Adult Growth Hormone Deficiency Research Articles

Reduced Bone Mineral Density in Middle-Aged Male Patients with Adult Growth Hormone Deficiency.

The aim of the work was to investigate the bone mineral density (BMD) in middle-aged male patients with both childhood-onset (CO) and adulthood-onset (AO) adult growth hormone deficiency (AGHD). In this retrospective cross-sectional study in a major medical center in China, dual X-ray absorptiometry was performed in 50 male AGHD patients (average age was 35.2±9.8 years) and 50 age- and BMI-matched non-athletic healthy men. BMD was compared between AGHD patients and controls. Compared with healthy controls, AGHD group had significantly decreased IGF-1 (p1<0.001) and IGF-1 SDS (p1<0.001). Serum testosterone levels were significantly lower in AGHD patients (p1<0.001), mainly in AO AGHD patients (p3<0.001). The BMD of the femoral neck, trochanter, femoral shaft, total hip, and lumbar spine were significantly lower in all AGHD patients compared with healthy controls (all p1<0.05), especially in CO AGHD patients (all p2<0.05). Multiple stepwise linear regression indicated AGHD was negatively correlated with BMD at each site (β<0, p<0.05). Additionally, serum testosterone level was an independent influencing factor of BMD of the femoral neck (β=0.256, p=0.018) and lumbar spine (β=0.219, p=0.040). BMD was significantly reduced in AGHD patients, especially in CO AGHD patients. Our data suggested that the status of growth hormone deficiency and testosterone level were important for maintaining of bone mineral density in middle-aged male patients with AGHD.

The effect of hypothalamic involvement and growth hormone treatment on cardiovascular risk factors during the transition period in patients with childhood-onset craniopharyngioma.

Hypothalamic damage may increase the risk of adulthood obesity and cardiovascular disease in patients with craniopharyngioma. We evaluated the effects of hypothalamic involvement (HI) and growth hormone (GH) discontinuation on cardiovascular risk factors during the transition period in patients with childhood-onset craniopharyngioma. Thirty-three patients (17 males, 16 females) underwent retesting for adult GH deficiency (GHD) between 2005 and 2020 at Seoul National University Children's Hospital. Postoperative HI was graded by Puget's criteria and data regarding GH replacement were collected. At retesting, body mass index (BMI), fasting blood glucose, insulin, high-density lipoprotein cholesterol (HDL-C), triglycerides, and blood pressure were assessed. The mean age of commencement and discontinuation of GH replacement for childhood GHD was 10.0±3.6 and 15.3±3.1 years, respectively. The mean age at retesting for adult GHD was 17.7±2.5 years. When patients were categorized by post-GH discontinuation duration, those with durations >6 months (n=27) showed lower HDL-C levels than those with <6 months (P=0.037). Patients with extensive HI (n=16) had higher BMI z-scores than did those with no HI or mild HI (P=0.020). Both the extent of HI and longer post-GH discontinuation duration were significantly predictive for decreased HDL-C levels (P<0.05, for both). The extent of HI and GH discontinuation duration during the transition period can increase cardiovascular risks in patients with childhood-onset craniopharyngioma.

Growth hormone deficiency and NAFLD: An overlooked and underrecognized link.

Growth hormone and its mediator insulin‐like growth factor‐1 exert their effect on different organs and control various physiologic metabolic processes. Adult growth hormone deficiency (AGHD) presents with one or more components of metabolic syndrome and can be associated with nonalcoholic fatty liver disease (NAFLD). AGHD is present in spectrum of hypothalamic/pituitary disorders as well as cranial radiation of brain tumors and often remains underdiagnosed or untreated due to its nonspecific symptoms, relatively difficult diagnosis in some clinical scenarios, and various barriers to treatment. NAFLD usually develops soon after diagnosis of AGHD and might progress rapidly to nonalcoholic steatohepatitis (NASH) with advanced fibrosis, eventually requiring liver transplantation. A timely initiation of growth hormone replacement therapy might be important, although studies so far have demonstrated controversial results on NAFLD, primarily due to small sample size and different diagnostic methods of NAFLD. Increased awareness of the association between AGHD and NAFLD would facilitate early diagnosis of NAFLD and NASH if present. Therefore, a multidisciplinary approach involving hepatology and endocrinology should become a standard of care for these patients.

EE413 Budget Impact Analysis of Macimorelin, an Oral Growth Hormone Stimulation Test, As a Diagnostic Test for Adult Growth Hormone Deficiency (AGHD) across 5 European Countries

Macimorelin is a novel, oral growth hormone stimulation test approved by EMA and FDA for the diagnosis of adult growth hormone deficiency (AGHD). The objective of this study is to investigate the budget impact arising from the introduction of macimorelin as a diagnostic test for AGHD across France, Germany, Italy, Spain and the United Kingdom.

Development of a Novel Algorithm to Identify People with High Likelihood of Adult Growth Hormone Deficiency in a US Healthcare Claims Database.

Objective Adult growth hormone deficiency (AGHD) is an underdiagnosed disease associated with increased morbidity and mortality. Identifying people who may benefit from growth hormone (GH) therapy can be challenging, as many AGHD symptoms resemble those of aging. We developed an algorithm to potentially help providers stratify people by their likelihood of having AGHD. Design The algorithm was developed with, and applied to, data in the anonymized Truven Health MarketScan® claims database. Patients. A total of 135 million adults in the US aged ≥18 years with ≥6 months of data in the Truven database. Measurements. Proportion of people with high, moderate, or low likelihood of having AGHD, and differences in demographic and clinical characteristics among these groups. Results Overall, 0.5%, 6.0%, and 93.6% of people were categorized into groups with high, moderate, or low likelihood of having AGHD, respectively. The proportions of females were 59.3%, 71.6%, and 50.4%, respectively. People in the high- and moderate-likelihood groups tended to be older than those in the low-likelihood group, with 58.3%, 49.0%, and 37.6% aged >50 years, respectively. Only 2.2% of people in the high-likelihood group received GH therapy as adults. The high-likelihood group had a higher incidence of comorbidities than the low-likelihood group, notably malignant neoplastic disease (standardized difference −0.42), malignant breast tumor (−0.27), hyperlipidemia (−0.26), hypertensive disorder (−0.25), osteoarthritis (−0.23), and heart disease (−0.22). Conclusions This algorithm may represent a cost-effective approach to improve AGHD detection rates by identifying appropriate patients for further diagnostic testing and potential GH replacement treatment.

Patient-reported outcomes (PRO) in adult growth hormone deficiency (aghd) for an improved patients' management: results from the management of AGHD(MAGHD) study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Growth hormone (GH) replacement therapy (GHRT) in patients with adult GH deficiency (AGHD) aged ≥60 years: data from NordiNet® IOS and the ANSWER Program

Growth hormone (GH) replacement therapy (GHRT) in patients with adult GH deficiency (AGHD) aged ≥60 years: data from NordiNet® IOS and the ANSWER Program

Role of new peptide biomarkers in metabolic profiling of adult growth hormone deficiency patients: preliminary data on neudesin and its relationship with LEAP-2

Role of new peptide biomarkers in metabolic profiling of adult growth hormone deficiency patients: preliminary data on neudesin and its relationship with LEAP-2

The burden of adult growth hormone deficiency diagnostic tests: results of a patient experience survey in the UK

The burden of adult growth hormone deficiency diagnostic tests: results of a patient experience survey in the UK

The cut-off limits of GH response to GHRH + arginine test related to body mass index for the diagnosis of adult GH deficiency: do we need to review our diagnostic criteria?

The cut-off limits of GH response to GHRH + arginine test related to body mass index for the diagnosis of adult GH deficiency: do we need to review our diagnostic criteria?

Quality of life after long-term biochemical control of acromegaly.

To assess long-term quality of life (QoL) in patients with sustained biochemical control of acromegaly, comparing those receiving vs not receiving pharmacotherapy (primary analysis); to assess change in QoL over time (secondary analysis). Cross-sectional study, with a secondary longitudinal component, of 58 patients with biochemically controlled acromegaly. All had participated in studies assessing QoL years previously, after having undergone surgery ± radiotherapy. One cohort received medical therapy [MED (n = 33)]; the other did not [NO-MED (n = 25)]. QoL was assessed by the 36-Item-Short-Form Health Survey (SF-36), Acromegaly Quality of Life Questionnaire (AcroQoL), Gastrointestinal Quality of Life Index (GIQLI), Symptom Questionnaire, and QoL-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). Mean (± SD) duration of biochemical control was 15.0 ± 6.4years for MED and 20.4 ± 8.2years for NO-MED (p = 0.007). 58% of subjects scored < 25% of normal on ≥ 1 SF-36 domain and 32% scored < 25% of normal on ≥ 4 of 8 domains. Comparing MED vs NO-MED and controlling for duration of biochemical control, there were no significant differences in QoL by SF-36, AcroQOL, GIQLI, Symptom Questionnaire, or QoL-AGHDA. Growth hormone deficiency (GHD) but not radiotherapy predicted poorer QoL. In MED, QoL improved over time in three AcroQoL domains and two GIQLI domains. In NO-MED, QoL worsened in two SF-36 domains and two Symptom Questionnaire domains; QoL-AGHDA scores also worsened in subjects with GHD. A history of acromegaly and development of GHD, but not pharmacologic or radiotherapy, are detrimental to QoL, which remains poor over the long-term despite biochemical control.

Metabolic Impacts of Discontinuation and Resumption of Recombinant Human Growth Hormone Treatment during the Transition Period in Patients with Childhood-Onset Growth Hormone Deficiency.

Background Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.Methods This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.Results Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.Conclusion GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

Somatropin therapy in italian adults with growth hormone deficiency

BackgroundIn adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed.In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell’Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions.MethodsAim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces.ResultsFrom 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21 ± 0.33 visits/year).The diagnoses were: hypopituitarism (n = 579); hypophysectomy (n = 383); and congenital GHD (n = 3). Five subjects were addressed with diagnoses not included in the regulation.The starting posology of somatropin was 0.320 (± 0.212) mg/day, 0.292 (± 0.167) mg/day in male and 0.360 (± 0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420 ± 0.225 mg/day), with a progressive decrease of the dosage during the follow-up.ConclusionsThis is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.

Growth hormone deficiency in childhood brain tumors and acute lymphoblastic leukemia survivors

Thanks to modern treatment protocols, childhood cancer survivors (CCS) are a very fast-growing population nowadays. Cancer therapy inevitably leads to different late adverse effects, where endocrine disorders are highly prevalent, including growth hormone deficiency (GHD) which is the most common endocrine outcome after cancer treatment in childhood and contributes to impaired growth. Short stature is a big issue, which leads to problems in psychological and social adaptation of patients and reduces their quality of life. Impact of GH treatment on various physiological processes and global outcome of CCS is of great interest. Several studies have demonstrated an influence of GH and IGF-1 on the development/tumour growth, cell proliferation. In this regard, the issue of increasing the risk of cancer recurrence and/or the development of secondary neoplasms in CCS, causes a lot of controversy and is the subject of continuous evaluation. In this review, we went through the available data on the prevalence and pathogenesis of GHD following chemo- and radiotherapy, in particular after treatment of brain tumors and acute lymphoblastic leukaemia in childhood. In addition, here we discuss the existing problems in the diagnosis of GHD, the safety of GH replacement therapy, as well as the treatment algorithm of the GHD in adults.

Efficacy and safety of long-acting growth hormone in adult growth hormone deficiency: A systematic review and meta-analysis

Background & aimsNo meta-analysis has analysed efficacy and safety of long-acting growth hormone (GH) therapy in adult GH deficiency. We undertook this meta-analysis to address this gap in knowledge MethodsElectronic databases were searched for RCTs involving adult GH deficiency patients receiving weekly long-acting GH as compared to daily GH/placebo controls. Primary outcome was to evaluate changes in body-composition parameters. Secondary outcomes were to evaluate alterations in glycaemia and adverse-events. ResultsData from 5 studies involving 648 patients were analysed (4 studies having daily GH as active controls; 1 study having placebo as passive controls). Over 24–34 weeks clinical use, patients receiving long-acting GH had comparable change in lean mass [MD-0.28 kg (95%CI: 0.94 – 0.38); P = 0.41; I2 = 29% (low heterogeneity)] and fat mass [MD-0.10 kg (95%CI: 1.97–1.78); P = 0.92; I2 = 77%(considerable heterogeneity)] as compared to daily GH injections. Long-acting GH use was associated with significantly lower visceral adipose tissue [MD-1.75 cm2(95%CI: 2.14 to −1.35); P < 0.01; I2 = 0% (low heterogeneity)] and higher gynoid fat-mass [MD 0.14 kg(95%CI:0.02–0.26); P = 0.03] compared to daily GH injections. Total adverse events [Risk ratio (RR) 1.65 (95% CI: 0.83–3.29); P = 0.15; I2 = 68%] and severe adverse events [RR 0.60 (95% CI: 0.30–1.19); P = 0.14; I2 = 0%] were not significantly different in long-acting GH group compared to controls. Occurrence of headache, arthralgia, nasopharyngitis, new onset diabetes, anti-GH antibodies were comparable among groups. Long-acting GH users had significantly higher treatment adherence compared to controls [OR 4.80 (95%CI:3.58–6.02); P < 0.01; I2 = 0%]. ConclusionLong-acting GH has comparable beneficial impact on body composition parameters in adult GH deficiency, is well tolerated without any increased adverse events.

Adult Growth Hormone Deficiency : A Practical Approach to Diagnosis and Treatment for Neurosurgeons

Adult Growth Hormone Deficiency : A Practical Approach to Diagnosis and Treatment for Neurosurgeons

Should patients with adult GH deficiency receive GH replacement?

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Increased glycated albumin levels in patients with acromegaly related to glucose fluctuation caused by growth hormone excess but not albumin metabolism.

Acromegaly is often complicated by impaired glucose tolerance. The accuracy of glycated hemoglobin (HbA1c) and glycated albumin (GA) levels in representing glycemic profiles in patients with endocrine disorders, such as acromegaly, is unclear. This retrospective study reviewed data from patients whose GA levels had been recorded. 14 patients with acromegaly without diabetes mellitus (DM) (the acromegaly group), 15 patients with severe adult GH deficiency without DM (the growth hormone deficiency (GHD) group), and 55 nondiabetic patients (the control group) were included in this study. GA levels were significantly increased in the acromegaly group compared with the control and GHD groups, but no significant differences were observed between the control and GHD groups. The three groups were matched using propensity score matching (13 patients with acromegaly, 13 with GHD, and 13 control patients). Nonetheless, the results after matching were the same as those before matching. GA levels in the acromegaly group were significantly associated with plasma glucose (PG) levels at 0, 30, and 120 min after a 75-g oral glucose tolerance test (OGTT). Further, GH levels at 120 min after a 75-g OGTT in the acromegaly group were significantly correlated with GA levels and the difference in PG levels at baseline and 30 min. Our findings suggest that increases in PG levels attributable to excess GH after glucose loading are related to increases in GA levels in patients with acromegaly without DM. Hence, both HbA1c and GA should be checked to accurately assess impaired glucose tolerance in patients with acromegaly.

State of the Art of Patient-reported Outcomes in Acromegaly or GH Deficiency: A Systematic Review and Meta-analysis.

ContextInsight into the current landscape of patient-reported outcome (PRO) measures (PROM) and differences between PROs and conventional biochemical outcomes is pivotal for future implementation of PROs in research and clinical practice. Therefore, in studies among patients with acromegaly and growth hormone deficiency (GHD), we evaluated (1) used PROMs, (2) their validity, (3) quality of PRO reporting, (4) agreement between PROs and biochemical outcomes, and (5) determinants of discrepancies.Evidence AcquisitionWe searched 8 electronic databases for prospective studies describing both PROs and biochemical outcomes in acromegaly and GHD patients. Quality of PRO reporting was assessed using the International Society for Quality of Life Research (ISOQOL) criteria. Logistic regression analysis was used to evaluate determinants.Evidence SynthesisNinety studies were included (acromegaly: n = 53; GHD: n = 37). Besides nonvalidated symptom lists (used in 37% of studies), 36 formal PROMs were used [predominantly Acromegaly Quality of Life Questionnaire in acromegaly (43%) and Quality of Life-Assessment of Growth Hormone Deficiency in Adults in GHD (43%)]. Reporting of PROs was poor, with a median of 37% to 47% of ISOQOL items being reported per study. Eighteen (34%) acromegaly studies and 12 (32%) GHD studies reported discrepancies between PROs and biochemical outcomes, most often improvement in biochemical outcomes without change in PROs.ConclusionsProspective studies among patients with acromegaly and GHD use a multitude of PROMs, often poorly reported. Since a substantial proportion of studies report discrepancies between PROs and biochemical outcomes, PROMs are pivotal in the evaluation of disease activity. Therefore, harmonization of PROs in clinical practice and research by development of core outcome sets is an important unmet need.

Cтан серцево-судинної системи та ліпідний спектр при соматотропній недостатності у молодих дорослих із маніфестацією в дитячому віці (огляд літератури та власні спостереження)

Проведено аналіз наукової літератури стосовно особливостей клінічного перебігу дефіциту гормона росту (ДГР), що маніфестував у дитячому віці, у молодих дорослих. Акцент зроблено на стані ліпідного обміну, а також серцево-судинної системи хворих із ДГР, які не отримували лікування рекомбінантним гормоном росту (рГР). Наведені власні дані, отримані при обстеженні молодих дорослих із ДГР до лікування рГР та на його тлі. Встановлено наявність суттєвих порушень з боку показників ліпідного, вуглеводного обмінів і кардіальних параметрів у хворих, які довготривало не отримували патогенетичного лікування, а також позитивні зміни на тлі призначення препаратів рГР.