Thyroid Gland Disorders in African Children A. A. 0. Laditan, MB, MRCP, DCH, and A. 0. K. Johnson, MD, MRCP, DCH Ibadan, Nigeria
Although endocrine disorders are uncommon in black African children, thyroid gland disorders made up 37 percent of all types of 27 endocrine disorders seen at University College Hospital, Ibadan, Nigeria over a five-year period. The age range of the children was four months to 14 years. Diagnoses largely depended on clinical acumen and a few simple laboratory tests. Even the patients with congenital thyroid gland disorders tended to present late with florid classical clinical features, including disturbances of physical and mental development. In most parts of Africa and other underdeveloped areas of the world, pediatricians are preoccupied with the problems of malnutrition and infectious diseases. Thus, little attention or interest is often directed to childhood endocrine disorders which are therefore infrequently reported in the literature.' It would appear, however, that children in these areas are subject to essentially the same diseases of the thyroid gland as are adults, only that there are some differences in terms of frequency, manifestations, and the course of the disorders in the two age groups. 23
The purpose of this paper is to describe the clinical patterns of thyroid gland disorders in a group of children seen in the Department of Paediatrics, University College Hospital (UCH), Ibadan, over a five-year period between 1972 and 1976.
Patients and Methods This study was both retrospective and prospective in that some of the cases were first seen, diagnosed, and treated during this study. Most of the cases were identified by examining the case notes of children seen at the endocrine/metabolic children's clinic and of those admitted into the paediatric wards at the University College Hospital, Ibadan. The diagnoses of thyroid gland disorders were based on clinical features as well as some thyroid function tests which included serum cholesterol, serum thyroxine, and triiodothyronine resin binding. RadioRequests for reprints should be addressed to Dr. A. 0. K. Johnson, Department of Paediatrics, University College Hospital, Ibadan, Nigeria.
active iodine (1131) uptake was also measured in the older children by scintillation counting six and 24 hours after oral administration of 2 to 5 ,uCi of the isotope. Other investigations done included measurements of linear growth and body proportions as well as radiographs for skeletal maturation and maldevelopments.
Results Incidence During the five-year period under review, 14,400 new cases were seen at the Pediatric Consultative Outpatients' Clinics of UCH. Of these, there were 27 children with endocrine disorders, giving an incidence of about 0.2 percent of all new cases. Ten (37 percent) of the children with endocrine disorders had thyroid gland problems. The types of endocrine disorders are shown in Table 1. The children with thyroid gland disorders were made up of three patients with sporadic cretinism, two with endemic goitrous hypothyroidism, one with nongoitrous congenital hypothyroidism, a euthyroid girl with goiter and three with thyrotoxicosis. Nine of the children were female and only one was male. The age at diagnosis varied from four months to 14 years (Table 2). Family history of thyroid gland disorders was obtained in three of the ten children.
Clinical and Laboratory Findings The three children with congenital cretinism presented between the ages of four and five months with histories of constipation. They also had coarse and striking features which included depressed bridge of the nose with up-
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 2, 1979
turning of the nares, wrinkled foreheads, large tongues, short necks with poor head control, dry rough skins, dry sparse hair, hypotonia, and umbilical hernias. Figure 1 shows one of the children before treatment; Skeletal maturation, as demonstrated by the presence or absence of ossification centers on radiological examnination, was retarded in all three children. The serum thyroxine (T4) level was very low in each case while the triiodothyronine resin binding activities were very elevated (Table 3). The two children with endemic goitrous hypothyroidism presented in the hospital at 2'/2 years and seven years, although their thyroid gland enlargements had been observed at birth and at 5'/2 years, respectively. They were both dwarfed, with infantile body proportions; they also showed retardation of bone age. Figure 2 is a photograph of one of the children. The male child with nongoitrous congenital hypothyroidism presented with delayed developmental milestones. He was unable to walk or talk at five years of age. Clinical examination showed severe physical and mental retardation with delayed dentition and hypotonia. The radioactive iodine uptake with perchlorate flush in this child suggested a deficiency of peroxidase enzyme. The ten-year-old euthyroid girl presented with goiter without symptoms while her physical examination revealed no abnormality. She had a markedly elevated radioactive iodine uptake, but her serum cholesterol, thyroxine, and triiodothyronine resin uptake were all within normal limits. The three patients with thyrotoxicosis presented with weight loss despite good appetite, hyperactivity, exophthalmos, and thyroid gland enlargement. The striking weight loss and exophthalmos in one of these children is shown in Figure 3. Radioactive iodine uptake by the thyroid gland was carried out in two of the three children. The values obtained confirmed the presence of toxic goiter in each case (Table 3). 139
Discussion Previous reports from other parts of Africa have indicated that thyroid gland disease is less common in children than in adults. In a study by Oluwasanmi and Alli,2 it was observed that of 404 patients with simple goiter, less than two percent were under ten years of age. Olurin and others3 observed that of
.,~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~A it -X..
Figure 1Coarse facial features and short neck in sporadic cretinism. Date of birth is tatooed on the chest and abdomen.
1,000 patients with thyroid gland diseases, 845 of whom had simnple goiter, only three were between five and ten years of age, while 62 others were between 11 and 20 years. In the same study, 64 of 1,000 patients had thyrotoxicosis and only two of these were between five and ten years, while seven others were between 11 and 20 years of age. Patel4 reported five cases of thyrotoxicosis from Mulago Hospital, Kampala, Uganda seen over a seven year period. None of these was less than 20-years old, their ages ranging between 23 and 39 years. Three of the children in the present study were less than six months of age at presentation. Etiologically, hypothyroid states in infants and young children may result from a congenital defect of the thyroid gland which either may fail to develop at all or may be lacking in one of the enzymes necessary for synthesis of the thyroid hormones. It may also be due to local iodine deficiency as occurs in certain areas of the world or it may be a result of ingestion of goitrogens. There is a high incidence of endemic goiter in certain parts of Nigeria. It is prevalent in the areas north of Ondo province which lie far away from the sea and in areas south of Ibadan province, for example, Abeokuta and Uebu where cassava, with its high cyanide
content, is the staple diet.2'5 Three of the patients with goiter came from this area: two were hypothyroid while the third was in a euthyroid state. One of the four patients with nongoitrous hypothyroidism was subsequently diagnosed as a case of congenital intrathyroid peroxidase enzyme deficiency. The three others were athyroidal cretins. Endemic cretinism is often associated with goitrogenesis and usually results from local iodine deficiency or occurs in babies of hypothyroid mothers, whereas sporadic cretinism is often due to aplasia or hypoplasia of the thyroid gland. The clinical features of hypothyroidism in childhood differ from those in adults because of the accompanying retardation in the rate of growth and development and these are usually very striking. The changes in the skin, hair, sub-
Table 1. Types of Endocrine Disorders in 27 Children Seen Over Five Years
Type Thyroid disorders Diabetes mellitus Adrenogenital syndrome Incomplete testicular feminization Nephrogenic diabetes insipidus Total
Number of Cases
of Total
10 8 5 3 1 27
37 30 18 11 4 100
Percent
._.
Fiu2 e olrfriggien grwhstnigin7ya-odgr wit en hpty rodim
emi otos
Table 2. Age and Sex Distribution of Ten Children with Various Thyroid Disorders
Patients
Thyroid Disorders
Age at Presentation (years)
Sex
i 2 3 4 5 6
Sporadic cretinism Sporadic cretinism Sporadic cretinism Goitrous hypothyroidism Goitrous hypothyroidism Nongoitrous congenital hypothyroidism Endemic goiter Thyrotoxicosis Thyrotoxicosis Thyrotosicosis
4/12 4/12 5/12 21/2 7
F F F F F
5 10 7 8 14
M F F F F
7 8 9 10
140
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 2, 1979
Table 3. Mean Cholesterol, Thyroxine (T4) Triiodothyronine (T3) Resin Binding and Radioactive Iodine (1131) Uptake in Children with Various Thyroid Disorders Thyroid Disorder
Cretinism Goitrous hypothyroidism Thyrotoxicosis Endemic goiter *Normal
Cholesterol
(mg/lOOml)
T4 (mg/lOOml)
T3 resin binding
272 233 134 130 100-200
0.6 1.2 11.6 6.8 3.5-12.5
137 131 108 107 90-120
(percent)
1131 Uptake At 6 hrs At 24 hrs (percent) 42.0 54.5 58.1 7-25
42.5 66.6 70.9 15-40
*Normal values in our laboratory.
cutaneous tissues, and muscle are similar to those in adult myxedema. Thus, the unique changes in childhood hypothyroidism include a coarse ugly facial appearance, delayed developmental milestones, dwarfism, and infantile body proportions.6 In hypothyroid states, especially when of
congenital origin, radiological examination often shows marked retardation in osseous development with some other characteristic changes such as epiphyseal dysgenesis and vertebral body deformity.7 The etiology of thyrotoxicosis is multifactorial. In childhood, thyrotoxicosis is rarer than hypothyroidism. It occurs more frequently among adolescent females. Three of our patients demonstrated features of thyrotoxicosis but since serum antithyroglobulin antibodies, as well as thyroid-stimulating hormone levels, could not be determined, the exact cause of the disease was not established. Acute infections have been reported to be implicated in the etiology of thyrotoxicosis.8 However, no antecedent infections were evident in these patients, and as infections are so common in this environment, one would have expected to see more cases of thyrotoxicosis in childhood. These manifestations include nervousness, goiter, exophthalmos, and tachycardia. All of these were observed in the three patients with thyrotoxicosis. Nervousness characterized by restlessness, emotional instability, personality changes, and deteriorating school performance is very common and is usually the first evidence that is observed, either by the parents or school teacher. Diffuse enlargement of the thyroid gland occurs almost without exception and it generally develops early in the course of the disease.
Conclusion
Figure 3. A child with thyrotoxicosis; note the muscle wasting and the exophthalmos.
Although childhood thyroid gland disease is uncommon in Africa, it does occur in as wide a spectrum as it occurs in adults. Early diagnosis and prompt treatment are very important, as delay may lead to permanent physical and
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 2, 1979
mental retardation. However, the diagnosis often is not made early, partly because the parents may not have observed the odd features and behavior of their child until much later. Furthermore, since medical centers are few and located mainly in urban centers, parents in rural areas seldom bother to make the usually long, expensive, and tedious journey from their rural homes except when the child is severely affected. When the child does finally present at a hospital, the diagnosis often can be made clinically, and indeed, has to be made clinically because of the little or scanty diagnostic aids available in most medical centers in Africa. Adadevoh and others9 have stressed the importance of laboratory facilities in the diagnosis of childhood endocrine disorders and it is possible that lack of these diagnostic facilities may have contributed to the underestimation of the incidence of some of these disorders in many parts of Africa. Acknowledgement The authors wish to thank their colleagues who were involved in the care of some of the patients.
Literature Cited 1. Adedevoh BK: Endocrine patterns in Africans: Clinico-biochemical assessment. Trop
Geog Med 22:125-141, 1970 2. Oluwasanmi JO, Alli AF: Goitres in western Nigeria. Trop Geog Med 20:357-366, 1968 3. Olurin EO, Itayemi SO, Oluwasanmi JO, et al: Pattern of thyroid gland disease in Ibadan. Niger Med J 3:58-65, 1973 4. Patel KM: Thyrotoxicosis at Mulago Hospital. East Afr Med J 39:600-604, 1963 5. Osuntokun BO: Cassava diet and cyanide metabolism in Wistar rats. Br J Nutr 24:377-380, 1970 6. Hutchison JH: Practical Paediatric Problems. London, Lloyd-Luke, 1972 7. Familusi JB, Lagundoye SB: Congenital sporadic athyrotic cretinism-a review with three additional cases in Nigerian children. Dokita 2:1-8, 1970 8. Alexander WD, Harden RM, Shimmins J: Emotional and nonspecific infection as possible aetiological factors in Graves' Disease: Their relation to thyroid suppressibility. Lancet 2:196197, 1968 9. Adedevoh BK, Francis TI, Ajayi 00: Endocrine disorders in African children. Niger Med J 2:2-6, 1972
141
Although endocrine disorders are uncommon in black African children, thyroid gland disorders made up 37 percent of all types of 27 endocrine disorders seen at University College Hospital, Ibadan, Nigeria over a five-year period. The age range of the children was four months to 14 years. Diagnoses largely depended on clinical acumen and a few simple laboratory tests. Even the patients with congenital thyroid gland disorders tended to present late with florid classical clinical features, including disturbances of physical and mental development. In most parts of Africa and other underdeveloped areas of the world, pediatricians are preoccupied with the problems of malnutrition and infectious diseases. Thus, little attention or interest is often directed to childhood endocrine disorders which are therefore infrequently reported in the literature.' It would appear, however, that children in these areas are subject to essentially the same diseases of the thyroid gland as are adults, only that there are some differences in terms of frequency, manifestations, and the course of the disorders in the two age groups. 23
The purpose of this paper is to describe the clinical patterns of thyroid gland disorders in a group of children seen in the Department of Paediatrics, University College Hospital (UCH), Ibadan, over a five-year period between 1972 and 1976.
Patients and Methods This study was both retrospective and prospective in that some of the cases were first seen, diagnosed, and treated during this study. Most of the cases were identified by examining the case notes of children seen at the endocrine/metabolic children's clinic and of those admitted into the paediatric wards at the University College Hospital, Ibadan. The diagnoses of thyroid gland disorders were based on clinical features as well as some thyroid function tests which included serum cholesterol, serum thyroxine, and triiodothyronine resin binding. RadioRequests for reprints should be addressed to Dr. A. 0. K. Johnson, Department of Paediatrics, University College Hospital, Ibadan, Nigeria.
active iodine (1131) uptake was also measured in the older children by scintillation counting six and 24 hours after oral administration of 2 to 5 ,uCi of the isotope. Other investigations done included measurements of linear growth and body proportions as well as radiographs for skeletal maturation and maldevelopments.
Results Incidence During the five-year period under review, 14,400 new cases were seen at the Pediatric Consultative Outpatients' Clinics of UCH. Of these, there were 27 children with endocrine disorders, giving an incidence of about 0.2 percent of all new cases. Ten (37 percent) of the children with endocrine disorders had thyroid gland problems. The types of endocrine disorders are shown in Table 1. The children with thyroid gland disorders were made up of three patients with sporadic cretinism, two with endemic goitrous hypothyroidism, one with nongoitrous congenital hypothyroidism, a euthyroid girl with goiter and three with thyrotoxicosis. Nine of the children were female and only one was male. The age at diagnosis varied from four months to 14 years (Table 2). Family history of thyroid gland disorders was obtained in three of the ten children.
Clinical and Laboratory Findings The three children with congenital cretinism presented between the ages of four and five months with histories of constipation. They also had coarse and striking features which included depressed bridge of the nose with up-
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 2, 1979
turning of the nares, wrinkled foreheads, large tongues, short necks with poor head control, dry rough skins, dry sparse hair, hypotonia, and umbilical hernias. Figure 1 shows one of the children before treatment; Skeletal maturation, as demonstrated by the presence or absence of ossification centers on radiological examnination, was retarded in all three children. The serum thyroxine (T4) level was very low in each case while the triiodothyronine resin binding activities were very elevated (Table 3). The two children with endemic goitrous hypothyroidism presented in the hospital at 2'/2 years and seven years, although their thyroid gland enlargements had been observed at birth and at 5'/2 years, respectively. They were both dwarfed, with infantile body proportions; they also showed retardation of bone age. Figure 2 is a photograph of one of the children. The male child with nongoitrous congenital hypothyroidism presented with delayed developmental milestones. He was unable to walk or talk at five years of age. Clinical examination showed severe physical and mental retardation with delayed dentition and hypotonia. The radioactive iodine uptake with perchlorate flush in this child suggested a deficiency of peroxidase enzyme. The ten-year-old euthyroid girl presented with goiter without symptoms while her physical examination revealed no abnormality. She had a markedly elevated radioactive iodine uptake, but her serum cholesterol, thyroxine, and triiodothyronine resin uptake were all within normal limits. The three patients with thyrotoxicosis presented with weight loss despite good appetite, hyperactivity, exophthalmos, and thyroid gland enlargement. The striking weight loss and exophthalmos in one of these children is shown in Figure 3. Radioactive iodine uptake by the thyroid gland was carried out in two of the three children. The values obtained confirmed the presence of toxic goiter in each case (Table 3). 139
Discussion Previous reports from other parts of Africa have indicated that thyroid gland disease is less common in children than in adults. In a study by Oluwasanmi and Alli,2 it was observed that of 404 patients with simple goiter, less than two percent were under ten years of age. Olurin and others3 observed that of
.,~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~A it -X..
Figure 1Coarse facial features and short neck in sporadic cretinism. Date of birth is tatooed on the chest and abdomen.
1,000 patients with thyroid gland diseases, 845 of whom had simnple goiter, only three were between five and ten years of age, while 62 others were between 11 and 20 years. In the same study, 64 of 1,000 patients had thyrotoxicosis and only two of these were between five and ten years, while seven others were between 11 and 20 years of age. Patel4 reported five cases of thyrotoxicosis from Mulago Hospital, Kampala, Uganda seen over a seven year period. None of these was less than 20-years old, their ages ranging between 23 and 39 years. Three of the children in the present study were less than six months of age at presentation. Etiologically, hypothyroid states in infants and young children may result from a congenital defect of the thyroid gland which either may fail to develop at all or may be lacking in one of the enzymes necessary for synthesis of the thyroid hormones. It may also be due to local iodine deficiency as occurs in certain areas of the world or it may be a result of ingestion of goitrogens. There is a high incidence of endemic goiter in certain parts of Nigeria. It is prevalent in the areas north of Ondo province which lie far away from the sea and in areas south of Ibadan province, for example, Abeokuta and Uebu where cassava, with its high cyanide
content, is the staple diet.2'5 Three of the patients with goiter came from this area: two were hypothyroid while the third was in a euthyroid state. One of the four patients with nongoitrous hypothyroidism was subsequently diagnosed as a case of congenital intrathyroid peroxidase enzyme deficiency. The three others were athyroidal cretins. Endemic cretinism is often associated with goitrogenesis and usually results from local iodine deficiency or occurs in babies of hypothyroid mothers, whereas sporadic cretinism is often due to aplasia or hypoplasia of the thyroid gland. The clinical features of hypothyroidism in childhood differ from those in adults because of the accompanying retardation in the rate of growth and development and these are usually very striking. The changes in the skin, hair, sub-
Table 1. Types of Endocrine Disorders in 27 Children Seen Over Five Years
Type Thyroid disorders Diabetes mellitus Adrenogenital syndrome Incomplete testicular feminization Nephrogenic diabetes insipidus Total
Number of Cases
of Total
10 8 5 3 1 27
37 30 18 11 4 100
Percent
._.
Fiu2 e olrfriggien grwhstnigin7ya-odgr wit en hpty rodim
emi otos
Table 2. Age and Sex Distribution of Ten Children with Various Thyroid Disorders
Patients
Thyroid Disorders
Age at Presentation (years)
Sex
i 2 3 4 5 6
Sporadic cretinism Sporadic cretinism Sporadic cretinism Goitrous hypothyroidism Goitrous hypothyroidism Nongoitrous congenital hypothyroidism Endemic goiter Thyrotoxicosis Thyrotoxicosis Thyrotosicosis
4/12 4/12 5/12 21/2 7
F F F F F
5 10 7 8 14
M F F F F
7 8 9 10
140
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 2, 1979
Table 3. Mean Cholesterol, Thyroxine (T4) Triiodothyronine (T3) Resin Binding and Radioactive Iodine (1131) Uptake in Children with Various Thyroid Disorders Thyroid Disorder
Cretinism Goitrous hypothyroidism Thyrotoxicosis Endemic goiter *Normal
Cholesterol
(mg/lOOml)
T4 (mg/lOOml)
T3 resin binding
272 233 134 130 100-200
0.6 1.2 11.6 6.8 3.5-12.5
137 131 108 107 90-120
(percent)
1131 Uptake At 6 hrs At 24 hrs (percent) 42.0 54.5 58.1 7-25
42.5 66.6 70.9 15-40
*Normal values in our laboratory.
cutaneous tissues, and muscle are similar to those in adult myxedema. Thus, the unique changes in childhood hypothyroidism include a coarse ugly facial appearance, delayed developmental milestones, dwarfism, and infantile body proportions.6 In hypothyroid states, especially when of
congenital origin, radiological examination often shows marked retardation in osseous development with some other characteristic changes such as epiphyseal dysgenesis and vertebral body deformity.7 The etiology of thyrotoxicosis is multifactorial. In childhood, thyrotoxicosis is rarer than hypothyroidism. It occurs more frequently among adolescent females. Three of our patients demonstrated features of thyrotoxicosis but since serum antithyroglobulin antibodies, as well as thyroid-stimulating hormone levels, could not be determined, the exact cause of the disease was not established. Acute infections have been reported to be implicated in the etiology of thyrotoxicosis.8 However, no antecedent infections were evident in these patients, and as infections are so common in this environment, one would have expected to see more cases of thyrotoxicosis in childhood. These manifestations include nervousness, goiter, exophthalmos, and tachycardia. All of these were observed in the three patients with thyrotoxicosis. Nervousness characterized by restlessness, emotional instability, personality changes, and deteriorating school performance is very common and is usually the first evidence that is observed, either by the parents or school teacher. Diffuse enlargement of the thyroid gland occurs almost without exception and it generally develops early in the course of the disease.
Conclusion
Figure 3. A child with thyrotoxicosis; note the muscle wasting and the exophthalmos.
Although childhood thyroid gland disease is uncommon in Africa, it does occur in as wide a spectrum as it occurs in adults. Early diagnosis and prompt treatment are very important, as delay may lead to permanent physical and
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 2, 1979
mental retardation. However, the diagnosis often is not made early, partly because the parents may not have observed the odd features and behavior of their child until much later. Furthermore, since medical centers are few and located mainly in urban centers, parents in rural areas seldom bother to make the usually long, expensive, and tedious journey from their rural homes except when the child is severely affected. When the child does finally present at a hospital, the diagnosis often can be made clinically, and indeed, has to be made clinically because of the little or scanty diagnostic aids available in most medical centers in Africa. Adadevoh and others9 have stressed the importance of laboratory facilities in the diagnosis of childhood endocrine disorders and it is possible that lack of these diagnostic facilities may have contributed to the underestimation of the incidence of some of these disorders in many parts of Africa. Acknowledgement The authors wish to thank their colleagues who were involved in the care of some of the patients.
Literature Cited 1. Adedevoh BK: Endocrine patterns in Africans: Clinico-biochemical assessment. Trop
Geog Med 22:125-141, 1970 2. Oluwasanmi JO, Alli AF: Goitres in western Nigeria. Trop Geog Med 20:357-366, 1968 3. Olurin EO, Itayemi SO, Oluwasanmi JO, et al: Pattern of thyroid gland disease in Ibadan. Niger Med J 3:58-65, 1973 4. Patel KM: Thyrotoxicosis at Mulago Hospital. East Afr Med J 39:600-604, 1963 5. Osuntokun BO: Cassava diet and cyanide metabolism in Wistar rats. Br J Nutr 24:377-380, 1970 6. Hutchison JH: Practical Paediatric Problems. London, Lloyd-Luke, 1972 7. Familusi JB, Lagundoye SB: Congenital sporadic athyrotic cretinism-a review with three additional cases in Nigerian children. Dokita 2:1-8, 1970 8. Alexander WD, Harden RM, Shimmins J: Emotional and nonspecific infection as possible aetiological factors in Graves' Disease: Their relation to thyroid suppressibility. Lancet 2:196197, 1968 9. Adedevoh BK, Francis TI, Ajayi 00: Endocrine disorders in African children. Niger Med J 2:2-6, 1972
141
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