Thyroid Dysfunction in Down Syndrome Cases Attending the School for the Disabled Children, Yangon

Thitsar Htet Htet Htoo, San San Htwe, Win Pa Pa Naing, Ye Myat Oo , Aye Aye Lwin1, Moh Moh Hlaing, Aye Mya Khine, Win Win Mar, Yee Mar Tin

Myanmar Health Sciences Research Journal, 2020; 32(2): 146-151

Down syndrome (DS) is the most common chromosomal anomaly in live births. It is a common cause for mental retardation and associated with many congenital anomalies. Among them the endocrine disorders effecting thyroid functions are more frequent in DS. The prevalence of hypothyroidism is higher than that of hyperthyroidism in DS. The aim of this study,carried out from August 2017 to July 2018, is to investigate the thyroid dysfunction in Down syndrome cases attending the School for the Disabled Children, Yangon. A total of 80 DS cases between 6 to 46 years were analysed for thyroid function test (serum free T4 and TSH level) by Enzyme-Linked Immuno Sorbent Assay (ELISA). Of the 80 cases, 50 were males (62.5%) and 30 were females (37.5%). Over fifty-six percent of cases (56.2%) were between 11-19 years with the median age of 14 years. Out of 80 cases, 49(61.25%) showed normal thyroid function (euthyroid) and 31 (38.8%) showed hypothyroidism. Among 31 cases (38.8%) of hypothyroidism, 30(37.5%) showed subclinical hypothyroidism (SCH) and only one case (1.2%) was overt hypothyroidism. No children or cases were found to be hyperthyroid in this study. The occurrence of hypothyroidism was found to be higher  in female than in male. There was a statistically significant association between gender and prevalence of hypothyroidism (p=0.04). Mean serum TSH level in male was 3.6±1.9 mU/L and in female was 5.6±5.1 mU/L. There was a statistically significant association between gender and TSH level (p=0.02). Mean serum free T4 (FT4) level in whole group was 1.1±0.2 ng/dl. These findings highlighted the need to implement the standardized guidelines regarding thyroid function testing, annual thyroid surveillance in all newborns with DS and monitoring and treatment of thyroid dysfunctions associated with Down syndrome.

A total of 80 DS cases between 6 to 46 years were analysed for thyroid function test (serum free T4 and TSH). Background characteristics of DS cases are shown in Table 1.In the present study, out of 80 DS cases: 50 cases (62.5%) were male and 30 (37.5%) were female. (M:F was 1.6:1) The highest numbers of cases (56.2%) were between 11-19 years and the mean age of DS cases was 15.7±6.8 years. In this study, the maternal age at the time of delivery mostly between 35-40 years (48.8%), 35% were <35 years and16.2% were >40 years The mean maternal age at the time of birth was 35.8± 5.3 years, ranged 23 to 48 years.

 

Table 1. Background characteristics of Down Syndrome cases

 

Fig. 1. Thyroid function status in Down Syndrome cases

 

The prevalence of thyroid dysfunction is shown in Figure 1.Out of 80 DS cases: 49(61.2%) had normal thyroid function (euthyroid) and 31(38.8%) showed hypo-thyroidism (HT). Among the 31 cases (38.8%) of hypothyroidism: 30 cases (37.5%) showed subclinical hypothyroidism (SCH) and only one case (1.2%) showed overt hypothyroidism. No children or cases were found to be hyperthyroid in this study.

The association between background characteristics and thyroid function status are summarized in Table 2. Of the 31 cases of hypothyroidism (HT); 15(30%) were male and 16(53.3%) were female. In the present study, the occurrence of HT was found to be higher in female (53.3%) than male (30%).There was a statistically significant association between different gender and thyroid dysfunction (p=0.04). Among hypo-thyroidism cases, 7(38.9%) were between 6-10 years, 17(37.9%) between 11-19 years and 7(41.2%) were at the age of 20 years and above. In this study, the prevalence of HT was found to be more common in older age but there was no statistically significant association between them.

 

Table 2. Association between background characteristics and thyroid function status

 

Table 3. Association between age, sex and thyroid hormone status

TSH=Thyroid-stimulating hormone,FT4=Free thryoxine

 

Table 3 shows association between age, sex and thyroid hormone status. Mean TSH level in male was 3.6±1.9 mU/Land female was 5.6±5 mU/L. There was a statistically significant association between gender and mean TSH level (p value of 0.02). Mean FT4 level in the whole group was 1.1±0.2 ng/dl and there was no significant differences between them.

 

Among the endocrine abnormalities, thyroid dysfunction is the most frequent and estimated to occur in 4-18% of children with DS.6 Hypothyroidism (HT) is the most common thyroid problem associated with DS. This can be present at birth (congenital) or may occur at any age (acquired). In newborns and infants with DS, the most common reason for HT is that the thyroid didn’t form correctly in the fetus (thyroid hypoplasia). In acquired HT, the most common reason in toddlers and older children with DS is due to auto-immunity or thyroiditis.7The various forms of thyroid dysfunction encountered in DS include congenital hypothyroidism, subclinical hypo-thyroidism (SCH), overt hypothyroidism (OHT) and yperthyroidism.8

The prevalence of hypo-thyroidism is higher than that of hyper-thyroidism in DS and the frequency of thyroid dysfunction increase with age. The diagnosis of hypothyroidism in DS is complicated by the overlap between thyroid associated symptoms and clinical features of DS.9, 10If left untreated, hypo-thyroidism causes impaired cognition, irreversible physical and mental handicaps. As it is treatable, early detection and treatment could contribute to better intellectual and developmental outcomes.11Subclinical hypo-thyroidism (SCH) is the most common form of thyroid dysfunction detected in 7-40% of subjects with DS.1

SCH is defined by a normal free T4 level and mildly elevated TSH level, is common in children.12 Moreover, SCH and low to normal FT4 levels in DS patients may have significant clinical sequelae such as hypotonia, and anemia.13 It is estimated that the incidence of progression of SCH to overt hypothyroidism is less than 50%.14 In most cases, SCH is asymptomatic and detected upon laboratory testing or neonatal screening.

In many parts of the world, patients with DS have neonatal screening included in newborn screening (NBS) programmes.15 The American Academy of Pediatrics (AAP) recommends screening for thyroid function in DS cases at birth, 6 months, 1 year of age and annually thereafter, regardless of their growth.15

Diagnosis based solely on clinical features is therefore unreliable; laboratory findings that confirm diagnosis are essential.Consistent and routine screening for thyroid dysfunction is also recommended for adults with DS since the risk for hypothyroidism increases with age in individuals with DS. The aim of this study is to investigate the thyroid dysfunction in children with Down syndrome attending the School for the Disabled Children, Yangon.

History taking, physical examination for typical features of DS were undertaken. All the informations were recorded in proforma. Thyroid function test (serum free T4 and TSH level) were analysed by Enzyme- Linked Immuno Sorbent Assay (ELISA) method (Stat Fax 4200, Awareness Technology). Typical range of reference for serum TSH level is 0.3-4mU/Land serum free T4 (FT4) is 0.8-2 ng/dl.

Operational definition16

Subclinical hypothyroidism (SCH)

-Serum TSH level mildly elevated (more than 4 to 15 mU/L)

      -Normal serum FT4 level             

       -No clinical evidence of thyroid disease

Overt hypothyroidism (OHT)

-   High serum TSH level, in excess of 20mU/L

-   Low serum FT4 level

Hyperthyroidism

-    Low serum TSH level

-    High serum FT4 level

(TSH=thyroid-stimulating hormone;FT4=free thryoxine)

Statistical analysis

Data entry was performed with Excel and data analyses were conducted with Statistical Package for Social Science Study (SPSS) software. Mean±SD was calculated for quantitative variables such as subject’s age, sex and maternal age. Chi square test and ‘t’ test were used to find out the association between background characteristics and thyroid dys-function. The ‘p’ value of <0.05 was regarded as statistically significance.

Ethical consideration

This proposal was approved by the Ethics Review Committee, Department of Medical Research. Informed consent was taken from their parents/ guardians after explaining about the nature of the study, objectives, procedure and benefit of this study. The results were relayed back to concerning persons before it is made widely available to the public.

The prevalence of DS pregnancies varies with maternal age and more than 50% babies with DS are born to mothers with advanced maternal age (AMA) (>35 years). In a study of South Africa, the maternal age at birth of DS children ranged from 18 to 45 years and 42% were >35 years.17In this study, the maternal age at the time of delivery was mostly between 35-40 years (48.8%), <35 years (35%) and >40 years (16.2%). The mean maternal age at the time of birth was 35.8±5.3 years (ranged 23-48 years).

Thyroid dysfunction is occurs at all ages of DS patients and incidence may be varied between countries.The older the DS patient, the more likely is the development of thyroid dysfunction. Toledo et al studied 105 DS patients between 3 months to 21 years found that 54(51%) had hypothyroidism.18 In the present study, the prevalence of hypo-thyroidism were: 38.9% (7 cases) in age group of 6-10 years, 37.8% (17 cases) in 11-19 years and 41.2% (7 cases) in age of 20 years and above.

Wong et al stated that the proportion of HT in male patient with DS was 33% and in female was 31%. There was no statistically significant difference between the two sexes.19 Inthe present study, the occurrence of HT was found to be higher in female (53.3%) than in male (30%). In contrast to previous study, this study showed correlation between different sexes and HT in DS cases (p=0.04).

Shaw CK et al, reported that hypothyroidism was seen in 5 out of 32 DS cases (15.6%) of which 1(3.1%) had uncompensated while the other 4(12.5%) had a compensated hypothyroidism. Hyperthyroidism was not observed in any of the cases.20In a study conducted in Thailand, the prevalence of subclinical hypothyroidism was found in 32.9% and hyperthyroidism in 2.1% of DS children from 3 days-13 years.21 The study of Moosaet al., observed that subclinical hypothyroidism (SCH) was the most common form of thyroid dysfunction in DS (28.7%).22

In the present study, hypothyroidism was seen in 31 out of 80 DS cases (38.8%), of which 30(37.5%) were subclinical hypo-thyroidism and 1(1.2%) showed overt hypo-thyroidism. No children or cases were found to be hyperthyroid in this study. The prevalence of SCH in this study is similar to other studies that ranged from 7-40% of DS.1 In the present study, most cases of SCH were asymptomatic and exhibit mild symptoms such as hypotonia, constipation or weight gain, but these symptoms often exist in patients with DS also.

Peirce et al reported that out of 52 SCH,30 were TSH5-10 mU/Land 22 cases were TSH >10mU/L.23 In this study, out of 30 SCH,28 were TSH >4-10 mU/L and 2 cases were TSH >mU/L. One case of overt hypothyroidism was found in 25-year-oldfemale subject with TSH value of 22.2 mU/L and FT4of 0.7ng/dl. Mean TSH value in male subject was 3.6±1.9 mU/L and female was 5.6±5.1mU/L(p value=0.02). There was a statistically significant association between different genders and mean TSH level. Mean FT4 level in whole group was 1.1±0.2 ng/dl. There was no significant association between them. It was suggested that treatment of SCH should be reserved  to patients who progress to overt hypo-thyroidism, and those with TSH >10 mU/Lin the presence of goitre or positive thyroid auto antibodies.1

The natural course of SCH in DS is variable. It may show a spontaneous decrease to normal serum TSH levels or developed to overt hypothyroidism on follow-up. Since the risk for hypothyroidism increases with age of individuals with DS, regular thyroid function screening should be performed in all age groups of persons with DS.

Conclusion

Thyroid disease occurs with greater frequency in individuals with Down syndrome and the majorities are asymptomatic subclinical hypothyroidism. Thyroid disease is difficult to diagnose clinically in individuals with DS because of an overlap of symptoms.In many parts of the world, patients with DS have neonatal screening included in newborn screening (NBS) programmes. This study highlighted to implement the standardized guidelines regarding thyroid function screening and annual thyroid surveillance is important for all newborns with DS in Myanmar. This study would also like to recommend further studies to clarify whether treatment is indicated for patient with subclinical hypothyroidism with mildly elevated TSH.