{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:08:02Z","timestamp":1790788082967,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T00:00:00Z","timestamp":1620518400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T00:00:00Z","timestamp":1620518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008349","name":"Universit\u00e4t Duisburg-Essen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008349","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Child Adolesc Psychiatry"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>With this case report we support our medical hypothesis that metreleptin treatment ameliorates starvation related emotional, cognitive and behavioral symptomatology of anorexia nervosa (AN) and show for the first time strong effects in a male patient with AN. A 15.9 year old adolescent with severe AN of eight-month duration was treated off-label with metreleptin. Hyperactivity was assessed with accelerometry. Visual analogue scales (VAS), validated self- and clinician rating scales and lab results tracked changes from baseline to end of the 24-day dosing period and a five-month follow-up. Substantial improvements of mood and eating disorder related cognitions and hyperactivity set in after two days of treatment. During dosing, sub-physiological testosterone and TT3 levels normalized; clinically libido reemerged. Weight did not increase substantially during the dosing period. During follow-up target weight was attained; mood did not deteriorate; hyperactivity ceased. The results substantiate the strong effects seen in female cases and underscore the need for a double-blind placebo-controlled trial to confirm the observed strong, multiple and rapid onset beneficial effects of metreleptin in AN.<\/jats:p>","DOI":"10.1007\/s00787-021-01778-7","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T04:02:39Z","timestamp":1620532959000},"page":"1573-1579","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Rapid amelioration of anorexia nervosa in a male adolescent during metreleptin treatment including recovery from hypogonadotropic hypogonadism"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7992-5684","authenticated-orcid":false,"given":"Jochen","family":"Antel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin","family":"Grabler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Lohkemper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Brandenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Barth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Hinney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Libuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Remy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Milos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Hebebrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,9]]},"reference":[{"issue":"11","key":"1778_CR1","doi-asserted-by":"publisher","first-page":"3861","DOI":"10.1210\/jcem.81.11.8923829","volume":"81","author":"S Grinspoon","year":"1996","unstructured":"Grinspoon S, Gulick T, Askari H, Landt M, Lee K, Anderson E, Ma Z, Vignati L, Bowsher R, Herzog D, Klibanski A (1996) Serum leptin levels in women with anorexia nervosa. J Clin Endocrinol Metab 81(11):3861\u20133863. https:\/\/doi.org\/10.1210\/jcem.81.11.8923829","journal-title":"J Clin Endocrinol Metab"},{"issue":"8990","key":"1778_CR2","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1016\/s0140-6736(95)91955-4","volume":"346","author":"J Hebebrand","year":"1995","unstructured":"Hebebrand J, van der Heyden J, Devos R, Kopp W, Herpertz S, Remschmidt H, Herzog W (1995) Plasma concentrations of obese protein in anorexia nervosa. Lancet 346(8990):1624\u20131625. https:\/\/doi.org\/10.1016\/s0140-6736(95)91955-4","journal-title":"Lancet"},{"issue":"4","key":"1778_CR3","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/sj.mp.4000282","volume":"2","author":"J Hebebrand","year":"1997","unstructured":"Hebebrand J, Blum WF, Barth N, Coners H, Englaro P, Juul A, Ziegler A, Warnke A, Rascher W, Remschmidt H (1997) Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration. Mol Psychiatry 2(4):330\u2013334. https:\/\/doi.org\/10.1038\/sj.mp.4000282","journal-title":"Mol Psychiatry"},{"issue":"8","key":"1778_CR4","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1002\/eat.20875","volume":"44","author":"J Hebebrand","year":"2011","unstructured":"Hebebrand J, Bulik CM (2011) Critical appraisal of the provisional DSM-5 criteria for anorexia nervosa and an alternative proposal. Int J Eat Disord 44(8):665\u2013678. https:\/\/doi.org\/10.1002\/eat.20875","journal-title":"Int J Eat Disord"},{"issue":"6588","key":"1778_CR5","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/382250a0","volume":"382","author":"RS Ahima","year":"1996","unstructured":"Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS (1996) Role of leptin in the neuroendocrine response to fasting. Nature 382(6588):250\u2013252. https:\/\/doi.org\/10.1038\/382250a0","journal-title":"Nature"},{"issue":"2","key":"1778_CR6","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/s0026-0495(99)90037-9","volume":"48","author":"Y Nakai","year":"1999","unstructured":"Nakai Y, Hamagaki S, Kato S, Seino Y, Takagi R, Kurimoto F (1999) Leptin in women with eating disorders. Metabolism 48(2):217\u2013220. https:\/\/doi.org\/10.1016\/s0026-0495(99)90037-9","journal-title":"Metabolism"},{"issue":"4","key":"1778_CR7","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/s00702-002-0800-x","volume":"110","author":"K Holtkamp","year":"2003","unstructured":"Holtkamp K, Mika C, Grzella I, Heer M, Pak H, Hebebrand J, Herpertz-Dahlmann B (2003) Reproductive function during weight gain in anorexia nervosa Leptin represents a metabolic gate to gonadotropin secretion. J Neural Transm (Vienna) 110(4):427\u2013435. https:\/\/doi.org\/10.1007\/s00702-002-0800-x","journal-title":"J Neural Transm (Vienna)"},{"issue":"1","key":"1778_CR8","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/sj.mp.4000478","volume":"4","author":"A Ballauff","year":"1999","unstructured":"Ballauff A, Ziegler A, Emons G, Sturm G, Blum WF, Remschmidt H, Hebebrand J (1999) Serum leptin and gonadotropin levels in patients with anorexia nervosa during weight gain. Mol Psychiatry 4(1):71\u201375. https:\/\/doi.org\/10.1038\/sj.mp.4000478","journal-title":"Mol Psychiatry"},{"issue":"7","key":"1778_CR9","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1210\/jcem.86.7.7685","volume":"86","author":"M Wabitsch","year":"2001","unstructured":"Wabitsch M, Ballauff A, Holl R, Blum WF, Heinze E, Remschmidt H, Hebebrand J (2001) Serum leptin, gonadotropin, and testosterone concentrations in male patients with anorexia nervosa during weight gain. J Clin Endocrinol Metab 86(7):2982\u20132988. https:\/\/doi.org\/10.1210\/jcem.86.7.7685","journal-title":"J Clin Endocrinol Metab"},{"key":"1778_CR10","doi-asserted-by":"publisher","first-page":"769","DOI":"10.3389\/fpsyg.2019.00769","volume":"10","author":"J Hebebrand","year":"2019","unstructured":"Hebebrand J, Milos G, Wabitsch M, Teufel M, Fuhrer D, Buhlmeier J, Libuda L, Ludwig C, Antel J (2019) Clinical trials required to assess potential benefits and side effects of treatment of patients with anorexia nervosa with recombinant human leptin. Front Psychol 10:769. https:\/\/doi.org\/10.3389\/fpsyg.2019.00769","journal-title":"Front Psychol"},{"issue":"11","key":"1778_CR11","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/s41419-018-1129-1","volume":"9","author":"T Ge","year":"2018","unstructured":"Ge T, Fan J, Yang W, Cui R, Li B (2018) Leptin in depression: a potential therapeutic target. Cell Death Dis 9(11):1096. https:\/\/doi.org\/10.1038\/s41419-018-1129-1","journal-title":"Cell Death Dis"},{"issue":"2","key":"1778_CR12","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/0196-9781(96)00025-3","volume":"17","author":"WA Banks","year":"1996","unstructured":"Banks WA, Kastin AJ, Huang W, Jaspan JB, Maness LM (1996) Leptin enters the brain by a saturable system independent of insulin. Peptides 17(2):305\u2013311. https:\/\/doi.org\/10.1016\/0196-9781(96)00025-3","journal-title":"Peptides"},{"issue":"6","key":"1778_CR13","doi-asserted-by":"publisher","first-page":"E1158","DOI":"10.1152\/ajpendo.2000.278.6.E1158","volume":"278","author":"WA Banks","year":"2000","unstructured":"Banks WA, Clever CM, Farrell CL (2000) Partial saturation and regional variation in the blood-to-brain transport of leptin in normal weight mice. Am J Physiol Endocrinol Metab 278(6):E1158\u2013E1165. https:\/\/doi.org\/10.1152\/ajpendo.2000.278.6.E1158","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"1","key":"1778_CR14","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41398-020-00977-1","volume":"10","author":"G Milos","year":"2020","unstructured":"Milos G, Antel J, Kaufmann LK, Barth N, Koller A, Tan S, Wiesing U, Hinney A, Libuda L, Wabitsch M, von Kanel R, Hebebrand J (2020) Short-term metreleptin treatment of patients with anorexia nervosa: rapid on-set of beneficial cognitive, emotional, and behavioral effects. Transl Psychiatry 10(1):303. https:\/\/doi.org\/10.1038\/s41398-020-00977-1","journal-title":"Transl Psychiatry"},{"key":"1778_CR15","volume-title":"The golden cage The enigma of anorexia nervosa, with a new foreword by Catherine Steiner-Adair Ed. D","author":"H Bruch","year":"2001","unstructured":"Bruch H (2001) The golden cage The enigma of anorexia nervosa, with a new foreword by Catherine Steiner-Adair Ed. D. Harvard University Press, Boston"},{"issue":"9900","key":"1778_CR16","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1016\/S0140-6736(13)62094-2","volume":"382","author":"R Parsa-Parsi","year":"2013","unstructured":"Parsa-Parsi R, Blackmer J, Ehni HJ, Janbu T, Kloiber O, Wiesing U (2013) Reconsidering the Declaration of Helsinki. Lancet 382(9900):1246\u20131247. https:\/\/doi.org\/10.1016\/S0140-6736(13)62094-2","journal-title":"Lancet"},{"issue":"3","key":"1778_CR17","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1024\/1422-4917\/a000090","volume":"39","author":"F Keller","year":"2011","unstructured":"Keller F, Grieb J, Ernst M, Sprober N, Fegert JM, Kolch M (2011) Children\u2019s depression rating scale-revised (CDRS-R): development of a German version and psychometric properties in a clinical sample. Z Kinder Jugendpsychiatr Psychother 39(3):179\u2013185. https:\/\/doi.org\/10.1024\/1422-4917\/a000090","journal-title":"Z Kinder Jugendpsychiatr Psychother"},{"key":"1778_CR18","first-page":"979","volume":"21","author":"EO Poznanski","year":"1985","unstructured":"Poznanski EO, Freeman LN, Mokros HB (1985) Children\u2019s depression rating scale revised. Psychopharmacol Bull 21:979\u2013989","journal-title":"Psychopharmacol Bull"},{"key":"1778_CR19","volume-title":"Beck depression inventory\u2014manual","author":"AT Beck","year":"1987","unstructured":"Beck AT, Steer RA (1987) Beck depression inventory\u2014manual. The Psychological Corporation, San Antonio"},{"key":"1778_CR20","volume-title":"Das Beck Depressionsinventar II","author":"M Hautzinger","year":"2006","unstructured":"Hautzinger M, Keller F, K\u00fchner C (2006) Das Beck Depressionsinventar II. Deutsche Bearbeitung und Handbuch zum BDI II Harcourt Test Services, Frankfurt a. M"},{"issue":"9\u201310","key":"1778_CR21","first-page":"365","volume":"47","author":"A Thiel","year":"1997","unstructured":"Thiel A, Jacobi C, Horstmann S, Paul T, Nutzinger DO, Schussler G (1997) A German version of the Eating Disorder Inventory EDI-2. Psychother Psychosom Med Psychol 47(9\u201310):365\u2013376","journal-title":"Psychother Psychosom Med Psychol"},{"issue":"3","key":"1778_CR22","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1093\/ajcn\/75.3.453","volume":"75","author":"DA Fields","year":"2002","unstructured":"Fields DA, Goran MI, McCrory MA (2002) Body-composition assessment via air-displacement plethysmography in adults and children: a review. Am J Clin Nutr 75(3):453\u2013467. https:\/\/doi.org\/10.1093\/ajcn\/75.3.453","journal-title":"Am J Clin Nutr"},{"key":"1778_CR23","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-018-1244-7","author":"R Meister","year":"2018","unstructured":"Meister R, Abbas M, Antel J, Peters T, Pan Y, Bingel U, Nestoriuc Y, Hebebrand J (2018) Placebo response rates and potential modifiers in double-blind randomized controlled trials of second and newer generation antidepressants for major depressive disorder in children and adolescents: a systematic review and meta-regression analysis. Eur Child Adolesc Psychiatry. https:\/\/doi.org\/10.1007\/s00787-018-1244-7","journal-title":"Eur Child Adolesc Psychiatry"},{"issue":"9","key":"1778_CR24","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1177\/1060028013503127","volume":"47","author":"JC Sebaaly","year":"2013","unstructured":"Sebaaly JC, Cox S, Hughes CM, Kennedy ML, Garris SS (2013) Use of fluoxetine in anorexia nervosa before and after weight restoration. Ann Pharmacother 47(9):1201\u20131205. https:\/\/doi.org\/10.1177\/1060028013503127","journal-title":"Ann Pharmacother"},{"issue":"1","key":"1778_CR25","doi-asserted-by":"publisher","first-page":"5145","DOI":"10.1038\/s41467-020-18885-9","volume":"11","author":"P Chrysafi","year":"2020","unstructured":"Chrysafi P, Perakakis N, Farr OM, Stefanakis K, Peradze N, Sala-Vila A, Mantzoros CS (2020) Leptin alters energy intake and fat mass but not energy expenditure in lean subjects. Nat Commun 11(1):5145. https:\/\/doi.org\/10.1038\/s41467-020-18885-9","journal-title":"Nat Commun"},{"key":"1778_CR26","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.2147\/TCRM.S66521","volume":"11","author":"AJ Rodriguez","year":"2015","unstructured":"Rodriguez AJ, Mastronardi CA, Paz-Filho GJ (2015) New advances in the treatment of generalized lipodystrophy: role of metreleptin. Ther Clin Risk Manag 11:1391\u20131400. https:\/\/doi.org\/10.2147\/TCRM.S66521","journal-title":"Ther Clin Risk Manag"},{"issue":"3","key":"1778_CR27","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1007\/s12020-019-01862-8","volume":"64","author":"EA Oral","year":"2019","unstructured":"Oral EA, Gorden P, Cochran E, Araujo-Vilar D, Savage DB, Long A, Fine G, Salinardi T, Brown RJ (2019) Long-term effectiveness and safety of metreleptin in the treatment of patients with partial lipodystrophy. Endocrine 64(3):500\u2013511. https:\/\/doi.org\/10.1007\/s12020-019-01862-8","journal-title":"Endocrine"}],"container-title":["European Child &amp; Adolescent Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00787-021-01778-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00787-021-01778-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00787-021-01778-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T08:06:40Z","timestamp":1664870800000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00787-021-01778-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,9]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["1778"],"URL":"https:\/\/doi.org\/10.1007\/s00787-021-01778-7","relation":{},"ISSN":["1018-8827","1435-165X"],"issn-type":[{"value":"1018-8827","type":"print"},{"value":"1435-165X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,9]]},"assertion":[{"value":"9 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors declare no conflicts of interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"Due to German law not applicable for an off-label application of an otherwise approved drug in an individual patient.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Both patient and parents agreed to an off-label treatment with metreleptin and provided written informed consent in accordance with the latest version of the Declaration of Helsinki.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Both patient and parents reviewed and agreed to the publication. Written consent available.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}