Current evidence on thyroid related adverse events in patients treated with protein tyrosine kinase inhibitors

Katalin Gabora1,2, Andra Piciu2, Iulian Claudiu Bădulescu2

  • 1Department of Nuclear Medicine, Prof. Dr. Ion Chiricuță Institute of Oncology, Cluj Napoca, Romania.

Drug Metabolism Reviews
|November 14, 2019
PubMed

Insights

Tyrosine kinase inhibitors (TKI) can cause thyroid dysfunction in cancer patients, with about 33% developing hypothyroidism. Monitoring thyroid-stimulating hormone (TSH) is crucial for managing side effects and potentially improving patient outcomes.

Area of Science:

  • Oncology
  • Endocrinology
  • Pharmacology

Background:

  • Tyrosine kinase inhibitors (TKIs) are crucial targeted therapies in oncology.
  • Side effects of TKIs can limit treatment efficacy and impact patient quality of life.
  • Thyroid dysfunction is a recognized adverse effect of TKI therapy.

Purpose of the Study:

  • To review the literature on TKI-induced thyroid dysfunction in cancer patients.
  • To assess the impact of TKIs on thyroid function and disease prognosis.
  • To evaluate the need for thyroid hormone monitoring and intervention.

Main Methods:

  • Systematic literature review of studies published between 2010 and 2019.
  • Search of the PubMed database for TKI-related hypothyroidism and hyperthyroidism.
  • Inclusion of 22 original studies encompassing 1641 patients.

Main Results:

  • Thyroid dysfunction is a common side effect of TKI treatment, affecting approximately 33% of patients with clinical hypothyroidism.
  • Around 25% of patients required thyroid hormone substitution therapy.
  • A correlation was observed between hypothyroidism and progression-free survival in TKI-treated patients.

Conclusions:

  • Thyroid dysfunction is a frequent complication of TKI therapy, affecting patient quality of life and treatment continuation.
  • Baseline and regular monitoring of thyroid-stimulating hormone (TSH) levels are essential for patients receiving TKIs.
  • Early detection and management of hypothyroidism may be important for optimizing cancer treatment outcomes.

Related Concept Videos

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
399
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.6K
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
17.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.2K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
3.8K
Chronic Kidney Disease III: Interprofessional Care01:28

Chronic Kidney Disease III: Interprofessional Care

Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
304