A 17-Year-old Boy With Nodular Lesions in the Thyroid and Lymphadenopathy.

Abstract

CASE A previously healthy 17-year-old boy of Somalian origin was referred to the pediatric endocrinology department of our university hospital in the Netherlands because of swelling in his neck where an ultrasound had revealed an inhomogeneous structure in the left thyroid lobe. He reported a painless left-sided cervical swelling for 2 weeks. After a few days, he also developed bilateral cervical lumps. The boy had no other complaints, no fever and his family history was unremarkable. Physical examination showed normal vital signs. There were bilateral cervical and supraclavicular swellings suspicious for lymphadenopathy. In addition, the thyroid gland was slightly enlarged. The rest of his physical examination was normal. His laboratory parameters revealed increased inflammatory markers: erythrocyte sedimentation rate of 34 mm/h (normal range [NR]: 0–15) and C-reactive protein of 24.2 mg/L (NR: <5). Complete blood count showed white blood cell count of 5.1 × 109/L (NR: 4.0–10.5), with eosinophils 3.2%, basophils 0.3%, neutrophils 55.6%, lymphocytes 24.6%, monocytes 16.3%; hemoglobin of 7.5 mmol/L (NR: 8.5–10.5); and platelet count of 447 × 109/L (NR: 150–400). The lactate dehydrogenase level was slightly increased at 284 U/L (NR: <248). Thyroid function was normal with thyroid-stimulating hormone of 2 mU/L (NR: 0.5–5) and free thyroxine of 15.1 pmol/L (NR: 12–22). Chest radiograph and abdominal ultrasonography were normal. Ultrasound evaluation of the thyroid and neck showed nodular lesions in the left thyroid lobe and isthmus and multiple enlarged, heterogeneous cervical and supraclavicular lymph nodes (Fig. 1). Magnetic resonance imaging of the neck confirmed the nodular lesions in the left thyroid lobe (Fig. 2) and enlarged left cervical, bilateral supraclavicular, and mediastinal lymph nodes. Ultrasound-guided fine-needle aspiration (FNA) for cytologic evaluation of both the thyroidal lesion and pathologic lymph nodes was performed and revealed the diagnosis.FIGURE 1.: Transverse ultrasound image through the thyroid. Normal aspect of the right thyroid lobe. Mixed hypo- and hyperechoic lesion in the left thyroid lobe.FIGURE 2.: T1-weighted axial postgadolinium image showing a heterogeneous left thyroid lobe (small arrow) and multiple enlarged lymph nodes with central necrosis (large arrows).For Denouement see P. 1154. Denouement (Pediatr Infect Dis J 2021;40:1154–1156) Continued from P. 1153. Based on the presenting symptoms and first ultrasound results, the differential diagnoses in this patient included primary thyroid carcinoma with lymphatic metastases, lymphoma and tuberculosis (TB) with a thyroid localization. The patient had been living in the Netherlands and had not visited Somalia or other TB endemic countries nor had contact with visitors from Somalia or other TB endemic countries in the last ten years. Polymerase chain reaction (PCR) performed on the cytologic aspirate from one of the supraclavicular lymph nodes was positive for Mycobacterium tuberculosis, establishing the diagnosis TB. In addition, the patient had a positive tuberculin skin test and a positive interferon-gamma release assay (IGRA: >10.00 kU/L [NR: 0–0.34]). There were no malignant cells, granulomas nor necrotizing granulomatous inflammation visible on cytologic or histologic examination of the lymphoid tissue. Evaluation of the cytologic aspirate from the thyroidal lesion showed no signs of thyroid cancer (Bethesda 2) but did show focal granulomas without signs of necrosis. Mycobacterial cultures of both the thyroidal lesion and lymph node tissue were positive for M. tuberculosis, susceptible to ethambutol, isoniazid, pyrazinamide and rifampicin. The patient was started on quadruple therapy with isoniazid, rifampicin, pyrazinamide and ethambutol according to (inter)national guidelines.1 An underlying infection with HIV was ruled out. During outpatient follow-up over the subsequent months, the patient responded very well to treatment with a reduction in size of the thyroid lesion and lymph nodes. After 2 months, the boy continued treatment with only isoniazid and rifampicin, until he developed isoniazid-induced peripheral neuropathy. After unsuccessful addition of pyridoxine (vitamin B6) to reduce the paresthesia, the isoniazid was stopped, and treatment was continued with higher doses of rifampicin and ethambutol. He fully recovered without any (long-term) side effects, and the thyroid appeared completely normal at ultrasonography 6 months after the start of treatment. This case describes a presentation of extrapulmonary TB (EPTB) in the thyroid and lymph nodes with a long latency. TB has a high burden of disease worldwide. According to the World Health Organization, an estimated ten million people fell ill with TB in 2018, of which children made up approximately 11%. Most TB cases reported by the World Health Organization were in South-East Asia (44%), Africa (24%) and the Western Pacific (18%). The incidence of TB differed greatly between high-income and certain low-income countries: the estimated incidence rates were 0–9.9 per 100,000 people per year in Europe, compared with over 500 per 100,000 people per year in certain countries in Africa (eg, South Africa, Namibia and Somalia).2 Like in adults, pulmonary TB is the most common form of TB in children.3 Immunocompromised children, infants and adolescents are at a higher risk of developing EPTB. Extrapulmonary involvement is seen in more than 50% of patients with concurrent HIV infection.4 The most common locations of EPTB in children are lymph nodes (67%), followed by meninges (13%), pleura (6%), miliary dissemination (5%) and musculoskeletal system (4%). An EPTB infection can represent primary disease or secondary following hematogenous or lymphatic dissemination. Diagnosing pulmonary TB and EPTB can be difficult as the symptoms are nonspecific and thus can easily resemble other diseases. Although every organ can be affected by TB, even in endemic regions, thyroid TB (TTB) is a rare condition,5 with an overall prevalence estimated at 0.1%–1%. However, it is more frequently observed during autopsy (2%–7%). Worldwide around 200 cases of TTB have been reported.6 We only found 7 cases of pediatric TTB (Table 1).7–13 This explains why the disease is generally not included in the differential diagnosis of a thyroid enlargement, often leading to a delayed diagnosis.14 Table 1. - Overview of Published Pediatric Cases of Thyroidal TB Gender (Age) Country Clinical Presentation Thyroid Function Diagnosis Treatment Outcome Lindsay and Mead (1934)7 Male (3) Canada Convulsions, fever and firm mass left side thyroid Unknown Pulmonary TB, TTB and cervical lymph node involvement. Pathology also revealed a tuberculoma of the epicardium, and a solitary tuberculoma of the brain Unknown Death Abdullah et al (1996)8 Male (13) Saudi-Arabia Goiter Unknown TTB Partial excision and ATD Remission Surer et al (2000)9 Female (11) Pakistan/ Turkey Anterior neck mass Normal TTB, cervical tubercular lymphadenitis Surgical exploration, ATD Remission Bodh et al (2014)10 Female (11) India Enlarged thyroid Normal TTB, pleural TB, cervical and mediastinal tubercular lymphadenitis ATD Remission Sood et al (2015)11 Female (11) India Unilateral enlarged thyroid (left) Normal TTB, cervical tubercular lymphadenitis, pulmonary TB ATD Remission Sharma et al (2016)12 Female (6) India Neck swelling, low grade fever Unknown TTB ATD Remission Qamar et al (2017)13 Male (14) Pakistan Painful swelling of fingers and toes and thyroid nodule Unknown TTB and tuberculous dactylitis ATD Remission Hoevenaren et al (current report) Male (17) The Netherlands Slightly enlarged thyroid and painless cervical swelling, nodular lesion in the thyroid at ultrasound Normal TTB with lymph node involvement ATD Remission ATD indicates anti-tuberculosis drugs; TTB, thyroidal tuberculosis. The thyroid’s relative immunity to TB is not fully understood. Several factors may play a role in this context: the thyroid gland’s high iodine levels, its high vascularity, the relative impermeability of the thyroid capsule, the bactericidal action of the colloid, or a combination of these factors.15 Previously, a relationship between hyperthyroidism and TB of the thyroid was described, and it was hypothesized that a hypertrophic gland would be more susceptible to invasion by M. tuberculosis.16 However, this association has not been confirmed in later studies. The thyroid can be infected either by hematogenous or lymphogenic dissemination from the lungs, via miliary dissemination, or via direct extension from affected lymph nodes.17 TTB can present as localized enlargement of a nodule in the thyroid, as a cold abscess, or rarely as an acute abscess. Five types of TTB have been described based on autopsy reports: diffuse TB, miliary TB, caseous lesion(s), sclerosing lesion(s) and TB abscess within the thyroid gland.18 Clinically TTB may cause both systemic and local symptoms like fever, weight loss and dysphagia.19,20 In most cases, patients with TTB have normal thyroid function, although in individual cases hypothyroidism and even thyrotoxicosis have been reported.5,21,22 The differential diagnosis encompasses benign or malignant thyroid nodules, subacute thyroiditis, goitrous autoimmune thyroiditis, sarcoidosis, lymphoma or other bacterial infections. Ultrasound examination, CT and magnetic resonance imaging may be additional tools in the diagnostic workup.23,24 The backbone of diagnosing TTB is culturing acid-fast bacilli. FNA of the thyroid (and affected regional lymph nodes) is the method of choice to obtain material for culture, PCR, susceptibility testing and cytologic evaluation. PCR of the FNA specimen is helpful and should be performed on all specimens that have cytologic features of granulomatous inflammation and may point towards the diagnosis of TTB.25 Biopsy of lymph nodes can be performed for histopathologic evaluation. In the case of TTB, caseous granulomas will often be found during cytologic and histopathologic evaluation.26 If TTB is suspected, tuberculin skin test and interferon-gamma release assay can add to a possible diagnosis. In case of TTB, the patient should also be examined for other TB foci. Treatment of EPTB is similar in children and adults, although treatment of TB in children can be challenging due to a lack of pediatric formulations, drug toxicity and adherence challenges.27 The anti-tuberculous drug treatment consists of a 6–9-month regimen (2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by 4–7 months of isoniazid and rifampicin). Therapy may be prolonged to 12 months or longer for patients with central nervous system TB, skeletal TB, and in patients with incomplete response. There is no role for surgery, although in some patients the diagnosis of TTB was only made after a diagnostic hemithyroidectomy was performed.28 In conclusion, the herein reported case is an example of a pediatric patient with EPTB in the thyroid gland and lymph nodes. EPTB and especially TTB can be difficult to diagnose as the symptoms are not specific and mimic other diseases. Our patient originated from Somalia and he and his family members had not visited nor had contact with people from Somalia or other TB endemic countries. Most likely our patient was infected with TB in Somalia, and therefore this case demonstrates the possible long latency between primary infection and presentation with active TB. Family members were checked after diagnosing our patient with TB and were found negative. Although rare in non-endemic countries, TTB must be considered in patients with a thyroidal mass, especially if accompanied by lymphadenopathy, and/or in patients originating from TB endemic countries. ACKNOWLEDGMENTS Written consent for the use of case presentation and figures, and consent for publication in print and electronically has been given by the patient. The authors thank the patient for his permission.