{"doi":"10.1210/clinem/dgaf498","title":"Longitudinal Characterization and Sonographic Staging of Testicular Adrenal Rest Tumors","abstract":"CONTEXT: Testicular adrenal rest tumors (TART) frequently develop and are the most common cause of male infertility in classic congenital adrenal hyperplasia (CAH). Little is known about the natural course. OBJECTIVE: We aimed to investigate age of onset and associated factors and characterize the sonographic natural history of TART in males with classic CAH followed prospectively from childhood to adulthood. METHODS: Longitudinal study of clinical and hormonal data and serial scrotal ultrasounds performed every 6 months during childhood and annually in adulthood. Survival analysis and longitudinal models were used to determine age of TART onset and factors associated with TART progression. RESULTS: Seven hundred eighty-three ultrasounds from 36 males were evaluated. Twenty-seven (75%) developed TART; the mean age of onset was 13.6 ± 4.9 years, with ∼22% risk before age 10. TART presence was associated with elevated ACTH, 17-hydroxyprogesterone, androstenedione, and plasma renin activity, younger age at diagnosis, salt-wasting (SW) phenotype, and null/In2G mutations. Multivariable analysis revealed SW phenotype [odds ratio (OR): 6.83, 95% confidence interval (CI) 2.36-19.77; P < .001], treatment with higher hydrocortisone dose equivalents (OR: 1.10, 95% CI 1.03-1.18; P = .006), and elevated ACTH (OR: 1.0011, 95% CI 1.0005-1.0017; P < .01) increased risk of TART at any given visit. Of 19 patients with TART at last visit, the hydrocortisone dose equivalent was 16.0 ± 7.9 mg/m2/day, lower than 21.3 ± 7.5 mg/m2/day observed in patients whose TARTs resolved. Serial sonograms showed a characteristic pattern of TART progression from a single hypoechoic nodule to multiple hypoechoic nodules to a single conglomerate mass near the mediastinum testis. CONCLUSION: TART formation in CAH is frequently found in prepubertal boys, with a characteristic pattern of development resulting in a proposed radiologic staging. Pediatric screening is recommended, especially in those with a SW phenotype/genotype.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2025,"id":526810,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8272,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"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":472970,"name":"Sarah Kulkarni","orcid":"0000-0002-0807-339X","position":1,"is_corresponding":false},{"id":294767,"name":"Jamie Marko","orcid":"0000-0002-4281-0306","position":2,"is_corresponding":false},{"id":321283,"name":"Ninet Sinaii","orcid":"0000-0003-4045-1386","position":3,"is_corresponding":false},{"id":1289057,"name":"Charles Sukin","orcid":"0009-0009-5105-4475","position":4,"is_corresponding":false},{"id":781852,"name":"Deepika Burkardt","orcid":"0000-0002-1743-7503","position":5,"is_corresponding":false},{"id":1403440,"name":"Quentin Eustace","orcid":null,"position":6,"is_corresponding":false},{"id":414564,"name":"Ashwini Mallappa","orcid":"0000-0003-0637-4559","position":7,"is_corresponding":false},{"id":404052,"name":"Deborah P. Merke","orcid":"0000-0002-3746-0460","position":8,"is_corresponding":false},{"id":1402912,"name":"Sonal Vaid","orcid":"0009-0007-5522-7666","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:50:34.851930Z","pmid":"40921717","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":[]}