & Methods: Prospective follow-up of all (N=63) AGHD patients at one single center. All patients with adult GHD followed at single center. All participants were replaced with daily injection of recombinant human (rh) GH in IGF-1 normalizing regimen according to Endocrine Society Guidelines. Every 2 years, lumbar spine (L-spine) and total hip (TH) BMD using dual X-ray absorptiometry on Hologic Discovery device, was assessed. All patients were assessed for bone turnover markers; carboxy-terminal collagen crosslinks (CTx) and osteocalcin (OC), and 25(OH)D levels. Deficiencies of other pituitary axes were treated if necessary. All patients were supplemented with 800 IU /day of cholecalciferol and 1000-1200mg/day of calcium as recommended by International Osteoporosis Foundation. Results: Study group consisted of 38 males and 25 females (35 with adult onset (AO) /28 with childhood onset (CO); mean age at diagnosis 25,1 yrs) AGHD patients. All patients ended 8 years follow-up period without any treatment discontinuation during this period. Treatment was well tolerated, without any serious adverse event. IGF-1 has reached the normal ranges during first 6 months and remains normal during whole study period documenting good adherence to treatment (average dose of rhGH=0,4 mg/day). Both, L-spine and TH BMD increased significantly after 8 years of GH replacement (+8 % for L-spine BMD, +7,7% for TH BMD, both p&lt;0,01). The highest peak of BMD was observed after 6 years of treatment. CTx increased by 35% (p&lt;0,05) and remain stable, and no significant change in OC was observed during study period. Levels of 25(OH)D increased by 32% (p&lt;0,05) from baseline. No clinical fractures were observed. Conclusion: Long-term GH replacement in adult GHD together with sufficient levels of vitamin D levels led to increase in BMD and CTx. This study supported fact that GH has sustained effect on bone mass and bone turnover and is safe and well -tolerated for the long time period.

scholarly journals Real-World Treatment Patterns and Outcomes of Growth Hormone Treatment Among Children in Israel Over the Past Decade (2004–2015)

2021 ◽  
Vol 9 ◽  
Author(s):  
Tal Ben-Ari ◽  
Gabriel Chodick ◽  
Varda Shalev ◽  
Dalit Goldstein ◽  
Roy Gomez ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Real World ◽  
Standard Deviation Score ◽  
Healthcare Services ◽  
Treatment Patterns ◽  
Good Adherence ◽  
Gh Therapy ◽  
Gh Treatment

Objective: To assess a decade of growth hormone (GH) treatment patterns and outcomes in a real-world setting in Israel using a state-of-the-art computerized database.Methods: This large retrospective database study included 2,379 children initiating GH treatment in Maccabi Healthcare Services (between January 2004 and December 2014). Good adherence with therapy (proportion of days covered &gt;80%) was assessed during follow-up.Results: At GH treatment initiation: 62.1% were boys; height standard deviation score (SDS) was −2.36 ± 0.65 (mean ± SD); age was 9.8 ± 3.1 years; and time from short stature diagnosis to first GH purchase was 4.8 ± 3.3 years. Mean treatment period was 3.5 ± 0.95 years; 79.4% of children were treated for more than 3 years. The two main indications for GH therapy were idiopathic short stature (ISS) (n = 1,615, 67.9%) and GH deficiency (GHD) (n = 611, 25.7%). Children in the highest socio-economic-status (SES) tertile comprised 61.3% of ISS and 59.7% of GHD. After 3 years, mean height gain SDS was 1.09 ± 0.91 for GHD and 0.96 ± 0.57 for ISS (p = 0.0004). Adult height (age 15 for girls and 17 for boys) was recorded for 624 patients (26.2%) with better outcomes for GHD than ISS (−1.0±0.82 vs. −1.28±0.93, respectively; p = 0.0002). Good adherence was achieved in 78.2% of the cohort during the first year and declined thereafter to 68.1% during the third year of the treatment.Conclusions: Children who initiate GH therapy are predominantly male, belong mainly to the upper SES, commence treatment a long period after initial recognition of short stature, and have suboptimal adherence. Appropriate referral, diagnosis, and follow-up care may result in better treatment outcomes with GH therapy.

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