|Year : 2021 | Volume
| Issue : 2 | Page : 67-73
Pattern of short-term adverse effects in patients undergoing low-dose radioactive iodine therapy
Ancy George1, Y Annapurna1, P Harilal2, Anila Kumari Vatakke Purayil2
1 Department of Pharmacology, Government Medical College, Kozhikode, Kerala, India
2 Department of Nuclear Medicine, Government Medical College, Kozhikode, Kerala, India
|Date of Submission||13-Feb-2022|
|Date of Decision||14-Jun-2022|
|Date of Acceptance||15-Jun-2022|
|Date of Web Publication||22-Jul-2022|
Dr. Ancy George
Mattathil House, Puthiya Road, Eroor South, Thrippunithura, Ernakulam, Kerala - 682 306
Source of Support: None, Conflict of Interest: None
Introduction: The disorders of the thyroid gland are on the rise. It involves the dysregulation of hormone synthesis and release and carcinoma of the thyroid gland among others. Radioactive iodine (RAI – I-131) is now used for the treatment of hyperthyroidism and thyroid carcinoma. This helps in the destruction of the follicular cells, and the radiation helps in annulling the cancer cells. RAI has many adverse effects including short term and long term; the short-term effects include gastrointestinal disorder, salivary dysfunction, and thyroiditis, while the long-term adverse effects include secondary carcinomas. The facilities for giving RAI therapy (RAIT) are fewer in the state of Kerala and even less in the government sector; further, the adverse effects of RAIT are less studied in our population. Thus, this study aims at finding the pattern of short-term adverse effects of low doses of RAI.
Objectives: To evaluate the pattern of short-term adverse effects following low doses of RAIT in patients with hyperthyroidism and thyroid cancer.
Materials and Methods: This study was designed as a prospective, observational study conducted in patients attending the department of nuclear medicine for low-dose radioiodine therapy in a tertiary care center. Patients were followed up for any occurrences of adverse effects at 1, 3, and 6 months. Data were analyzed using SPSS software version 18, and Chi-square test was done to find the association between dose and adverse drug reactions.
Results: The study comprised 53 participants, of which 38 (72%) were female. The adverse reactions were reported by 39 participants (74%). Loss of taste and smell in 19 participants (39%), xerostomia in 17 patients (32%), and hair loss in 14 patients (26%) were reported. After 1 month of RAIT, these subsided. The association between gender, age, dose, and adverse effects due to RAIT was tested but was found to have no association (P = 0.979, 0.504, and 0.494, respectively). The complaint of hair loss was higher in female participants, showing a statistically significant association with a P = 0.04. The complete blood counts done pre- and post-RAIT showed a statistically significant decrease in platelet count (P = 0.00) and lymphocytes (P = 0.003), with no clinically significant symptoms or signs.
Conclusion: RAI produces short-term adverse effects such as loss of taste and smell, xerostomia, and hair loss which are self-limiting. However, there is a need to identify and manage it for better treatment and patient compliance.
Keywords: Adverse effects, hyperthyroidism, radioactive iodine therapy, thyroid cancer, thyroid disorders
|How to cite this article:|
George A, Annapurna Y, Harilal P, Vatakke Purayil AK. Pattern of short-term adverse effects in patients undergoing low-dose radioactive iodine therapy. Thyroid Res Pract 2021;18:67-73
|How to cite this URL:|
George A, Annapurna Y, Harilal P, Vatakke Purayil AK. Pattern of short-term adverse effects in patients undergoing low-dose radioactive iodine therapy. Thyroid Res Pract [serial online] 2021 [cited 2022 Dec 2];18:67-73. Available from: https://www.thetrp.net/text.asp?2021/18/2/67/351791
| Introduction|| |
Disorders of thyroid glands are observed mostly in women, the reason is unknown. It is estimated that 42 million people in India are affected by thyroid disorders. The prevalence of hyperthyroidism in the Western population is 2.5–4.7/1000 females, which is comparable to the prevalence in the South Indian population of subclinical and overt hyperthyroidism being 1.6% and 1.3%, respectively.
It can be differentiated, poorly differentiated, or undifferentiated variants. Differentiated carcinoma of the thyroid gland can be papillary thyroid carcinoma and follicular thyroid carcinoma, the most common variant of thyroid carcinoma with a good prognosis accounting for 80-90% of the cases. History and clinical examination of thyroid swelling can be followed by thyroid function test tests, thyroid ultrasound scan, and FNAC to confirm the diagnosis.
The treatment modalities consist of surgery and radioactive iodine (RAI) followed by levothyroxine. Surgical therapy – total thyroidectomy – is the cornerstone for all types. Postoperative ablation therapy with RAI has been established as an adjunct therapy. RAI benefits the destruction of malignant cells.
The prevalence of hyperthyroidism is low all over the world. Coming to India, the prevalence of overt and subclinical hyperthyroidism is 1.3% and 1.6%, respectively. The most common cause of hyperthyroidism is Graves' disease. Other causes include infection, inflammation, autoimmune causes, and drug-induced.
The current treatment modalities of hyperthyroidism include antithyroid drugs, RAI, and iodine and its salts.
It is used in medical therapies as a treatment and diagnostic tool. As iodine is naturally taken up in the thyroid gland, this mechanism is utilized by radioactive isotopes for entry and localization inside the gland. When administered, it emits beta rays and gamma rays. Beta rays kill overactive thyroid cells, and gamma rays can affect the persons in the vicinity.
Radioiodine ablation refers to the destruction of the residual macroscopically normal thyroid tissue after completing the gross surgical resection of cancer. RAI collects mainly in thyroid cells and the radiation kills the cancer cells with little effect on the rest of the body. In the case of hyperthyroidism, RAI is taken up by the iodide transporter; the beta particles destroy the follicle cells, leading to control of thyrotoxicosis symptoms.
The oral dosage form is available as sodium iodide and when it is taken in, is absorbed and distributed in extracellular fluid. It is trapped by thyroid cells and exerts its action. I-131 decays by beta emission and the half-life is 8.04 days. It is later eliminated by the kidneys.
RAI therapy (RAIT) is used in low, moderate, high, and very high doses. For hyperthyroidism, a low dose (<30 mCi) is usually used. For differentiated thyroid cancer (DTC), the doses are moderate (31–50 mCi), high (51–150 mCi), and very high (>150 mCi).
RAI has also been shown to decrease mortality and recurrence in high-risk patients and is important in the treatment of invasive or metastatic disease.
RAIT also has its adverse effects which can be classified as short-term and long-term adverse effects. Long-term effects include increased risk of malignancy – leukemia and secondary cancers, radiation pulmonary fibrosis, permanent bone marrow suppression, genetic defects, and chronic xerostomia. The short-term adverse effects, even though mild, are more frequent and include gastritis – nausea and vomiting, radiation thyroiditis, sialadenitis/xerostomia, bone marrow depression, dry eye, and nasolacrimal obstruction.
In males, RAIT may cause hypospermia, and in females, it can cause complications in pregnancy and also ovarian complications. However, the female patients who had undergone radioiodine ablative therapy in childhood did not develop any abnormalities of their reproductive tracts later in life.
Among the short-term adverse effects, gastrointestinal discomforts, salivary gland dysfunction, and swelling of the neck are most common. Gastrointestinal discomforts include nausea and vomiting and are more frequent in children in whom nausea is the rule. Sialadenitis is salivary gland inflammation that leads to xerostomia. It can also cause pain, tenderness, and bitter taste. Dry mouth can be managed pharmacologically as well as nonpharmacologically. The drugs used are pilocarpine and amifostine but are usually avoided due to their high side effects. Nonpharmacological treatment includes administration of sialagogues – Vitamin C, Vitamin E, lemon juice, lemon candy, and chewing gum. Sialagogues administration can lead to decreased damage to the salivary gland.
The different categories of the patient based on RAI dosing are:
- Low dose (<30 mCi)
- Moderate dose (31–50 mCi)
- High dose (50–150 mCi)
- Very high dose (>150 mCi).
The incidence of short-term adverse effects following RAIT is 44%, of which gastritis accounts for 30%, sialadenitis/xerostomia for 30%, and radiation thyroiditis for 20%. The first I-131 ablative therapy was shown to impair the salivary uptake and secretory function of patients with DTC.
RAIT has also been shown to cause hematological changes. White blood cells (WBCs) and platelet decrease after 1 month of RAIT, whereas red blood cells and hemoglobin showed a transient drop after 1 month.
This study aims to identify the short-term adverse effects following RAI at low doses for hyperthyroidism and DTC. It also aims to assess the use of different sialagogues for dry mouth. Because identifying the adverse effects can help in better managing the patient which is worthwhile for his/her further course of treatment, this study is being done for the beneficence of the participants.
To evaluate the pattern of short-term adverse effects following low doses of RAIT in patients with hyperthyroidism and thyroid carcinoma.
| Materials and Methods|| |
All the patients undergoing RAIT at a low dose, that is, below 30 mCi, for hyperthyroidism and DTC fulfilling the inclusion criteria attending the Department of Nuclear Medicine, Government Medical College, Kozhikode.
This was a prospective observational study.
Fifty-three cases (37 cases of hyperthyroidism and 16 cases of DTC).
The study was approved by the Ethics Committee of Government Medical College, Kozhikode, and was conducted in the Department of Nuclear Medicine, Government Medical College, Kozhikode, and the Department of Pharmacology, Government Medical College, Kozhikode.
The study was conducted for a period of 1 year from January 2019 to January 2020.
- Patients with hyperthyroidism were treated with an average dose of 10 mCi and DTC with 30 mCi
- Patients giving written informed consent.
- Patients who had undergone treatment with a dose of more than 30 mCi
- Known case of hematological malignancies
- Patients not giving informed consent.
Written, informed consent was taken from the patient before the study.
The study was started after obtaining scientific research and ethics committee approval. After screening, patients who fulfilled the inclusion criteria were enrolled in the study.
The demographic details of the patients were collected, followed by details regarding present RAIT including date, the dose of RAIT, TSH values, and diagnosis of the patient. Baseline complete blood routine values were also collected and adverse effects following RAIT. Post - RAIT Blood routine values were also noted.
The outcome was the pattern of short-term adverse effects following a low dose of radioactive iodine therapy. The common short-term adverse effects include gastritis, sialadenitis, xerostomia, neck pain, thyroiditis, and decreased total peripheral count. The severity of hematological abnormalities was assessed by blood routine examination.
Statistical analysis was done using Statistical Package for Social Science (SPSS) software version 18 (IBM). All the participants who underwent low-dose radioiodine therapy were included in the statistical analysis. The outcome was expressed in percentages. Chi-square test was used to find the statistical significance of the association of dose of RAIT, age, and gender of the patient to adverse reactions following RAIT.
| Results|| |
A total of 53 participants were included in this study, of which 38 (72%) were females. The mean (standard deviation [SD]) of the age was 42. The low dose of RAIT ranged from 5 mCi to 30 mCi, the mean (SD) of which is 11.7 (8.3). The different types of adverse drug reactions (ADRs) were reported by 39 participants (74%). Out of 53, 37 participants (70%) were treated for hyperthyroidism and the rest 16 (30%) for thyroid carcinoma. Among the 37 hyperthyroid cases, 25 participants (47%) developed ADR, and 14 participants (26%) developed ADR among carcinoma patients.
The most common adverse effect reported following RAIT was the loss of taste and smell in 19 patients (39%) as cited in [Table 1], followed by xerostomia in 17 patients (32%) and hair loss in 14 patients (26%) after 1 month of RAIT which subsided soon. These were not recorded in the follow-up visit.
Chi-square test was done to find the significant association between gender and adverse effects due to RAIT. However, the test revealed no significant association between them (P = 0.979). An independent t-test was done to find the significance between age and dose with adverse effects following RAIT. No significant association between age and the presence of ADR due to RAIT (P = 0.504) was found. Although three different doses of 5, 10, and 30 mCi were given, there was no significant association with increased dose on ADR (P = 0.494).
The loss of taste and smell, xerostomia, and hair loss, which were the frequent ADRs, were tested for their association with age, dose with independent t-test, and gender with Chi-square test [Table 2]. The complaint of hair loss was higher in female participants (47%) which showed a statistically significant association (P = 0.04), as explained by more female participants. Rest of the adverse effects were not found be significantly associated with age (P = 0.645), gender (P = 0.381), or dose (P = 0.829).
|Table 2: Adverse drug reactions based on different dosing ranges in hyperthyroidism and differentiated thyroid cancer|
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The complete blood counts done before and after RAIT which was tested using paired t-test showed a statistically significant decrease of platelet count (P = 0.00) and lymphocytes (P = 0.003) with no clinically significant symptoms or signs.
| Discussion|| |
The disorders of the thyroid gland are common worldwide. There are multiple factors for the prevalence of thyroid gland disorders which include age, sex, and ethnic group. As thyroid hormones are an essential component for metabolism and survival, such disorders need to be identified and treated. Both dysregulations of hormone levels in the body and thyroid cancers are on the high.
In DTC, RAIT in the management of DTC has been employed postsurgery to ablate residual tissue and reduce recurrence. Oral administration of I-131 is done 4–6 weeks postthyroidectomy. In hyperthyroidism, the purpose of RAIT is to destroy enough thyroid tissue to make the patient euthyroid. The contraindications of RAIT are pregnancy, breastfeeding, and severely uncontrolled hyperthyroidism.
The adverse effects of RAIT are usually mild and can be divided based on the duration: short-term and long-term adverse effects. Short-term adverse effects are those that occur within 6 months of RAIT, whereas long-term adverse effects are those occurring after 6 months. The short-term adverse effects are fairly common. The study by Charalambous revealed that the usual short-term adverse effects mainly include gastrointestinal discomfort, salivary dysfunction, neck pain and swelling, insomnia, and fatigue. The long-term adverse effects include pulmonary fibrosis, secondary leukemia, early onset of menopause, and azoospermia rarely.
Lu et al. have reported in their study the short-term adverse effects of RAIT, which accounts for 67.5% of gastrointestinal adverse effects, whereas the symptoms of gastritis, nausea, and vomiting were 21%, 9%, and 7%, respectively, in this study. It may also be due to the administration of corticosteroids post-RAIT. The gastrointestinal adverse effects in the study by Van Nostrand et al. also are 67%, whereas it accounted for 34% in the study by Mohan and Agnihotri. Our study reported less number of gastrointestinal tract adverse reactions due to the use of proton pump inhibitors such as pantoprazole and H2 blockers such as ranitidine.
Apart from gastrointestinal adverse effects, the next important one was salivary gland dysfunction. Markitziu et al. have reported a case of parotid gland enlargement even one-year post-surgery and RAIT. Our study had 7% salivary gland swelling, 17% pain over the salivary gland, and 32% cases of xerostomia, which was comparable to the study of Van Nostrand et al. Christof et al. in their 33% of cases of salivary gland dysfunction, whereas Mohan et al found 47% cases of xerostomia alone. The least cases obtained is 12.8%.
The next common adverse effect encountered was the loss of taste and smell which was 39% in our study. Compared to other studies (27%), it was a bit high. 7% also complained of a metallic taste in the mouth.
The other adverse effects were thyroiditis (11%), hair loss (26%), and conjunctivitis (6%) in our study. The incidence of thyroiditis was low in our study owing to the low amount of residual tissue in postthyroidectomy patients compared to 47% in Lu et al. and 39% in Mohan and Agnihotri. Benua et al. in their study found that 7.3% of patients reported having neck pain.
Hair loss can occur as a part of hyperthyroidism, hypothyroidism, and dysfunction of parathyroid glands. Furthermore, hormone replacement can lead to a substantial amount of hair follicle loss, and hair may become brittle. Hence, the causality of hair loss cannot be attributed as a whole to RAIT.
One of the rare adverse effects encountered was hoarseness of voice, the less frequent and comparable to other studies. Vocal cord paralysis was found to be unusually high (17%) in the study by Alexander et al. Vocal cord paralysis can occur as part of the thyroid carcinoma or may follow injury to the vocal cord or nerves supplying it during surgery. Snyder reported a case of vocal cord paresis in a 61-year-old female 1 week following RAIT, suggesting the possible causality of RAIT.
Hoarseness of voice reported by our patients may or may not be due to vocal cord paralysis as we did not assess the vocal cord status or recurrent laryngeal nerve status pre- and post-treatment with RAI.
The association between dose, gender, and age to the ADR following RAIT could not be established in our study owing to the small sample size. Hair loss (P = 0.04) was found to be associated with the female gender.
Salivary gland dysfunction is a common adverse effect following radiotherapy to the head and neck. Parasympathomimetic drugs are used on and off for this purpose but are restricted due to their adverse effects. Pilocarpine is licensed for use in xerostomia induced by radiotherapy. Another drug used is cevimeline for xerostomia secondary to Sjogren's syndrome as used as a gargle by Takagi et al. Due to these reasons, alternative nonpharmacological approaches are undertaken to prevent the destruction of the salivary gland and xerostomia following it.
Christou et al. have done a systematic review of 8 studies involving nonpharmacological measures including Vitamin E, Vitamin C, lemon candy, lemon juice, and parotid massage to minimize salivary gland damage.
Hu et al. demonstrated a significant dip in WBC, hemoglobin, and platelets following RAIT at higher doses which persisted for 6 months. Molinaro et al. produced similar results of significant lowering of WBC and platelets following a single 100 mCi RAIT which lasted for 1 year. Our study produced a statistically significant lowering of lymphocytes (P = 0.003) and platelets (P = 0.000). However, clinically, this is not a significant fall for the patient to develop symptoms and consequences.
Prinsen et al. noted in their study that bone marrow function is not compromised in long term following RAIT, even though peripheral blood cell counts decreased.
There were a few limitations to our studies. This was carried out on patients with hyperthyroidism and thyroid carcinoma. The study was not able to prove statistical significance between dose and ADRs owing to the small sample size. This limitation can be overcome by conducting the study in a larger sample size. In addition, this study focused only on the short-term adverse effects of RAIT, and long-term adverse effects were not included due to the limited time period of this study.
| Conclusion|| |
This study was conducted to find out the pattern of short-term adverse effects of low-dose RAIT in patients with hyperthyroidism and DTC. The adverse effects reported were mostly mild and self-limiting. The predominant ADR was the loss of taste and smell, xerostomia, fatigue, hair loss, and gastritis. Due to the smaller sample size, the actual association of ADR could not be proved which can be rectified by taking a larger sample size study.
The proper monitoring of the ADRs and analysis is very important as it causes significant discomfort to the patients. The proper knowledge about the pattern of adverse effects is very important so that we can appraise the patient to take precautionary measures to reduce them. Low-dose radioiodine therapy is a safe and noninvasive procedure.
I profusely thank my guide Dr. Y. Annapurna, Professor, Department of Pharmacology, Government Medical College, Kozhikode, who with her able guidance, optimistic attitude and constant encouragement gave me all the confidence and determination to complete my dissertation.
I would like to express my deepest sense of gratitude and thanks to my co-guides Dr. Anila, Professor and Head of Department, and Dr. Harilal, Assistant Professor, Department of Nuclear Medicine, Government Medical College, Kozhikode, for their able guidance and support during the study. I would also like to thank Dr. Ali, Assistant Professor, Department of Nuclear Medicine, Government Medical College, Kozhikode, for his guidance in this study.
I express my sincere gratitude to Dr. M. Anuradha, Professor and Head, Department of Pharmacology, Government Medical College, Kozhikode.
I express my heartfelt respect to Dr. P. S. Jayan, Associate Professor, Dr. T. Reema, Dr. Salim, Dr. Manu Jose, Assistant Professors, Department of Pharmacology, Government Medical College, Kozhikode, for their valuable suggestions and support extended to this study.
I am thankful to Dr. Biju George, Assistant Professor, Department of Community Medicine, for his help in the statistical analysis of this study.
I express my gratitude to Dr. T. V. Sulaiman, Dr. Shabna, and other staff members for their help in undertaking the study.
I express my gratitude to Dr. C. Krishnendu, Dr. G. Laxmi, Dr. Anatte Antony, Dr. K. R. Sarath, Dr. Ashna, Dr. S. Anulakshmi, Dr. T. Anu Mohan, Senior Residents, Department of Pharamcology, for their helping hands whenever I needed.
I also thank my co-postgraduate, Dr. N. Sruthi and other junior residents for helping me to keep the enthusiasm all throughout my study period.
I thank my parents Mr. V. T. George and Mrs. Ammini George and my sisters Anitha George and Anuja George for their support and prayers and above all God Almighty for His Blessings without which the study would have been impossible.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]