{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:19:41Z","timestamp":1790011181951,"version":"4.0.1"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2013NextGenerationEU","award":["BG-RRP-2.004-0004-C01"],"award-info":[{"award-number":["BG-RRP-2.004-0004-C01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background and Clinical Significance: Anti-M\u00fcllerian hormone (AMH) is a dimeric glycoprotein secreted from the granulosa cells of the preantral and small antral follicles, which has entered routine clinical practice as a valuable tool for the diagnosis of different ovarian disorders. Increased AMH levels have been recommended as a criterion for polycystic ovary syndrome (PCOS). However, its widespread use remains limited due to analytical diversity and contradictory age-specific thresholds, among other factors that modulate AMH levels. Case Presentation: Herein, we present a rare case series of women with increased AMH levels. The difficulties in the differential diagnosis of patients with elevated AMH levels, because of PCOS combined with pituitary dysfunction, increased ovarian volume, or granulosa cell tumors (GCTs), are discussed. Conclusions: The presented rare cases of increased AMH emphasize the important role of AMH as a diagnostic marker in women with hypogonadotropic hypogonadism and granulosa cell tumors. On the other hand, it is still unknown if increased AMH produced by unusually enlarged or supernumerary ovaries should be considered as actual PCOS cases or as a specific subgroup. Additionally, the unusual case of GCTs with pronounced AMH and LH increase but normal steroids supports the pathophysiological role of AMH for the development of neuroendocrine dysfunction. Moreover, it suggests that GCTs should be considered in the differential diagnosis of chronic anovulation even in women with normal ovarian steroid production in case of unusually high AMH levels for the age. Further studies are needed to explain PCOS heterogeneity and to ensure proper differential diagnosis for every affected woman.<\/jats:p>","DOI":"10.3390\/diagnostics16010123","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T09:18:56Z","timestamp":1767345536000},"page":"123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AMH in PCOS and Beyond\u2014Rare Case Series"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4007-9713","authenticated-orcid":false,"given":"Ralitsa","family":"Robeva","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Faculty of Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria"},{"name":"USHATE \u201cAcad. Iv. Penchev\u201d, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzvetozar","family":"Mehandjiev","sequence":"additional","affiliation":[{"name":"In Vitro Gynecological Medical Center \u201cDimitrov\u201d, 1750 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roumen","family":"Dimitrov","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital of Obstetrics and Gynecology \u201cMaichin dom\u201d, Faculty of Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Hranov","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital of Obstetrics and Gynecology \u201cMaichin dom\u201d, Faculty of Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Andonova","sequence":"additional","affiliation":[{"name":"Genetic Medico-Diagnostic Laboratory \u201cGenica\u201d, 1463 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Mladenova","sequence":"additional","affiliation":[{"name":"Genetic Medico-Diagnostic Laboratory \u201cGenica\u201d, 1463 Sofia, Bulgaria"},{"name":"IMDL \u201cGenome Center Bulgaria\u201d, 1612 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atanaska","family":"Elenkova","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Faculty of Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria"},{"name":"USHATE \u201cAcad. Iv. Penchev\u201d, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6917-9887","authenticated-orcid":false,"given":"George","family":"Hadjidekov","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Hospital \u201cLozenetz\u201d, 1407 Sofia, Bulgaria"},{"name":"Department of Physics, Biophysics and Radiology, Medical Faculty, Sofia University \u201cSt. Kliment Ohridski\u201d, 1504 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Zacharieva","sequence":"additional","affiliation":[{"name":"USHATE \u201cAcad. Iv. Penchev\u201d, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1365-2265.2006.02533.x","article-title":"Anti-M\u00fcllerian hormone (AMH) in female reproduction: Is measurement of circulating AMH a useful tool?","volume":"64","author":"Volpe","year":"2006","journal-title":"Clin. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1210\/clinem\/dgaa513","article-title":"Anti-M\u00fcllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function","volume":"105","author":"Moolhuijsen","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1210\/clinem\/dgad463","article-title":"Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome","volume":"108","author":"Teede","year":"2023","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s12958-015-0134-9","article-title":"Role of Anti-M\u00fcllerian Hormone in pathophysiology, diagnosis and treatment of Polycystic Ovary Syndrome: A review","volume":"13","author":"Dumont","year":"2015","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1210\/endrev\/bnab012","article-title":"Anti-M\u00fcllerian Hormone in Female Reproduction","volume":"42","author":"Racine","year":"2021","journal-title":"Endocr. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/humupd\/dmw027","article-title":"Interactions between androgens, FSH, anti-M\u00fcllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary","volume":"22","author":"Dewailly","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1093\/humrep\/des460","article-title":"Loss of LH-induced down-regulation of anti-M\u00fcllerian hormone receptor expression may contribute to anovulation in women with polycystic ovary syndrome","volume":"28","author":"Pierre","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/cen.14704","article-title":"Treatments targeting neuroendocrine dysfunction in polycystic ovary syndrome (PCOS)","volume":"97","author":"Garg","year":"2022","journal-title":"Clin. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.1210\/jc.2003-030727","article-title":"Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: Relationship to the ovarian follicle excess and to the follicular arrest","volume":"88","author":"Pigny","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1210\/jc.2005-2076","article-title":"Serum anti-Mullerian hormone as a surrogate for antral follicle count for definition of the polycystic ovary syndrome","volume":"91","author":"Pigny","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.fertnstert.2024.08.243","article-title":"Anti-m\u00fcllerian hormone as a diagnostic biomarker for polycystic ovary syndrome and polycystic ovarian morphology: A systematic review and meta-analysis","volume":"122","author":"Laven","year":"2024","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kotlyar, A.M., and Seifer, D.B. (2021). Ethnicity\/Race and Age-Specific Variations of Serum AMH in Women-A Review. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.593216"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1093\/ejendo\/lvad065","article-title":"AMH as part of the diagnostic PCOS workup in large epidemiological studies","volume":"188","author":"Piltonen","year":"2023","journal-title":"Eur. J. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1055\/s-0044-1786731","article-title":"Utility of Serum Anti-M\u00fcllerian Hormone Measurement as Part of Polycystic Ovary Syndrome Diagnosis","volume":"42","author":"Piltonen","year":"2024","journal-title":"Semin. Reprod. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1002\/ijc.29532","article-title":"The clinical utility of serum anti-M\u00fcllerian hormone in the follow-up of ovarian adult-type granulosa cell tumors--A comparative study with inhibin B","volume":"137","author":"Koskela","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1007\/s10815-018-1280-8","article-title":"In vitro fertilization with granulosa cell tumor: A report of two cases","volume":"35","author":"Bartels","year":"2018","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_17","first-page":"381","article-title":"Ovarian granulosa cell tumor and clomiphene citrate resistance. A case report and review of the literature","volume":"22","author":"Triantafyllidou","year":"2018","journal-title":"JBRA Assist. Reprod."},{"key":"ref_18","first-page":"345","article-title":"Three different ways to miss a granulosa cell tumor\u2014A lesson to be learned","volume":"6","author":"Kunnath","year":"2021","journal-title":"Asian Pac. J. Cancer Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1007\/s12020-023-03404-9","article-title":"Plasma-free metanephrines, nerve growth factor, and renalase significance in patients with PCOS","volume":"81","author":"Robeva","year":"2023","journal-title":"Endocrine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.rbmo.2012.03.010","article-title":"Anti-M\u00fcllerian hormone in women with hypopituitarism diagnosed before or during adolescence","volume":"25","author":"Sonntag","year":"2012","journal-title":"Reprod. Biomed. Online"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"E1045","DOI":"10.1210\/jc.2013-4250","article-title":"Anti-mullerian hormone deficiency in girls with congenital multiple pituitary hormone deficiency","volume":"99","author":"Deubzer","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s12958-022-00961-y","article-title":"Basal and dynamic relationships between serum anti-M\u00fcllerian hormone and gonadotropins in patients with functional hypothalamic amenorrhea, with or without polycystic ovarian morphology","volume":"20","author":"Hager","year":"2022","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/cen.14402","article-title":"Clinical and biochemical discriminants between functional hypothalamic amenorrhoea (FHA) and polycystic ovary syndrome (PCOS)","volume":"95","author":"Phylactou","year":"2021","journal-title":"Clin. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/humupd\/dmae030","article-title":"Functional hypothalamic amenorrhoea and polycystic ovarian morphology: A narrative review about an intriguing association","volume":"31","author":"Ott","year":"2025","journal-title":"Hum. Reprod. Update"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ajog.2015.12.055","article-title":"Increased anti-Mullerian hormone levels and ovarian size in a subgroup of women with functional hypothalamic amenorrhea: Further identification of the link between polycystic ovary syndrome and functional hypothalamic amenorrhea","volume":"214","author":"Carmina","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1210\/jc.2017-00131","article-title":"Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline","volume":"102","author":"Gordon","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1007\/s43032-023-01195-y","article-title":"Serum Anti-Mullerian Hormone (AMH) Levels Among Different PCOS Phenotypes and Its Correlation with Clinical, Endocrine, and Metabolic Markers of PCOS","volume":"30","author":"Malhotra","year":"2023","journal-title":"Reprod. Sci."},{"key":"ref_28","first-page":"e43848","article-title":"M\u00fcllerian Duct Anomalies and Anti-M\u00fcllerian Hormone Levels in Women With Polycystic Ovary Syndrome","volume":"15","author":"Yang","year":"2023","journal-title":"Cureus"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000512676","article-title":"Prevalence and Phenotypic Impact of Robertsonian Translocations","volume":"12","author":"Poot","year":"2021","journal-title":"Mol. Syndromol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1093\/aje\/kwy266","article-title":"Mortality and Cancer Incidence in Carriers of Balanced Robertsonian Translocations: A National Cohort Study","volume":"188","author":"Schoemaker","year":"2019","journal-title":"Am. J. Epidemiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ygyno.2004.12.014","article-title":"Molecular cytogenetics of ovarian granulosa cell tumors by comparative genomic hybridization","volume":"97","author":"Lin","year":"2005","journal-title":"Gynecol. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1007\/s12029-020-00408-w","article-title":"Coexistence of Ovarian Granulose Cell Tumor, Congenital Adrenal Hyperplasia, and Triple Translocation: Is a Consequence or Coincidence?","volume":"52","author":"Akbulut","year":"2021","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.22551\/2023.40.1003.10256","article-title":"Polycystic ovary syndrome due to the novel translocation 46XX t(2;9)(q21;p24)","volume":"10","author":"Finsterer","year":"2023","journal-title":"Arch. Clin. Cases."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chi, H., Huang, N., Liang, H., Li, R., Liu, C., and Qiao, J. (2021). Abnormal Elevation of Anti-Mullerian Hormone and Androgen Levels Presenting as Granulosa Cell Tumor. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.641166"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.3802\/jgo.2017.28.e31","article-title":"Adult granulosa cell tumors of the ovary: A retrospective study of 30 cases with respect to the expression of steroid synthesis enzymes","volume":"28","author":"Kitamura","year":"2017","journal-title":"J. Gynecol. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13048-023-01134-0","article-title":"AMH producing purely cystic virilizing adult granulosa cell tumor in 17 years old girl: A case report and review of literatures","volume":"16","author":"Kitajima","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10055","DOI":"10.1038\/ncomms10055","article-title":"Novel role for anti-M\u00fcllerian hormone in the regulation of GnRH neuron excitability and hormone secretion","volume":"7","author":"Cimino","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/s41591-018-0035-5","article-title":"Elevated prenatal anti-M\u00fcllerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood","volume":"24","author":"Tata","year":"2018","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Dewailly, D., Barbotin, A.L., Dumont, A., Catteau-Jonard, S., and Robin, G. (2020). Role of Anti-M\u00fcllerian Hormone in the Pathogenesis of Polycystic Ovary Syndrome. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00641"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.fertnstert.2025.05.147","article-title":"Prospective validation of anti-M\u00fcllerian hormone cutoff to determine polycystic ovarian morphology: HARMONIA study","volume":"124","author":"Piltonen","year":"2025","journal-title":"Fertil. Steril."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/1\/123\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T14:05:47Z","timestamp":1774533947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/1\/123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["diagnostics16010123"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16010123","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]}}}