Evolution of Graves’s Disease: Impact of Socio-Demographic and Clinical Factors in Senegalese Subject

Background: In Graves’s disease, there is a lack of description specific to the gender and age among sub-Saharan African subject. The objective was to evaluate the impact of gender and age on the profile of Graves’ disease in Senegalese subject in order to understand the evolution and improve the therapeutic choices. Methods: This is a retrospective study conducted from January 1, 2010 to December 31, 2017 (07 years) at Abass Ndao University Hospital (Senegal), focused on patients with Graves’ disease followed up under antithyroid drugs treatment for at least 18 months. Results: There were 244 men, 404 subjects between [0 - 25 years], and 101 subjects more than 50 years old. Factors associated with goitre size were male gender (p < 0.001), young age (p < 0.001). Graves orbitopathy was correlated with male gender (p = 0.015), and young age (p < 0.001). Among 580 patients who had stopped medical treatment after more than 18 months of follow-up, relapse involved in 30.3%. Durable remission was achieved in 38.8% of all included patients and 69.7% of subjects who had a cessation of medical treatment. The factors associated with sustained remission were female gender (p


Background
Graves's disease is an autoimmune disease described by Karl Adolph Von Basedow with a triad associating a vascular diffuse goiter, an acquired exophthalmia, in a young woman with palpitations. The emotional experience seems to precipitate the outbreak of the disease in more than 73% of cases [1] [2]. It's the most common cause of hyperthyroidism (60% to 90%). Young women are the one mainly affected. However, it does not spare men and children and elderly population [1] [2] [3]. It is reported in children and teens in 2% to 10.7%, elderly in 3.2% and male subjects in 28.79% [4] [5] [6]. In Senegal, the first-line treatment choice is based on antithyroid drugs (ATD) [3]. International guidelines recommend an adjustment of the initial dose according to the intensity of hyperthyroidism and the profile of the patient in order to simultaneously obtain antithyroid and immunosuppressive actions without important side effects [7] [8].
The typical patient at risk of failure would be the young smoker with a voluminous goiter, exophthalmos on highly active auto immunity. Smoking represents an independent and powerful factor of relapse [9]. The other therapeutic modalities are ablative surgery and radioactive iodine.
However, despite the frequency and the number of subjects suffering from this disease, the literature's data from the literature are characterized by a lack of description specific to the male, children and elderly subjects. In 2000, Allahabadia et al. [10] had conducted a similar retrospective study of 536 British subjects received for Graves' disease. Gender was not significantly associated with volume of goiter (p = 0.65), and frequency of exophthalmos (p = 0.16), while male subjects were significantly associated with high intensity of thyrotoxicosis (p = 0.04), and failure of medical treatment (p < 0.01). Young age (<40 years) was positively associated with greater goiter (p < 0.0001), frequency of exophthalmos (p < 0.0001), intensity of thyrotoxicosis (p < 0.01), and failure of medical treatment (p = 0.01). We have decided, through a comparative study to review the impact of gender and age on the clinical and evolutionary aspects of Graves' disease in Senegalese subjects at the Medical Clinic II of the Abass Ndao Hospital Center of Dakar (Senegal). The practical aspect will be a better understanding of the evolution and improving the therapeutic choices according to the profile of the patient.

Patients and Methods
The study is carried out at the Medical Clinic II of Abass Ndao University Hospital (Senegal). Any admitted patient for thyroid disease had a follow-up medical file. This was a descriptive and analytic retrospective study conducted from Janu-  [12].

Therapeutic Aspects
All patients had initially received medical treatment with antithyroid drugs (such as methimazole or carbimazol). The average daily dose of the initial treatment was  Table 2). Other side effects were agranulocytosis in 10 subjects (0.4%), transient allergic reaction in 231 subjects (10.3%), and hepatitis in 30 subjects (1.3%).
At 3 months of follow-up, a therapeutic maintenance dose of antithyroid drugs was introduced for more than 9 months in only 314 patients (30.2%). Factors most associated with the early onset of maintenance therapy were small goitre volume (p = 0.016) and absence of orbitopathy (p = 0.001). We did not find significant correlation with age and gender (p > 0.05). The frequency of hypothyroidism and the time in putting on maintenance treatment are shown in Table 2.

Evolutionary Aspects
Failure of medical treatment was found in 460 cases (44.2%). Among them, only 274 patients (59.6%) were able to benefit from a thyroidectomy. The others had chosen the long-term medical treatment option. We report that irratherapy is not currently available in Senegal. Weaning from medical treatment was found in 580 cases (55.8%). Among them, the relapse after antithyroid drugs withdrawal  Table 3).

Discussion
We corroborate the existence of a clinical and evolutionary feature of the Grave's

Epidemiological Aspects
The female predominance in Grave's disease is known. The poorly described profile is the male particularities with frequencies ranging from 12.1% to 17.2% in the West [10] [13] and 8.6% to 28.7% in Africa [3] [5] [14]. The inclusion of children and teenagers in our study explains the decline in the average age at 31.1 years. However, no age difference could be reported by sex [3] [7]. The importance of environment and genetics in the genesis of Graves' disease is known [15] [16] [17]. According to Manji et al. [18], the existence of familial history of thyreopathy was associated with the male subject (p = 0.004). In our series, it increased rather with the young age. In the specific case of the male population, Manji et al. [18] and Allahabadia et al. [10] reported a history of familial thyropathy in (40% and 42.5%) and smoking in (31.4% and 44%) respectively.
In our series, apart from the young age (p < 0.05), gender and the patient's environment did not seem to influence the intensity of thyrotoxicosis. Manji et al. [18] from an English cohort of 2405 Grave's diseases, reported that the presence of goiter was independently associated with the severity of the disease at diagnosis (p < 0.001). In addition, free T4 (p < 0.05) and active smoking (p < 0.001) were two others independent predictors of Grave's orbitopathy.
In sub-Saharan Africa, therapeutic disruption and delayed management explain in part the high rate of complications mainly cardiovascular [22]. The typical profile at risk of acute thyrotoxic crisis is the young woman with an orbitopathy.
The male subject with goiter and smoking is at risk of moderate to severe orbitopathy [12] [23]. As for cardiothyrosis, it seems more to be the prerogative of the elderly with goitre. It was reported at 9.8% and 16.6% respectively in Senegal [24] and Morocco [25]. Among the risk factors for cardiothyrosis, Diedhiou et al. [24] reported that female gender were at risk of rhythm disturbance (p = Open Journal of Internal Medicine 0.01) and right ventricular dysfunction (p = 0.007) and the intensity of thyrotoxicosis at risk of pulmonary arterial hypertension (p = 0.05).

Therapeutic and Evolutionary Aspects
Medical treatment remains the preference in Europe, Latin America and Japan [7]. In our series, the factors most associated with early maintenance therapy were the small volume of goiter and advanced age. In case of persistent hyperthyroidism, the surgical indication should be considered. However, the option of low-dose prolonged medical treatment may be selected based on the patient's preference [7] [26]. In the absence of irratherapy not available in Senegal, many of our patients preferred the long-term medical option despite its inefficiency.
The sustainable remission rate varies considerably by geographic area. We report a sustained remission of 38.8% according to the initial population. In the US, remission rates from 20% to 30% were reported after 12 to 18 months of medical treatment [27]. In a prospective study introducing the quantitative predictive "GREAT" score for Graves's disease, 37% of patients with a first episode of Graves' hyperthyroidism relapsed within 2 years after antithyroid drugs withdrawal. Lower age, higher serum TSH-Receptor antibody and free T4, larger goiters at diagnosis were independent predictors for recurrence [32].

Conclusion
We corroborate the existence of a clinical and evolutionary feature of the Grave's disease according to the age and gender in Senegalese subjects. In our study, male subject is particularized by a greater frequency of the orbitopathy, a high D. Boundia et al. Open Journal of Internal Medicine frequence of voluminous goitre and a low rate of remission. In the young patient, it is the high frequency of familial dysthyroidism, a tendency to bulky goiter and a high rate of therapeutic failure that prevails. Apart from environmental factors (stress, smoking, therapeutic accessibility), the large volume of goitre remains a determining factor of failure or recurrence after a well-conducted medical treatment. These data remain a basis for predicting the outcome of medical treatment and making timely use of radical treatments such as surgery or irratherapy in the presence of risk factors for recurrence. A prospective study using the same therapeutic modalities and monitoring of the TSH receptor auto antibodies would be highly suitable.

Limitation of the Study
The study weaknesses were mainly due to the fact that it was an observational study, that some files were incomplete for reasons of accessibility, and lastly, the difficulties of long-term follow-up.

Thanks
To all who contributed to the development of this work.

Conflicts of Interest
The authors do not declare any conflict of interest.