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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Endocrinol.</journal-id>
<journal-title>Frontiers in Endocrinology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Endocrinol.</abbrev-journal-title>
<issn pub-type="epub">1664-2392</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fendo.2024.1371424</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Endocrinology</subject>
<subj-group>
<subject>General Commentary</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Commentary: Postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement in patients with childhood-onset craniopharyngioma</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Andereggen</surname>
<given-names>Lukas</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/853567"/>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Christ</surname>
<given-names>Emanuel</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/938000"/>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
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</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Department of Neurosurgery, Kantonsspital Aarau</institution>, <addr-line>Aarau</addr-line>, <country>Switzerland</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Faculty of Medicine, University of Bern</institution>, <addr-line>Bern</addr-line>, <country>Switzerland</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Department of Endocrinology, Diabetology and Metabolism, University Hospital of Basel</institution>, <addr-line>Basel</addr-line>, <country>Switzerland</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Elena Varlamov, Oregon Health and Science University, United States</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Giulia Rodari, IRCCS Ca &#x2018;Granda Foundation Maggiore Policlinico Hospital, Italy</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Lukas Andereggen, <email xlink:href="mailto:lukas.andereggen@ksa.ch">lukas.andereggen@ksa.ch</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>27</day>
<month>02</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>15</volume>
<elocation-id>1371424</elocation-id>
<history>
<date date-type="received">
<day>16</day>
<month>01</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>15</day>
<month>02</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2024 Andereggen and Christ</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Andereggen and Christ</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<related-article id="RA1" related-article-type="commentary-article" xlink:href="10.3389/fendo.2023.1241145" ext-link-type="doi">A Commentary on <article-title>Postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement in patients with childhood-onset craniopharyngioma</article-title> by Miao Y, Fan K, Peng X, Li S, Chen J, Bai RN, Wei Y, Deng Y, Zhao C, Wu Q, Ge M, Gong J and Wu D (2023) <italic>Front. Endocrinol.</italic> 14:1241145. doi:&#xa0;<object-id>10.3389/fendo.2023.1241145</object-id>
</related-article>
<kwd-group>
<kwd>craniopharyngioma</kwd>
<kwd>hormone replacement therapy</kwd>
<kwd>obesity</kwd>
<kwd>hypothalamic involvement</kwd>
<kwd>recurrence</kwd>
<kwd>neuropsychological health</kwd>
</kwd-group>
<counts>
<fig-count count="0"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="32"/>
<page-count count="4"/>
<word-count count="1108"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Pituitary Endocrinology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<p>We read with great interest the article by Miao et&#xa0;al. (<xref ref-type="bibr" rid="B1">1</xref>) reporting the long-term results of patients who underwent surgery for childhood-onset (CO) craniopharyngioma (CP). The number of patients included in the study is impressive, with 200 CP patients having CO. However, long-term follow-up data (median 29.7 months, range 19.0 to 40.3) was available for only about one third (71 patients, 36%), and among them, only 62 patients (31%) had documented regular visits at the endocrine department. The study recorded significant endocrinological sequelae post-surgery, with 94% of the 62 patients having undergone at least one form of hormone replacement therapy during the noted long-term follow-up. Miao et&#xa0;al. eloquently detailed the treatment plan for patients with endocrine dysfunction, emphasizing the crucial role of monitoring by an experienced pediatric endocrinologist. In addition to detailing the subsequent hormonal replacement therapy and the recorded tumor recurrence rate in 18 (26%) patients, it is crucial to incorporate long-term strategies into the adjuvant treatment plan in this patient cohort. Namely, in a comprehensive 10-year follow-up study of CP patients, we observed significant occurrences of hypothalamic obesity (HO) and enduring endocrine deficiencies (<xref ref-type="bibr" rid="B2">2</xref>). In addition to ongoing monitoring of endocrine deficiencies, it is imperative to implement early weight control programs and maintain continuous multidisciplinary care for this patient cohort (<xref ref-type="bibr" rid="B2">2</xref>).</p>
<p>As suffering from CP is currently a chronic, lifelong condition, the incorporation of long-term follow-up data as an outcome measure is essential to ensure and validate the therapy&#x2019;s long-term safety and efficacy. It serves as a vital control mechanism for evaluating and adjusting the provided medical treatment (<xref ref-type="bibr" rid="B3">3</xref>). In particular, being a chronic disease (<xref ref-type="bibr" rid="B4">4</xref>), it highlights the necessity of conducting extended follow-up studies on the outcomes of surgical interventions to understand the sequelae experienced by individuals with CP over time. Namely, beside to the potential lifelong morbidity caused by the tendency of CP for local recurrence (<xref ref-type="bibr" rid="B5">5</xref>), it&#x2019;s important to note risk factors that affect resection rates (i.e. prior radiation, tumor size) (<xref ref-type="bibr" rid="B6">6</xref>&#x2013;<xref ref-type="bibr" rid="B8">8</xref>), recurrences (i.e. extent of resection, tumor size), and the quality of life (QoL, i.e. tumor size and entity, surgical approach, vision impairment, endocrine dysfunction, hypothalamic involvement) (<xref ref-type="bibr" rid="B9">9</xref>&#x2013;<xref ref-type="bibr" rid="B12">12</xref>) during a longitudinal follow-up period. Regarding the likelihood of recurrence following transsphenoidal compared to transcranial approach, it would be intriguing to delve into more detailed information, such as the extent of tumor resection or the initial size of the tumor (<xref ref-type="bibr" rid="B1">1</xref>).</p>
<p>In terms of the specified hormonal replacement therapy, the use of recombinant growth hormone (rGH) therapy in CP patients has been found to be safe, with no reported association with the recurrence or progression of pituitary adenoma or benign tumors (<xref ref-type="bibr" rid="B13">13</xref>). Although traditionally a waiting period of at least one year for stable disease is recommended for malignant lesions, recent evidences suggest that this interval could be as short as three months for children with radiologically confirmed stable CP, especially those with significant growth failure and metabolic disturbances, as specified in the childhood cancer survivors (CCS) Consensus Statement (<xref ref-type="bibr" rid="B14">14</xref>). For children who have stable disease and concomitant GH deficiency, it is recommended to consider rGH therapy, which serves not only to improve adult height but also offers valuable metabolic benefits (<xref ref-type="bibr" rid="B15">15</xref>). Furthermore, it is cautioned against substituting ACTH deficiency with prednisolone in children due to the well-documented growth impairment associated with it (<xref ref-type="bibr" rid="B16">16</xref>). Additionally, the diagnosis of central hypothyroidism depends on low free thyroxine levels combined with inappropriately normal or low levels of thyroid-stimulating hormone (TSH), rather than relying solely on low TSH levels (<xref ref-type="bibr" rid="B17">17</xref>).</p>
<p>Traditionally, treatment strategies for CP have favored a radical approach involving gross-total resection, aiming to cure CP patients. We noted that none of the CPs recurred after gross total resection, compared to about one-fifth of patients following subtotal resection (<xref ref-type="bibr" rid="B2">2</xref>). However, evolving insights into risk-adapted therapy regimens have emerged over time, particularly for unfavorably located CP with hypothalamic involvement (HI) (<xref ref-type="bibr" rid="B18">18</xref>). The hypothalamic syndrome encompassing sleep-wake cycle disorders, temperature dysregulation, behavioral problems, and hypothalamic obesity (HO), poses significant challenges in the treatment strategy of CP patients (<xref ref-type="bibr" rid="B19">19</xref>). Namely, HO associated with impaired QoL are frequent and severe disabilities among CP patients (<xref ref-type="bibr" rid="B19">19</xref>). Therefore, strategies that spare the hypothalamus are highly recommended (<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B21">21</xref>), balancing radical resection for maximum safety with adjuvant treatment to control the disease in pediatric CP cases (<xref ref-type="bibr" rid="B22">22</xref>). Consequently, outcome parameters such as assessing HO are of paramount importance. Miao et&#xa0;al. (<xref ref-type="bibr" rid="B1">1</xref>) observed obesity in 54% of patients with recorded follow-up, while at baseline, it was noted in 76 out of 200 patients (38%). It can be assumed that weight gain was a substantial issue in this patient cohort. However, in CO cases, age-specific changes in weight gain and metabolic parameters should also be considered (<xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B24">24</xref>), as they have been reported to significantly change during long-term follow-ups (<xref ref-type="bibr" rid="B2">2</xref>).</p>
<p>Regarding the comprehensive assessment of hypothalamic-pituitary dysfunction, evaluating treatment-related lesions of the optic apparatus and endocrine deficiencies only partially captures the therapeutic challenges in CP patients. This condition, especially in CO cases, is a chronic, incurable disease with anticipated lifelong effects, necessitating ongoing and multidisciplinary care for proper management of clinical and neuropsychological sequelae post-surgery. The assertion by the authors that ensuring adequate pituitary hormone replacement therapy and increasing engagement in sports activities are effective in managing postoperative obesity (<xref ref-type="bibr" rid="B25">25</xref>) is an overstatement. Namely, regarding the treatment of HO in CO CP patients, the results are ambiguous. While pharmacotherapies (<xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B27">27</xref>) and bariatric procedures (<xref ref-type="bibr" rid="B28">28</xref>) demonstrate varying efficacy (<xref ref-type="bibr" rid="B29">29</xref>), none have been proven effective in randomized controlled trials (<xref ref-type="bibr" rid="B30">30</xref>). Thus, the impact of HO on quality of life and neuropsychological health, including social functioning during education and independent living, is considerable for long-term survivors (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B31">31</xref>, <xref ref-type="bibr" rid="B32">32</xref>). Therefore, it is advisable to prevent HO throughout hypothalamus-sparing surgical and radio-oncological strategies (<xref ref-type="bibr" rid="B21">21</xref>).</p>
<p>In summary, the treatment strategies for CO CP patients involve various complexities. Long-term follow-up studies are crucial to validate therapy effectiveness and ensure safety in managing this chronic disease. Strategies sparing the hypothalamus are advised to balance radical resection with the need for effective disease control. The impact of HO on patients&#x2019; quality of life is substantial, necessitating ongoing multidisciplinary care post-surgery. However, treatments for HO, such as pharmacotherapies and bariatric procedures, exhibit diverse effectiveness, emphasizing the need for further exploration in improving the well-being of long-term CP survivors.</p>
<sec id="s1" sec-type="author-contributions">
<title>Author contributions</title>
<p>LA: Conceptualization, Writing &#x2013; original draft, Writing &#x2013; review &amp; editing. EC: Conceptualization, Writing &#x2013; review &amp; editing.</p>
</sec>
</body>
<back>
<sec id="s2" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article. No funding was received.</p>
</sec>
<sec id="s3" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s4" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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