Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb;45(2):291-300.
doi: 10.1007/s40618-021-01613-5. Epub 2021 Jul 20.

Thyroid autoimmunity and hypothyroidism are associated with deep molecular response in patients with chronic myeloid leukemia on tyrosine kinase inhibitors

R Rodia #  1 , F Pani #  2 , G Caocci  3 , G La Nasa  3 , M P Simula  3 , O Mulas  3 , F Velluzzi  1 , A Loviselli  1 , S Mariotti  1 , F Boi  4
Affiliations

Thyroid autoimmunity and hypothyroidism are associated with deep molecular response in patients with chronic myeloid leukemia on tyrosine kinase inhibitors

R Rodia et al. J Endocrinol Invest. 2022 Feb.

Abstract

Purpose: Thyroid alterations including de novo appearance of thyroid autoimmunity are adverse effects of tyrosine kinase inhibitors, used in solid and hematologic cancer therapy, but the relationship between thyroid alterations during this treatment and the outcome of chronic myeloid leukemia remains unclear. Aim of this study was to investigate whether the presence of thyroid alterations may affect the clinical outcome of chronic myeloid leukemia on tyrosine kinase inhibitors.

Methods: We evaluated thyroid function and autoimmunity in 69 chronic myeloid leukemia patients on long-term therapy looking at the association between thyroid abnormalities and disease molecular response.

Results: Overall, 24 of 69 (34.8%) had one or more thyroid abnormalities during therapy. A high percentage of patients (21/69, 30.4%) showed thyroid autoimmunity (positive thyroid autoantibodies with ultrasound hypoechogenicity), while clinical and subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, found in 4 of 69 (5.8%) and 3 of 69 (4.3%) of cases. Second-generation tyrosine kinase inhibitors resulted significantly associated (14/32, 43.7%) with Hashimoto's thyroiditis, compared to first generation (7/37, 18.9%; p = 0.03). Interestingly, we also found a significant association between euthyroid (14/26, 53.8%) and hypothyroid Hashimoto's thyroiditis (4/26, 15.4%) in patients with deep molecular response, as compared to euthyroid (3/43, 7%; p = 0.0001) and hypothyroid (0/43, 0%; p = 0.02) Hashimoto's thyroiditis patients with major molecular response.

Conclusions: Our study confirms and extends our knowledge on the tyrosine kinase inhibitors effects on thyroid, showing that thyroid autoimmunity is frequently observed in chronic myeloid leukemia patients on long-term therapy and is associated with a better oncological response.

Keywords: Chronic myeloid leukemia; Molecular response; Thyroid abnormalities; Thyroid autoimmunity; Tyrosine kinase inhibitors.

PubMed Disclaimer

Conflict of interest statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow diagram showing protocol followed in patients’ recruitment
Fig. 2
Fig. 2
a Prevalence of thyroid alterations (TA+ presence; TA− absence) in deep molecular response (DMR) and in major molecular response (MMR) of chronic myeloid leukemia (CML), observed in patients treated with first- and second-generation tyrosine kinase inhibitors (TKIs). b Prevalence of Hashimoto’s thyroiditis (HT+ presence; HT– absence) in DMR and in MMR of CML, observed in patients treated with first- and second-generation TKIs. c Prevalence of euthyroid Hashimoto’s thyroiditis (E-HT+ presence; E-HT– absence) in DMR and in MMR of CML, observed in patients treated with first- and second-generation TKIs. The number of patients with thyroid abnormalities (TA, HT, and E-HT) is reported in each column of the figure
See this image and copyright information in PMC

References

    1. Ahmadieh H, Salti I. Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment. Biomed Res Int. 2013;2013:725410. doi: 10.1155/2013/725410. - DOI - PMC - PubMed
    1. Breccia M, Molica M, Alimena G. How tyrosine kinase inhibitors impair metabolism and endocrine system function: a systematic updated review. Leuk Res. 2014;38(12):1392–1398. doi: 10.1016/j.leukres.2014.09.016. - DOI - PubMed
    1. Caocci G, Atzeni S, Orrù N, Azzena L, Martorana L, Littera R, Ledda A, La Nasa G. Gynecomastia in a male after dasatinib treatment for chronic myeloid leukemia. Leukemia. 2008;22(11):2127–2128. doi: 10.1038/leu.2008.106. - DOI - PubMed
    1. Hershman JM, Liwanpo L. How does sunitinib cause hypothyroidism? Thyroid. 2010;20(3):243–244. doi: 10.1089/thy.2010.1620. - DOI - PubMed
    1. Illouz F, Laboureau-Soares S, Dubois S, Rohmer V, Rodien P. Tyrosine kinase inhibitors and modifications of thyroid function tests: a review. Eur J Endocrinol. 2009;160(3):331–336. doi: 10.1530/EJE-08-0648. - DOI - PubMed

MeSH terms