Journal of Human Endocrinology Category: Clinical Type: Research Article
Graves' Disease in Men's Subjects
- Demba Diedhiou1*, Diallo Ibrahima Mane1, Michel Assane Ndour1, Djib Sow1, Abdou Karim Diallo2, Djibril Boiro3, Marie Ka-Cisse1, Anna Sarr1, Maimouna Ndour-Mbaye1
- 1 Department Of Internal Medicine, University Hospital Center Of Dakar, Cheikh Anta Diop University, Dakar, Senegal
- 2 Department Of Preventive Medicine And Public Health, University Hospital Center Of Dakar, Cheikh Anta Diop University, Dakar, Senegal
- 3 Department Of Pediatrics, University Hospital Center Of Dakar, Cheikh Anta Diop Unive Dakar, Senegal
*Corresponding Author:Demba Diedhiou
Department Of Internal Medicine, University Hospital Center Of Dakar, Cheikh Anta Diop University, Dakar, Senegal
Received Date: Mar 12, 2018 Accepted Date: May 16, 2018 Published Date: May 31, 2018
Hyperthyroidism is the most common endocrinopathy whose major etiology is Graves' disease. Graves' disease is characterized by a thyrotoxicosis syndrome associated with a vascular diffuse goiter, a Graves' orbitopathy and presence of anti-TSH receptor antibodies. It is more common in women with a peak frequency between 40 and 60 years [1,2]. Graves' disease is an autoimmune thyroid disorder with a genetic component and environmental factors predisposing to its occurrence. Associated environmental factors include stress, infection and peripartum [3,4]. The pathophysiology of Graves' disease is based on an auto-stimulatory by TSH-Receptor Antibodies (TRAb) on the thyroid gland (vascular goiter), retro-orbital smooth muscle and retro-bulbar fibroblasts (Graves' orbitopathy), and subcutaneous tissue (dermopathy) . The diagnosis associates a thyrotoxicosis and specific signs such as Graves' orbitopathy, vascular goiter and pretibial myxoedema in rare cases. The medical treatment is mainly based on Antithyroid Drug (ATD) treatment over a period of 18 to 24 months. Ablative treatments (i.e., radioiodine therapy and surgery) are the cornerstones of healing. Although the particularities in women are sufficiently well documented , specific data in male subjects remain rare, most often embedded in an overall description of Graves' disease. A moroccan series reports on 6 years of follow-up, a mean age of 45 years, a more severe Graves' orbitopathy and a higher relapse rate compared to the female sex . The objective of this work was to study the epidemiological, clinical and evolutionary characteristics of Graves' disease in male subjects at the Medical Clinic II of Abass Ndao University Hospital Center in Dakar (Senegal).
PATIENTS AND METHODS
Treatment and evolution
For the descriptive analysis, the data were presented as a percentage for the qualitative variables and as averages with standard deviation for the quantitative variables. The statistical tests used were the Chi-2 test for qualitative variables and the student's test for quantitative variables. We also made a univariate analyze to evaluate the factors associated with relapse. A p value < 0.05 was considered statistically significant with a 95% Confidence Interval (CI). The capture and the exploitation were carried out by the software Epi info version 126.96.36.199.
Epidemiological and clinical data
The average delay of consultation was 11.79±25 months (range 1 to 36 months). The mean heart rate was 104 pulses/mn and tachycardia was found in 308 patients (50.08%). It was a goiter in 561 cases (89.90%), a Graves' orbitopathy in 455 cases (72.92%). All patients had a TSH 70 pmol/l [OR=2.85(1.53-5.30) p=0.0002]. Graves' orbitopathy was statistically correlated with the size of goiter [OR=2.08(1.42-3.07) p=0.0001]. We found no significant correlation with family history thyropathy, trigger or self-maintenance factors, delay of consultation, and age. Table 1 shows the epidemiological and clinical profile of subjects on admission.
|Characteristics of Patients on Admission||Values|
|Mean age||32.1±13 years|
|Children||28 cases (04.49%)|
|Teenager||82 cases (13.40%)|
|Adults||514 cases (82.37%)|
|Triggers or self maintaining factor||265 cases (42.46%)|
|Abandonment or isolation||67 cases (10.74%)|
|Family conflict||65 cases (10.42%)|
|Professional difficulties||137 cases (21.10%)|
|Clinical and para clinical data|
|Delay of consultation||11.79±25 months|
|Thinness||321 cases (51.44%)|
|Overweight and obesity||22 cases (03.52%)|
|Mean heart rate||104±16 pulses/mn|
|Graves' orbitopathy||455 cases (72.92%)|
|Goiter||561 cases (89.90%)|
|Goiter grade 2||212 cases (33.97%)|
|Goiter grade 3||254 cases (40.71%)|
|Goitre and Graves' orbitopathy||415 cases (66.5%)|
|Mean free T4||71.8±51 pmol/l|
Table 1: Epidemiological and clinical profile of subjects at admission.
After 30 months, only 250 subjects were regularly followed, with a percentage of 40.06%. Remission was observed in 96 patients (38.40%). Among them, 26 subjects (27.03%) had relapse. The 70 patients (28%) with full remission had a remission delay of 15 months in 45 cases (64.29%), 18 months for 14 cases (20%), and 21 months in 10 cases (14.29%). A failure of medical treatment was found in 154 patients (61.60%). Among the subjects with treatment failure, 48 (31.17%) had a thyroidectomy; the others (68.83%) are still under ATD treatment. Indications for thyroidectomy were failure of medical treatment in 33 cases, thyrotoxic heart diseases in 11 cases (23.40%), moderate-to-severe or sight-threatening orbitopathy in 2 cases (04.25%) and agranulocytosis in 2 cases.
Failure to medical treatment was significantly correlated with age < 30 years [OR=1.96(1.11-3.47), p=0.009], presence of goiter [OR=3.43(1, 41-8.37), p=0.003], grades of goiter [OR=2.50(1.34-4.64), p=0.002] and initial values of free T4 > 70 pmol [OR=1.89(1.04-4.22), p=0.017]. Other parameters such as body mass index, family history of thyropathy, trigger or self-maintenance factors, delay of consultation, Graves' orbitopathy, and Carbimazol initial dose were not shown to be significant. Table 2 shows the factors associated with the failure of medical treatment in the 250 male subjects who completed 30 months of treatment.
Evolutionary Criteria(n=250 subjects)
Odds Ratio (95% IC),p value
|Yes (n=180)||No (n=70)|
|Age < 30 years||94 (52.22%)||25 (35.71%)||
|Body mass index < 25 kg/m²||145 (96.03%)||47 (94%)||
|Delay of consultation < 12 mois||125 (70.22%)||45 (67.16%)||
|Triggers or self maintaining factor||95 (52.78%)||30 (42.86%)||
|Family thyropathy||36 (20.00%)||10 (14.28%)||
|Goiter||169 (93.88%)||59 (83.10%)||
|Goiter grades 2 et 3||147 (81.66%)||46 (65.71%)||
|Graves' orbitopathy||138 (76.66%)||51 (72.85%)||
|Free T4 value > 70 pmol/l||77 (44.77%)||21 (30%)||
|Initial Carbimazol dose < 40 mg/24h||126 (70%)||48 (68.57%)||
Table 2: Factors associated with failure of medical treatment in the 250 subjects followed for 30 months.
Epidemiological and clinical data
The frequency of the specific signs of Graves' disease was almost identical to the literature data [10,13,14,25, 26]. The presence of goiter seems less frequent compared to the female sex [12,18]. But male subjects would be characterized by a larger goiter [18,23]. As previously described in the literature, the presence of goiter in the male subject was statistically correlated with young age, Graves' orbitopathy, and free T4 value [12,18,19,23].
If the patient remains in persistent hyperthyroidism beyond 2 years of medical treatment, the surgical indication should be considered. However, the option of prolonged low-dose medical treatment may be used in case of patient preference [10,30]. In the absence of radioiodine therapy not available in Senegal, many of our patients preferred the long-term medical option despite its inefficiency.
The frequency of remission varies considerably by geographical area. After 30 months of follow-up, we report a complete remission in 28%. In the USA, remissions in 20 to 30% were reported after 12 to 18 months of medication . A European study of 5 to 6 years of medical treatment reports a remission in 50 to 60% . However, the remission rate in adults would not be improved by medical treatment beyond 18 months  or high doses of initial treatment by ATD . In addition, the male sex is more likely to recur, especially in smokers and those with large goiter [6,12,36,37]. In our study, failure in medical treatment was significantly correlated with young age [OR=1.96(1.11-3.47), p=0.009], goiter size [OR=2.50(1.34-4.64), p=0.002] and intensity of hyperthyroidism [OR = 1.89(1.04-4.42), p=0.017].
Graves' disease in male subjects remains an underrated reality. It is characterized by a delay in diagnosis, a larger goiter, a high rate of lost sight and more relapse. Apart from therapeutic education, patient support remains essential. The follow-up will have to take into account the risk factors of failure to improve the choices and therapeutic recourses. The fear of thyroidectomy should lead us to more advocacies to make available radioiodine therapy.
CONFLICT OF INTEREST
The authors do not declare any conflict of interest.
- Girgis CM, Champion BL, Wall JR (2011) Current concepts in Graves' disease. Ther Adv Endocrinol Metab 2: 135-144.
- Franklyn JA, Boelaert K (2012) Thyrotoxicosis. The Lancet 379: 1155-1166.
- Phillipe JM (2009) Graves's disease in 2009. Rev Med Suisse 5: 764-768.
- Brent GA (2008) Clinical practice Graves disease. N Engl J Med 358: 2594-2605.
- Orgiazzi J (2013) Thyroid autoimmunity. Bull Acad Natle Méd 197: 43-63.
- Bouziane T, Larwanou M, El Ouahabi H (2017) The predictive factors of relapse in Graves disease treated by ATS: About 72 cases. Ann Endocrinol 78: 326-352.
- Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall-Taylor P, Marcocci C, et al. (2008) Consensus statement of the European Group on Graves' Orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 158: 273-285.
- World Health Organization (1994) United nation children's fun & international council for control of iodine deficiency disorders Indicators for assessing iodine deficiency disorders and the control through salt iodization. World Health Organization, Geneva, Switzerland. Pg no: 1-55.
- Goichot B, Caron P, Landron F, Bouée S (2016) Clinical presentation of hyperthyroidism in a large representative sample of outpatients in France: Relationships with age, etiology and hormonal parameters. Clin Endocrinol (Oxf)84: 445-445.
- Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, et al. (2016) American thyroid association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 26: 1343-1421.
- Dahl P, Danzi S, and Klein I (2008) Thyrotoxic cardiac disease. Curr Heart Fail Rep 5: 170-176.
- Allahabadia A, Daykin J, Holder RL, Sheppard MC, Gough SCL, et al. (2000) Age and gender predict the outcome of treatment for Graves' hyperthyroidism. J Clin Endocrinol Metab 85: 1038-1042.
- Sarr A, Diédhiou D, Ndour-Mbaye NM, Sow D, Diallo IM, et al. (2016) Graves' disease in Senegal: Clinical and evolutionary aspects. Open Journal of Internal Medicine 6: 77-82.
- Diagne N, Faye A, Ndao AC, Djiba B, Kane BS, et al. (2016) Epidemiological, clinical, therapeutic and evolutive aspects of Basedow-Graves disease in the Depatment of Internal Medicine at CHU Aristide Le Dantec, Dakar (Senegal). Pan Afr Med J 25: 6.
- Bilosi M, Binquet C, Goudet P, Lalanne-Mistrih ML, Brun JM, et al. (2002) [Is subtotal bilateral thyroidectomy still indicated in patients with Grave's disease?]. Ann Chir 127: 115-120.
- Hussain YS, Hookham JC, Allahabadia A, Balasubramanian SP (2017) Epidemiology, management and outcomes of Graves' disease - Real life data. Endocrine 56: 568-578.
- Abodo J, Kélie E, Koffi Dago P, Kouassi F, Hué LA, Lokrou A (2016) Profile of the thyroid pathologies in sub-Saharan Africa: About 503 cases. Ann Endocrinol 77: 372-412.
- Manji N, Carr-Smith JD, Boelaert K, Allahabadia A, Armitage M, et al. (2006) Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype. J Clin Endocrinol Metab 91: 4873-4880.
- Boiro D, Diédhiou D, Niang B, Sow D, Mbodj M, et al. (2017) [Hyperthyroidism in children at the University Hospital in Dakar (Senegal)]. Pan Afr Med J 28: 10.
- Akossou SY, Napporn A, Goeh-Akuee E, Hillah A, Sokpoh-Diallo K, et al. (2001) Problems in the management of thyrotoxicosis in Black Africa: The Tongolese experience. Ann Endocrinol 62: 516-520.
- Léger J, Carel JC (2013) Hyperthyroidism in Childhood: Causes, when and how to treat. J Clin Res Pediatr Endocrinol 5: 50-56.
- Deleveaux I, Chamoux A, Aumaître O (2013) Stress and auto-immunity. Rev Med Interne 34: 487-492.
- Magri F, Zerbini F, Gaiti M, Capelli V, Ragni A, et al. (2016) Gender influences the clinical presentation and long-term outcome of Graves disease. Endocr Pract 22: 1336-1342.
- Diop SN, Diédhiou D, Sarr A, Ndour Mbaye M, Sylla O, et al. (2011) Psychological aspects and psychiatric manifestation of grave's disease about 104 cases. Rev Cames 12: 62-64.
- Hadj Ali I, Khiari K, Chérif L, Ben Abdallah N, Ben Maiz H, et al. (2004) [Treatment of Graves' disease: 300 cases]. Presse Med 33: 17-21.
- Morax S, Badelon I (2009) Basedow exophthalmos. J Fr Ophtalmol 32: 589-599.
- Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, et al. (2007) Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease. J Clin Endocrinol Metab 92: 2157-2162.
- Page SR, Sheard CE, Herbert M, Hopton M, Jeffcoate WJ (1996) A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism. Clin Endocrinol (Oxf) 45: 511-516.
- Wartofsky L, Glinoer D, Solomon B, Nagataki S, Lagasse R, et al. (1991) Differences and similarities in the diagnosis and treatment of Graves' disease in Europe, Japan, and the United States. Thyroid 1: 129-135.
- Villagelin D, Romaldini JH, Santos RB, Milkos A, Ward LS (2015) Outcomes in relapsed Graves' disease patients following radioiodine or prolonged low dose of methimazole treatment. Thyroid 25: 1282-1290.
- Diédhiou D, Sow D, Lèye MM, Diallo IM, Bodian M, et al. (2017) Cardiothyreosis: Risk factors and clinical profile. Open Journal of Internal Medicine 7: 1-11.
- Klein I, Becker DV, Levey GS (1994) Treatment of hyperthyroid disease. Ann Intern Med 121: 281-288.
- Mazza E, Carlini M, Flecchia D, Blatto A, Zuccarini O, et al. (2008) Long-term follow-up of patients with hyperthyroidism due to Graves' disease treated with methimazole. Comparison of usual treatment schedule with drug discontinuation versus continuous treatment with low methimazole doses: A retrospective study. J Endocrinol Invest 31: 866-872.
- Abraham P, Avenell A, Park CM, Watson WA, Bevan JS (2005) A systematic review of drug therapy for Graves' hyperthyroidism. Eur J Endocrinol 153: 489-498.
- Kruljac I, Solter D, Vrkljan AM, Solter M (2015) Remission of Graves' disease is not related to early restoration of euthyroidism with high-dose methimazole therapy. Endocr Res 40: 25-28.
- Bolanos F, Gonzalez-Ortiz M, Duron H, Sanchez C (2002) Remission of Graves' hyperthyroidism treated with methimazole. Rev Invest Clin 54: 307-310.
- Kimball LE, Kulinskaya E, Brown B, Johnston C, Farid NR (2002) Does smoking increase relapse rates in Graves' disease? J Endocrinol Invest 25: 152-157.
Citation: Diedhiou D, Diallo IM, Ndour MA, Sow D, Diallo AK, et al. (2018) Graves'Disease in Men's Subjects. J Hum Endocrinol 3: 012.
Copyright: © 2018 Demba Diedhiou, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.