Study suggests thyroid cancer increases coronary heart disease risk

10th November 2022

Having thyroid cancer is linked to a higher risk of coronary heart disease and which persists in those under 65 years for at least 5 years

Patients with thyroid cancer (TC) have a greater risk of developing coronary heart disease and in those under 65 years of age, this elevated risk persists for at least five years after their cancer diagnosis according to an observational study by Taiwanese researchers.

In 2020, the global estimated rate of thyroid cancer was 10·1 per 100 000 women and 3·1 per 100 000 men, although mortality rates were lower at 0·5 per 100 000 and 0·3 per 100 000 for women and men respectively. Surgery is the mainstay of treatment in nearly every case of thyroid cancer although radiotherapy can also be used. If the thyroid is removed, then patients will require life-long therapy with levothyroxine both to replace the hormone and lower the risk of cancer recurrence. However, long-term use of levothyroxine may cause marked impairment of cardiac functional reserve and physical exercise capacity. Whether these changes increase the subsequent risk of cardiovascular disease remains uncertain with some evidence that such patients have a higher incidence of cardiovascular disease morbidity. In contrast however, other work has shown that the incidence of cerebrovascular disease, cerebral infarction, ischaemic heart disease, ischaemic heart attack and heart failure are no different between those with TC and the general population.

With some uncertainty over the relationship between TC and the risk of cardiovascular diseases, in the current study, the Taiwanese researchers turned to data contained within a nationwide population-based cohort to retrospectively examine this relationship. They chose a baseline date for their analysis as the time when TC patients underwent a thyroidectomy but excluded those aged < 20 and > 85 years and anyone with a history of coronary heart disease (CHD) or atrial fibrillation. They set the primary endpoint of interest as hospitalisation for CHD defined in terms of fatal and non-fatal CHD. Secondary outcomes included ischaemic stroke (IS) that required hospitalisation and atrial fibrillation, which again required hospitalisation. The researchers calculated a standardised incidence ratio (SIR) as the ratio of observed to expected CHD cases, stratified by age and gender within the general population.

Thyroid cancer and risk of coronary heart disease

A total of 4,274 individuals who had thyroid cancer without CHD and a mean age of 49 years (24.4% male) were included in the analysis and followed-up for a mean of 3.5 years.

During follow-up, there were 69 CHD events in those with TC and the SIR was significantly higher than expected in the age-standardised population (SIR = 1.57, 95% CI 1.2 – 1.93). However, the rate of IS was not significantly different (SIR = 0.74, 95% CI 0.47 – 1), neither was the incidence of cardiovascular disease (SIR = 0.88, 95% CI 0.70 – 1.05) or atrial fibrillation (SIR = 0.74, 95% CI 0.42 – 1.06).

When researchers considered the SIR over time, particularly among those under 65 years of age, the elevated risk remained significant, 5 years after the date of their TC diagnosis (SIR = 2.08, 95% CI 1.5 – 2.66) although it was non-significant among those over 65 years of age (SIR = 1.0, 95% CI 0.57 – 1.42).

The authors concluded that thyroid cancer patients had a greater risk of CHD than the general population without the cancer and that this risk persisted for at least 5 years. They called for future research to further investigate this observed association.

Citation
Tsai MC et al. Association between thyroid cancer and cardiovascular disease risk: a nationwide observation study. Sci Rep 2022

Autoimmune thyroiditis in children associated with thyroid cancer

5th September 2022

Autoimmune thyroiditis has been found to be independently linked to an increased risk of thyroid cancer in children with thyroid nodules

The presence of autoimmune thyroiditis is independently associated with a higher risk of thyroid cancer among children with thyroid nodules according to the findings of a cross-sectional study by researchers based at Harvard Medical School, US.

Autoimmune thyroiditis (AIT) is characterised by the presence of thyroid autoantibodies in serum and is the most common cause of thyroid disorder among children and adolescents although it is mostly asymptomatic.

AIT, also known as Hashimoto’s thyroiditis, is frequently associated with papillary thyroid cancer and may indeed be a risk factor for developing this type of cancer. However, other work suggests that a correlation between AIT and a higher incidence of thyroid cancer is still undefined.

In children there is also some uncertainty of this relationship. Some data suggest that AIT seems to influence the development of thyroid nodules, but not cancer, whereas other data indicate a relationship with malignancy.

Whilst the presence of thyroid nodules are more common in children with AIT, whether this increases the risk of thyroid cancer is unclear, although there is a clear relationship between the presence of AIT, nodules and malignancy in adults.

In the present study, the researchers sought to better understand the relationship between AIT in children and thyroid cancer, among a cohort who underwent thyroid nodule evaluation over an extended period of time. Included participants were < 19 years of age and who had undergone fine needle aspiration of a nodule between 1998 and 2020.

The presence of thyroid cancer was defined by histopathology for resected nodules and the researchers set the primary outcome as the presence of thyroid cancer.

Autoimmune thyroiditis and cancer in children

A total of 385 individuals with a mean age of 15.5 years (81% female) with 458 nodules, were included in the retrospective analysis.

Thyroid cancer was present in 108 nodules (24%) and AIT was seen 95 (25%) of the study population. The most common type of thyroid cancer was papillary (82%) followed by follicular carcinoma (14%).

The presence of clinical AIT was independently associated with an increased risk of thyroid cancer (odds ratio, OR = 2.19, 95% CI 1.32 – 3.62). Moreover, thyroid cancer was directly associated with the diameter of the nodules (OR = 1.05, 95% CI 1.03 – 1.06, p < 0.001) and inversely associated with age (OR = 0.90, 95% CI 0.83 – 0.97, p = 0.007).

Interestingly, female sex and the presence of multiple nodules were both independently associated with a lower risk of thyroid cancer.

The authors concluded that among children with thyroid nodules, the presence of AIT was associated with an increased risk of thyroid cancer. They suggested that a clinical diagnosis of AIT may inform the assessment of thyroid cancer risk and surgical decision-making in children who had thyroid nodules.

Citation
Keefe G et al. Autoimmune Thyroiditis and Risk of Malignancy in Children with Thyroid Nodules Thyroid 2022

Apatinib therapy improves progression-free survival in iodine-refractory thyroid cancer

22nd December 2021

Apatinib therapy in patients with radioactive iodine-refractory thyroid cancer is safe and able to improve progression-free survival

The use of apatinib therapy in patients with radio-active iodine-refractory thyroid cancer has been found to be safe and effective, improving progression-free survival. This was the main result from the Efficacy of Apatinib in Radioactive Iodine-refractory Differentiated Thyroid Cancer [REALITY] trial, undertaken by a team from the Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking, China.

The incidence of thyroid cancer has been increasing globally over the past three decades and affects around 5 to 6% of men and women. Differentiated thyroid cancer (DTC) , which includes papillary and follicular histologies, is the most common type, accounting for over 90% of all thyroid cancers. Although radioactive iodine therapy is effective for a large proportion of patients with DTC, unfortunately around 5 to 15% of patients become refractory to therapy, prompting the need for alternatives.

Apatinib is a small-molecule angiogenesis inhibitor which suppresses vascular endothelial growth factor (VEGF) signalling. The value of apatinib therapy in radioactive iodine-refractory DTC has been examined in two small studies. In the first including 10 patients, the drug was described as a promising therapy, whereas in the second, dosing schedule study, undertaken with 20 patients, the drug produced a similar efficacy with both doses.

Based on these preliminary studies, the Chinese team, decided to undertake a randomised, double-blind, placebo trial of apatinib in patients with progressive, locally advanced or metastatic radioactive iodine-refractory DTC. The REALITY trial was conducted in adults (18 years and over) and the inclusion criteria were those whose target lesion had lost iodine uptake function, where the lesion had progressed within 12 months after radioactive iodine treatment. In addition, iodine refractory patients receiving chemotherapy or radiotherapy, at least one month prior to the first use of study treatment were also included. Participants were randomised 1:1 to apatinib, given at a dose of 500 mg once daily until disease progression or intolerable side-effects developed or matching placebo. Tumour assessment was performed with CT or MRI imaging and the primary endpoint was investigator assessed progression-free survival (PFS), which was defined as the time from randomisation to disease progression or death from any cause. Secondary endpoints included overall survival (OR) and the objective response rate (ORR).

Findings

A total of 92 patients with a mean age of 57.7 years (60.9% female) were randomised to apatinib therapy or placebo.

With a median follow-up time of 18.1 months, the median PFS was 22.2 months in the apatinib group and 4.5 months in the placebo group (hazard ratio, HR = 0.26, 95% CI 0.14 – 0.47). The 12-month PFS rate was 60.3% for apatinib compared to 12.4% in the placebo arm although this decreased to 37.2% and 4.1% (apatinib vs placebo). The ORR was 54.3% for apatinib compared to 2.2% (placebo) and the overall 12-month survival rate was 95.4% vs 79.7% (apatinib vs placebo).

In terms of safety, the most common adverse event (grade 3 or higher) was hypertension (34.8%), hand-foot syndrome (17.4%) and proteinuria (15.2%) and none of these effects were observed in the placebo group.

The authors concluded that apatinib therapy significantly improved PFS and suggested that it should be considered as a new treatment for patients with radioactive iodine-refractory DTC.

Citation

Lin Y et al. Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine–Refractory Differentiated Thyroid Cancer. The REALITY Randomized Clinical Trial JAMA Oncol 2021