Managing Long-Term Health Risks in Thyroid Cancer Survivors

CHICAGO — New research is illuminating the long-term health consequences faced by patients with thyroid cancer in areas related to fertility, bone health, and cardiovascular disease.

According to researchers, thyroid cancer may increase the likelihood that women, but not men, are later diagnosed with infertility. Additionally, although patients with thyroid cancer appear more likely to experience osteoporosis, they may actually have a lower fracture risk than healthy controls. Finally, the relationship between thyroid cancer, cardiovascular disease risk, and thyroid hormone replacement remains poorly understood, indicating a need for further research.

These are a few takeaways from a clinical session at the American Thyroid Association (ATA) 2024 Meeting.

Fertility in Thyroid Cancer Survivors

Among women, thyroid cancer itself is not associated with a reduced chance of pregnancy or future adverse pregnancy outcomes, but factors related to its treatment may make it more likely to be diagnosed with infertility. And among men, thyroid cancer does not make a difference in the long-term ability to father a child, gynecologist Rima Dhillon-Smith, MBChB, PhD, of the University of Birmingham in Birmingham, United Kingdom, told ATA attendees.

Dhillon-Smith referred attendees to a 2020 meta-analysis that found that female survivors of thyroid cancer, melanoma, and non-Hodgkin lymphoma had the same childbirth rates as women who had not had cancer.

Regardless of cancer history, a woman’s age is the most important predictor of fertility, Dhillon-Smith said, adding that taking a full history is vital, including the patient’s menstrual cycle pattern, previous pregnancies, and overall gynecological history.

For a fertility workup in women, Dhillon-Smith relies on a pelvic ultrasound. She also measures ovarian reserve in the form of follicle-stimulating hormone, anti-mullerian hormone, and antral follicle count laboratory values. Thyroid function testing rounds out the investigation of female fertility but, she cautioned, it’s important to perform semen analysis on the male partner early in the process to avoid unnecessary workups of the female patient.

The timing of radioactive iodine (RAI) therapy plays a crucial role in later attempts at pregnancy, Dhillon-Smith said, noting that RAI is associated with both a drop in anti-mullerian hormone levels and menstrual irregularities, particularly during the first 12 months following treatment completion. Long-term fertility and obstetric outcomes aren’t any different after RAI (regardless of dose) if there is at least a 6-month interval after treatment before conception, she said, referring colleagues to the relevant ATA guideline. It’s anticipated that the guidelines will be updated early in 2025. 

Much less is known about the fertility prospects of male thyroid cancer survivors, Dhillon-Smith said, but the advice is to start with a full history. Physicians should inquire whether there has been any trauma to the testes and whether sexual function and libido are normal. Investigations include semen analysis and follicle-stimulating hormone, luteinizing hormone, and testosterone levels.

Endocrinologists should be prepared to discuss whether male patients should consider freezing their sperm, said Dhillon-Smith. If the patient wants to try for conception within 12 to 18 months of completing RAI, this relatively affordable, noninvasive procedure might make sense. However, she noted, the fact that these male thyroid cancer survivors have no difference in their long-term fertility could argue against freezing, particularly since conceiving when euthyroid and cancer-free would be ideal.

Bone Health in Thyroid Cancer Survivors

There are two physiological reasons to be concerned about the potential for osteoporosis in thyroid cancer survivors, Megan Haymart, MD, of the University of Michigan in Ann Arbor, Michigan, told attendees. Thyroid hormone excess shortens the bone remodeling cycle and accelerates bone turnover, and thyroid stimulating hormone (TSH) is a negative regulator of bone turnover and has an inhibitory effect on bone resorption, she said.

To date, much of the literature contains conflicting data regarding the effect of TSH suppression on bone in patients with thyroid cancer based on differences in study design, methodology, degree of TSH suppression, and other factors, said Haymart. 

However, she commended a case-control study using US Veterans Administration data that found osteoporosis was associated with lower TSH, female sex, older age, and androgen use in patients with thyroid cancer. 

“Osteoporosis was more frequent in patients with thyroid cancer, but the fracture risk was lower,” said Haymart. 

In her role as a member of the ATA TSH suppression goals guideline revision work group, Haymart unofficially shared the group’s progress, noting that the guideline has not yet received full peer review. The group’s draft recommendation is to define TSH suppression as “below reference range,” or

“When we had the 0.1-0.5 category, a lot of us were making frequent dose adjustments of levothyroxine trying to hit that little target range,” she said. “We often have trouble hitting it, and the data are all over the place on whether or not that’s even beneficial, so the revised guideline gives a little bit more liberty to the physician.”

Cardiovascular Health in Thyroid Cancer Survivors

The relationship between thyroid cancer, cardiovascular disease risk, and thyroid hormone replacement is complex, with a variety of potential confounding factors, said Anna Sawka, MD, PhD, of the University Health Network in Toronto, Ontario, Canada, including the fact that obesity and metabolic syndrome are risk factors for both thyroid cancer and cardiovascular disease.

“Most meta-analyses of observational studies on cardiovascular risks in thyroid cancer survivors do not adequately adjust for cardiovascular risk factors and/or the degree of TSH suppression,” said Sawka.

Current avenues of research include exploring whether there is a possible limited underlying genetic association between thyroid cancer and congestive heart failure and whether all thyroid cancer patients should receive a screening electrocardiogram, said Sawka, adding that to date, there is insufficient evidence to support the latter approach. 

Dhillon-Smith and Harmart disclosed no relevant financial relationships. 

Sawka’s disclosures included research grants from the Canadian Institutes of Health Research, Canadian Cancer Society, and University Health Network. Additionally, she is the editor-in-chief of Thyroid, the American Thyroid Association.