Introduction:
Hyperthyroidism is a rare endocrinopathy of various causes, severe and poorly documented in children from Saharan Africa.
Objective:
Describe the epidemiological, diagnostic, therapeutic and prognostic aspects of child hyperthyroidism to improved prognosis.
Materials and methods: This was a retrospective, descriptive and analytical study carried out in the pediatric department of the Universityand Teaching Hospital of Treichville from January 2012 to December 2016. It included all children aged 0 to 15 years hospitalized for
hyperthyroidism diagnosed on clinical grounds and biological. The variables studied were the epidemiological, diagnostic, therapeutic andissue aspects.
Results:
We recorded 24,000 admissions, where 27 cases was of hyperthyroidism, so let say 1 case per thousand admissions. Hyperthyroidism
involved 22 girls and 5 boys. Age was between 11 and 15 years in 89% of cases. The main signs were tachycardia (100%), goitre (100%),
exophthalmia (89%), weight loss (81.5%), dyspnea (63%) and tremor (44%). T3, T4 levels were above normal in 99% of cases. TSH was low in
96% of the cases. The causes were Graves-Basedow disease (81.4%), toxic adenoma (11.1%), multinodular goitre (3.7%) and thyroiditis (3.7%).
Synthesis of antithyroid drugs was marked by remission (52%), discharge against medical advice (33%) and death (15%). The age of more
than 10 years (P = 0.031) and the synthetic antithyroid attack dose ≥ 1 mg / kg / day (P = 0.023) were significantly associated with remission.
Conclusion:
The hyperthyroidism rare pathology of the child, affects especially the teenager with a female predominance. Graves-
Basedow disease remains the most common etiology. The treatment is based on synthetic antithyroid drugs (ATS). Thyroidectomy is a
therapeutic alternative. To improve the forecast, we needs a close cooperation between the pediatrists, the endocrinologists and the
surgeon-pediatrists
Keywords: Child, Hyperthyroidism, Exophthalmos, Basedow’s Disease, Cote d’Ivoire
Introduction:
Hyperthyroidism is an endocrinopathy characterized by hypersecretionof thyroid hormones T3 and T4. The prevalence in children varies
between 0.5 and 2% of the world population [1]. In Africa sub-Saharan,particularly in Côte d’Ivoire, the incidence of this condition is poorly
understood at the national level. However hospital series performed ininternal medicine departments [2, 3] have reported cases in adolescents.
These pediatric cases demonstrated a delayed diagnosis, at the stageof cardiovascular and neurological complications, with the consequent
difficulty of management. And yet, discovered and cared early, theprognosis of hyperthyroidism becomes excellent. How to bring the
pediatrician to early recognize the hyperthyroidism of the child in amedical environment characterized by the prevalence of infectious
diseases? To answer this question, we undertook this work whoseobjective was to describe the main epidemiological, diagnostic,
therapeutic and evolutionary aspects of the hyperthyroidism of thechild for the improvement of prognosis and professional practice.
Patients and methods
Patients
This was a retrospective, descriptive and analytical study conductedin the pediatric ward of the University Teaching Hospital of Treichvillefrom January 2012 to December 2016. The study population consisted
of children aged 0 to 15 years hospitalized during the the study.Included were all medical records of patients who had hyperthyroidism
diagnosed on clinical grounds (signs of thyrotoxicosis with or withoutocular signs, a goiter or nodule) and / or biological (free T3 ≥ 8.3pmol /
Free T4≥19.4 pmol / L, TSH ≤0.25 μIU / ml). Not included were childrenwho had hyperthyroidism with an unusable medical record and those
whose diagnosis was not confirmed by biology.
Methods
The children in the study were examined for signs of thyrotoxicosiswith or without ocular signs, goiter, or thyroid nodule. At the end
of the clinical examination, the suspected hyperthyroidism wasconfirmed by the assay of thyroid hormones free T3, free T4 coupled if
possible to Thyroid Stimulating Hormone (TSH). Hyperthyroidism wasdefined as a free T3 level higher than the normal reference value (4.0
- 8.3 pmol / ml) and a free T4 level higher than the normal referencevalue (10.6 - 19, 4 pmol / L) associated with a Thyroid Stimulating
Hormone (TSH) level below the normal reference value (0.25 - 5 μIU /ml). Other paraclinical examinations required to assess the impact of
hyperthyroidism or to identify the etiology included ECG, ultrasoundof the thyroid, and standard skeleton of the skull centered on the sella
turcica. Once the diagnosis was made, the child was given carbamizole,a synthetic antithyroid drug sometimes associated with a betablocker,
an anxiolytic, or surgery. Clinical and para-clinical examinationdata were recorded in the child’s medical record. Medical records
were used to populate the standardized survey form with the studyvariables. These variables were hospital frequency, sex, age, clinical
signs, paraclinical signs, treatment received and treatment progressTo carry out the study, we requested and obtained the authorization
of the Scientific Medical Director of the establishment. In addition, thesurvey card used was anonymous and guaranteed the confidentiality
of the information collected in the files of the children selected forthe study. The collected data were captured and analyzed on the SPSS
11 computer software. The analysis was descriptive. It consisted indetermining the numbers, calculating averages and proportions. For
the comparison of proportions we used the Chi-square test with asignificance level below 5%.
Results
Epidemiological aspects
We recorded 24,000 admissions during the study period, of which 27cases of hyperthyroidism was a hospital frequency of one case per
thousand admissions. Hyperthyroidism involved 22 girls and 5 boys.The average age was 147 months (range 64 to 180 months). The 11 to
15 age group accounted for 89% of the cases. The mother had adversesocioeconomic conditions in 92.6% of cases. All cases lived in rural
areas and drinking water was poor in iodine. The history of the 27children is marked by familial goiter in all cases (27/27, 100%), the death
of a parent (13/27, 48%), a family conflict (8/27; 6%), a lack of affection(6/27, 22%).
Diagnostic aspects
The average time of consultation was 8.6 months (extreme 4 and18 months). The main functional and physical signs are presented in
Table I. The goiter was homogeneous in 81.5% of cases and nodularin 18.5%. Exophthalmos was bilateral in 85.2% and unilateral in 3.7% of
cases. In 97% of cases there was a clinical picture of adiastole. Bloodlevels of free thyroid hormone T3 and free T4 were abnormally high
in 99% of cases. TSH was abnormally low in 96% of cases. Thyroidultrasound in 19 children revealed in 84% of cases a hypertrophied,
spherical, homogeneous and hypoechoic gland. There was veryintense hypervascularization of the Pulsed Color Doppler gland with
maximal systolic velocities (MSV) greater than 100 cm / s (often 150 cm/ sec) in the lower thyroid artery and a lowered resistance index. The
electrocardiogram performed in all patients showed sinus tachycardiain 100% of cases and atrial fibrillation in 14.8%. The causes classified by
age are presented in Table II.
Therapeutic and evolutionary aspects
All patients received synthetic antithyroid drugs. Eleven (11) childrenor 41% have had a thyroidectomy. The evolution under synthetic
antithyroid was marked during hospitalization by remission (52%),discharge against medical advice (33%) and death (15%). Follow-up
after hospitalization of the 14 cases in remission showed in the thirdyear that 9 (64%) children were still in remission and 5 (36%) relapsed.
Age greater than 10 years (P = 0, 031) and the peak dose of syntheticantithyroid drug ≥ 1 mg / kg / day (P = 0.023) were significantly
associated with remission.
Table 1:Functional and physical signs of childhood hyperthyroidism in Abidjan
Table 2:Etiologies of childhood hyperthyroidism in Abidjan
* Secondarily Toxic Multinodular Goiter.
Discussion
The aim of the study is to describe the main epidemiological, diagnostic,therapeutic and prognostic aspects of the child’s hyperthyroidism for
the improvement of the prognosis. It emerges from this work thathyperthyroidism accounted for 1 case per thousand admissions and
mainly concerned the girl aged 11 to 15 years. The clinical manifestationsare varied and Grave-Basedow disease (81% of cases) is the main
cause. The evolution under antithyroid treatment of synthesis ismarked by the remission in 52% of the cases. Lethality is high, 15% of
cases. However, these results must be qualified because the workis mono-centric and retrospective. In fact, important biological data
such as the antithyroid antibody assay, iodine and iodine levels havenot been performed. This would have made it possible to specify the
iodine status of patients and the potential role of iodine deficiency.However, the clinical and biological context was sufficient to carry the
diagnosis. Despite the limitations described above, the work raises thefollowing points of discussion at the level of the main epidemiological,
diagnostic, therapeutic and evolutionary aspects.
Epidemiologically
The hospitalization frequency of 1 case per 1000 admissions that we report is less than those of 2 and 9.9 per thousand respective of
Wemeau and al. in France [1] and Sidibé and al. in Mali [4]. This difference
can be explained not only by the methodological bias related tohospital studies but also by the lack of knowledge of the disease by
some practitioners, the absence of a specialized health structure inrural areas and the high cost of hormonal assays which does not allow
for the diagnosis of the disease. Always have the positive diagnosis.The study does not report cases of neonatal hyperthyroidism probably
due to the fact that screening for hypothyroidism in the neonatalperiod is not yet systematic in Côte d’Ivoire. The study reports 22 girls
(81%) and 5 boys (19%) with an average age of 147 months (extreme:64 and 180 months). The predominance of this condition in girls has
already been reported by other authors in the literature [1, 5]. It rarelstarts before the age of 10 years with a high frequency in adolescents
and young adults [5]. All the children in the study lived in rural areas with
modest living conditions and a history of familial goiter. The majoritycame from western Côte d’Ivoire, a mountainous region where the
iodine content of drinking water (<2 μg / kg) and cassava (<5 μg /kg) kg) is very low [6]. Cassava contains cyanogenic glycosides whose
cyanide hydrolysis in the gastrointestinal tract and then in thiocyanatein the liver inhibit the uptake of iodides by the thyroid, thus creating
the conditions for hyperthyroidism [4].
At the diagnostic level
The average consultation time is 8.6 months (4 and 18 months) withthe main reasons for admission are weight loss (59.3%), behavioral
disorders (44.4%), behavioral disorders are often mistakenlyconsidered as neurotic or reactive to a disturbed family situation. In
the study, 13 children experienced psycho-emotional shocks due todeath of parents, 8 children for family disputes and 6 children for lack
of affection. These behavioral signs, at the forefront of the study,are sources of misdiagnosis; so that hyperthyroidism is recognized
late in the complication stage as reported in other series [4, 5, 7, 8]. Inlabor, 77.8% of patients show signs of dyspnea, dysphonia, dysphagia
and bilateral exophthalmos compressions in our study. The delayeddiagnosis explains why 89% of the patients of the study are discovered
between 11 and 15 years with an average age of 12 years. The parents’indigence, ignorance, the therapeutic route with traditional healers,
lack of qualified human resources are all factors that could also explainthis delay diagnosis. In the study nearly 41% of children have a statural
advance in the study. Meziani et al. [9] reported a rate of 75%. The firstcause of hyperthyroidism in the study is Graves-Basedow disease
(81.5%). This finding has already been made by other authors in theliterature [10-11]. In the literature, Grave-Basedow disease accounts
for 10 to 15% of thyroid pathologies in children [12]. It is an autoimmunedisease, as evidenced by the presence in the affected subjects of
anti-thyroperoxidase (anti-TPO Ac) and anti-thyroglobulin (anti-TG)antibodies [13, 14]. However, the absence of these antithyroid antibodies
characteristic of the disease does not eliminate the diagnosis [15]. HLAsubjects (HLAA1, HLAB8, HLA DR3) are subject to Graves-Basedow
disease. The risk of developing this condition is multiplied by 2.4 and by5.2 in the HLA-B8 and HLA-DR3 subjects [16, 17]. In the study, the presence
of a “coffee with milk” skin spot associated with lameness, bone painwith scoliosis and early development of breast tissue in a 9-yearold
girl with Graves’ disease in the study, evokes Mc Cune-Albrightsyndrome [18]. The assay of anti-thyroperoxidase autoantibodies to
confirm this hypothesis has not been realized due to the insufficiencyof the technical plateau. For those children with Graves-Basedowdisease, cardiothyrosis is in the foreground. They all show paroxysmal
tachycardia complicated by fibrillation in 14.8% of cases. This cardiaccomplication has already been reported by Osman and al. [19]. The toxic
adenoma (11.1%), second cause in the study, is a benign tumor, usuallymonoclonal. It can be linked to somatic activating mutations of the
TSH receptor or the alpha subunit of the G protein [20]. In the literature,the frequency of toxic adenoma is variable according to the studies,
10.5% in the study of Sidibé and al. [4] in Mali and 16.7% in M’Badingaand al. [21] in Congo. Secondarily toxic multinodular goitres (GMNT)
represent 3.7% of cases. This rate, comparable to that of M’Badingaand al. (2.8%) in the Congo [21], is half of the 7.6% reported in Cameroon
by Nouedou and al. [22]. In this nosology of goitre, the somaticactivating mutations of the TSH receptor have been described; they
are distinct from one nodule to another within the same goitre [20]. Thissituation, which is very rare in children and adolescents [5], is the main
cause of hyperthyroidism in elderly patients, occurring on pre-existinggoiter with one or more nodules becoming self-supporting. The studyreports 3.7% subacute thyroiditis. In Mali, Sidibé and al. [4] reported a
rate of 2.6%. In the study, the only case of thyroiditis had a fever withrespiratory signs suggestive of a viral infection. The insufficiency of the
technical platform did not make it possible to isolate the virus in cause.
Therapeutic and evolutionary plan
In the study, the antithyroid synthesis used is carbamizole(Neomercazole) for cost and availability reasons. In Côte d’Ivoire
radical treatment by radioiodine (131) (131I) is not yet available.This therapeutic attitude has also been used by other authors [23,
24, 25] because carbamizole inhibits hormone synthesis by blockingthe activity of thyroperoxidase. Synthetic antithyroid is associated
with betablocker and sometimes anxiolytic. Betablocker is used toslow the heart in case of palpitations (81.5%). And anxiolytic to treat
nervousness (44%) or irritability too important (44%). For all patientsin the study, euthyroidism was obtained after 8 months of regular
treatment. Remission is achieved in 52% of cases with such factorssignificantly associated, age greater than 10 years (P = 0, 031) and
the dose of the antithyroid synthesis ≥ 1 mg / kg / day (P = 0.023). Therate of remission, 52%, that we report in the study is in the range of
50 to 75% reported in adults in the literature [26, 27]. This remissionis observed much earlier in the girl in our series. This fact has already
been reported by Glaser [28] in California, USA. This is related to thesmall volume of goitre and weight in relation to height without weight
loss in girls [29]. In the study, 11 euthyroid patients underwent surgicaltreatment to prevent relapse. The possibility of relapse under wellconducted
medical treatment is around 40% in the literature [30]. Theoption of surgery, as a preventive modality, was also the choice of
Nouedou et al. [20] in Yaoundé, Cameroon. The parents’ indigence, thecost of treatment and the duration of treatment are all factors that
explain the discontinuation of treatment found in 5 patients in thestudy.
Conclusions
Hyperthyroidism is a rare endocrinopathy common in girls. Thediagnosis is late in children and Graves-Basedow disease is the main
cause. Antithyroid synthesis allows remission in the majority ofcases with however frequent relapses hence the need for regular
monitoring of the patient. Improving the prognosis of patientsrequires multidisciplinary management including the pediatrician, the
pediatric surgeon and the endocrinologist.
Ethical considerations
We obtained the ethical approval from the National Ethics Committeefor Health Research (CNER), Ministry of Health Côte d’Ivoire (Arrêté n°
164 MSP/ CAB)
Competing interests
The authors declare that there is no conflict of interests regarding thepublication of this paper.
Funding
We were not financing for this study
Contribution of the authors:
All authors contributed intellectually to the writing and editing of the
manuscript.
Acknowledgments
Aholi Wognin Jean Michel, head of theComputer and Statistical Unit of the Pediatric Department of the
Treichville University Hospital
