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Primary Adrenal Insufficiency During Lenvatinib or Vandetanib and Improvement of Fatigue After Cortisone Acetate Therapy
Open accessAbstract
Context: Two tyrosine kinase inhibitors (TKIs), lenvatinib and vandetanib, are often used to treat advanced radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) and medullary thyroid cancer (MTC), respectively. Fatigue is a common adverse event during treatment with these and other TKIs and a common cause of drug discontinuation or dosage reduction. Cases Description: We evaluated the basal and stimulated adrenal function in 12 patients with advanced RAI-R DTC and MTC treated with lenvatinib or vandetanib, respectively. Ten patients complaining of fatigue showed a progressive ACTH increase with normal cortisol levels. Moreover, six of 10 patients had a blunted cortisol response after ACTH stimulation, thus confirming the diagnosis of primary adrenal insufficiency (PAI). The causal relationship between TKIs and PAI onset was also demonstrated by the repeated testing of adrenal function before and during treatment. Patients with PAI received cortisone acetate replacement therapy, with a substantial and prompt improvement in the degree of fatigue, as assessed by the Common Terminology Criteria for Adverse Events version 4.03, thus supporting the major impact of impaired adrenal function in the genesis of this adverse event. Conclusions: We show that the occurrence of PAI may be a common cause of fatigue during lenvatinib and vandetanib treatment, and we therefore recommend testing adrenal function for a prompt start of replacement therapy to avoid treatment discontinuation, dosage reduction, and potentially severe PAI complications.
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Metadata
- Authors
- Colombo, C., De Leo, S., Di Stefano, M., Vannucchi, G., Persani, L., & Fugazzola, L.
- Affiliations
- University of Milan (IT)
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
- IRCCS Istituto Auxologico Italiano (IT)
- Corresponding author
- Fugazzola, Laura
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2018-10-31
- Volume
- 104
- Issue
- 3
- Pages
- 779-784
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC6402317
- OpenAlex
- W2899099793
- Cited by
- 44
- References
- 10
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 1 · 2023: 6 · 2022: 13 · 2021: 7 · 2020: 3 · 2019: 5
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, cc-by)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion)
- Funders
- Sanofi
- Università degli Studi di Milano
- Eisai
- Istituto Auxologico Italiano
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- Addison's disease, lenvatinib, vandetanib, tyrosine kinase inhibitors, fatigue, ACTH stimulation test, adrenal function testing, radioiodine-refractory thyroid cancer, medullary thyroid carcinoma, adverse drug reactions
- MeSH terms
- Addison Disease, Adult, Aged, Child, Cortisone, Dose-Response Relationship, Drug, Fatigue, Female, Follow-Up Studies, Humans, Male, Middle Aged, Phenylurea Compounds, Piperidines, Quinazolines, Quinolines, Thyroid Neoplasms, Treatment Outcome, Carcinoma, Neuroendocrine, Protein Kinase Inhibitors, Young Adult
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