Thyroid Disorders in Childhood and Adolescence : Analysis of Clinical Data and Management Challenges in Patients Seen in a Nigerian Teaching Hospital

Background: In Nigeria, and perhaps other African countries, thyroid disorders in childhood and adolescence have not been sufficiently studied. Where studies are available, they were either conducted decades ago or they involved only adults. Objective: To describe the pattern of thyroid disorders among children and adolescents seen in a Nigerian teaching hospital and highlight the management challenges encountered. Methods: In this retrospective study, the case notes of all the children and adolescents with thyroid disorders seen in the Paediatric Endocrine-Metabolic Clinic and of those admitted into the wards of the University of Benin Teaching Hospital (UBTH) were audited. Information extracted included age, gender, duration of symptoms before presentation, clinical features, laboratory test results, management challenges and admission outcome. The total number of new cases seen at the paediatric clinics of the Department of Child Health, UBTH was derived from the clinic attendance register of the department. Results: Of the 8,350 new cases seen during the 7-year period, 9(0.12%) had thyroid disorders, representing one per 1000 new cases. Of the 9 patients with thyroid disorders, 6 (66.7%) had hyperthyroidism, 2(22.2%) had nongoitrous hypothyroidism and 1(11.1%) had euthyroid goiter. The overall mean age at presentation for thyroid disorders was 11.2+4.3 years (95% Confidence Interval, CI = 8.4-14.0)and female-to-male ratio was 4:1. For the patients with hyperthyroidism, the mean age of presentation was 12.8+3.1 years (95% CI= 10.3-15.3) and female-to-male ratio was 5:1. The mean age at presentation of the two children (a boy and a girl) with hypothyroidism was 4.75 years (range 3.5 and 6 years). The mean duration of symptoms before presentation was as follows: thyroid disorders 1.72+1.2 years (95% CI=0.94-2.50), hyperthyroidism 8.5+1.5 months (95% CI=7.3-9.7). The only case of euthyroid goiter (female) presented at the age of 14 years. The management challenges encountered included suboptimal diagnostic facilities and high clinic default rate. Conclusion: Hyperthyroidism was the most common form of thyroid disorder observed and patients with thyroid disorders tended to present late. Suboptimal diagnostic facility and high clinic default rate were the principal management challenges encountered.


INTRODUCTION
Thyroid disorders is one of the endocrine disorders commonly encountered in childhood and adolescence and they manifest with qualitative or quantitative alterations in thyroid hormone secretion, goiter or both (Desai 2009;LaFranchi 2007).Insufficient hormone secretion results in hypothyroidism and excessive secretion causes hyperthyroidism or thyrotoxicosis.Sometimes goiter exists with normal thyroid function.Although thyroid dysfunction causes disturbances of metabolic function in both children and adults, the effect on cognitive function, growth and development are unique to children (Desai 2009).Despite this well recognized profound effect of thyroid dysfunction in children, there are very few studies that have examined childhood and adolescent thyroid disorders in Nigeria and other developing countries (Laditan 1979).Majority of the available studies, either involved only adults or were conducted decades ago (Laditan 1979;Edino et al 2004;Tsegaye and Ergete 2003;Ogbera 2010).The aetiology, prevalence, clinical presentation, and clinical course of thyroid disorders in children and adolescents substantially differ from that of adults (Bettendorf 2002).
The incidence of thyroid disorders in children and adolescents appears to be increasing.For instance, Rallison et al reported an initial incidence of 3.7% for thyroid disorders but 20 years later, a repeat study in the same population by the same investigators found an incidence of 10.7% (Rallison 1991).Reports from Nigeria and other African countries suggested an increase in number of cases of hyperthyroidism among adults (Tood et al 1995;Ogbera 2007;Delange et al 1999;Kalk and Kalk 1989).Laditan et al (1979), reported that 37.0% of children with endocrine disorders seen at the University College Hospital (UCH) over a five-year period had thyroid disorders.In most parts of Africa and other resource-poor countries, the diagnosis of thyroid disorders depends largely on clinical acumen supported by a few simple laboratory tests, accounting partly for the observed paucity of studies on thyroid disorders from this region (Famuyiwa 1990a).
It has been documented that the most common presentation of thyroid disease during adolescence is an asymptomatic goiter with an incidence of 9 per 1000 per year and a female preponderance (Famuyiwa 1990a). 13It has also been stated that hyperthyroidism is less common than euthyroid goiter in children and young adolescents (Neinstein and Kaufman 1996).Various reports indicate that iodine deficiency is the commonest cause of thyroid disorders in Africa (Tsegaye and Eegete 2003;Ogbera and Kuku 2011;Brown 2009).Laditan (1979), reported that late presentation with florid clinical features including impaired physical growth and mental development is the rule rather than the exception in Nigeria and, perhaps, other developing countries (Tsegaye and Ergete 2003).In a comparative study between adult Blacks and Whites in South Africa, Kalk (1980)reported some atypical features of hyperthyroidism among the Blacks, indicating the need to study clinical pattern of thyroid disease in our local environment.Indeed, some studies have separately concluded that the pattern of thyroid disorders in a given population was dependent on its iodine-intake status ( Laurberg et al 1998;Doufas et al 1999;Boudoux et al 1996).Iodine-intake status varies from one population to another.
The purpose of this study was to describe the clinical pattern of thyroid disorders in children and adolescents seen in the Department of Child Health, University of Benin Teaching Hospital (UBTH), Benin City, Nigeria between 2005 and 2011 and highlight some of the management challenges encountered.

SUBJECTS AND METHODS
The study was conducted in the Department of Child Health, UBTH, Benin City, Nigeria and involved patients seen between 2005 and 2011.Patients seen in the hospital came mainly from Edo state and the neighbouring states of Delta, Ondo and Kogi.The Paediatric Endocrine-Metabolic Clinic of UBTH receives referrals from both within and outside the hospital (UBTH).
In this retrospective study, the cases were identified by examining the relevant hospital attendance/ admission registers and auditing the case notes of children seen at the Paediatric Endocrine-Metabolic Clinic and of those admitted into the paediatric wards at the University of Benin Teaching Hospital (UBTH), Benin City, Nigeria.The diagnosis of thyroid disorders was based on clinical features and thyroid function tests which included determination of serum levels of thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone(TSH).Information extracted included age, gender, clinical features, duration of symptoms before presentation, laboratory tests results, management challenges, and outcome of admission.The total number of new cases seen in the paediatric clinics of the Department of Child Health, UBTH was noted.Statistical analysis involved calculation of percentages, means, ratios and confidence intervals.

RESULTS
During the 7-year period under review, a total of 8,350 new cases were seen at the Paediatric Consulting Clinic of the Department of Child Health, UBTH.Of these number, 9(0.12%) had thyroid disorders, representing one per 1000 new cases.Forty nine (0.6%) patients with endocrine disorders was seen during this period and 9(18.4%) had thyroid disorders.Of the 9 patients with thyroid disorders, 6(66.7%) had hyperthyroidism, 2(22.2%) had nongoitrous hypothyroidism and 1(11.1%) had euthyroid goiter(Table 1).The mean age at presentation of thyroid disorders was 11.2 +4.3 years (95% Confidence Interval, CI=8.4-14.0)and female-to-male ratio was 4:1(Table 1).For patients with hyperthyroidism, the mean age at presentation was 12.8+3.1 years (95% CI=10.3-15.3)and female-to-male ratio was 5:1.The mean duration of symptoms before presentation for all the thyroid disorders combined was 1.72+1.2years (95% CI= 0.94-2.50)while for hyperthyroidism it was 8.5+1.5 months (95% CI= 7.3-9.7).The mean duration of symptoms before presentation in the two children with nongoitrous hypothyroidism was 4.75 years (range 3.5-6.0years).The 6-year old boy with hypothyroidism had globally delayed developmental milestones: crawled after age of 12 months, walked at about age of 3 years but unable to run at 6 years of age.Started talking at the age of 4 years but words are not clearly pronounced.The patient is in KG 1 at the age of 7 years; can say "2" and "A" but can neither count nor recite alphabets.Height was 101cm at 6 years of age.He is the only male child out of four children in this family.The mother admitted she did not notice the child's problems on time and that when she eventually did, she had hoped the child will overcome the developmental challenges with time.The 14-year old girl with goiter was found to be euthyroid and physical examination did not reveal any abnormality.She achieved menarche at the age of 13 years.There was no positive family history of thyroid disorders in any of the patients.The presenting complaint in both patients with hypothyroidism was "Does not play/dull/sluggish."Physical examination revealed that both patients had growth retardation, facial puffiness, mental retardation and delayed language development (Table 2).The 17-year old girl with hyperthyroidism had goiter for 8 months and amenorrhoea for 12 months before presentation.No history of use of oral contraceptive.Examination of the goiter revealed a diffuse, enlarged, soft gland with smooth skin and a bruit.As shown in Figure 1, goiter, lid retraction/stare, weight loss, tachycardia were present in all the six patients with hyperthyroidism.The two patients with hypothyroidism had low serum levels of T4 and T3 with elevated TSH whereas the patients with hyperthyroidism had elevated serum levels of T4 and T3 with either low or normal TSH levels (Table 3).Clinic attendance was generally poor except for one of the children with hypothyroidism.Of the six patients with hyperthyroidism, only one still attends follow up clinic.One of the adolescents with hyperthyroidism was abandoned after discharge by the parents, necessitating employing the services of law enforcement agents to repatriate the child to the parents.

DISCUSSION
The prevalence of thyroid disorders found in the present study was 1.7 fold higher than the prevalence (0.07%) reported, three decades ago, from the University College Hospital (UCH), Ibadan ( Laditan 1979).There is no readily available explanation for the higher prevalence found in the present study.In this study, the prevalence of thyroid disorders is higher in girls than boys with a ratio of 4:1.This is not surprising as other studies have reported a similar female preponderance (Laditan 1979;Rallison et al 1991;Ogbera and Kuku 2011).In the present study, hyperthyroidism accounted for two-third of all the thyroid disorders observed among the patients.This is in sharp contrast to what was found 33 years ago in UCH, Ibadan where hyperthyroidism accounted for less than one-third of all the thyroid disorders (Laditan 1979).Although the present study was not designed to examine the effect of iodine intake on the pattern of thyroid disorder in our local environment, it is possible that the universal salt iodization (USI) policy adopted by the Nigerian government might have a bearing to the relatively greater proportion of patients with hyperthyroidism in the present study compared to the study in UCH which was conducted before the USI programme (Laditan 1979).This view is reinforced by the report of several recent studies which have conclusively shown that the risk of hyperthyroidism is increased in chronically iodine-deficient individuals who are exposed to sharp increases in iodine intake (Todd et al 1995;Delange et al 1999;Laurberg et al 1998;Doufas et al 1999;Boudoux et al 1996).Considering the recent successful USI policy in Nigeria, (Federal Ministry of Health 2005) this scenario is possible and may partly explain the greater proportion of hyperthyroidism in the present study compared to the previous study in UCH, Ibadan.
As in other reports, (Rallison et al 1991;Ogbera and Kuku 2011) the present study revealed that majority of thyroid disorders presented during the period of adolescence with 11.2 years as the mean age at presentation.In contrast, the study in UCH about three decades ago, reported a much lower mean age (5.4 years) at presentation (Laditan 1979).This difference might be due to the fact that 60% of the cases in their series had congenital hypothyroidism and half of them presented before the age of six months with cretinism.The age range of their patients was 4 months to 14 years compared to 3.5 to 17 years in the present study.The absence of infants with cretinism in the present series might be related to the recent Universal Salt Iodization (USI) policy adopted by the Nigerian government Federal Ministry of Health 2005) which might have reduced the contribution of iodine deficiency to the occurrence of endemic goiter and cretinism, and ultimately, to thyroid disorders.
The unique features of the patients seen in the present study were late presentation with florid signs of either hypothyroidism or hyperthyroidism and poor clinic attendance.Similar observation has been documented in another Nigerian study (Laditan 1979).The reason for the late presentation might be due to a general lack of awareness concerning endocrine disorders in our society; a factor that has been previously emphasized by Famiyuwa in UCH, Ibadan (Famuyiwa 1990a).This view is supported by the comment made by the mother of the child with hypothyroidism (probably congenital) who presented at the age of 6 years.When this mother was asked why she delayed seeking medical help she said, "I did not notice it on time."Also she had hoped the child will overcome those developmental challenges with time (the index patient is her only male child out of four children).The well known insidious onset of hypothyroidism may have contributed to the mother overlooking the presenting features of hypothyroidism in her only son until it became florid (Desai 2009;LaFranchi 2007;Neinstein and Kaufman 1996).The present study revealed that duration of symptoms before presentation was shorter in hyperthyroidism compared with hypothyroidism, suggesting that patients with hyperthyroidism tended to present comparatively earlier than patients with hypothyroidism.This finding may be explained by the more insidious onset of hypothyroidism compared with hyperthyroidism.In addition, the presence of goiter might have contributed to the relatively shorter duration of symptoms before presentation in the case of hyperthyroidism compared to nongoitrous hypothyroidism.This in keeping with the social and cosmetic implication of the presence of goiter, particularly for teenage girls whose parents might be considering giving them out in marriage in the near future.The high clinic default rate made it difficult to document outcome of treatment and subsequent smooth transfer to adult physicians for continuation of care.This not surprising because Famuyiwa (1990b) has emphasized that majority of their patients (adults) were also lost to follow-up making it difficult to document outcome of treatment.The high level of illiteracy and widespread poverty in the country (Nigeria) might be responsible for high clinic default rate observed in this study.
The principal clinical features observed among patients with hypothyroidism in the present study included growth retardation, mental retardation, delayed language development and absence of goiter.These clinical features are in tandem with those reported among the patients seen in UCH, Ibadan (Laditan 1979).There were no cases with thyroid nodules whether solitary or multiple among the patients seen in the present study.This observation is in agreement with the report from the study at the UCH, Ibadan, suggesting that thyroid nodules are not common in childhood and adolescence (Laditan 1979).In the present study, the most common thyroid disorder observed among the adolescents was hyperthyroidism.This is in contrast to reports from the United States which stated that the most common presentation of thyroid disorders in adolescence was asymptomatic goiter (Neinstein and Kaufman 1996).The reason for this difference is not clear.It might be related to availability of more sophisticated diagnostic facility in the United States, enhancing their diagnostic capability.Inadequate laboratory facility for detailed evaluation of endocrine disorders has been previously documented as one of the major management challenges with regard to practice of endocrinology in developing countries (Famuyiwa 1990a).
For the purpose of this discussion, the management challenges encountered in these patients with thyroid disorders may be categorized into two: diagnosis and therapy.Although Graves' disease has been well documented as the commonest cause of hyperthyroidism in children and adolescents, (Desai 2009;LaFranchi 2007;Neinstein and Kaufman 1996) there was no laboratory facility to determine the presence of thyroid-stimulating immunoglobulins (TSIs) and TSH-binding inhibiting immunoglobulin (TBII) to confirm that Graves' disease was indeed the cause of hyperthyroidism among the subjects in the present study.Facilities for thyroid imaging which is known to be useful in establishing the cause of congenital hypothyroidism was not available.In the two cases with nongoitrous hypothyroidism, it would have been worthwhile to investigate for perioxidase deficiency because this is one of causes of congenital hypothyroidism with insidious onset (LaFranchi 2007).In the only case of euthyroid goiter, it would have been useful to establish the presence or absence of thyroid antibodies but we could not do this because of suboptimal diagnostic facility.Famiyuwa (1990b)in UCH, Ibadan, Nigeria has also emphasized that non-availability of tests for thyroid disorders on a regular basis greatly hinders the evaluation of patients and might contribute to missed diagnosis and under-estimation of prevalence (Hanna and LaFranchi 2002).The only treatment available for hypothyroidism is levo-thyroxine and sometimes, it is in short supply.In such a situation, apart from the difficulty in finding a pharmacy shop that stocks it, the price is inhibiting, resulting in omission of some doses by the patient or a change in the brand of levo-thyroxine.Changes in brand has been observed to influence the effective dose.Scarcity of L-thyroxine in Nigeria presents a source of serious agony not only to the patients' parents, but also, the physician because there is no substitute or alternative to this synthetic product.
In conclusion, it was observed that hyperthyroidism constituted the greatest proportion of the thyroid disorders seen between 2005 and 2011 and that most patients with thyroid disorders tended to present late.Management challenges included suboptimal diagnostic facility, a high clinic default rate, and lack of regular availability of levo-thyroxine.

Table 1 :
Age and gender distribution of nine children with thyroid disorders.

Table 2 :
Clinical features seen in two children with hypothyroidism
Figure 1: Presenting features seen in six patients with hyperthyroidism