{"doi":"10.1089/thy.2023.0616","title":"Progression of Gestational Subclinical Hypothyroidism and Hypothyroxinemia to Overt Hypothyroidism After Pregnancy: Pooled Analysis of Data from Two Randomized Controlled Trials","abstract":"Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86–1.9 ng/dL). HT was diagnosed with normal TSH (0.08–3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6–10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8–10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43–36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1–84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.","journal":"Thyroid","year":2024,"id":440790,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8969,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":515119,"name":"Lisa Mele","orcid":"0000-0002-4471-9725","position":1,"is_corresponding":false},{"id":372222,"name":"Brian M. Casey","orcid":"0000-0001-5452-3761","position":2,"is_corresponding":false},{"id":515117,"name":"Alan M. Peaceman","orcid":"0000-0002-4515-4850","position":3,"is_corresponding":false},{"id":592159,"name":"Uma M. Reddy","orcid":"0000-0002-8599-6040","position":4,"is_corresponding":false},{"id":262909,"name":"Ronald J. Wapner","orcid":"0000-0003-0727-1244","position":5,"is_corresponding":false},{"id":377145,"name":"John M. Thorp","orcid":"0000-0002-4598-0271","position":6,"is_corresponding":false},{"id":262903,"name":"George R. Saade","orcid":"0000-0001-7925-5302","position":7,"is_corresponding":false},{"id":331594,"name":"Alan Tita","orcid":"0000-0002-7244-9056","position":8,"is_corresponding":false},{"id":460635,"name":"Dwight J. Rouse","orcid":"0000-0002-9336-9688","position":9,"is_corresponding":false},{"id":505950,"name":"Baha M. Sibai","orcid":"0000-0001-9982-7873","position":10,"is_corresponding":false},{"id":317452,"name":"Maged M. Costantine","orcid":"0000-0003-4076-469X","position":11,"is_corresponding":false},{"id":456043,"name":"Brian M. Mercer","orcid":null,"position":12,"is_corresponding":false},{"id":331590,"name":"Steve N. Caritis","orcid":"0000-0002-2169-0712","position":13,"is_corresponding":false},{"id":388820,"name":"Michael W. Varner","orcid":"0000-0001-9455-3973","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-19T02:01:01.842286Z","pmid":"39028022","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":[]}