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ORIGINAL ARTICLE
Year : 2017  |  Volume : 24  |  Issue : 4  |  Page : 183-189  

Epidemiology and clinical features of thyroid-associated orbitopathy in Accra


1 Department of Surgery, Eye Unit, School of Medicine and Dentistry, University of Ghana, Accra, Ghana
2 Department of Medicine and Therapeutics, School of Medicine and Dentistry, University of Ghana, Accra, Ghana

Date of Web Publication12-Jan-2018

Correspondence Address:
Edith Mawunyo Ackuaku-Dogbe
Department of Surgery, Eye Unit, School of Medicine and Dentistry, University of Ghana, Accra
Ghana
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/meajo.MEAJO_91_17

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   Abstract 

PURPOSE: Thyroid-associated orbitopathy (TAO), a clinical manifestation of Graves' disease, is an autoimmune disorder of the orbital and periorbital tissue. Data on the epidemiology and clinical presentation of TAO in Africa are generally scarce and unavailable in Ghana. We investigated the epidemiology and clinical features of TAO among patients with thyroid disorders attending the Korle Bu Teaching Hospital, Accra.
SUBJECTS AND METHODS: This was a descriptive cross-sectional study of patients diagnosed with thyroid disorders which was conducted at the endocrine and orbital clinics of the Korle Bu Teaching Hospital. Diagnosis was based on clinical features and confirmed by a thyroid function test. Data collected and analyzed included demography, systemic and ocular features of thyroid disorder, and thyroid function tests.
RESULTS: Of the 194 patients with thyroid disorders recruited, 117 (60.30%) had TAO. The mean age was 45.22 years (standard deviation: 13.90). The male:female ratio was 1:4.45. The most common ocular symptoms were “bulging eyes” (76/65.00%) and “puffy eyelid” (62/53.00%), and the common signs were eyelid retraction (97/82.91%) and proptosis (80/68.38%). Mild TAO was diagnosed in 64.96% of patients with only 6.84% having the severe form. The outcomes of the thyroid function test, thyroid disorder, and severity of TAO did not record any statistically significant differences.
CONCLUSIONS: The epidemiology is similar to those reported from other parts of the world, but the ocular presentation seems to be milder than in Caucasians.

Keywords: Goiter, Graves' disease, ophthalmopathy, thyroid, thyroid-associated orbitopathy


How to cite this article:
Ackuaku-Dogbe EM, Akpalu J, Abaidoo B. Epidemiology and clinical features of thyroid-associated orbitopathy in Accra. Middle East Afr J Ophthalmol 2017;24:183-9

How to cite this URL:
Ackuaku-Dogbe EM, Akpalu J, Abaidoo B. Epidemiology and clinical features of thyroid-associated orbitopathy in Accra. Middle East Afr J Ophthalmol [serial online] 2017 [cited 2018 Feb 20];24:183-9. Available from: http://www.meajo.org/text.asp?2017/24/4/183/223113




   Introduction Top


Thyroid-associated orbitopathy (TAO) is a clinical manifestation of Graves' disease (GD), an autoimmune disorder that can affect the orbital and periorbital tissue, the thyroid gland, and rarely, the pretibial skin or digits (thyroid acropachy).[1],[2],[3] Data on annual incidence in Africa are generally unavailable. The annual incidence rate of TAO has been estimated at 16 cases/100,000 women and 2.9 cases/100,000 men in a US community.[4] There appears to be a female preponderance, in which women are affected 2.5–6 times more frequently than men; however, severe cases occur more often in men than in women. Most patients are aged 30–50 years, with severe cases appearing to be more frequent in those older than 50 years.[1],[2]

Other reported factors associated with TAO include thyroid status, treatment with radioactive iodine, and smoking. It has been suggested that radioactive iodine-131 therapy may exacerbate TAO compared with antithyroid drugs or surgical ablation.[5] TAO has been reported to be strongly associated with smoking; the more severe the eye disease, the stronger the association.[2],[6] Thyroid status was influential in determining the clinical course of ophthalmopathy in several reports.[7]

The epidemiology and clinical associations of TAO have been described in Western literature with hardly any literature on Africans or Ghanaians. This study investigates the epidemiology and clinical features of TAO among patients with thyroid disorders attending the Korle Bu Teaching Hospital, Accra. The findings of the study will assist in the planning of a structured multidisciplinary approach to the management of patients with thyroid disease.


   Subjects and Methods Top


Methods

Consecutive patients presenting to the endocrine and orbital clinics of the Korle Bu Teaching Hospital, Accra, from April 2014 to July 2016 with thyroid disorders were recruited into this study after obtaining informed consent. This included patients with previously diagnosed thyroid disorders within 2 years of the study period and newly diagnosed patients presenting to the clinic for the first time. Data collection included demography, ocular and systemic features of thyroid disorder, thyroid function tests, and other medical comorbidities. In the selection of cases diagnosed earlier, reference was made to their case files and systemic characteristics and thyroid function test on presentation were documented. Results of thyroid ultrasound and thyroid autoantibodies tests were documented. There was cross referral to and from either clinic for data collection. The study was approved by the Ethics and Protocol Review Committee of the College of Health Sciences, University of Ghana (ID: MS-Et/M.7-P 4.7/2013-2014). The procedure adheres to the tenets of Declaration of Helsinki.

Ophthalmological assessment

The diagnosis of mild TAO was made based on minor lid retraction (<2 mm), mild soft-tissue involvement, exophthalmos <3 mm above normal for race and gender, no or intermittent diplopia, and corneal exposure responsive to lubricants. Moderate-to-severe TAO (thyroid eye disease) patients were those with two or more of the following: lid retraction ≥2 mm, moderate or severe soft-tissue involvement, or exophthalmos ≥3 mm above normal for race and gender, inconstant, or constant diplopia. Patients with very severe TAO patients were those with dysthyroid optic neuropathy (DON) and/or corneal breakdown due to severe exposure. Optic neuropathy was diagnosed using the following criteria: acutely reduced vision, abnormal color contrast, relative afferent pupillary defect, visual field defect by Humphrey visual field testing, disc edema, and swelling. Color vision was assessed using the Ishihara color plates' book (the abbreviated version with 24 plates). Color defects were recorded where a patient could not identify 13 or more of the numbers in the book correctly or trace correctly the colored wiggly lines in the book. The extraocular motility (EOM) function was assessed by asking the patient to move their eyes in an H-shaped pattern while severity of EOM was defined as the presence of chemosis, lid edema, and ocular proptosis.

Systemic examination

Blood pressures were measured using an automated digital blood pressure monitor (Omron 907XL pro, Healthcare, Inc., Vernon Hills, IL, USA) with subjects resting, at least for 5 min, in a seated position with a back support. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or being on antihypertensive medication.[8]

All the patients were examined for thyroid disease and had their current thyroid function tests (thyroid stimulating hormone, free triiodothyronine, and free thyroxine) done and results recorded. The thyroid gland was examined clinically to determine the grade and consistency. Grade 1 goiter was defined as a palpable but not visible thyroid gland with the head in a normal position while a visible thyroid gland with the neck in the normal position was classified as Grade 2 goiter. The clinical thyroid state at diagnosis was documented.

Statistical analysis

Data analysis was performed with the IBM SPSS Statistics for Windows, Version 20.0. (Armonk, NY: IBM Corp). Data were first examined for normality and similarity of distribution using the Kolmogorov–Smirnov test. Normally distributed continuous variables were presented as mean (standard deviation [SD]) while those which were nonnormally distributed were presented median (interquartile range). Demographical and clinical characteristics of the study participants were analyzed. Categorical variables such as ophthalmic features, clinical thyroid status, types, and grade of goiters were expressed as counts and percentages. Independent Samples t-test and Chi-square or Fisher's exact tests were used to test for associations for continuous variables and categorical variables, respectively. P < 0.05 was considered statistically significant.


   Results Top


A total of 194 patients with thyroid disorders were recruited into the study. Of these, 117 (60.30%) had TAO. The basic characteristics of patients with TAO are shown in [Table 1]. The mean age of these patients was 45.22 years (SD: 13.90), with a male-to-female ratio of 1:4.45. Only two (1.70%) participants smoked cigarette. Majority (64.96%) of the patients had mild TAO and only 6.84% had severe TAO.
Table 1: Demographic characteristics of patients with thyroid-associated orbitopathy at the KBTH

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From [Table 2], comorbid type 2 diabetes (T2DM) and hypertension were seen in 8 (6.8%) and 71 (60.7%), patients, respectively. Majority of the participants with T2DM were females (87.50%). Hypertension was also found among 87.30% of the female participants. The data did not show any statistically significant difference between males and females for both T2DM and hypertension (P = 0.589 and 0.093). Out of the 76 patients with mild TAO, majority were females (86.10%) while 13.90% were males. Severe TAO was present in eight patients (4 females and 4 males, respectively). There was no statistically significant difference in severity of TAO (P = 0.075).
Table 2: Clinical characteristics of patients with thyroid-associated orbitopathy at the KBTH

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The most common reported symptom was “bulging eyes” in 76 (65.00%) patients followed by “puffy eyelid” in 62 (53.00%) patients, while the most common signs were eyelid retraction and proptosis in 97 (82.91%) and 80 (68.38%) patients, respectively. Various degrees of extraocular muscle restrictions were found in 43 (36.75%) patients [Table 3]. The ocular features were bilateral in the majority (90.23%) of patients irrespective of thyroid status at the time of enrollment [Table 4].
Table 3: Ophthalmic features and signs among patients at presentation

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Table 4: Common eye features and thyroid status in patients with thyroid-associated orbitopathy

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Clinically, a total of 79 (67.50%) patients with TAO had goiters, and the clinical characteristics of these goiters are shown in [Table 5]. The biochemical status of patients with TAO at the time of diagnosis based on their initial time to first treatment is also displayed on [Table 5]. Majority (104/88.90%) were hyperthyroid and 77 (65.81%) of them were diagnosed with GD.
Table 5: Clinical characteristics of goiters and thyroid hormonal status with their etiologies among patients with TAO at the KBTH

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The outcomes of the thyroid function test, thyroid disorder, and severity of TAO did not record any statistically significant differences [Table 6].
Table 6: Initial thyroid function test, thyroid disorder, and severity of thyroid-associated orbitopathy patients at the KBTH

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   Discussion Top


Epidemiology

Reported prevalence of TAO among GD patients varies geographically and ranges between 25% and 50% among Caucasians.[9],[10],[11] Among Malaysians and Indians, a prevalence of 34.7% and 28% has been reported, respectively.[12],[13] An annual incidence of 16 cases/100,000 for women and 2.9 cases for men has been documented in a population in the USA.[4] The prevalence and severity have, however, been observed to have declined in recent years.[14],[15] This trend might be as a result of earlier diagnosis and treatment, enhanced attention of the ophthalmologists to the link between the initial ocular manifestations and thyroid dysfunction, and changes in smoking behavior.[14]

TAO poses clinical and therapeutic challenges. The severity of the disease is mild to moderate and self-limiting in a majority of patients. It may precede, coincide, or follow the systemic manifestations of GD. Ocular manifestations range from mild symptoms to more significant findings including vision loss from compressive optic neuropathy.[1],[3],[4]

Published data among West Africans are limited. In a Nigerian study, 30.77% of patients with thyroid disease had TAO.[16] In our study, the prevalence of TAO among patients with thyroid disease was 60.3% which is higher than the prevalence from the other studies discussed.[4],[10],[11],[12],[13],[16] Although TAO most commonly occurs in the presence of hyperthyroidism, up to 10% have been reported in the euthyroid and hypothyroid state.[11],[17]

Several studies suggest that GD and TAO occur more frequently in middle-aged women,[4],[14],[18],[19] and the female-to-male ratio of 4.45:1 recorded in our study is consistent with available data. A study in an Indian population, however, reported a much lower female-to-male ratio of 2.1:1, with a mean age of 33 years.[13]

Ophthalmic features

In the majority of patients, clinical manifestations of TAO are mild and self-limiting; however, 3%–5% of patients have severe and progressive disease.[3] In our study, 64.96% had mild, 28.20% moderate, and 6.84% severe TAO. Almost all our patients had inactive disease and only one patient had chemosis and two others had conjunctival injection. Similar results from India showed mild disease in most (83%) patients and severe sight-threatening disease in only 2% with 97% having clinically inactive TAO.[13] Studies among Nigerians reported similar finding in severity and activity.[19] Among Caucasians, however, higher prevalence of severe and active disease has been reported. In the European Group on Graves' Orbitopathy (EUGOGO) multicenter study, 28% had severe TAO with 60% having clinically active disease.[18] These differences may be explained by the higher prevalence of smoking in these populations, the possible influence of genetic variations, and other environmental factors. Smoking has been noted as an important risk factor for the onset of TAO and the development of severe TAO.[6] The prevalence of smokers has been reported to be higher in patients with TAO than in those without TAO.[20] In Ghana, a study revealed a low prevalence of 4.8% for smoking among adult men in both rural and urban areas and a corresponding nonexistence of smoking among adult females in these areas.[21] These data correspond with data from other sub-Saharan African countries.[22],[23] The phenomenon was attributed to the dominance of Christianity in these areas and the dominance of cultural norms which discourages people from smoking.[24],[25] Both our study and the Nigerian study[19] recorded low rates of smoking, and this could explain why severe disease was not commonly diagnosed.

Ethnic variability in clinical presentation of TAO exists. Our ocular findings were not much different from what has been reported in Nigeria except that we recorded diplopia in 22% of our patients against 5.3% in theirs.[19] In both studies, majority of the clinical signs were bilateral. Significantly, both studies recorded no cases of severe proptosis, optic nerve compression, or ocular dysmotility.[19] In contrast among Caucasians, the most common clinical manifestations reported were eyelid swelling (75%), proptosis (63%), and extraocular muscle restriction (49%) with 5% having unilateral disease.[18] In India, upper eyelid retraction (83%), exophthalmos (89%), and soft-tissue involvement (40%) were the common manifestations with 3% having unilateral disease.[13] Thus, generally, unilateral TAO seems to be an uncommon presentation, and the disease seems to be more severe in cigarette smoking communities.

In patients with TAO, increase in intraocular pressure (IOP) of between 1 and 15 mm upon upgaze is a common finding (60%–100%).[26] This is thought to be due to inferior rectus muscle fibrosis compressing the globe in upgaze and increasing episcleral venous pressure. In our study, this phenomenon was seen in 41% of the patients. The effect of this intermittent rise in IOP on optic nerve function was not studied.

Systemic features

TAO is the most common extrathyroidal manifestation of GD and is associated with hyperthyroidism in 90% of cases among Caucasians.[11],[17]

Similar findings have been reported in studies among Nigerians.[16],[27] In one such study, 70% of cases had GD; with hyperthyroidism in 78% of TAO patients and hypothyroidism and euthyroidism in 9.8% and 11.8% of TAO patients, respectively.[27] These support findings from our study, in which majority of patients with TAO had GD, and in addition, 88.9% of TAO patients were hyperthyroid, with 4.3% and 6.8% being hypothyroid and euthyroid, respectively.

In that Nigerian study, 68.6% of patients had a goiter with 20% classified as Grade 1, 48% as Grade 2, and 32% as Grade 3.[27] About two-thirds (67.5%) of our patients had enlarged thyroid glands with about half of them being categorized as Grade 1 goiter and the other half as Grade 2. The prevalence of goiter from the two studies is similar although it must be noted that different thyroid grading definitions were used in the studies.

Other autoimmune diseases are known to be associated with GD and TAO.[27] Type 1 diabetes mellitus and autoimmune thyroid disorder have a well-recognized association through a shared genetic susceptibility.[27] Studies have also shown a higher prevalence of thyroid dysfunction in T2DM patients with reports of a link between thyroid autoimmunity and T2DM.[28],[29] Comparing the proportion of TAO patients with comorbid diabetes, our finding (6.8%) was lower than in the EUGOGO study (9%) but marginally higher than that among Nigerians (5%).[16],[18]

Patients with coexisting TAO and DM tend to have a higher incidence of DON (15%–35%) compared to TAO patients without DM (3%–4%).[14],[30] This could be explained by a marginal oxygenation of the optic nerve in diabetic patients due to the vasculopathy, rendering the optic nerve more susceptible to the pressure of enlarged extraocular muscles.[14],[30]

Limitations

This was a hospital-based study, and the findings may not be representative of the general population.


   Conclusions Top


We report data on epidemiology and clinical presentation of patients with TAO in Ghana which to the best of our knowledge has not been reported elsewhere. Findings from our study indicate that TAO is highly prevalent among Ghanaian patients with thyroid dysfunction. The epidemiology is similar to those reported from other parts of the world. However, the ocular presentation seems to be milder than that in Caucasians. This we suspect may be as a result of the differences in smoking habits and the influence of genetic variations in these societies.

Acknowledgment

We would like to extend thanks to Madam Grace Awuah and Miss Margaret Reindolf at the Department of Medicine and Therapeutics, Korle Bu Teaching Hospital, for their assistance in the recruitment of patients for this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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