{
  "abstract": "Background and Importance Apalutamide is an androgen receptor inhibitor, widely used in prostate cancer (PC). Hypothyroidism is a recognised adverse event; however, its incidence and clinical management in real-world practice remain underreported.Aim and Objectives To evaluate the incidence, management, and outcomes of hypothyroidism in PC patients treated with apalutamide.Material and Methods This retrospective observational study included all PC patients treated with apalutamide between 1 August 2020, and 30 September 2025. Collected variables included age, oncologic diagnosis, TSH, T4, time to thyroid alteration, prior hypothyroidism, endocrine diagnoses and thyroid treatment during follow-up. Data were obtained from SIGLO, Farmis, and Mambrino XXI.Results Eighty-five men were included, median age 73 years, (IQR 52–91); 97.6% had metastatic castration-sensitive PC and 2.4% non-metastatic castration-resistant PC. Six patients had pre-existing hypothyroidism.Hypothyroidism occurred in 27.8% patients without prior thyroid disease (12.7% subclinical, 15.2% primary iatrogenic). Median time to detection was 68 days (IQR 12–880). Median TSH increase was 7.34 mU/L (IQR 1.41–21.36) in patients with prior hypothyroidism versus 3.15 mU/L (IQR 2.12–5.64) in those without.Levothyroxine was initiated in 72.7% patients without prior hypothyroidism (100% of primary iatrogenic, 40% of subclinical cases). Among treated patients, TSH normalised in 75% with primary hypothyroidism and 50% with subclinical disease.All patients with pre-existing hypothyroidism required initiation or adjustment of levothyroxine.Seven patients on levothyroxine discontinued apalutamide due to progression or toxicity; After discontinuation 85.7% maintained the same dose of levothyroxine. Two of them developed suppressed TSH.Conclusion and Relevance Apalutamide–induced hypothyroidism in our cohort was higher than reported in the label (8%), particularly in patients without prior thyroid disease. Most cases occurred within the first months of therapy, although late onset was also observed, highlighting the need for long–term monitoring.Patients with pre–existing hypothyroidism require closer monitoring, as all needed levothyroxine initiation or dose adjustment.Levothyroxine effectively managed primary hypothyroidism, while outcomes in subclinical cases were less consistent in clinical practice.Reassessment of thyroid function after apalutamide discontinuation is recommended to avoid unnecessary therapy.Implementing standardised protocols for diagnosis, monitoring, treatment initiation, and post–discontinuation management through multidisciplinary collaboration (Urology, Oncology, Endocrinology, Primary Care) could optimise patient care.References and/or Acknowledgements 1. AEMPS. Erleada 60 mg – Product label (apalutamida) (CIMA); 2025 https://cima.aemps.es/cima/dochtml/ft/1181342001/FT_1181342001.htmlConflict of Interest No conflict of interest",
  "authors": [
    {
      "affiliations": [
        "University Hospital of Guadalajara, Pharmacy, Guadalajara, Spain"
      ],
      "name": "A Baldominos Cordon"
    },
    {
      "affiliations": [
        "University Hospital of Guadalajara, Pharmacy, Guadalajara, Spain"
      ],
      "name": "P De Juan-García Torres"
    },
    {
      "affiliations": [
        "University Hospital of Guadalajara, Pharmacy, Guadalajara, Spain"
      ],
      "name": "S Corrales Krohnert"
    },
    {
      "affiliations": [
        "University Hospital of Guadalajara, Biochemistry, Guadalajara, Spain"
      ],
      "name": "G Calero Rodriguez"
    },
    {
      "affiliations": [
        "University Hospital of Guadalajara, Pharmacy, Guadalajara, Spain"
      ],
      "name": "I Marin Espinosa"
    },
    {
      "affiliations": [
        "University Hospital of Guadalajara, Pharmacy, Guadalajara, Spain"
      ],
      "name": "I Heras Hidalgo"
    },
    {
      "affiliations": [
        "University Hospital of Guadalajara, Pharmacy, Guadalajara, Spain"
      ],
      "name": "H Gavilan Gigosos"
    },
    {
      "affiliations": [
        "University Hospital of Guadalajara, Pharmacy, Guadalajara, Spain"
      ],
      "name": "A Domenech Millán"
    },
    {
      "affiliations": [
        "University Hospital of Guadalajara, Pharmacy, Guadalajara, Spain"
      ],
      "name": "AM Horta Hernández"
    }
  ],
  "title": "4CPS-245 Real-world incidence and management of hypothyroidism secondary to apalutamide in patients with prostate cancer",
  "uid": "56039dd2-4546-5bc3-80b9-cf314482f404"
}