Autoimmune thyroiditis in adolescents: Two different presentations

INTRODUCTION

Autoimmune thyroiditis, also known as chronic lymphocytic thyroiditis or Hashimoto’s thyroiditis, is the most common aetiology of thyroid disease in children and adolescents.^[1-3] Both goitrous (Hashimoto’s thyroiditis [HT]) and a non-goitrous (atrophic thyroiditis/primary myxoedema) variant of autoimmune thyroiditis have been distinguished.^[2] The prevalence of autoimmune thyroiditis in childhood is an estimated 1–2% with female predominance with male-to-female ratio of 4:1–8:1 depending on the geographical region.^[1,3-5] The aetiology of autoimmune thyroiditis is complex and multifactorial. The development of autoimmune thyroiditis depends on an immune defect in an individual with genetic susceptibility (80%) in conjunction with environmental factors (20%).^[2,3] Approximately 50% of cases have a family history of autoimmune thyroid disease.^[1] Several syndromes are associated with an increased risk for developing autoimmune hypothyroidism, including Down syndrome and Turner syndrome.^[1,6] Thyroiditis is defined as evidence of ‘intrathyroidal lymphocytic infiltration’ with or without follicular damage.^[5] The natural history is not completely known in paediatric population, it is variable, with remission, recurrence as well as the evolution to permanent hypothyroidism.^[3,4] Euthyroidism is the most common initial pattern (about 52% of patients), followed by overt hypothyroidism (22.2%), subclinical hypothyroidism (19.2%) and hyperthyroidism (6.5%).^[6]

CASE REPORTS

DISCUSSION

Autoimmune thyroid diseases constitute both HT and Graves’ disease. Both are characterised by infiltration of the thyroid by T and B lymphocytes that react against thyroid antigens and thereby producing thyroid autoantibodies. The autoantibodies are directed against thyroid peroxidase (anti-TPO), thyroglobulin (anti-TG) and thyroid-stimulating hormone receptors (TRABs).^[4] Two types of autoimmune thyroiditis are causes of persistent hypothyroidism: Hashimoto’s disease (goitrous form) and atrophic thyroiditis (non-goitrous form).^[5]

Several studies have shown that autoimmune thyroid disease has definite genetic propensity for thyroid autoimmunity and they run in families.^[7] Direct cytotoxicity by CD8 T cells is believed to be the main mechanism of hypothyroidism in vivo.^[5] The autoimmune injury of the gland is responsible for clinical and biochemical alterations. The natural history of the disease is as follows: (1) Toxic, transient and self-limited thyroiditis; (2) euthyroid goitre and (3) hypothyroidism with/ without goitre.^[4] There is no fixed duration for each stage. Conversion of Hashimoto’s thyroiditis into Grave’s disease has been observed in at least 3–4% of children and adolescents.^[8,9]

The high incidence of autoimmune thyroid diseases in females suggests the participation of X chromosome genes or even an influence by the absence of chromosome Y.^[3,4,10] There is also increased risk for other autoimmune diseases, most commonly diabetes, alopecia, vitiligo and celiac disease.^[11-13] In the present case, one was female and the other one was male, the patient did not meet criteria for other associated autoimmune comorbidities.

The most common symptoms of hypothyroidism include easy fatiguability, constipation, cold intolerance and menstrual irregularities. Oligomenorrhoea and/or menometrorrhagia are frequent, due to a poor conversion of oestrogen precursors.^[7,14] Children may present with pubertal delay or precocious puberty.^[7,13] Other features include dry, cold, yellow and thickened skin, secondary to the accumulation of hydrophilic mucoproteins in the dermis (such as hyaluronic acid) as well as the atrophy of the sweat glands. There will also be a history of obesity and short stature.^[5,15,16] The most common physical examination finding is a goitre. Other findings include bradycardia, delayed reflexes and oedema of the face and extremities (myxoedema). Hypothyroidism causes poor linear growth and/or growth failure and, if undiagnosed, may compromise adult height.^[3,5] In the present case, it was observed that the clinical manifestations presented by the patient correspond to the most frequently reported in the literature.

The diagnosis of autoimmune thyroiditis is established by clinical characteristics, elevated TSH, detection of serum antibodies against thyroid antigens (mainly thyroid peroxidase and thyroglobulin) as well as the presence of goitre. The serum TSH concentration is elevated in primary hypothyroidism and its determination is an appropriate screening test for thyroid dysfunction.^[5] The presence of goitre on examination or elevated TSH levels should prompt the measurement of anti-TPO antibodies. Anti-thyroperoxidase (anti-TPO) antibodies are the most sensitive and best screening test in the diagnosis of autoimmune thyroiditis.^[2,5] They are found in approximately 90% of the patients.^[5] Antithyroid peroxidase antibody titres correlate well with the number of autoreactive lymphocytes that infiltrate the thyroid.^[8] Antibodies to thyroglobulin (anti-TG), the most abundant protein in the thyroid gland, are less sensitive (positive in only 60–80% of patients) and less specific (positive in a greater proportion of healthy controls) than antithyroid peroxidase antibodies.^[17] The typical patient with hypothyroidism secondary to autoimmune thyroiditis will have an elevated TSH (>10IU/mL), a low FT4 and positive anti-TPO antibodies.^[5]

In the present case, both the cases had elevated TSH, low T4 and elevated anti-TPO antibodies, however, only Case 1 had elevated anti-TG antibodies while the Case 2 had normal anti-TG antibodies.

Thyroid ultrasound is an important laboratory test for the diagnosis and follow-up of cases of autoimmune thyroiditis. An irregular texture in the parenchyma in the scan is suggestive of thyroiditis. The presence of nodules or cysts requires special attention to rule out the possibility of carcinoma.^[4] In adults, USG thyroid has been shown to have definite value in the diagnosis of autoimmune thyroiditis. However, the role of USG in the evaluation of autoimmune thyroiditis in paediatric population is not yet defined.^[18] Imaging studies (thyroid ultrasonography and/ or thyroid uptake and scan) may be performed if thyroid Ab tests are negative or if a nodule is palpable, but are rarely necessary.^[19] Improvements in the measurement of circulating autoantibodies and ultrasonography have obviated the need for biopsy or FNAC in the diagnosis of autoimmune thyroiditis. Both of our cases had normal ultrasound neck findings.

The treatment of acquired hypothyroidism is similar to that of congenital hypothyroidism. Levothyroxine tablets are the treatment of choice administered once daily, 15–30 min before food consumption, avoiding coadministration with calcium, iron, soy products, sucralfate, potassium-binding resins, antacids containing aluminium and bile acids binding resins.^[5] Levothyroxine dosing is based on body surface area (100 μg/m²/d) or on age and weight following the general pattern, as shown in [Table 6].^[4,20]

TSH normalisation is the goal of replacement. In our practice, we aim to reach values in the lower part of the normal range (0.5–2 micro IU/mL), FT4 in the upper half of the normal range.^[5] Thyroid function tests should be obtained about 6–8 weeks after the initiation or every 6–8 weeks following a change in levothyroxine dose. Once biochemical euthyroidism has been achieved, TSH can be monitored every 4–6 months, up to the attainment of final height.^[5] The goals of treatment are to achieve clinical and biochemical euthyroidism and to attain normal linear growth and development throughout childhood and adolescence.^[2]

Accordingly, both the cases have been started with levothyroxine tablets 2 mcg/kg/day. Thyroid function tests done after 6 weeks showed improvement.

CONCLUSION

The patient showed improvement in clinical symptoms after the replacement of levothyroxine, along with significant decrease in serum levels of TSH. As thyroid ultrasound was normal showing no calcification or increased vascularity or any nodule, there was no need for biopsy or fine needle aspiration cytology (FNAC) in this case, but follow-up should be continued to carry out further evaluations. These two case scenarios help us to know the clinical presentation of autoimmune thyroiditis in the paediatric population and hence being the most common thyroid disease in this age group.