|Year : 2015 | Volume
| Issue : 3 | Page : 100-103
Pharmacoeconomics of treatment options for hyperthyroidism: The Ibadan experience
Karounwi Omotayo Ogunjobi1, John Enyi Ejeh1, Aduragbenro Deborah Adedapo2, Kayode Solomon Adedapo3
1 Department of Nuclear Medicine, University College Hospital, Ibadan, Oyo State, Nigeria
2 Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Oyo State, Nigeria
3 Department of Nuclear Medicine, University College Hospital, Ibadan, Oyo State; Department of Chemical Pathology, College of Medicine, Ibadan, Oyo State, Nigeria
|Date of Web Publication||16-Oct-2015|
John Enyi Ejeh
Department of Nuclear Medicine, University College Hospital, PMB 5116 Dugbe Postoffice, Ibadan, Oyo State
Source of Support: None, Conflict of Interest: None
Objective: Hyperthyroidism is treated with anti-thyroid drugs (ATD), radioactive iodine and surgery. Debate is ongoing over which treatment option is better in terms of producing long term remission and production of fewer side effects. The cost of each option must be considered as well. Therefore, in this study, we analyzed the outcome and actual cost of treatment of patients with hyperthyroidism at our center to see which treatment modality is better. Materials and Methods: Retrospective analysis of patients' treatment records from Jan 2007 to December 2012 was carried out. 52 subjects were considered. We determined the cost of serum thyroid function tests (TSH, FT4 and FT3), hospital visit or hospitalization where necessary, pertechnetate scan, RAI therapy, ATDs and surgery in US Dollars (US$). To calculate the costs of each treatment modality, we analyzed the number of visits during this period, the laboratory data and the drugs needed. Results: All the 52 patients had received initial treatment with thionamides. 12 patients (23.1%) had subtotal thyroidectomy before coming for RAI therapy. Results showed that 12 months following RAI, 32 patients were hypothyroid and 17 became euthyroid and only 3 remained hyperthyroid; giving a remission of about 94.3%. The total average cost of treatment with lifelong ATD for average of 20 years is $1200; the mean total cost of surgery is $1500, while RAI therapy cost an average of $1000. Conclusion: In our environment the most cost effective treatment option for hyperthyroidism is RAI hence, we recommend it as first line in suitable patients.
Keywords: Anti-thyroid drugs, hyperthyroidism, Pharmacoeconomics, radioiodine therapy, thyroidectomy
|How to cite this article:|
Ogunjobi KO, Ejeh JE, Adedapo AD, Adedapo KS. Pharmacoeconomics of treatment options for hyperthyroidism: The Ibadan experience. Thyroid Res Pract 2015;12:100-3
|How to cite this URL:|
Ogunjobi KO, Ejeh JE, Adedapo AD, Adedapo KS. Pharmacoeconomics of treatment options for hyperthyroidism: The Ibadan experience. Thyroid Res Pract [serial online] 2015 [cited 2021 Dec 3];12:100-3. Available from: https://www.thetrp.net/text.asp?2015/12/3/100/159525
| Introduction|| |
Hyperthyroidism, a disease that is 10 times more common in women than men , is majorly caused by Graves' disease, followed by toxic nodular goiter.  Treatment options include anti-thyroid drugs (ATDs), radioactive iodine (RAI), and surgery. There is a large variation among physicians in the preferred modality and the method of administration. ,
In Nigeria, clinicians favor ATD or alternatively surgery (thyroidectomy). Patients with hyperthyroidism may be prescribed thionamides over a period of 18-24 months with a view to inducing a long-term remission. These drugs are also often given for a short period to render the patient euthyroid before definitive therapy with radioiodine or thyroidectomy.  Two main regimen of RAI therapy are used. These are: use of the lowest dose maintaining euthyroidism for 18 to 24 months and use of high doses with additional levothyroxine in a block-replacement strategy. None has clear advantages in terms of outcome, but the latter method is associated with more frequent side-effects. ,,
The use of RAI as first-line treatment for hyperthyroidism is growing. , This is because it is well tolerated, with the only long-term sequel being the risk of developing radioiodine induced hypothyroidism.  It may also cause deterioration in Graves' ophthalmopathy (GO) but corticosteroid cover may reduce the risk of this complication.  Dosages of RAI that are in use for treatment can be done empirically or by dosimetric calculations.  After the first dose of RAI, the follow-up schedule is typically every 2 months for up to 6 months, until the patient becomes either euthyroid or hypothyroid. 
Surgery has limited but specific roles to play in the treatment of hyperthyroidism. This approach is common with patients with toxic nodular goiter or a large goiter causing symptoms of compression in the neck. The goal of surgery is to cure the underlying pathology while leaving residual thyroid tissue to maintain postoperative euthyroidism. All patients in this category will then be placed on levo-thyroxine for life and would be monitored annually. ,,,,
The three modality of management of hyperthyroidism attracts varied cost while some patients may undergo more than one modality of treatment before remission is obtained. The purpose of this study is to analyze the outcome, and actual cost incurred in the medical treatment of patients with hyperthyroidism at our center to see if one treatment modality is superior to the other.
| Materials and Methods|| |
A retrospective analysis of patients' treatment records from January 2007 to December 2012 was carried out. A total of 67 patients diagnosed with hyperthyroidism seen at the endocrine clinic of our hospital and referred to the nuclear medicine clinic were recruited into the study. Those considered for the analysis had a minimum follow-up of at least 1-year after diagnosis and treatment. We excluded children (below 16 years of age), pregnant women, and lactating mothers. Demographic data for 52 subjects were finally considered for this study. We determined the cost of analysis of serum thyroid function tests (thyroid stimulating hormone, FT4 and FT3), hospital visit or hospitalization where necessary, cost of pertechnetate scan, RAI therapy, ATDs and surgery in US Dollars (US $). To calculate the costs of each treatment modality, we analyzed the number of visits during this period, the laboratory data and the drugs needed. Descriptive analysis was done for demographic and clinical features and results presented as number (percentage) for qualitative variables. All analyses were carried out with Statistical Package for Social Science SPSS (release I 1.5.0. standard version, copyright© SPSS: 1989-02).
| Results|| |
A total of 52 patients, 4 men (7.7%) and 48 women (92.3%), with male to female ratio 1:12 were studied. [Table 1] shows the characteristics of the subjects. The majority of the patients, about 42 (80.8%) presented with Graves' disease (diffuse toxic goiter) while 10 (19.2%) were diagnosed with toxic nodular goiter. The mean age of the group was 47.5 years with a peak incidence in the fifth decade. All the 52 patients had received initial treatment with thionamides, 49 (94.2%) patients were treated with carbimazole while 3 (5.8%) patients were treated with propylthiuracil (PTU). Twelve patients (23.1%) had subtotal thyroidectomy before coming for RAI ablative therapy [Table 2].
The occurrence of hypothyroidism 12 months following RAI therapy revealed that 32 (61.5%) patients were hypothyroid, and 17 (32.7%) became euthyroid and only 3 (5.8%) remained hyperthyroid; giving a remission of about 94.3% [Table 3]. The 32 hypothyroid patients were maintained on levo-thyroxine for 6-12 months until euthyroid status was achieved while the 3 hyperthyroid patients were retreated with a second dose of RAI successfully. The approximate cost of treatment with lifelong ATD for average of 20 years is 1200 dollars (192, 000 Naira). This is because the group needed a higher number of visits and laboratory measurements. The mean total cost of surgery is 1500 dollars (240, 000 Naira), while RAI therapy cost an average of 1000 dollars (160, 000 Naira) [Table 4].
| Discussion|| |
Debate is ongoing over which treatment is better in terms of producing long-term remission and production of fewer side effects (short- and long-term). For a developing country like Nigeria, an important aspect of the management of any medical condition also includes the cost of treatment, diagnostic testing and hospital visits. ATDs known as thionamides (carbimazole or methimazole and PTU) are usually given prior to radioiodine therapy and thyroidectomy for hyperthyroidism.
At our center, the Methimazole derivative Carbimazole is used. This is because methimazole is the active metabolite of carbimazole (carbimazole is converted to methimazole). The usual practice of our physicians is to treat patients who do not become euthyroid after 24 months of antithyroid medication with lifelong low-dose ATD. This treatment is effective, but requires continuous monitoring for possible side-effects and potential conversion to hypothyroidism. Patients will incur ATD costs. In this study, 49 patients were on carbimazole while 3 patients were on PTU for 24 months before presentation for RAI therapy. Although, the use of long-term ATDs is the most common therapeutic approach, long-term remission with ATDs can be expected in 20-50% of adults and 20-30% of children. ,
Possible side effects of ATDs include agranulocytosis and hepatotoxicity. The probabilities of these occurrences and the costs associated with each complication, including additional hospital visits, laboratory tests, and hospitalization for agranulocytosis, were taken into account. Other effects of choosing long-term ATD, including the risk of missed thyroid cancer; need for additional treatment because of uncontrolled Graves's disease, and development of goiter, nodules, or ophthalmopathy.
Surgery is rarely used in patients with Graves' disease unless radioiodine has been refused, or when there is a large goiter causing symptoms of compression in the neck. Surgery has the advantage of allowing direct tissue examination, and it offers a prompt resolution of symptoms. After surgery, thyroid function returns to normal in 90% and 98% of patients.
Thyroidectomy is a particularly good choice for patients with very large goiters since they seldom respond adequately to RAI. Surgery is also recommended for patients who plan to eventually become pregnant or patients who react severely to ATDs. The mortality of thyroidectomy is close to zero. However, there are two rare complications, recurrent laryngeal nerve damage and hypoparathyroidism, which occur in 1-2% of cases. 
Both conditions can cause lifelong disability. Other transient complications include hypocalcemia, postoperative bleeding, wound infection, keloid formation, and scars. Finding a well-experienced surgeon is of paramount importance. Hypothyroidism is said to occur in 12- 50% of patients in the 1 st year after surgery and late onset hypothyroidism develops in an additional 1-3% of patients each year, , although this may be due to the natural progression of the disease. Recurrences may develop many years after surgery. Forty-three percent of recurrences occur within 5 years after surgery. This was responsible for the 12 out of the 52 patients studied that came for RAI ablative therapy after thyroidectomy.
Cost of thyroidectomy includes a number of hospital visits, laboratory tests, and bundled costs of operation, including hospital admission associated with the procedure, follow-up and possible complications of the operation. All patients in our study were placed on levo-thyroxine for life and were monitored annually.
Radioiodine (I-131) has become the most widely used treatment of adults with thyrotoxicosis in the United States and beyond. It is also the cheapest and fastest form of therapy and has the most potential to cause hypothyroidism.  Thyroid cells can not distinguish between natural iodine and its radioisotopes, so the thyroid follicular cells take up radioiodine in the same way iodine is absorbed. Once taken by the cells, radioiodine atoms release energy in the form of beta particles and gamma rays, destroying whatever cells are at the end of their path length. The immediate effect of radioiodine is cellular necrosis (death), which provokes an inflammatory response. Tissue studies show bizarre nuclear changes "reminiscent of carcinoma," which persist for many years. Thus, radioiodine is contraindicated in children and women of childbearing age. There is no optimal dose for RAI and protocols for determining an optimal dose are controversial.  Radioiodine ablation has also been found to induce and/or exacerbate GO and pretibial myxedema. A short course of prednisone used in conjunction with radioiodine helps in preventing the development of GO.
In our study, an evaluation, including laboratory tests and pertechnetate scan, was done for all patients before RAI treatment. A single empirical dose of RAI was given to all the patients. An earlier study  established the effectiveness of a fixed dose of RAI in the treatment of hyperthyroidism. After the first dose of RAI, the follow-up schedule is typically every 3 months for up to 12 months, until the patient becomes euthyroid, hypothyroid, or it is determined that RAI needs to be repeated. In this study, in 3 out of 10 patients diagnosed with toxic nodular goiter, The first RAI therapy was not effective, and these patients were given a second dose of RAI.
This study demonstrated that RAI treatment has the lowest cost and the most effective treatment modality in the management of hyperthyroidism among the three management options considered. In a developing economy such as Nigeria where the poverty level is high and the cost of health services are largely borne by the patients and their relatives, it is instructive to recommend the use of RAI therapy for this group of patients.
| Conclusion|| |
We conclude that in our environment, the most cost effective modality of treatment for hyperthyroidism is RAI therapy and therefore recommend it as first-line in suitable patients.
| References|| |
Sandler MP, Coleman RE, Patton JA, Th Wackers FJ, Gottschalk A. Diagnostic Nuclear Medicine. 4 th
ed. USA: Lippincott Williams and Wilkings; 2003. p. 591-653.
Shargel L, Mutnic AH, Souney PF, Swanson LN. Comprehensive Pharmacy Review. 6 th
ed. New Delhi: Wolters Kluwer; 2007. p. 1179-96.
Jukic T, Stanicic J, Petric V, Kusic Z. Radioiodine versus surgery in the treatment of Graves' hyperthyroidism. Lijec Vjesn 2010;132:355-60.
Abraham P, Acharya S. Current and emerging treatment options for Graves' hyperthyroidism. Ther Clin Risk Manag 2010;6:29-40.
Wartofsky L, Glinoer D, Solomon B, Nagataki S, Lagasse R, Nagayama Y, et al.
Differences and similarities in the diagnosis and treatment of Graves' disease in Europe, Japan, and the United States. Thyroid 1991;1:129-35.
Siegel JA. Guide for Diagnostic Nuclear Medicine and Radiopharmaceutical Therapy. Virginia: SNM; 2006. p. 1-79.
Bartalena L, Tanda ML, Bogazzi F, Piantanida E, Lai A, Martino E. An update on the pharmacological management of hyperthyroidism due to Graves' disease. Expert Opin Pharmacother 2005;6:851-61.
Abraham P, Avenell A, Park CM, Watson WA, Bevan JS. A systematic review of drug therapy for Graves' hyperthyroidism. Eur J Endocrinol 2005;153:489-98.
Cooper DS. Antithyroid drugs. N Engl J Med 2005;352:905-17.
Adedapo KS, Fadiji IO, Orunmuyi AT, Onimode Y, Osifo BO. Radioactive iodine ablation therapy: A viable option in the management of Graves' disease in Nigeria. Afr J Med Med Sci 2012;41 Suppl: 193-6.
Ogunjobi KO, Ejeh JE, Adedapo KS and Eniojukan JF. Effectiveness of fixed dose radioactive iodine (RAI) for the treatment of hyperthyroidism: Experience of a Teaching Hospital in South West Nigeria. Mol Imaging Radionucl Ther 2013;22:36-41.
Ahmad AM, Ahmad M, Young ET. Objective estimates of the probability of developing hypothyroidism following radioactive iodine treatment of thyrotoxicosis. Eur J Endocrinol 2002;146:767-75.
Eckstein AK, Lax H, Lösch C, Glowacka D, Plicht M, Mann K, et al.
Patients with severe Graves' ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission. Clin Endocrinol (Oxf) 2007;67:607-12.
Sinclair D. Clinical and laboratory aspects of thyroid autoantibodies. Ann Clin Biochem 2006;43:173-83.
Grodski S, Stalberg P, Robinson BG, Delbridge LW. Surgery versus radioiodine therapy as definitive management for graves' disease: The role of patient preference. Thyroid 2007;17:157-60.
Boostrom S, Richards ML. Total thyroidectomy is the preferred treatment for patients with Graves' disease and a thyroid nodule. Otolaryngol Head Neck Surg 2007;136:278-81.
Schüssler-Fiorenza CM, Bruns CM, Chen H. The surgical management of Graves' disease. J Surg Res 2006;133:207-14.
Alsanea O, Clark OH. Treatment of Graves' disease: The advantages of surgery. Endocrinol Metab Clin North Am 2000;29:321-37.
Bhattacharyya N, Fried MP. Assessment of the morbidity and complications of total thyroidectomy. Arch Otolaryngol Head Neck Surg 2002;128:389-92.
Barrio R, López-Capapé M, Martinez-Badás I, Carrillo A, Moreno JC, Alonso M. Graves' disease in children and adolescents: Response to long-term treatment. Acta Paediatr 2005;94:1583-9.
Allahabadia A, Daykin J, Sheppard MC, Gough SC, Franklyn JA. Radioiodine treatment of hyperthyroidism-prognostic factors for outcome. J Clin Endocrinol Metab 2003;88:978-83.
[Table 1], [Table 2], [Table 3], [Table 4]