Editorial
Two decades of growth hormone treatment in adulthood
Dos décadas de tratamiento con hormona de crecimiento en la edad adulta
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"Two decades of growth hormone treatment in adulthood" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "55" "paginaFinal" => "57" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Jordi Mesa, Carlos del Pozo" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Jordi" "apellidos" => "Mesa" "email" => array:1 [ 0 => "jmesa@vhebron.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Carlos" "apellidos" => "del Pozo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Hospital Universitario Vall d’Hebron, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Hospital Universitario Mútua de Terrassa, Terrassa, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Dos décadas de tratamiento con hormona de crecimiento en la edad adulta" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Adult growth hormone deficiency (AGHD) has been recognized for almost 20 years as a specific syndrome<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> consisting of changes in body composition, increased cardiovascular risk and mortality, decreased exercise tolerance, and impaired bone mineral composition and health-related quality of life (HRQoL).</p><p id="par0010" class="elsevierStylePara elsevierViewall">AGHD has multiple causes, among which tumors are the most common. Other associated pituitary hormone deficiencies are found in a majority of cases. AGHD also includes cases of GHD starting in childhood that persist into adulthood.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The availability of recombinant GH (rGH) from 1985 led to early studies on its benefits in adulthood, and showed that most manifestations of the syndrome improved with replacement therapy.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> Based on these studies, treatment with rGH of adults with GHD was approved by the European Medicine Agency in 1995, by the US FAD in 1996, and in Spain one year later.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the subsequent 20 years of use of rGH, a very high number of patients have been treated, and efficacy and safety data additional to those collected in pre-approval clinical trials are therefore available.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Favorable short- and mid-term effects, up to the first three years of treatment, on body composition, lipid profile, muscle strength, bone mineral remodeling and density, cognitive function, and HRQoL have been clearly established.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> Many studies are available on the short-term benefits, and there is little doubt in this regard. By contrast, few long-term studies with at least five years of treatment have been conducted. Most data come from observational postmarketing studies, mainly the Pfizer International Metabolic Database and the Hypopituitary Control and Complications Study, some national registers, and some series, usually retrospective.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4–6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Long-term benefits include those related to body composition, including increased lean mass and decreased fat mass as measured by DEXA, which has been shown to be the best method currently available, despite the fact that it does not allow for calculating the body water compartment. This improved body composition results in increased muscle strength during the first five years of treatment which does not persist in some studies, but may provide these patients with some protection against the general effects of decline characteristic of aging. These changes are more marked in males as compared to females, with similar IGF-1 levels.</p><p id="par0035" class="elsevierStylePara elsevierViewall">As regards bone mineral density, the increases reported range from 4% to 10% depending on the series, mainly occur in trabecular bone, and are more marked in males. Ten-year studies continue to show this positive effect, but the femoral neck appears to stabilize from the fifth year. Unfortunately, no randomized, controlled studies are available showing fracture rate reductions in patients treated with rGH.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Improvement in HRQoL and psychological well-being was another aspect in which the treatment was considered positive, given that it was approved. The experience accumulated over this period suggests that the effects on HRQoL are very heterogeneous: there are both patients with normal HRQoL scores at baseline who do not therefore improve, and others with great initial impairments who show dramatic responses. Overall, it may be stated that patients with poorer baseline scores will experience the greatest improvements, and that patients with GHD starting in childhood usually have normal scores, and no improvement is thus achieved.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The increased cardiovascular morbidity and mortality reported in patients with GHD has been related to an unfavorable pattern in both traditional and emerging cardiovascular risk factors.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> In most studies reported, treatment with rGH has a beneficial effect on most factors, especially on lipid profile, with reductions in both total and LDL cholesterol and improved HDL and triglyceride levels.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">3,8</span></a> Using the Framingham and European Cardiology Society scoring systems, cardiovascular risk has been found to be reduced by up to a half after two years of treatment.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Few studies have been reported relating treatment with rGH to cardiovascular and cerebrovascular morbidity and mortality, and their conclusions regarding the benefits achieved are far from being unanimous.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> Unexpectedly, the four studies with the largest patient samples found no decrease in morbidity and mortality as compared to the untreated group. These results have created some controversy and have been attributed to multiple reasons, including study duration, lack of information about other factors, and even concomitant medications. Despite the limitations of the available data, there is currently insufficient evidence to recommend treatment with rGH based on the cardiovascular status of patients.</p><p id="par0055" class="elsevierStylePara elsevierViewall">As regards the safety of treatment with rGH, the greatest concern is its potential to increase or promote the occurrence of cancer. Although there have been some reports suggesting a potential increase in some tumor types in adults treated with GH during childhood,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> most follow-up studies have not shown such an increase,<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">11,12</span></a> but longer studies will be required to confirm this.</p><p id="par0060" class="elsevierStylePara elsevierViewall">There has also been concern about the effect on carbohydrate metabolism. Although treatment with rGH decreases visceral fat, it also causes decreased insulin sensitivity in the short term. Although this is not a generalized effect, rGH may induce in some patient subgroups impaired blood glucose levels, and even the occurrence of diabetes in a small proportion of patients.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">13,14</span></a> This requires special monitoring during treatment, and the use of rGH is not recommended in diabetic patients.</p><p id="par0065" class="elsevierStylePara elsevierViewall">In pharmacoeconomic terms, the benefits of replacement therapy in deficient adult patients result in improvements in quality of life tests. Various studies, particularly those related to large long-term follow-up registers such as the Pfizer International Metabolic Database, have found a positive economic evaluation related to the decreased use of healthcare system resources and the reduction in work time lost and disability in these patients. These data support the value of this treatment also from the economic viewpoint.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In Spain, the prescription of rGH to both children and adults has been subject to special regulation and control by regional departments of health because of its high price and potential misuse. Thus, the different regional authorities created advisory committees or boards of experts intended to verify that prescriptions were for the approved indications and were based on the established diagnostic criteria, and to ensure monitoring of their efficacy. A second control mechanism was added at national level by which the drug could only be dispensed by hospital pharmacies. This surveillance by the corresponding committees was generally very well accepted by the prescribing professionals, whose prescriptions were supported. The governments of some regions, such as Catalonia, have now eliminated their advisory committees and have transferred prescription and expense control to each hospital.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In recent years, biosimilar drugs, copies of biotechnological preparations whose patent has expired, have been approved for clinical use. Approval is based on the consideration that they are therapeutic equivalents to the innovative agents in terms of both safety and efficacy. The first such drug approved by the European Medicines Agency was a biosimilar for Genotropin<span class="elsevierStyleSup">®</span> in 2006, and according to regulations it is approved for all indications of the original drug in both children and adults.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The main doubts about these preparations relate to safety, as biosimilars have not undergone the long drug surveillance periods that the original drugs did. In the PATRO Adults (SAN-SOM-2011-02) postmarketing surveillance study, currently ongoing, it is planned to recruit 1500 adults with hypopituitarism treated for a period of 5 years. On the other hand, the advent of these preparations, with the resultant price competition, has caused adjustments in the market and decreased the high costs, which will undoubtedly contribute to the financial sustainability of healthcare systems. It should be noted in this regard that the applicable Spanish regulations prevent the automatic replacement of an innovative drug by a biosimilar, and only the prescribing physician may make such a replacement if deemed appropriate.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The experience accumulated over almost 20 years of treatment with rGH in adults, and in a shorter time in children, confirms its benefits in patients with GHD. Moreover, rGH has a good safety profile and does not usually cause adverse effects when used in individualized doses and with adequate monitoring. Future challenges include a deeper understanding of its efficacy, especially as regards mortality reduction, long-term safety, and improvements in the selection of patients who may benefit from this treatment.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0090" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Mesa J, del Pozo C. Dos décadas de tratamiento con hormona de crecimiento en la edad adulta. Endocrinol Nutr. 2016;63:55–57.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The growth hormone deficiency syndrome in adults" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "T.R.C. Cuneo" 1 => "F. Salomon" 2 => "G.A. MacGauley" 3 => "P.H. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 1 | 8 |
| 2024 October | 32 | 6 | 38 |
| 2024 September | 26 | 4 | 30 |
| 2024 August | 29 | 1 | 30 |
| 2024 July | 29 | 4 | 33 |
| 2024 June | 22 | 1 | 23 |
| 2024 May | 24 | 2 | 26 |
| 2024 April | 33 | 9 | 42 |
| 2024 March | 40 | 1 | 41 |
| 2024 February | 56 | 14 | 70 |
| 2024 January | 52 | 3 | 55 |
| 2023 December | 46 | 6 | 52 |
| 2023 November | 48 | 11 | 59 |
| 2023 October | 57 | 11 | 68 |
| 2023 September | 47 | 5 | 52 |
| 2023 August | 51 | 8 | 59 |
| 2023 July | 52 | 17 | 69 |
| 2023 June | 57 | 8 | 65 |
| 2023 May | 101 | 6 | 107 |
| 2023 April | 62 | 8 | 70 |
| 2023 March | 60 | 9 | 69 |
| 2023 February | 41 | 11 | 52 |
| 2023 January | 62 | 38 | 100 |
| 2022 December | 32 | 13 | 45 |
| 2022 November | 42 | 11 | 53 |
| 2022 October | 46 | 19 | 65 |
| 2022 September | 46 | 22 | 68 |
| 2022 August | 38 | 23 | 61 |
| 2022 July | 17 | 11 | 28 |
| 2022 June | 63 | 10 | 73 |
| 2022 May | 54 | 11 | 65 |
| 2022 April | 30 | 12 | 42 |
| 2022 March | 33 | 15 | 48 |
| 2022 February | 33 | 15 | 48 |
| 2022 January | 39 | 15 | 54 |
| 2021 December | 39 | 13 | 52 |
| 2021 November | 33 | 10 | 43 |
| 2021 October | 22 | 10 | 32 |
| 2021 September | 27 | 11 | 38 |
| 2021 August | 22 | 2 | 24 |
| 2021 July | 9 | 10 | 19 |
| 2021 June | 21 | 12 | 33 |
| 2021 May | 20 | 5 | 25 |
| 2021 April | 33 | 18 | 51 |
| 2021 March | 29 | 12 | 41 |
| 2021 February | 41 | 8 | 49 |
| 2021 January | 30 | 4 | 34 |
| 2020 December | 23 | 9 | 32 |
| 2020 November | 24 | 9 | 33 |
| 2020 October | 16 | 7 | 23 |
| 2020 September | 17 | 13 | 30 |
| 2020 August | 18 | 12 | 30 |
| 2020 July | 24 | 13 | 37 |
| 2020 June | 10 | 7 | 17 |
| 2020 May | 16 | 5 | 21 |
| 2020 April | 13 | 2 | 15 |
| 2020 March | 21 | 4 | 25 |
| 2020 February | 19 | 4 | 23 |
| 2020 January | 11 | 6 | 17 |
| 2019 December | 23 | 9 | 32 |
| 2019 November | 7 | 12 | 19 |
| 2019 October | 6 | 12 | 18 |
| 2019 September | 13 | 5 | 18 |
| 2019 August | 9 | 12 | 21 |
| 2019 July | 13 | 26 | 39 |
| 2019 June | 25 | 19 | 44 |
| 2019 May | 113 | 40 | 153 |
| 2019 April | 10 | 13 | 23 |
| 2019 March | 9 | 4 | 13 |
| 2019 February | 13 | 9 | 22 |
| 2019 January | 15 | 2 | 17 |
| 2018 December | 14 | 3 | 17 |
| 2018 November | 27 | 1 | 28 |
| 2018 October | 10 | 4 | 14 |
| 2018 September | 17 | 6 | 23 |
| 2018 August | 13 | 1 | 14 |
| 2018 July | 4 | 2 | 6 |
| 2018 June | 8 | 2 | 10 |
| 2018 May | 7 | 0 | 7 |
| 2018 April | 9 | 1 | 10 |
| 2018 March | 13 | 2 | 15 |
| 2018 February | 4 | 1 | 5 |
| 2018 January | 16 | 0 | 16 |
| 2017 December | 12 | 0 | 12 |
| 2017 November | 21 | 0 | 21 |
| 2017 October | 11 | 3 | 14 |
| 2017 September | 10 | 2 | 12 |
| 2017 August | 33 | 3 | 36 |
| 2017 July | 19 | 1 | 20 |
| 2017 June | 11 | 1 | 12 |
| 2017 May | 12 | 4 | 16 |
| 2017 April | 21 | 1 | 22 |
| 2017 March | 29 | 30 | 59 |
| 2017 February | 35 | 2 | 37 |
| 2017 January | 8 | 3 | 11 |
| 2016 December | 12 | 4 | 16 |
| 2016 November | 22 | 1 | 23 |
| 2016 October | 27 | 6 | 33 |
| 2016 September | 21 | 2 | 23 |
| 2016 August | 18 | 1 | 19 |
| 2016 May | 0 | 1 | 1 |
| 2016 March | 1 | 0 | 1 |
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