Epiphora After Radioactive Iodine Ablation for Thyroid Cancer

Introduction

R adioactive iodine ablation (RIA) therapy to destroy residual thyroid tissue and to eradicate microscopic cancer is an important adjunct in the treatment of thyroid carcinoma. Since its initial use in 1946 in combination with surgery in the treatment of thyroid cancer, the side effects of radioactive iodine (¹³¹I) therapy have been generally well tolerated (1). Typical complications of this therapy are minor, and serious complications are rare. However, minor complications do not necessarily mean benign and asymptomatic manifestations for patients. Overlooking symptoms of nasolacrimal system complications can delay diagnosis and treatment in such patients (2,3). We present a young woman with epiphora due to nasolacrimal duct obstruction (NDO) after RIA, and a literature review of this condition, highlighting the importance of early recognition and intervention.

Patient

Six months after RIA therapy for well-differentiated thyroid cancer, a 23-year-old Caucasian woman presented with bilateral epiphora. The surgical pathology from her total thyroidectomy showed the largest cancer focus to be 2.4 cm (classical and follicular growth patterns of papillary cancer) with bilateral microscopic foci and eight of nine positive cervical lymph nodes. The pretreatment ¹²³I whole-body scan (WBS) at 24 hours showed 2.7% uptake with an iodine-intense area in the right thyroid bed consistent with residual tissue and four iodine-avid lymph nodes (two on the right and two on the left). The 10-day post-treatment (148 mCi) ¹³¹I WBS showed no additional uptake compared to the pretreatment scan. Three weeks after the start of her excessive tearing symptoms, she was referred to an ophthalmologist who noted total right NDO and partial left duct obstruction as the cause. She subsequently had endoscopic dacryocystorhinostomy for the bilateral outflow obstructions with resolution of her symptoms postoperatively. At her 12-month follow-up visit, the recombinant human thyrotropin WBS showed no residual disease, and she had no ophthalmic complaints.

Discussion

RIA has been used in the therapy of differentiated thyroid cancer since the 1940s (1). Mechanistically, RIA is an effective adjunct in thyroid carcinoma treatment because the sodium iodide symporter (NIS), expressed in follicular cells of the thyroid, is able to mediate uptake of iodine at the basolateral membrane of thyroid cells resulting in destruction of residual thyroid tissue (benign or malignant). Because NIS is also expressed in ductal cells of the salivary glands (4,5), painful sialoadenitis and/or decreased salivary function are the most commonly encountered sequelae of RIA. On the other hand, lacrimal drainage system complications, an intermediate to late complication of ¹³¹I therapy, are often overlooked. Further, patients may not realize that such symptoms are related to RIA, particularly since the manifestations of lacrimal damage may be delayed for up to a year or more (6). Xerophthalmia or dry eye, either by itself or part of sicca syndrome, occurs at least as frequently if not more often than salivary gland dysfunction. Epiphora, or excess tearing, in comparison, occurs less often, ranging from 4.6%–11% (2,7) with reported doses of ¹³¹I therapy as low as 100 mCi causing symptoms (8).

Complications in the lacrimal system after RIA are thought to arise via iodine uptake by NIS. NIS is present in the epithelial cells lining the nasolacrimal duct (4); it concentrates ¹³¹I in these tissues and this may result in inflammation, epithelial tissue swelling, and eventual fibrosis that can occlude these narrow ducts and canaliculi (9). Morgenstern and colleagues' study of NIS protein expression in surgically resected lacrimal system specimens obtained from non-RIA exposed patients supports this mechanism (4). Only stratified epithelial columnar cells of the basolateral membrane of the lacrimal sac and the nasolacrimal duct demonstrated positive immunohistochemical staining for NIS protein. Other areas of the lacrimal system, including the lacrimal gland, Wolfring and Klause glands (small accessory lacrimal glands), nasal mucosa, conjunctiva, and canaliculus, did not stain for NIS protein. Tissue samples from patients who had received ¹³¹I therapy were analyzed, and the samples demonstrated basolateral membrane cellular fibrosis with an absence of the NIS protein expression in the columnar cells (4). The involvement of the lacrimal sac is supported by various case reports demonstrating atypical ¹³¹I tracer accumulation on WBS congruent with the anatomic location of the lacrimal sac (9,10). ¹³¹I secretion in tears has also been documented (11).

Certain characteristics may put particular patients at risk for developing NDO, such as older age, female sex, anatomical variations, and inflammatory conditions such as sarcoid. Women appear to be at higher risk because of smaller nasolacrimal duct dimensions compared with men (12,13). In addition, ethnic differences in nasolacrimal anatomy (13) may influence the degree of stenosis that in turn determines if epiphora will be precipitated. Other risk factors for NDO include medications, such as timolol use in glaucoma treatment (14) or the chemotherapeutic agents, docetaxel (15), paclitaxel (16), and 5-fluorouracil (17).

No consistent dose-related risk, similar to that seen in other complications of RIA, has been demonstrated with lacrimal system dysfunction (18). Further, there are no clear preventative measures that have been reported. Perhaps the application of artificial tears may serve to prevent ophthalmic sequelae in the same way that sour candies have been used to potentially alleviate the complication of sialoadenitis.

Despite the fact that the precise pathophysiologic mechanisms underlying NDO after RIA therapy remain incompletely understood, it is still important for clinicians to query for eye symptoms during follow-up visits in patients who have received RIA. Recognition of features can ameliorate patient embarrassment and discomfort from excessive tearing through effective surgical interventions.