{"doi":"10.1210/clinem/dgaf062","title":"FSH and Sertoli Cell Biomarkers Accurately Distinguish Hypogonadotropic Hypogonadism From Self-limited Delayed Puberty","abstract":"CONTEXT: Delayed puberty is a frequent complaint in males. The differential diagnosis between self-limited delayed puberty (SLDP) and congenital hypogonadotropic hypogonadism (CHH) is challenging. Commonly used endocrine tests, focusing on stimulated levels of LH or testosterone, are not satisfactory in making a diagnosis. Because FSH action on Sertoli cells results in testis enlargement and anti-Müllerian hormone (AMH) and inhibin B increased secretion, and the FSH-Sertoli cell axis function is detectable during normal childhood and early puberty, we tested whether the assessment of serum FSH, AMH, and inhibin B would be informative to distinguish between SLDP and CHH. DESIGN: We performed a prospective, nested case-control study in a cohort of male adolescents presenting with delayed puberty, comparing baseline serum reproductive hormone levels to identify predictive biomarkers of CHH, after having followed all participants prospectively until a final diagnosis was ascertained based on gold-standard criteria (age 18 years or ≥4 years after testis volume reached 4 mL). RESULTS: Of 65 participants who completed follow-up, 33 had a final diagnosis of SLDP and 32 of CHH. Serum FSH, AMH, and inhibin B showed better diagnostic efficiency than LH and testosterone for these differential diagnoses. FSH (IU/L)×inhibin B (ng/mL) < 92 and FSH (IU/L)×AMH (pmol/L) < 537 showed high sensitivity (>93%), specificity (≥92%), predictive values (>92%), and positive likelihood ratio (>12) for CHH. The diagnostic performance remained 89.7% and 88.2% for FSH × inhibin B and FSH × AMH, respectively, when analyzed in patients without red flags (micropenis, cryptorchidism, and/or microorchidism). CONCLUSION: Serum FSH combined with inhibin B or AMH is highly predictive to accurately distinguish between SLDP and CHH in adolescent males.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2025,"id":561848,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9625,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1464040,"name":"Lourdes Correa Brito","orcid":"0000-0002-1583-1988","position":1,"is_corresponding":false},{"id":1464326,"name":"Patricia Bedecarrás","orcid":null,"position":2,"is_corresponding":false},{"id":1464041,"name":"Marı́a Gabriela Ballerini","orcid":"0000-0003-0312-7421","position":3,"is_corresponding":false},{"id":511503,"name":"Gabriela Sansó","orcid":"0000-0002-9590-6977","position":4,"is_corresponding":false},{"id":658405,"name":"Ana Keselman","orcid":"0000-0002-5612-0445","position":5,"is_corresponding":false},{"id":1464327,"name":"Hamilton Cassinelli","orcid":null,"position":6,"is_corresponding":false},{"id":1464042,"name":"Andrea Arcari","orcid":"0000-0001-7618-1950","position":7,"is_corresponding":false},{"id":1464043,"name":"Guillermo Alonso","orcid":"0000-0002-5780-7919","position":8,"is_corresponding":false},{"id":316640,"name":"Yee-Ming Chan","orcid":"0000-0003-0554-8502","position":9,"is_corresponding":false},{"id":829941,"name":"Wei He","orcid":"0000-0001-5801-9044","position":10,"is_corresponding":false},{"id":1274211,"name":"María Gabriela Ropelato","orcid":"0000-0003-0040-1210","position":11,"is_corresponding":false},{"id":658406,"name":"Ignacio Bergadá","orcid":"0000-0001-6546-1949","position":12,"is_corresponding":false},{"id":793973,"name":"Fernando Cassorla","orcid":"0000-0003-0958-5845","position":13,"is_corresponding":false},{"id":1292760,"name":"Rodolfo A. Rey","orcid":"0000-0002-1100-3843","position":14,"is_corresponding":false},{"id":1292759,"name":"Romina P. Grinspon","orcid":"0000-0002-6291-1518","position":15,"is_corresponding":false},{"id":1464039,"name":"Sebastián Castro","orcid":"0000-0002-8073-2046","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:56:01.883848Z","pmid":"39930628","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}