Impact of Nasolacrimal Dysfunction in Thyroid Cancer Survivors

Thyroid cancer is unique among malignancies for its inherent cellular properties that permit diagnostic imaging and therapy using isotopes of radioactive iodine (RAI). Therapy with the ¹³¹I isotope of RAI has benefits for selected patients with intermediate-risk thyroid cancer and for most patients with high-risk thyroid cancer, but generally has little benefit in patients with low-risk thyroid cancer (1 –3). However, side effects of ¹³¹I can impact patients of any risk category, regardless of whether they accrued any benefits from RAI therapy.

For the purpose of imparting accurate information to patients regarding risk versus benefit, comprehensive information about the frequency, severity, time course, and resolution of side effects is helpful. Of the known side effects of RAI, which include salivary gland damage, nasolacrimal impact, reproductive consequences, hematologic effects, and secondary malignancies (4 –11), perhaps salivary gland damage has been most well described in the literature (5,10 –12). Patients are routinely advised to incorporate use of sialogogues and increased hydration into their schedules for the period after their RAI therapy.

Nasolacrimal consequences of RAI therapy have been documented in the literature since the report of Kloos et al. in 2002 of 10 of 390 patients who developed epiphora after RAI therapy (13). Several reports of lacrimal and nasal toxicity from RAI therapy have followed (14 –17). However, there is a dearth of information regarding the frequency at which patients succumb to these particular side effects and their severity and time course. Other potential ophthalmologic side effects such as dry eyes are also sparingly documented (11,17).

The Korean cohort study conducted by Drs. Lee and Woo is extremely valuable in this regard as it utilizes a national health insurance database to study patients with thyroid cancer who either received or did not receive RAI therapy (18). During a mean follow-up period of 9 years they documented the occurrence and timing of procedures performed for diagnosis or treatment of nasolacrimal duct obstruction (NLDO). Diagnostic procedures included probing of the nasolacrimal duct or dacryocystography, while surgical interventions included silicone tube intubation, external/endonasal dacryocystorhinostomy, conjunctivodacryocystorhinostomy, or endoscopic laser dacryocystorhinostomy.

Potential predictors of the development of NLDO such as age, sex, cumulative RAI dose, and frequency of RAI administration were also documented. Based on Cox proportional hazards regression analyses adjusted for age, the authors found a hazard ratio of 7.26 (confidence interval [CI] 2.55–20.68) for undergoing surgery for NLDO after receipt of RAI in males and a hazard ratio of 7.54 (CI 5.85–9.72) in females. In both sexes higher cumulative RAI doses were associated with increased incidence of surgery for NLDO. Examining data stratified by age showed a higher risk of undergoing surgery for NLDO in patients younger than 50 years (hazard ratio 15.54 [CI: 9.76–24.72]) than in those 50 years of age and older (hazard ratio 4.58 [CI 3.40–6.18]). In both age groups higher cumulative RAI doses were associated with increased incidence of surgery for NLDO.

The 515 patients from the group of 55,371 patients treated with RAI who underwent surgery for NLDO represent a small percentage of 0.93%. Nevertheless, this exceeded the 0.13% of patients (72 out of 56,950) who underwent such surgery without having being treated with RAI therapy (18). It is likely that these numbers underestimate the frequency and magnitude of the problem. For example, a proportion of patients experiencing epiphora or other related problems may have not sought diagnostic or surgical interventions. It is also possible that development of nasolacrimal symptoms and seeking surgical intervention may not be directly proportional. For example, older patients with more comorbidities may be less likely to seek consultation for their symptoms.

Despite the small percentage of affected patients, the findings from this study will hopefully stimulate further investigations of the nasolacrimal manifestations of RAI therapy. Prospectively collected data may allow for more refined detection of side effects so that their magnitude, frequency, timing, and time course can be more accurately documented. Currently available studies suggest that lacrimal symptoms may be delayed in their onset, occurring at ∼10 months, compared with a few weeks for acute salivary gland side effects, with chronic salivary effects still occurring at 1 year in some patients and declining over time (5).

If chronic salivary side effects do not occur, nasolacrimal side effects may occur at a time that there is reduced vigilance for RAI therapy-related consequences. In addition to the evidence from this study that higher RAI dose and younger age may influence susceptibility to nasolacrimal damage, there may be other factors that merit investigation as potential risk factors. Examples of such factors might include method of preparation for RAI therapy (withdrawal from thyroid hormone vs. use of recombinant human TSH), timing of repeated RAI therapies, predisposing medications, hormonal status, the presence of Hashimoto's disease or other autoimmune conditions, adequacy of hydration, and avoidance of contact lens wearing shortly after RAI therapy.

In addition to stimulating studies that provide a deeper understanding of what factors might underlie susceptibility to nasolacrimal side effects, another opportunity that may arise from consideration of the data provided by Lee and Woo (18) is the need to educate both patients and providers about the potential for nasolacrimal side effects. Some studies have shown that patients were not aware that such side effects could occur (19,20). Furthermore, after their occurrence it is not often appreciated by either patients or clinicians that these side effects stem from RAI use.

Several studies have shown that thyroid cancer survivors have impaired quality of life after receiving their initial treatment (21 –24), with an impact from RAI therapy (25). It would be helpful to understand the degree to which nasolacrimal side effects from RAI could contribute to this impaired quality of life. Certainly data from focus groups illustrate the embarrassment and impaired social functioning experienced by patients who are asked why they are crying or have tears flowing down their faces (19). A recent consensus statement stressed the need to weigh the risk of salivary and lacrimal complications when considering RAI use (5). The authors also emphasized the need to better understand the incidence of these side effects and to study means for prevention and treatment (5). The current study by Lee and Woo (18) is a timely reminder of these needs.