Therapeutic efficacy of recombinant human growth hormone in children with different etiologies of dwarfism from a pharmacoeconomic point of view.

Treatment outcomes for different causes of childhood dwarfism vary widely, and there are no studies on the economic burden of treatment in relation to outcomes. This paper compared the efficacy and healthcare costs per unit height of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency (GHD) and idiopathic short stature (ISS) with a view to providing a more cost-effective treatment option for children. We retrospectively analyzed 117 cases (66 cases of GHD and 51 cases of ISS) of short-stature children who first visited Weifang People's Hospital between 2019.1 and 2022.1 and were treated with rhGH for 1 to 3 years to track the treatment effect and statistically analyzed by using paired t tests, non-parametric tests, and chi-square tests, to evaluate the efficacy of rhGH treatment for GHD and ISS children and the medicinal cost. The annual growth velocity (GV) of children with GHD and ISS increased the fastest during 3 to 6 months after treatment and then gradually slowed down. The GV of the GHD group was higher than that of the ISS group from 0 to 36 months after treatment (P < .05 at 3, 6, 9, and 12 months); the height standard deviation scores (HtSDS) of the children in the GHD and ISS groups increased gradually with the increase of the treatment time, and the changes in the height standard deviation scores (ΔHtSDS) of the GHD group were more significant than those of the ISS group (P < .05 at 3, 6, 9, and 12 months). (2) The medical costs in the pubertal group for a 1-cm increase in height were higher than those of children in the pre-pubertal group at the same stage (3 to 24 months P < .05). The longer the treatment time within the same group, the higher the medical cost of increasing 1cm height. RhGH is effective in treating children with dwarfism to promote height growth, and the effect on children with GHD is better than that of children with ISS; the earlier the treatment time, the lower the medical cost and the higher the comprehensive benefit.

Tackling access and payer barriers for growth hormone therapy in Saudi Arabia: a consensus statement for the Saudi Working Group for Pediatric Endocrinology.

Prompt diagnosis and early treatment are key goals to optimize the outcomes of children with growth hormone deficiency (GHD) and attain the genetically expected adult height. Nonetheless, several barriers can hinder prompt diagnosis and treatment of GHD, including payer-related issues. In Saudi Arabia, moderate-to-severe short stature was reported in 13.1 and 11.7 % of healthy boys and girls, respectively. Several access and payer barriers can face pediatric endocrinologists during the diagnosis and treatment of GHD in Saudi Arabia. Insurance coverage policies can restrict access to diagnostic tests for GHD and recombinant human growth hormone (rhGH) due to their high costs and lack of gold-standard criteria. Some insurance policies may limit the duration of treatment with rhGH or the amount of medication covered per month. This consensus article gathered the insights of pediatric endocrinologists from Saudi Arabia to reflect the access and payer barriers to the diagnostic tests and treatment options of children with short stature. We also discussed the current payer-related challenges endocrinologists face during the investigations of children with short stature. The consensus identified potential strategies to overcome these challenges and optimize patient management.

The economic burden of pediatric growth hormone deficiency in Italy: a cost of illness study.

PURPOSE: Growth hormone deficiency (GHD) is a rare condition with a worldwide prevalence of 1 patient in 4000 to 10,000 live births, placing a significant economic burden on healthcare systems. The aim of this study is to generate evidence on the economic burden of children and adolescents with GHD treated with rhGH and their parents in Italy. METHODS: A cost of illness analysis, adopting the prevalence approach, has been developed, producing evidence on the total annual cost sustained by the Italian National Health System (NHS) and by the society. The study is based on original data collected from a survey conducted among Italian children and adolescents with GHD and their parents. RESULTS: 143 children/adolescents with GHD and their parents participated to the survey, conducted from May to October 2021. Patients had a mean age of 12.2 years (SD: 3.1) and were mostly males (68.5%). The average direct healthcare cost sustained by the NHS was € 8,497.2 per patient/year; adding the out-of-pocket expenses (co-payments and expenses for private healthcare service), the total expense was € 8,568.6. The indirect costs, assessed with the human capital approach, were € 847.9 per patient/year. The total of direct and indirect cost is € 9,345.1 from the NHS perspective, and € 9,416.5 from a social perspective. The total cost incurred by the Italian NHS for children with GHD (range: 5,708-8,354) was estimated in € 48.5-71.0 million, corresponding to 0.04-0.06% of the total Italian public health expense in the year 2020. CONCLUSIONS: The total annual cost for GHD children is close to € 10,000, and is mainly due to the cost of rhGH treatment. This cost is almost entirely sustained by the NHS, with negligible out-of-pocket expenses. The economic burden on the Italian NHS for the health care of established GHD children is fourfold higher than the prevalence of the disease in the overall Italian population.

Longitudinal assessment of bone health index as a measure of bone health in short-statured children before and during treatment with recombinant growth hormone.

OBJECTIVES: The aim of our study was the longitudinal assessment of bone health index (BHI) in short-statured children during growth hormone (GH) treatment to estimate changes in their bone health. METHODS: 256 short-statured children (isolated GH deficiency (IGHD) n=121, multiple pituitary hormone deficiency (MPHD) n=49, intrauterine growth retardation (small for gestational age (SGA)) n=52, SHOX (short stature homeobox gene) deficiency n=9, Ullrich Turner syndrome (UTS) n=25) who started with GH between 2010 and 2018 were included. Annual bone ages (Greulich and Pyle, GP) and BHI were, retrospectively, analysed in consecutive radiographs of the left hand (BoneXpert software) from GH therapy start (T0) up to 10 years (T10) thereafter, with T max indicating the individual time point of the last available radiograph. The results are presented as the median (25 %/75 % interquartile ranges, IQR) and statistical analyses were performed using non-parametric tests as appropriate. RESULTS: The BHI standard deviation scores (SDS) were reduced (-0.97, -1.8/-0.3) as bone ages were retarded (-1.6 years, -2.31/-0.97) in all patients before start of GH and were significantly lower in patients with growth hormone deficiency (GHD) (-1.04, -1.85/-0.56; n=170) compared to non-GHD patients (-0.79, -1.56/-0.01; n=86; p=0.022). BHI SDS increased to -0.17 (-1/0.58) after 1 year of GH (T1, 0.5-1.49, p<0.001) and to -0.20 (-1/-0.50, p<0.001) after 5.3 years (T max, 3.45/7.25). CONCLUSIONS: BHI SDS are reduced in treatment-naive short-statured children regardless of their GH status, increase initially with GH treatment while plateauing thereafter, suggesting sustained improved bone health.

Cost-effectiveness and cost-utility analysis of somatrogon once-weekly injections vs. daily growth hormone injection for treating paediatric growth hormone deficiency in Ireland.

OBJECTIVES: Paediatric growth hormone deficiency (pGHD) manifests as growth failure associated with inadequate growth hormone (GH) production. Daily injections of recombinant human GH (dGH) [somatropin] is the current standard of care, which has been shown to be well tolerated and effective, but associated with suboptimal adherence, leading to reduced effectiveness. Somatrogon, a once-weekly injectable long-acting human GH, has demonstrated clinical non-inferiority and significantly lower life interference (i.e. treatment burden) vs. somatropin in two Phase 3 studies. This work evaluated cost-effectiveness and cost-utility of somatrogon vs dGHs from an Irish payer perspective. METHODS: A Markov model was developed for patients starting somatrogon or dGHs treatment at 3-12 years and continuing up to achievement of near adult height (NAH), with growth driven by trial-based height velocity (HV) and treatment-specific adherence. Patients could discontinue treatment at the end of Year 1 (4%). DGH adherence (95.3%-65% over treatment duration) and adherence-growth relationship were based on published evidence. Higher Year 1 adherence of 4%, tapering over time, for somatrogon vs. dGHs was based on clinical consultation. Treatment costs, monitoring costs and costs due to different wastage types (device setting and adherence) were sourced from local data. Health utilities based on height and injection frequency were derived from published literature. Scenario analysis, deterministic and probabilistic sensitivity analysis were performed. RESULTS: Somatrogon treatment led to 1.87-3.66 cm greater NAH gain and 0.21-0.50 higher quality adjusted life years (QALYs) vs. dGHs, across the base case and scenarios evaluated. Somatrogon treatment was associated with cost savings of €5,699-€21,974 and lower cost per cm gained vs. dGHs (€197-€527), per patient. Somatrogon was cost-effective vs. dGHs, with the result consistent across the sensitivity analyses conducted. CONCLUSION: Somatrogon weekly injections were estimated to result in higher NAH, higher QALYs, lower overall costs and lower costs per cm gained than dGHs, in pGHD.

Burden and Treatment of Achondroplasia: A Systematic Literature Review.

BACKGROUND: Achondroplasia is the most common form of skeletal dysplasia. Recent advances in therapeutic options have highlighted the need for understanding the burden and treatment landscape of the condition. This systematic literature review (SLR) aimed to identify health-related quality of life (HRQoL)/utilities, healthcare resource use (HCRU), costs, efficacy, safety and economic evaluation data in achondroplasia and to identify gaps in the research. METHODS: Searches of MEDLINE, Embase, the University of York Centre for Reviews and Dissemination (CRD), the Cochrane Library and grey literature were performed. Articles were screened against pre-specified eligibility criteria by two individuals and study quality was assessed using published checklists. Additional targeted searches were conducted to identify management guidelines. RESULTS: Fifty-nine unique studies were included. Results demonstrated a substantial HRQoL and HCRU/cost-related burden of achondroplasia on affected individuals and their families throughout their lifetimes, particularly in emotional wellbeing and hospitalisation costs and resource use. Vosoritide, growth hormone (GH) and limb lengthening all conferred benefits for height or growth velocity; however, the long-term effects of GH therapy were unclear, data for vosoritide were from a limited number of studies, and limb lengthening was associated with complications. Included management guidelines varied widely in their scope, with the first global effort to standardise achondroplasia management represented by the International Achondroplasia Consensus Statement published at the end of 2021. Current evidence gaps include a lack of utility and cost-effectiveness data for achondroplasia and its treatments. CONCLUSIONS: This SLR provides a comprehensive overview of the current burden and treatment landscape for achondroplasia, along with areas where evidence is lacking. This review should be updated as new evidence becomes available on emerging therapies.

Healthcare cost and survival in patients with non-functioning pituitary adenoma.

OBJECTIVE: Pituitary adenomas and their consequences impact mortality and morbidity. We studied the healthcare costs, survival, and cost-effectiveness of growth hormone (GH) vs no GH replacement in patients with non-functioning pituitary adenoma (NFPA). DESIGN AND METHODS: A cohort study including all NFPA patients followed from 1987 or the date of diagnosis until the time of death or December 31, 2019, in the Västra Götaland region, Sweden. Data to assess resource use, costs, survival, and cost-effectiveness were collected from patient records and regional/national healthcare registries. RESULTS: A total of 426 patients with NFPA (274 men) with a follow-up of 13.6 ± 6.8 years (mean ± SD) were included. The total annual healthcare cost was higher in patients receiving GH (€9287) than those without GH (€6770), mainly driven by a higher pharmaceutical cost. Glucocorticoid replacement therapy (P = .02), diabetes insipidus (P = .04), body mass index (BMI) (P < .01), and hypertension (P < .01) were all individually associated with a higher total annual cost. The survival rate was higher in the GH group (HR [hazard ratio] 0.60; P = .01) and reduced in patients with glucocorticoid replacement (HR 2.02; P < .01) or diabetes insipidus (HR 1.67; P = .04). The cost per gained life-year for GH vs no GH replacement was about €37 000. CONCLUSIONS: This healthcare utilization study identified several factors driving the cost of care in NFPA patients, such as GH replacement, adrenal insufficiency, and diabetes insipidus. Life expectancy was increased in those with GH replacement and reduced in patients with adrenal insufficiency and diabetes insipidus.

Cost-effectiveness analysis of herbal medicines in children with idiopathic short stature.

BACKGROUND: Herbal medicines have been used for a long time to treat idiopathic short stature (ISS) in children in East Asian countries. The aim of this study was to analyze the cost-effectiveness of 5 herbal medicines frequently used in clinical settings for children with ISS based on medical records. METHODS: Patients with ISS who had been prescribed a 60-day supply of herbal medicines in 1 Korean medicine hospital were included in this analysis. Their height and height percentile were measured before and after treatment within 6-months. The average cost-effectiveness ratios (ACERs) of 5 herbal medicines for height (cm) and height percentile were calculated for boys and girls, respectively. RESULTS: The ACERs per 1 cm height growth were USD 56.2 (Naesohwajung-Tang), USD 74.8 (Ogapi-Growth decoction), USD 86.6 (Gamcho-Growth decoction), USD 94.6 (Gwakhyangjeonggi-San plus Yukmijihwang-Tang), and USD 113.8 (Boyang-Growth decoction). The ACERs per 1 percentile height growth were USD 205 (Naesohwajung-Tang), USD 293 (Ogapi-Growth decoction), USD 470 (Gamcho-Growth decoction), USD 949 (Boyang-Growth decoction), and USD 1051 (Gwakhyangjeonggi-San plus Yukmijihwang-Tang). CONCLUSION: Herbal medicine might be a potential economical alternative treatment for ISS.

Pediatric growth hormone treatment in Italy: A systematic review of epidemiology, quality of life, treatment adherence, and economic impact.

OBJECTIVES: This systematic review aims to describe 1) the epidemiology of the diseases indicated for treatment with growth hormone (GH) in Italy; 2) the adherence to the GH treatment in Italy and factors associated with non-adherence; 3) the economic impact of GH treatment in Italy; 4) the quality of life of patients treated with GH and their caregivers in Italy. METHODS: Systematic literature searches were performed in PubMed, Embase and Web of Science from January 2010 to March 2021. Literature selection process, data extraction and quality assessment were performed by two independent reviewers. Study protocol has been registered in PROSPERO (CRD42021240455). RESULTS: We included 25 studies in the qualitative synthesis. The estimated prevalence of growth hormone deficiency (GHD) was 1/4,000-10,000 in the general population of children; the prevalence of Short Stature HOmeoboX Containing gene deficiency (SHOX-D) was 1/1,000-2,000 in the general population of children; the birth prevalence of Turner syndrome was 1/2,500; the birth prevalence of Prader-Willi syndrome (PWS) was 1/15,000. Treatment adherence was suboptimal, with a range of non-adherent patients of 10-30%. The main reasons for suboptimal adherence were forgetfulness, being away from home, pain/discomfort caused by the injection. Economic studies reported a total cost for a complete multi-year course of GH treatment of almost 100,000 euros. A study showed that drug wastage can amount up to 15% of consumption, and that in some Italian regions there could be a considerable over- or under-prescribing. In general, patients and caregivers considered the GH treatment acceptable. There was a general satisfaction among patients with regard to social and school life and GH treatment outcomes, while there was a certain level of intolerance to GH treatment among adolescents. Studies on PWS patients and their caregivers showed a lower quality of life compared to the general population, and that social stigma persists. CONCLUSION: Growth failure conditions with approved GH treatment in Italy constitute a significant burden of disease in clinical, social, and economic terms. GH treatment is generally considered acceptable by patients and caregivers. The total cost of the GH treatment is considerable; there are margins for improving efficiency, by increasing adherence, reducing drug wastage and promoting prescriptive appropriateness.

Evaluation of acromegaly treatment direct costs with respect to biochemical control and follow-up length.

PURPOSE: Acromegaly is a severe chronic endocrine disease. Achieving biochemical control often needs a multimodal treatment approach, including prolonged medical treatment. Aim of the study is to evaluate the burden of treatment direct costs with respect to the different therapeutic strategies, disease control, and follow-up length. METHODS: Single center retrospective study on 73 acromegaly patients. Costs of acromegaly treatments were computed based on a detailed revision of patients' clinical charts. RESULTS: Median total treatment cost/patient was €47,343 during the entire follow-up (8 years), while median treatment cost/patient/year was €6811. The majority of patients received medical therapy (71/73, 97.3%). Median cost for first-line medical treatment (first-generation somatostatin receptor ligands) was lower compared to second-line treatments (pegvisomant monotherapy or combination therapies), considering both total (€22,824 vs €76,140; p < 0.001), and yearly cost/patient (€4927 vs €9161; p < 0.001). Sixty patients (82.2%) reached biochemical control at last follow-up (IGF-1 ≤ 1 xULN). The percentage of patients treated with first- or second-line medical therapies was comparable between controlled and uncontrolled patients (p = 1.000), and the yearly cost/patient did not significantly differ between the two groups (€6936 vs €6680; p = 0.829). Follow-up duration was significantly longer in controlled patients compared to the uncontrolled ones (8.7 vs 3.5 years; p = 0.019). CONCLUSIONS: Direct costs for the management of acromegaly have a significant burden on the healthcare systems. However, more than 80% of our patients reached biochemical control using multimodal approaches. Treatment modalities and yearly costs did not significantly differ between controlled and uncontrolled patients, while follow-up length represented a major determinant of biochemical outcome.

Economic burden of growth hormone deficiency in a US pediatric population.

BACKGROUND: Pediatric growth hormone deficiency (GHD) is a rare disorder of short stature that is currently treated with daily injections of somatropin. In addition to short stature, GHD is associated with other comorbidities such as impaired musculoskeletal development, cardiovascular disease, and decreased quality of life. OBJECTIVE: To analyze somatropin utilization, adherence, and health care costs among children with GHD who had either Medicaid or commercial health insurance. METHODS: Children (aged < 18 years) with a GHD diagnosis between January 1, 2008, and December 31, 2017, were identified in the IBM MarketScan Commercial and Medicaid databases. Patients with at least 12- and 6-month continuous enrollment pre- and postdiagnosis were eligible. Children with GHD were direct matched (1:3) to controls without GHD (or other short stature-related disorders) on age, gender, plan type, region, and race (Medicaid only). Index date was the date of the first GHD diagnosis during the selection window for GHD patients and using random assignment for controls. Patients were followed until the end of continuous database enrollment or December 31, 2018. Baseline comorbidities and medications were measured during the 12 months pre-index, whereas somatropin treatment patterns along with all-cause and GHD-related health care costs were measured during the variable follow-up period. Multivariable modeling was used to compare costs between GHD patients and controls and between somatropin-treated and -untreated GHD patients while adjusting for baseline characteristics. RESULTS: There were 6,820 Medicaid and 14,070 commercial patients with GHD who met the study inclusion criteria. Mean (SD) age at index was 9.5 (4.5) years for Medicaid patients and 11.1 (3.7) years for commercial patients. The majority of patients were male (> 65%), and mean follow-up time for all cases and controls was 3-4 years. Overall, 63.2% of Medicaid and 68.4% of commercial GHD patients were treated with somatropin at some point during follow-up. Among Medicaid GHD patients, the treatment rate was highest among White males and lowest among Black females. Adherence was low as the proportion of days covered was ≥ 80% for only 18.4% of Medicaid patients and 32.3% of commercial patients and 49.1% of treated Medicaid and 24.3% of treated commercial patients discontinued before turning age 13. After adjusting for baseline characteristics, all-cause non-somatropin annualized costs were 5.67 times higher (Δ$19,309) for Medicaid GHD patients and 5.46 times higher (Δ$12,305) for commercial GHD patients than matched non-GHD controls. Adjusted all-cause non-somatropin annualized costs were 0.59 times lower (Δ$14,416) for treated Medicaid patients and 0.69 times lower (Δ$7,650) for treated commercial patients than for untreated patients. CONCLUSIONS: Pediatric GHD presents a significant health care burden, and many patients remain untreated or undertreated. Untreated GHD was associated with higher non-somatropin health care costs than treated GHD. Strategies to optimize treatment and improve adherence may reduce the health care burden faced by these patients. DISCLOSURES: This study was funded by Ascendis Pharma, Inc. Smith and Pitukcheewanont are employed by Ascendis Pharma, Inc. Manjelievskaia, Lopez-Gonzalez, and Morrow are employed by IBM Watson Health, which received funding from Ascendis Pharma, Inc., to conduct this study. Kaplowitz is a paid consultant of Ascendis Pharma, Inc.

Review of economic analysis of available interventions on idiopathic short stature: A protocol for systematic review and meta-analysis.

BACKGROUND: Idiopathic short stature (ISS) causes a high economic burden worldwide. As part of a research project that synthesizes economic evidence for Korean medicine treatment of ISS, we describe the methods that will be used for the comprehensive review of articles that analyze health-related economic evaluation for available interventions for ISS using a systematic review methodology. METHODS: Eight electronic English, Korean, and Chinese databases will be searched from their inception until December 2020 to identify studies on the economic evaluation of available interventions on ISS, without language, study design, or publication status restrictions. From the included studies, the effectiveness, utility, and cost data will be collected as the outcome measures by two researchers independently. Descriptive analysis of individual studies will be conducted. If it is judged that the interventions and outcomes of the included studies are sufficiently homogeneous, we will attempt a quantitative synthesis through meta-analysis using Review Manager version 5.4 software (Cochrane, London, UK). RESULTS: This study will summarize the evidence regarding the economic evaluation of available interventions for ISS. CONCLUSIONS: The findings of this review will help clinicians and patients in evidence-based decision-making in clinical settings and help policy makers develop effective policies and distribute resources based on the available evidence.

Important Tools for Use by Pediatric Endocrinologists in the Assessment of Short Stature

Assessment and management of children with growth failure has improved greatly over recent years. However, there remains a strong potential for further improvements by using novel digital techniques. A panel of experts discussed developments in digitalization of a number of important tools used by pediatric endocrinologists at the third 360° European Meeting on Growth and Endocrine Disorders, funded by Merck KGaA, Germany, and this review is based on those discussions. It was reported that electronic monitoring and new algorithms have been devised that are providing more sensitive referral for short stature. In addition, computer programs have improved ways in which diagnoses are coded for use by various groups including healthcare providers and government health systems. Innovative cranial imaging techniques have been devised that are considered safer than using gadolinium contrast agents and are also more sensitive and accurate. Deep-learning neural networks are changing the way that bone age and bone health are assessed, which are more objective than standard methodologies. Models for prediction of growth response to growth hormone (GH) treatment are being improved by applying novel artificial intelligence methods that can identify non-linear and linear factors that relate to response, providing more accurate predictions. Determination and interpretation of insulin-like growth factor-1 (IGF-1) levels are becoming more standardized and consistent, for evaluation across different patient groups, and computer-learning models indicate that baseline IGF-1 standard deviation score is among the most important indicators of GH therapy response. While physicians involved in child growth and treatment of disorders resulting in growth failure need to be aware of, and keep abreast of, these latest developments, treatment decisions and management should continue to be based on clinical decisions. New digital technologies and advancements in the field should be aimed at improving clinical decisions, making greater standardization of assessment and facilitating patient-centered approaches.

Effectiveness, economical and safety aspects of growth hormone (GH) therapy in growth promoting doses in patients with isolated GH deficiency after the attainment of near-final height. Is there a need to modify the criteria of therapy withdrawal?

INTRODUCTION: Apart from growth promotion, growth hormone (GH) has important metabolic effects. Patients with severe GH deficiency (GHD) should be treated with GH throughout life. Current criteria for growth promoting therapy withdrawal in Poland differ from the latest recommendations. Aim of the study To assess cost-effectiveness and safety of continuation of GH therapy in growth promoting doses in patients with isolated GHD after the attainment of near-final height (near-FH) and the incidence of persistent GHD after the therapy withdrawal. MATERIAL AND METHODS: 160 children with isolated GHD (height < 3 centile, GH peak < 10.0 µg/l), who continued GH therapy for growth promotion after the attainment of near-FH (height velocity   2.0) at near-FH and incidence of severe GHD in retesting (performed in 62 patients). RESULTS: Height gain after near-FH was 1.1 ±0.8 cm in boys and 1.0 ±0.8 in girls. Increase of height by 1.0 cm required on average 487 mg of GH (264 injections). IGF-1 concentrations at near-FH were increased in 39 patients, with no clinical side effects. None of the patients retested had GH peak   10.0 µg/l. CONCLUSIONS: There is no rationale to continue GH therapy in growth promoting doses in the patients with isolated GHD after fulfilling the criteria of near-FH.

The effectiveness of growth hormone replacement on energy expenditure and body composition in patients with adult growth hormone deficiency.

Numerous studies have shown that growth hormone (GH) replacement in adult GH deficiency (AGHD) improves the body composition and metabolic rate; however, data about the relationship between body composition and energy expenditure in these patients is scarce. Our study aimed to investigate the changes in resting energy expenditure (REE) and body composition after GH replacement in patients with AGHD. We enrolled 15 patients diagnosed with AGHD and evaluated the effect of GH replacement administered once daily for 12 months on REE, body composition measured by bioelectrical impedance analysis, and serological markers. GH replacement therapy significantly increased the serum insulin growth factor-1 levels after 4, 8, and 12 months. The REE and REE/basal energy expenditure (REE/BEE) ratio significantly increased from 1278.0 ± 490.0 kcal/day and 0.87 ± 0.23 at baseline to 1505.5 ± 449.2 kcal/day and 1.11 ± 0.21 at 4 months, 1,918.7 ± 631.2 kcal/day and 1.29 ± 0.27 at 8 months, and 1,511.1 ± 271.2 kcal/day, 1.14 ± 0.29 at 12 months (p < 0.005, p < 0.005; p < 0.01, p < 0.01; p < 0.01, p < 0.005, respectively). There was no change in the body weight, while the lean body mass increased significantly from 45.8 ± 9.5 kg at baseline to 46.9 ± 9.4 kg at 4 months and 47.5 ± 10.1 kg at 8 months (p < 0.005, p < 0.01, respectively). The fat mass also decreased at 12 months. Lipid metabolism improved after 4 and 8 months. GH replacement therapy in patients with AGHD significantly improved the REE and body composition.

Effect of growth hormone therapy on thyroid function in isolated growth hormone deficient and short small for gestational age children: a two-year study, including on assessment of the usefulness of the thyrotropin-releasing hormone (TRH) stimulation test.

Background The relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy. Methods We retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3). Results In groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy. Conclusions GH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.

Cost-effectiveness analysis of second-line pharmacological treatment of acromegaly in Spain.

Objective: To estimate the cost-effectiveness of second-line pharmacological treatments in patients with acromegaly resistant to first-generation somatostatin analogues (FG SSA) from the Spanish National Health System (NHS) perspective.Methods: A Markov model was developed to analyze the cost-effectiveness of pegvisomant and pasireotide in FG SSA-resistant acromegaly, simulating a cohort of patients from the treatment beginning to death. Treatment with pegvisomant or pasireotide was compared to FG SSA retreatment. Efficacy data were obtained from clinical trials and utilities from the literature. Direct health costs were obtained from Spanish sources (€2018).Results: The Incremental Cost Effectiveness Ratio (ICER) of pegvisomant vs. FG SSA was €85,869/Quality-adjusted life years (QALY). The ICER of pasireotide vs. FG SSA was €551,405/QALY. The ICER was mainly driven by the incremental efficacy (4.41 QALY for pegvisomant vs. FG SSA and 0.71 QALY for pasireotide vs. FG SSA), with a slightly lower increase in costs with pegvisomant (€378,597 vs. FG SSA) than with pasireotide (€393,151 vs. FG SSA).Conclusion: The ICER of pasireotide compared to FG SSA was six times higher than the ICER of pegvisomant vs. FG SSA. Pegvisomant is a more cost-effective alternative for the treatment of acromegaly in FG SSA-resistant patients in the Spanish NHS.

Assessment of anterior-posterior spinal curvatures in children suffering from hypopituitarism.

BACKGROUND: Body posture may be disordered by vestibular dysfunction, neurological disorders, problems with the distribution of muscle tone, brain injuries, and other dysfunctions. Growth hormone deficiency (GHD) can lead to many disorders, particularly of the musculoskeletal system. During treatment with recombinant human growth hormone (rhGH), an increase in muscle mass and an improvement in bone structure can be observed in children suffering from hypopituitarism from GHD. METHODS: The study involved 33 children suffering from hypopituitarism with GHD (9 girls and 24 boys), aged 10-14 years old. Measurements of the magnitude of their anterior-posterior spinal curvatures were made using an inclinometer. The children were examined at the medianus of the sacrum bone, the Th12-L1 intervertebral area, and the C7-Th1 intervertebral area. In order to characterize the anterior-posterior curvature of the spine, the results were compared with the general norms reported by Saunders. Statistical calculations were carried out using the statistical package Statistica 10 PL. RESULTS: Lumbar lordosis angles were higher in the patients currently receiving growth hormone (GH) treatment than in those who had yet to receive it. There is a statistically significant positive correlation between the length of growth hormone treatment and the alpha angle. There are also statistically significant correlations between age at the beginning of growth hormone therapy and the angle of lordosis. Statistically significant correlations were also seen between age at the beginning of growth hormone therapy and the alpha angle. CONCLUSIONS: Although there may be changes in posture at the beginning of rhGH treatment, the sooner growth hormone therapy begins, the better the body posture. The longer the growth hormone treatment, the better the posture, as expressed by the alpha angle in the sagittal plane.

Effect of growth hormone treatment on energy expenditure and its relation to first-year growth response in children.

PURPOSE: The effects of growth hormone (GH) treatment on linear growth and body composition have been studied extensively. Little is known about the GH effect on energy expenditure (EE). The aim of this study was to investigate the effects of GH treatment on EE in children, and to study whether the changes in EE can predict the height gain after 1 year. METHODS: Total EE (TEE), basal metabolic rate (BMR), and physical activity level (PAL) measurements before and after 6 weeks of GH treatment were performed in 18 prepubertal children (5 girls, 13 boys) born small for gestational age (n = 14) or with growth hormone deficiency (n = 4) who were eligible for GH treatment. TEE was measured with the doubly labelled water method, BMR was measured with an open-circuit ventilated hood system, PAL was assessed using an accelerometer for movement registration and calculated (PAL = TEE/BMR), activity related EE (AEE) was calculated [AEE = (0.9 × TEE) - BMR]. Height measurements at start and after 1 year of GH treatment were analysed. This is a 1-year longitudinal intervention study, without a control group for comparison. RESULTS: BMR and TEE increased significantly (resp. 5% and 7%). Physical activity (counts/day), PAL, and AEE did not change. 11 out of 13 patients (85%) with an increased TEE after 6 weeks of GH treatment had a good first-year growth response (∆height SDS > 0.5). CONCLUSIONS: GH treatment showed a positive effect on EE in prepubertal children after 6 weeks. No effect on physical activity was observed. The increase in TEE appeared to be valuable for the prediction of good first-year growth responders to GH treatment.