|Year : 2017 | Volume
| Issue : 1 | Page : 18-21
Ophthalmic manifestation as adverse factor for cure in radioiodine treatment of Graves' disease
Yetunde A Onimode1, Kayode S Adedapo2, Magbagbeola D Dairo3
1 Department of Radiation Oncology, College of Medicine, University of Ibadan; Nuclear Medicine Centre, University College Hospital, Ibadan, Oyo State, Nigeria
2 Nuclear Medicine Centre, University College Hospital; Department of Chemical Pathology, University College Hospital, Ibadan, Oyo State, Nigeria
3 Department of Epidemiology, Medical Statistics and Environmental Health, College of Medicine, University of Ibadan and the University College Hospital, Ibadan,
Oyo State, Nigeria
|Date of Web Publication||20-Feb-2017|
Yetunde A Onimode
Department of Radiation Oncology, Nuclear Medicine Unit, College of Medicine, University of Ibadan and Nuclear Medicine Centre, University College Hospital, Ibadan, Oyo State
Source of Support: None, Conflict of Interest: None
Context: Figures from several states indicate the prevalence of primary hyperthyroidism as 1.5%–5.4%. Goiters (including Graves' disease [GD]) and diabetes mellitus are the most common presentations at Nigerian endocrine clinics. Aim: This study aims to assess the efficacy of radioactive iodine-131 therapy (RAIT) of GD, evaluate factors affecting its outcome, and to find the impact of ophthalmic symptoms on response of GD to RAIT. Participants and Methods: A retrospective review of RAI-naϊve GD patients treated from 2006 to 2016 was performed. Results: Eighty-one treatments were made in this period to 75 patients; of these, 51 patients had had no prior RAI treatment. Overall, 41 patients (78.8%) were cured by mean time to cure 4.5 ± 2.36 months. Fourteen patients (26.9%) were cured by 3 months, an additional 19 (36.5%) by 6 months, an additional 5 (9.6%) by 9 months, and 1 more by 14 months, and 2 were cured later. Cure comprised euthyroidism in 14 patients (26.9%) and outright hypothyroidism in 27 (51.9%). Graves' ophthalmopathy (GO) is associated with less likelihood of cure (P = 0.025). Those with GO were ten times less likely to be cured than those without GO (odds ratio = 0.105, confidence interval = 0.11–0.979, P = 0.048). Conclusions: Findings suggest that GO is an adverse factor in RAIT for GD (as was found in an earlier study from this center) and also suggest that patients with GO will benefit from larger doses of RAI.
Keywords: Graves' disease, Graves' ophthalmopathy, radioactive iodine
|How to cite this article:|
Onimode YA, Adedapo KS, Dairo MD. Ophthalmic manifestation as adverse factor for cure in radioiodine treatment of Graves' disease. Thyroid Res Pract 2017;14:18-21
|How to cite this URL:|
Onimode YA, Adedapo KS, Dairo MD. Ophthalmic manifestation as adverse factor for cure in radioiodine treatment of Graves' disease. Thyroid Res Pract [serial online] 2017 [cited 2017 Mar 22];14:18-21. Available from: http://www.thetrp.net/text.asp?2017/14/1/18/200563
| Introduction|| |
Although country-level data are not available, figures from several states indicate prevalence levels of primary hyperthyroidism (PT) as 1.5%–5.4%. Goiter (including toxic goiter) along with diabetes mellitus is the most common patient presentation at Nigerian endocrine clinics., Graves' disease (GD) is the most frequent cause of PT (80–85%), and is diagnosed based on diffuse goiter, thyroid biochemistry (suppressed thyroid-stimulating hormone [TSH], and elevated thyroid hormone levels), and less commonly, pretibial myxoedema. GD is also the most common type of autoimmune thyroid diseases; the latter have a prevalence of 1.2%–9.9% in Africans., The development of GD has been attributed to the presence of autoantibodies against the TSH receptor (most specifically), thyroid-stimulating antibodies as well as autoantibodies against thyroid peroxidase in a sample of Nigerian patients.
The significance of PT is in its distressing symptoms of cosmesis (goiter, weight loss, and eye signs), heat intolerance, palpitations, hand tremors, frequent bowel motions, insomnia as well as complications, notably thyrotoxic heart disease.,,, Like the prostate, the thyroid may be described as “a small gland with big problems.”
Treatment options for GD are radioiodine therapy (RAIT), antithyroid drugs (ATDs), or thyroidectomy. RAIT for PT as part of the nuclear medicine (NM) service in this center began in 2006. The majority of patients (86.4%) who have presented for RAIT have GD. The first course of action usually involves medication with ATDs typically carbimazole, as this is cheaper, or thyroidectomy. However, a growing number of patients are opting for RAIT outright, usually to avoid surgery, viewing RAIT as a noninvasive alternative.
This study aims to assess the efficacy of RAIT of GD after 10 years of NM service, evaluate factors that affect outcome of RAIT as contribution to cure or otherwise, and to determine the impact of ophthalmic symptoms on the response of GD to RAIT.
| Participants and Methods|| |
Selection and description of participants
A retrospective review of all patients treated for GD from 2006 to 2016 was performed using data extracted from patients' records. All patients were RAIT-naïve, having never been treated with RAIT. Thyroid scans were performed to assess thyroid function and to plan RAIT. GD was typically empirically treated with radioactivity of 10 mCi of iodine-131. Larger quantities of RAI were reserved for larger goiters and nodular GD. Hypothyroidism with subsequent L-thyroxine replacement was a preferred endpoint for most patients and referring clinicians than the possibility of re-treatment with RAI (at present, patients pay out of pocket for all investigations and RAIT.) For patients with Graves' ophthalmopathy (GO), oral steroids were administered prior to RAIT to prevent exacerbation of GO which may occur following RAIT. ATDs were discontinued 5 days prior to the day of treatment. Cure was defined as euthyroidism or hypothyroidism on patients' thyroid function tests from 3 months following RAIT. Once hypothyroidism was observed in any patient, L-thyroxine replacement therapy was commenced.
Data analysis was performed using Statistical Software Package for the Social Sciences (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, version 21.0. Armonk, NY: IBM Corp.) for associations between groups of categorical data using the chi-square test. Analysis of variance was used to assess association between data. Statistical significance was set at 0.05.
Patients with significant missing data were excluded from the analysis as well as those who had received multiple treatments.
Research procedures followed were in accordance with the ethical standards of the Institutional Committees on human experimentation and with the Helsinki Declaration. Patient confidentiality was strictly maintained, and data rendered anonymous except for the purpose of patient identification during statistical analysis.
| Results|| |
Eighty-one treatments were made in this period; 71 of these treatments (87.7%) were for GD, 9 (11.1%) for toxic multinodular goiter (TMG), and 1 (1.2%) for toxic solitary adenoma (TSN). Fifteen patients (20%) were lost to follow-up as they had returned to their referring clinicians or simply defaulted follow-up. After excluding another 7 patients who had been multiply treated with RAI, 52 patients who had RAI treatments for GD were eligible for the study.
Patients were aged 16–74 years (mean age 45.71 ± 13.33); the modal age group was 40 years. The range of administered RAIT was 8.77–27.3 mCi (mean administered radioactivity of 12.84 mCi ± 3.09). Forty-six (88.46%) patients were female, with a resultant sex ratio of 1:8.
Evidence of GO was present in 18 patients (34.61%) while 16 (30.77%) did not exhibit GO; the status of 18 patients (34.61%) was not known.
Only one patient was underweight at presentation (body mass index [BMI] <18); 15 (28.84%) had normal BMI (BMI 18–24.9), 17 (32.69%) were overweight (BMI 25–30), 16 (30.77%) were obese (BMI >30), and BMI was unknown for three patients (5.77%). The average BMI was 27.25 ± 5.46.
Only 5 patients had undergone prior thyroidectomy, while 47 had not. Conversely, 49 patients had been treated with ATDs, while 3 had not; nearly 93.7% of those patients on ATDs had been on carbimazole.
For RAIT, 17 patients had been treated with ≤10 mCi, 34 with 11–20 mCi, and 1 with >20 mCi.
Overall, 41 patients (78.8%) were cured; the mean time to cure was 4.5 ± 2.36 months. Fourteen patients (34.1%) were cured by 3 months, an additional 19 (36.5%) by 6 months, an additional 5 (12.2%) by 9 months, and one more by 14 months. Cure comprised euthyroidism in 14 patients (34.15%) and outright hypothyroidism in 27 patients (65.85%).
Treated patients with BMI >24 were more responsive to RAIT than those with BMI ≤24 (χ2, P = 0.023). On bivariate analysis, the presence of GO is associated with less likelihood of cure (P = 0.025). Those with GO were ten times less likely to be cured than those without GO (odds ratio = 0.105, confidence interval = 0.11–0.979, P = 0.048).
| Discussion|| |
GD has a female preponderance, and peak age incidences were cited as the second to fourth decades of life and fourth to sixth decades of life.,, The peak age incidence for our study population was in the fifth decade of life. However, more patients were aged fifty and above (55.8%) than below fifty. Most patients had received similar quantities of RAI of 15 mCi or less for GD; this might explain why the quantity of RAI administered was not a significant factor in predicting the outcome of RAIT.
Approximately, one-third of our treated patients were cured by 3 months following RAIT in this study with 8.77–22.3 mCi. It is possible that more patients had been cured by 3 months but only presented later. A study from Abuja, Nigeria, had a cure rate of 96% by 3 months in 274 hyperthyroid patients (96%, 92%, and 100% in patients with 186 diffuse goiters, 73 TMG, and 12 TSN, respectively). However, this study from Abuja employed relatively higher RAI treatment regimens; the lowest administered dose was 20 mCi compared to 8.8 mCi in our study.
From the southwestern part of the country, the outcome of RAIT in 22 thyrotoxic patients with GD was described; 11 had GD, 6 were suspected of having GD, 2 had TSN, and 3 had thyrotoxicosis of unknown etiology. Thereafter, 12 patients (54.54%) were cured after a single dose of RAI.
Up to 50% of patients with PT are said to have GO. GO has a variety of manifestations including proptosis, lid lag, lid retraction, diplopia, epiphora, and visual loss at the end of the spectrum., A desire to improve the cosmetic appearance of the staring gaze is an additional motivation for patients to seek a cure for GD. Patients have disclosed that eye signs contribute largely to psychological discomfort experienced from GD.,
GO may be clinically assessed with the NOSPECS tool. Of those patients with GO who presented for RAIT at this center, the majority had at least Class III GO. However, incidents of GO occurring without or prior to discovery of a goiter have been published.,
A previous West African study involving 94 patients with PT had inferred GO as making a cure of GD less likely following RAIT. In a smaller Nigerian study involving RAIT in 22 patients (13 females and 9 males) of whom at least 50% had GD (and 2 had active GO), the authors observed that one of the patients with GO had experienced worsening of GO post-RAIT, which responded to steroid treatment. Worsening of GO post-RAIT is a recognized potential complication which can be successfully mitigated using steroids.
Regarding the departure from the expected underweight pattern in the case of patients' BMI at the first presentation can be explained by the fact that most patients had presented for RAIT on ATD therapy. An increase in weight has been observed while hyperthyroidism is being treated with ATDs. Preexisting obesity and GD as a diagnosis are risk factors for developing obesity posttreatment. Understandably, hypothyroidism and poor hormone replacement therapy are also risk factors for developing obesity post-RAIT.,,
We observed that overweight and obese patients who were treated with RAIT were more likely to be cured. These excessive BMI values could be attributed to the extent of response to prior therapy with ATDs, with relatively more improved thyroid status prior to treatment. Previous research has also shown that BMI could predict the outcome of RAIT.
The study was limited by the small sample size of the treated patients as well as the short period of follow-up due to patients' return to sources of referral.
| Conclusions|| |
These findings suggest that GO is an adverse factor in predicting cure from RAIT, as was found in an earlier, similar study from this center. This in turn suggests that GD patients with GO will benefit from larger doses of RAI than non-GO patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ogbera AO, Kuku SF. Epidemiology of thyroid diseases in Africa. Indian J Endocrinol Metab 2011;15 Suppl 2:S82-8.
Nmadu P. Thyroid diseases in Northern Nigeria - A 15 year review. Niger Med J 1990;20:161-5.
Brent GA. Clinical practice. Graves' disease. N Engl J Med 2008;358:2594-605.
Woeber KA. Triiodothyronine production in Graves' hyperthyroidism. Thyroid 2006;16:687-90.
Ogbera AO, Okosieme OE. Thyroid diseases in Africa: Epidemiology and management challenges. Thyroid Int 2014;1:1-20.
Okosieme OE, Taylor RC, Ohwovoriole AE, Parkes AB, Lazarus JH. Prevalence of thyroid antibodies in Nigerian patients. QJM 2007;100:107-12.
Watt T, Groenvold M, Rasmussen AK, Bonnema SJ, Hegedüs L, Bjorner JB, et al.
Quality of life in patients with benign thyroid disorders. A review. Eur J Endocrinol 2006;154:501-10.
Ponto KA, Binder H, Diana T, Matheis N, Otto AF, Pitz S, et al
. Prevalence, phenotype, and psychosocial well-being in euthyroid/hypothyroid thyroid-associated orbitopathy. Thyroid 2015;25:942-8.
Ogbera AO, Fasanmade OA, Adediran O. The scope of cardiac complications of thyrotoxicosis in Lagos, Nigeria. Pak J Med Sci 2007;23:651-5.
Akossou SY, Napporn A, Goeh-Akue E, Hillah A, Sokpoh-Diallo K, Soussou B, et al.
Problems in the management of thyrotoxicosis in Black Africa: The Togolese experience. Ann Endocrinol (Paris) 2001;62:516-20.
Kirby RS. Small Gland, Big Problem: A Guide to the Prostate, Prostate Disorders and Their Treatments. 2nd
ed. London: Prostate Research Campaign UK; 2002.
Weetman AP. Graves' disease. N Engl J Med 2000;343:1236-48.
Jawa ZM, Ahmed RI, Ismail A. Clinical efficacy of a single dose radioiodine therapy for hyperthyroidism. Nile J Med Sci 2015;1:13-20.
Agboola-Abu CF, Kuku SF. Experience in the use of radioactive iodine therapy for hyperthyroidism in Nigerian patients. A study of twenty-two patients. West Afr J Med 2003;22:324-8.
Wiersinga WM, Bartalena L. Epidemiology and prevention of Graves' ophthalmopathy. Thyroid 2002;12:855-60.
Khoo TK, Bahn RS. Pathogenesis of Graves' ophthalmopathy: The role of autoantibodies. Thyroid 2007;17:1013-8.
Farid M, Roch-Levecq AC, Levi L, Brody BL, Granet DB, Kikkawa DO. Psychological disturbance in Graves ophthalmopathy. Arch Ophthalmol 2005;123:491-6.
Coulter I, Frewin S, Krassas GE, Perros P. Psychological implications of Graves' orbitopathy. Eur J Endocrinol 2007;157:127-31.
Werner SC. Modification of the classification of the eye changes of Graves' disease. Am J Ophthalmol 1977;83:725-7.
Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc 1994;92:477-588.
Onimode YA, Ankrah A, Adedapo KS. Outcome of radioiodine therapy in a West African population. World J Nucl Med 2016;15:24-9.
Bartalena L, Marcocci C, Bogazzi F, Panicucci M, Lepri A, Pinchera A. Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism. N Engl J Med 1989;321:1349-52.
Scheidhauer K, Odatzidu L, Kiencke P, Schicha H. Body weight gain after radioiodine therapy in hyperthyroidism. Nuklearmedizin 2002;41:47-51.
Dale J, Daykin J, Holder R, Sheppard MC, Franklyn JA. Weight gain following treatment of hyperthyroidism. Clin Endocrinol (Oxf) 2001;55:233-9.
Brunova J, Bruna J, Joubert G, Koning M. Weight gain in patients after therapy for hyperthyroidism. S Afr Med J 2003;93:529-31.
Karyampudi A, Hamide A, Halanaik D, Sahoo JP, Kamalanathan S. Radioiodine therapy in patients with Graves' disease and the effects of prior carbimazole therapy. Indian J Endocrinol Metab 2014;18:688-93.