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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 17  |  Issue : 1  |  Page : 7-13

Pattern of autoimmune thyroiditis in Egyptian children and adolescence


1 Pediatric Endocrinology Unit, Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
2 Undergraduate Medical Student, Armed Forces College of Medicine, Cairo, Egypt

Date of Submission24-Jan-2020
Date of Acceptance11-Mar-2020
Date of Web Publication24-Apr-2020

Correspondence Address:
Prof. Kotb Abbass Metwalley
Pediatric Endocrinology Unit, Department of Pediatrics, Faculty of Medicine, Assiut University, B.O. 71111, Assiut
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/trp.trp_5_20

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  Abstract 


Background: Autoimmune thyroiditis (AIT) is the most common thyroid disorder in the pediatric age range.
Aim: The aim of the retrospective study is to analyze the demographic, clinical, ultrasonographical, hormonal, immunological, and histopathological characteristics of 362 children and adolescents with a diagnosis of AIT.
Patients and Methods: Data relating to the patient demographic and clinical characteristics both on presentation and during follow-up were collected. We also analyzed the investigations performed; these included thyroid function tests, immunological, radiological, and fine-needle aspiration biopsy (FNAB) results.
Results: Patients' age ranged from 8.2 to 16.5 years and a female: male ratio of 5.1:1. The common presenting features were goiter and short stature (138 [38.1%] and 68 [18.7%], respectively). At diagnosis, 83 (22.9%), 23 (6.3%), and 256 (67.0%) patients were euthyroid, subclinical hypothyroid, and overt hypothyroid, respectively. High-resolution thyroid ultrasound revealed higher rate of nodular pattern compared to clinical examination (17 vs. 13 for single nodule and 6 vs. 4 for multiple nodules). Fine-needle aspiration of the thyroid gland was performed in 12 patients; none of them was malignant. Patients were followed for a mean period of 38 months (range: 6–45 month). Only 3 (13%) patients with subclinical hypothyroidism progressed to overt hypothyroidism, and started on L thyroxine therapy, while the rest of the case had stationary course.
Conclusions: Our study reported the highest rate (68.7%) of overt hypothyroidism compared with other studies. The study reported that AIT in children and adolescents has benign course. Thyroid ultrasound can identify clinically unapparent thyroid nodules and play an important role in the selection of cases for FNAB. Careful follow-up of thyroid function is important to determine the necessity and timing of L-thyroxine replacement therapy.

Keywords: Adolescents, autoimmune thyroiditis, children, Egypt, hypothyroidism


How to cite this article:
Metwalley KA, Metwalley MK. Pattern of autoimmune thyroiditis in Egyptian children and adolescence. Thyroid Res Pract 2020;17:7-13

How to cite this URL:
Metwalley KA, Metwalley MK. Pattern of autoimmune thyroiditis in Egyptian children and adolescence. Thyroid Res Pract [serial online] 2020 [cited 2020 Dec 1];17:7-13. Available from: https://www.thetrp.net/text.asp?2020/17/1/7/283221




  Introduction Top


Autoimmune thyroiditis (AIT) is the most common thyroid disorder in the pediatric age range. Both a goitrous (Hashimoto's thyroiditis) and a nongoitrous thyroiditis, variant of AIT, have been distinguished.[1] In pediatrics, the most common age at presentation is adolescence, but the disease may occur at any time, rarely even in children under the age of 1 year.[2] The prevalence of this disorder varies from 3.0 to 8.2 per 1000 populations, depending on the geographic location, type of study, age, and gender of the patients.[3],[4] AIT has a wide spectrum of clinical presentations from euthyroid goiter and subclinical hypothyroidism to overt hypothyroidism.[5] The etiology and pathogenesis of AIT are still elusive. Moreover, little is known about progression of subclinical hypothyroidism to overt hypothyroid AIT, especially in children and adolescents.[6] Because there is growing evidence that unrecognized hypothyroidism is deleterious, early diagnosis of AIT would be advantageous in predicting thyroid failure.[7] To our knowledge, the detailed clinical and laboratory features of AIT in Egyptian children and adolescents have not been published before. In this study, we outlined the demographic, clinical, biochemical, immunological, ultrasonographic, and histopathological features of 362 children and adolescents with AIT presented to our hospital over a 5-year period.


  Patients and Methods Top


We conducted a retrospective study of pediatric AIT cases seen in the Pediatric Endocrinology Clinic of Assiut University Children Hospital, Assiut, Egypt, over a 5-year period (2011–2016). Our university hospital is a large tertiary care referral center with more than 500 beds that provides both primary and tertiary care for children and adolescents in all civil jurisdictions in Upper Egypt. The study group included 362 patients. Patients with incomplete data or irregular follow-up were excluded from the study. Data relating to the patient demographic and clinical characteristics of the patients both on presentation and during follow-up were collected. We have also analyzed the investigations performed for the evaluation of AIT; these included thyroid function tests, immunological, radiological, and fine-needle aspiration biopsy (FNAB) results. We also collected information with respect to the medical treatment of the patients.

Clinical evaluation

History included demographic data (age, gender, and duration of disease), in addition to symptoms suggestive of thyroid dysfunction, history of other autoimmune diseases, or family history of autoimmune disease and detailed treatment history including compliance. Height and weight were measured using a wall-mounted stadiometer and a calibrated weight scale, and the child was wearing the underwear only. BMI was calculated using the following formula: BMI=weight (kg)/height (m)2. BMI was expressed as standard deviation scores (SDSs) using the Egyptian Growth Reference Data.[8] Pubertal status was characterized by Tanner Stage as follows: prepubertal, Tanner 1; pubertal, Tanner 2–4; and postpubertal, Tanner 5.[9] Estimation of goiter size was made subjectively by the examiner (a member of the Pediatric Endocrinology Unit) at the patient's initial evaluation and graded according to the WHO criteria: Grade 0, not palpable; Grade I, palpable, visible only with neck extended; Grade II, easily visible with neck in the normal position; and Grade III, very large goiter.[10] Moreover, thyroid nodules either single or multiple that were detected by palpation were recorded. Short stature is defined as height <3rd centile and tall stature is defined as height >97 centile.[8] Delayed puberty was defined as delayed Tanner stage for age after exclusion of other causes of delayed puberty.

Hormonal investigations

Serum thyroid-stimulating hormone (TSH), FT3, and FT4 concentrations were measured by luminescence-based immunoassay using Immulite 2000 (Diagnostic Products Corp., Los Angeles, California, USA).[11] The reference ranges for TSH, FT3, and FT4 were 0.4–4.0 mU/L, 3.5–5.5 pmol/L, and 10.0–26.0 pmol/L, respectively. On the basis of the initial thyroid function studies, subclinical hypothyroidism was defined as an elevated TSH level >4.0 mU/L together with normal serum thyroid hormone levels. Overt hypothyroidism was defined as an elevated TSH together with a decreased serum thyroid hormone level.[12]

Immunological investigations

Serum antithyroid peroxidase antibodies (TPOAb) and antithyroglobulin (TgAb) were measured by rapid enzyme-linked immunosorbent assay using Diagnostika GmbH, Carl-Zeiss-Strase; 2010–2013, and Genesis Diagnostics, Littleport, UK; 2014–2015, respectively. TgAb and TPOAb concentrations >100 and 75 IU/mL were considered positive, respectively. Positivity of at least one antibody was considered as having autoimmunity of thyroid.[13]

Radiological investigations

High-resolution ultrasonographic reports of the thyroid gland were also evaluated. Volume of gland, echo texture, echogenicity, and vascularity were recorded in all cases. The echo structure of the thyroid gland was compared with adjacent muscles and connective tissue, and it was suggested the diagnosis of AIT if heterogeneous echo structure with diffuse or patchy hypoechogenicity was observed.[14] Ultrasound thyroid was also able to detect single nodule or multinodularity.

Fine-needle aspiration biopsy

A detailed cytological study was done in cases who have a suspicious nodule [1 cm or larger in size] associated with one of the followings criteria: a) irregular margins b) microcalcifications c) rim calcifications d) failure to decrease in size following suppressive treatment with thyroxine e) associated with lymph node with echographic features of a suspicious for malignancy.

Ethical considerations

The study protocol was approved by the Local Ethics Committee of Assiut Children University Hospital, Assiut, Egypt, and also by the Ethics Committee of Faculty of Medicine, Assiut, Egypt, in accordance with the Declaration of Helsinki.

Statistical analysis

The Statistical Package for the Social Sciences (SPSS) version 18.0 software (SPSS Institute, Chicago, IL, USA) was used to perform statistical analysis. Data are expressed as number (%) or means ± SD as appropriate. Clinical, anthropometric, and laboratory parameters by thyroid status were compared by ANOVA tests. Wilcoxon's signed rank test was used when analyzing two related samples (changes within groups). P <0.05 was considered statistically significant.


  Results Top


The descriptive analysis of the studied cases (n = 362) is shown in [Table 1]. The age of the patients ranged from 8.2 to 16.5 years, with a mean age of 12.2 ± 4.1 years. Female patients constituted 83.7% (n = 303) of all patients with a female-to-male ratio of 5.1:1. Regarding residence, 63.3% (n = 229) of the studied cases were from rural area, whereas the rest come from urban area. The most commonly presented complaint was thyroid gland enlargement in 38.1% (n = 138), followed by short stature in 18.7% (n = 68), positive screening in patients with positive family history of AIT in 7.2% (n = 27), abnormal thyroid functions in 5.2% (n = 19), and weight gain in 4.9% (n = 18). At the time of diagnosis, 22.9% of the patients (n = 83) were euthyroid, 6.3% (n = 23) had subclinical hypothyroidism, and 67% (n = 245) had overt hypothyroidism. Type 1 diabetes mellitus (T1DM) was associated with 4.4% (n = 16), whereas Down syndrome and Turner syndromes are associated with 2.4% (n = 9) of the studied cases.
Table 1: Characteristics of the studied patients (n =362)

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The comparison of clinical and laboratory characteristics at presentation in children and adolescents with AIT according to thyroid function tests is shown in [Table 2]. The mean age ± SD of patients was significantly older in the overt hypothyroidism (14.1 ± 2.1) group compared with other two groups (P < 0.05). The total rate of short stature was 14.6% (n = 53). It was significantly higher in the overt hypothyroid group compared to the subclinical hypothyroidism group and the euthyroid group (18.3%, 8.6%, and 7.2%, respectively; P < 0.05). The total rate of pubertal delay in the pubertal and postpubertal subjected according to Tanner staging was estimated to be 26.6% (n = 29). It was highest in the overt hypothyroid group (30.7%), followed by subclinical hypothyroid group (20%) and euthyroid group (11.1.4%); this difference was proved to be statistically significant (P < 0.01).
Table 2: Comparison between the autoimmune thyroiditis functional groups regarding demographic and clinical characteristics

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The comparison between the AIT functional groups regarding thyroid clinical and ultrasound examination findings is shown in [Table 3]. In addition to goiter, characteristic findings were hypoechogenicity as well as the heterogeneous appearance of thyroid tissue was detected in 93.6% (n = 339). Thyroid ultrasound reported a nodular pattern in 23 cases, 17 with a single nodule and 6 with multiple nodules.
Table 3: Comparison between the autoimmune thyroiditis functional groups regarding thyroid clinical and ultrasound examination findings

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The comparison between the AIT functional groups regarding immunological and hormonal findings as well as therapy is shown in [Table 4]. The mean ± SD of TSH, TPOAb, and TGAb was highest in the overt hypothyroidism group compared to the other groups, whereas the mean ± SD of FT4 was significantly lower in the overt hypothyroid group compared to the other groups (P < 0.01).
Table 4: Comparison between the autoimmune thyroiditis functional groups regarding immunological and hormonal findings as well as therapy

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Twelve of our patients underwent FNAB. None of those biopsies was diagnosed as malignant. Cytological results are as follows: ALT in seven patients, benign nodular findings in two patients, and normal thyroid tissue in three patients.

Treatment data revealed that all overt hypothyroid cases were started on single morning dose of L-thyroxine which was adjusted to keep the concentrations within normal range. However, 18% remain hypothyroid due noncompliance [malabsorption was excluded by clinical examination and laboratory investigations]. Follow-up of patients over a period with a mean of 38 months (6–45) revealed that 13% (n = 3) from subclinical hypothyroid group were started on L-thyroxine therapy due to emergence of overt hypothyroidism, whereas the rest of the patients in other groups had stationary course.


  Discussion Top


Our study reported that female children and adolescents have significantly higher rate of AIT compared to males (83.7% vs. 16.3%, P < 0.05), which is in concordance with the other studies from other countries.[15],[16] The reasons for the female predilection may be related to chromosomal factors, such as skewed X-chromosome inactivation[17] or to female sex steroids.[18]

In the present study, cases aged >12 years represented 60.4%, which is significantly higher than those aged 8–12 years (39.6%; P < 0.05). This is in agreement with other studies which reported the same findings.[19] Regarding residence of studied cases, cases coming from rural area represent (63.3%) while those coming from urban area represent (36.7%) (P < 0.05). To our knowledge, the residence of cases of AIT has not been studied to date. poor education of villagers in rural area leads to delayed seeking medical advice and late presentation.

In this study, the most common reason for seeking medical advice is a goiter, with a frequency of 38.1%. This is in agreement with published studies.[20],[21],[22] Matsuura et al.[19] reported that 71% and Greenberg et al. reported that 90.6% of their patients presented with goiter;[20] however, the actual prevalence of goiter (Grade 1–3) on examination in our study was almost two-fold higher (72%). This underscores the need for thorough thyroid examination as part of the routine physical examination in apparently healthy children.

In this study, 22.9% of the patients were euthyroid, 6.3% had subclinical hypothyroidism, and 67.8% had overt hypothyroidism. de Vries et al.[21] reported euthyroidism in 21.4%, subclinical hypothyroidism in 42.8%, and overt hypothyroidism in 35.7%. Demirbilek et al.[22] reported euthyroid in 43.2%, 24.1% had subclinical hypothyroidism, 21% had overt hypothyroidism, and 8.6% (n = 14) had overt hyperthyroidism. Variation in the frequency in different series may be explained by different geographical areas, female: male ratio, diagnostic criteria, and time elapsed between onset and diagnosis of the disease.

In the present study, 27 (7.2%) cases had positive family history of AIT, which supports previous findings of a familial clustering of AIT disease.[23] Furthermore, 16 (4.4%) of AIT cases were coexistent with T1DM and 7 (1.9%) with Down syndrome. Metwalley and El-Saied[24] reported a rate of 8.5% of AIT in an association with T1DM, while the reported association of AIT among children with Down syndrome varies from 3% to 28%.[25] AIT can be diagnosed in the absence of clinical symptoms, either incidentally or on routine screening for high-risk groups. Thus, periodic thyroid function tests may be indicated in people at high risk of AIT.[26]

In the present study, the rate of pubertal delay was highest in the overt hypothyroid group (86%), followed by euthyroid group (6.9%) and subclinical hypothyroid group (3.4%); this difference was proved to be statistically significant (P < 0.01). Delayed puberty in hypothyroidism can be explained by hyperplasia of not just thyrotrophs, but lactotrophs as well, causing hyperprolactinemia,[27] which has suggested an inhibitory effect of on the gonad.[28]

In the present study, the rate of short stature was highest in the overt hypothyroid group (18.3%), followed by subclinical hypothyroidism (8.6%) and euthyroid group (7.2%); this difference was proved to be statistically significant (P < 0.05). Hypothyroidism is associated with a reduction in the pulsatile growth hormone secretion and low levels of IGF-I and IGFBP-3.[29]

In the present study, thyroid ultrasonography was done to all cases with AIT, and in addition to goiter, characteristic findings were hypoechogenicity as well as the heterogeneous appearance of thyroid tissue was detected in 93.6% (n = 339). The reported occurrence of this finding in AIT varies from 19% to 95%.[30] Thyroid ultrasonography is used to select cases for FNAB. Although ultrasound cannot reliably discriminate between benign and malignant lesions, it does provide an index of suspicion. It also identifies clinically unapparent nodules and provides detailed nodule characterization for suspected malignant lesions. Sonographic features that increase the likelihood of malignancy are microcalcifications, lymph node alterations, and nodule growth under L-thyroxine treatment.[31]

The present study, thyroid ultrasound reported a nodular pattern of a rate 6.5% (n = 23; 17 with a single nodule and 6 with multiple nodules) among subjects with AIT. Corrias et al.[32] reported a higher rate of nodular pattern among 365 cases with AIT of 31.5% from six Italian centers. These data pointed to the importance of performing a thyroid ultrasound routinely for every case of AIT. In contrast, de Vries et al.[21] did not recommended thyroid ultrasound as routine in children and adolescents with AIT. The presence of either a solitary nodule or multiple nodules is generally considered suspicious for malignancy. Multiple nodules on sonography carries a greater risk of cancer compared with finding of a solitary nodule.[33] In the current study, 12 of our patients underwent FNAB either on initial presentation or on follow-up, which failed to detect any thyroid malignancy. This in agreement with de Vries et al.[21] who reported the same findings in five patients who underwent FNAB. However, Corrias et al.[32] reported that the prevalence of thyroid cancer in 365 patients with of AIT from six Italian centers of 3%. FNAB is reliable in selecting patients for surgery with a diagnostic accuracy of approximately 90%. Differences in patient selection and geographic and ethnic diversity contributed to this variability.[33],[34],[35]

Only a few studies have addressed the natural course of AIT in children and adolescents.[2],[36] In the present study, all included patients had stationary course for a mean of 16 months (11–47) after diagnosis, except that 13% (n = 3) from subclinical hypothyroid group were eventually started on L-thyroxine therapy due to the emergence of overt hypothyroidism. de Varies et al. reported that nineteen of the 24 euthyroid patients were treated with L-thyroxine within a mean of 16 months (3–36) after diagnosis. The other five euthyroid patients remained euthyroid without treatment during follow-up of 2–16.6 years; these data suggest that the balance between cellular damage of the thyroid by the autoimmune process and the better regenerative ability of children may partially explain the benign course of children with AIT.[37] The controversy about thyroxine therapy for subclinical hypothyroidism is due to the adverse effects of long-term over-replacement thyroid therapy. This can be minimized by careful monitoring of both FT4 and TSH concentrations.[38]

Limitations of the study

  1. As the study is retrospective, it did not give accurate measurement of the size of AIT in children and adolescents
  2. Follow-up period is short.



  Conclusions Top


Our study reported the highest rate (68.7%) of overt hypothyroidism compared with other studies. The study reported that AIT in children and adolescents has benign course. Thyroid ultrasound should identify clinically unapparent thyroid nodules and play an important role in the selection of cases for FNAB. Careful follow-up of thyroid function is important in order to determine the necessity and timing of thyroxine replacement therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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