Thyroiditis in children: clinical guidelines

List of Abbreviations

Abs – antibodies

TgAb – thyroglobulin antibodies

TPOAb – thyroid peroxidase antibodies

GD – Graves' disease

GCs – glucocorticoids

CT – computed tomography

NSAIDs – nonsteroidal anti-inflammatory drugs

CBC – complete blood count

ARVI – acute respiratory viral infection

AT – acute thyroiditis

ST – subacute thyroiditis

ESR – erythrocyte sedimentation rate

FT3 – free triiodothyronine

FT4 – free thyroxine

TSH – thyroid-stimulating hormone

FNA – fine-needle aspiration biopsy

RT – Riedel's thyroiditis

US – ultrasound examination

CAIT – chronic autoimmune thyroiditis

TG – thyroid gland

Terms and Definitions

Primary hypothyroidism is a clinical syndrome developing as a result of inadequate production of thyroid hormones due to a primary pathology within the thyroid gland itself.

Subclinical hypothyroidism is a condition characterized by an elevated concentration of thyroid-stimulating hormone (TSH) with a normal level of free thyroxine (T4) in blood serum.

Subclinical hyperthyroidism is a condition characterized by a decreased concentration of thyroid-stimulating hormone (TSH) with normal levels of free triiodothyronine (T3) and thyroxine (T4) in blood serum.

Fistulography is a type of X-ray examination of fistulous tracts (or fistulas) using a contrast agent.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Thyroiditis encompasses thyroid disorders varying in etiology, pathogenesis, and clinical manifestations, accompanied by damage to the organ parenchyma [1].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Although thyroiditis is an inflammatory disorder, it is not typically characterized (except for acute thyroiditis) by the classical signs of inflammation—pain, erythema, elevated temperature, and edema. Numerous infectious agents are known to provoke the development of thyroiditis, but in the majority of cases in children and adolescents, the non-infectious form of thyroiditis—autoimmune lymphocytic thyroiditis—is encountered [1].

Acute thyroiditis

Acute suppurative thyroiditis.

It is relatively rare in children. The disease develops against the background of an upper respiratory tract infection (tonsillitis, sinusitis, otitis media), which spreads either hematogenously or lymphogenously, or as a result of direct introduction of infection into the thyroid gland during trauma and wounds, as well as following invasive medical procedures (fine-needle aspiration biopsy, ethanol sclerotherapy, laser photocoagulation, radiofrequency thermoablation); penetration of infection from adjacent tissues upon fistula formation is also possible. Bacterial infections caused by Staphylococcus, Streptococcus, pneumococcus, Escherichia coli, or hematogenous/lymphogenous dissemination are among the most frequent causes of the disease [1,2,3].

Typically, one lobe of the thyroid gland is affected. One of the causes of recurrent thyroiditis (more common in childhood) is the presence of a communication (fistula) between the thyroid lobe and the pyriform sinus. A distinctive feature of this pediatric pathology is the involvement of only the left lobe of the thyroid gland.

Acute non-suppurative thyroiditis. Diagnosed exceptionally rarely in childhood. The disease proceeds as aseptic inflammation and most commonly arises due to trauma or minor hemorrhages into the thyroid gland [1].

Subacute thyroiditis (SAT)

A disease of viral etiology. There is a clear seasonality in its course (autumn – winter). It frequently occurs against the background of an epidemic of viral diseases: measles, influenza, adenoviral infection, coxsackievirus infection, infectious mononucleosis. Subacute thyroiditis also develops in association with sarcoidosis, Q fever, malaria, streptococcal infection, invasive medical procedures, following antibiotic therapy, or emotional stress.

The penetration of the virus into a thyrocyte causes its destruction with the release of follicular contents into the bloodstream (thyrotoxicosis without thyroid hyperfunction). A genetic predisposition to the development of the disease has been proven. Individuals carrying the HLA-Bw35 gene are 30 times more susceptible to infection. This gene is also associated with other conditions of presumably viral etiology, such as Balkan nephropathy, Henoch-Schönlein purpura, Hodgkin's disease, and infectious mononucleosis. Furthermore, there are reports of an increased frequency of HLA-DR5 genes in patients with subacute thyroiditis. This suggests the presence of a gene complex and antigenic marker determining susceptibility to viruses [4,5,6].

Chronic thyroiditis

Chronic autoimmune thyroiditis (CAIT, Hashimoto's thyroiditis, lymphocytic thyroiditis) is a chronic inflammatory disease of the thyroid gland of autoimmune origin, in which progressive lymphoid infiltration results in the gradual destruction of the thyroid parenchyma with a potential outcome of primary hypothyroidism. For a long period of time, sometimes throughout life, patients remain in a state of euthyroidism. With the gradual progression of the process, intensification of lymphocytic thyroid infiltration, and destruction of its follicular epithelium, the synthesis of thyroid hormones progressively declines. As a result, TSH levels rise, leading to hyperstimulation of the thyroid gland. Due to this hyperstimulation, T4 production can be maintained at a normal level for an indefinite period—the subclinical hypothyroidism phase. With further destruction of the thyroid gland, the number of functioning thyrocytes falls below a critical level, and the blood concentration of T4 also decreases (overt hypothyroidism phase). CAIT is the primary cause (in the absence of iodine deficiency) of acquired primary hypothyroidism in children [1,7,8].

Riedel's chronic fibrous thyroiditis

Riedel's thyroiditis (RT) is an extremely rare thyroid disorder of unclear etiology, characterized by the replacement of thyroid tissue with fibrous tissue invading surrounding structures. Currently, a number of authors consider this disease within the framework of Ormond's systemic fibrosing syndrome, which includes the combination of fibrous thyroiditis with retroperitoneal or mediastinal fibrosis, sclerosing cholangitis, and retrobulbar fibrosis [9].

Specific thyroiditis

Chronic specific thyroiditis represents inflammatory thyroid diseases caused by the impact of specific infectious etiologic factors. The causes of specific thyroiditis include tuberculosis, syphilis, actinomycosis, sarcoidosis, and Langerhans cell histiocytosis, which induce destructive changes in the thyroid gland and may lead to the development of hypothyroidism. Pneumocystis thyroiditis caused by Pneumocystis carinii has been described (P. Singer, 1999). The risk of developing this form of thyroiditis exists primarily in patients with AIDS [1].

1.3 Epidemiology of the Disease or Condition

Acute thyroiditis

AT is a rare disease. Within the structure of all thyroid pathologies, its prevalence is 0.1 – 0.7% [1,3]. Between the ages of 20 and 40, the disease is encountered in 8%, while the remaining 92% occur in children [2].

Subacute thyroiditis

A relatively rare disease accounting for no more than 1–2% of all thyroid disorders. The disease is more prevalent in regions with cold climates—Finland, Sweden, Canada, northern regions of the USA—but is also encountered in Israel, Iraq, Australia, Argentina, and Japan. ST predominantly affects middle-aged women; it rarely occurs in children and adolescents, with patients under 20 years old accounting for 2 to 7% [5].

Chronic autoimmune thyroiditis (CAIT)

Among the pediatric population in various countries, the prevalence of CAIT reaches 3%, peaking during adolescence [1,10].

According to A.V. Kiyaev [11], the age-related patterns of CAIT prevalence are as follows: its frequency among pre-pubertal children is extremely low (up to 0.5%), a regular increase in incidence is observed during puberty (up to 2%), occurring predominantly among females. Hypothyroidism as an outcome of CAIT is quite rare, accounting for approximately 1–2 cases per 1,000 adolescents, while the vast majority of cases at this age are detected without clinically significant impairments in thyroid function. The disease is twice as common in girls as in boys. Onset before the age of 4 years is extremely rare, although cases of acquired thyroiditis in newborns have been described. Among children suffering from type 1 diabetes mellitus, the frequency of chronic lymphocytic thyroiditis is 30–40%, and CAIT is observed with equal frequency in both girls and boys [1].

Riedel's chronic fibrous thyroiditis

The frequency of this pathology is 1.06 per 100,000 population. Women develop the disease 3–6 times more frequently than men [8].

Specific thyroiditis

Tuberculous, syphilitic, and actinomycotic thyroiditis are identified most frequently [1].

1.4 Features of Coding the Disease or Condition

E06.0 Acute thyroiditis

Thyroid abscess

Thyroiditis:

pyogenic

purulent

Use additional code, if desired, to identify infectious agent (B95–B98)

E06.1 Subacute thyroiditis

Thyroiditis:

de Quervain's

giant cell

granulomatous

non-suppurative

Excludes: autoimmune thyroiditis (E06.3)

E06.3 Autoimmune thyroiditis

Hashimoto's thyroiditis

Hashitoxicosis (transient)

Lymphoadenomatoid goiter

Lymphocytic thyroiditis

Lymphomatous struma

E06.5 Other chronic thyroiditis

Thyroiditis

chronic:

NOS

fibrous

ligneous

Riedel's

E06.9 Thyroiditis, unspecified

1.5 Classification of the disease or condition

Thyroiditis is classified depending on the acuteness of the process (acute, subacute, chronic) and the nature of inflammation (suppurative, autoimmune).

Currently, acute, subacute, chronic thyroiditis, and specific thyroiditis are distinguished in children [1].

Classification of thyroiditis.

1. Acute thyroiditis (suppurative, non-suppurative thyroiditis)

2. Subacute thyroiditis (viral, de Quervain)

3. Chronic thyroiditis:

Autoimmune thyroiditis (hypertrophic (Hashimoto's goiter), atrophic (primary myxedema)

Invasive fibrous thyroiditis (Riedel's thyroiditis).

4. Specific thyroiditis

Specific thyroiditis (in tuberculosis, lymphogranulomatosis, etc. [2].

1.6 Clinical presentation of the disease or condition

Acute thyroiditis.

In children, the disease begins with the sudden onset of pain and swelling in the thyroid gland area, fever, chills, sore throat, hoarseness, and often dysphagia. Frequently, pain is more pronounced on one side and radiates to the mandible, ear, or occiput. Neck flexion reduces pain, whereas extension exacerbates the pain syndrome and causes dysphagia. Sometimes symptoms appear a few weeks prior to the exacerbation of the disease. Examination reveals a temperature up to 38–40°C and tachycardia. Often, the child does not allow palpation of the thyroid gland due to severe tenderness. At the onset of the disease, examination often fails to reveal anything other than swelling in the thyroid area. Later, erythema in the thyroid area and regional lymphadenopathy develop; fluctuation is rarely detected. Involvement of one lobe and/or the entire gland is possible. In children, the left lobe is more commonly involved, whereas in adult patients, the right lobe is. Frequent recurrences of the disease and involvement of the left lobe of the gland indicate that in anomalies of the third branchial arch, infection penetrates via the fistula of the pyriform sinus between the nasopharynx and the thyroid gland. Subclavian and cervical lymph nodes are enlarged, and edema of the soft tissues of the neck is noted. In the absence of adequate antibiotic therapy, purulent mediastinitis, sepsis, abscess, neck phlegmon, and aspiration pneumonia may develop. In patients with acute thyroiditis, thyroid function is rarely impaired. Only in massive lesions involving the entire thyroid lobe can symptoms of destructive thyrotoxicosis appear [2,3,4,12].

Subacute thyroiditis (viral, granulomatous, de Quervain's thyroiditis).

The disease begins with a general inflammatory response, local pain, swelling, and tenderness upon palpation in the thyroid gland area. An asymptomatic course is possible, accompanied only by thyromegaly and a mild systemic inflammatory response, but in most cases, the clinical presentation of subacute thyroiditis is characterized by local pain in the thyroid area and thyrotoxicosis syndrome. General symptoms include malaise, weakness, fatigue, and low-grade fever. Pain in the thyroid area increases with neck extension and swallowing.

The duration of the course varies from several weeks to several months. The disease has two phases: the acute phase and the recovery phase. The acute phase lasts from 2 to 6 weeks and is characterized by increased levels of thyroid hormones, decreased TSH and iodinated protein levels, and decreased radioactive iodine uptake. At the same time, clinical manifestations of hyperthyroidism and tenderness upon palpation of the thyroid gland are observed. Symptoms disappear as thyroid hormone levels normalize. Meanwhile, enlargement and induration of the thyroid gland may persist.

In the recovery phase, a laboratory picture of hypothyroidism may be observed with elevated TSH levels and decreased _T4 levels, and thyroid radioactive iodine uptake increases. Hypothyroidism can persist from 2 to 7 months, while the size and consistency of the thyroid gland return to normal [1,5,6,12].

Table 1. Clinical phases of subacute thyroiditis

Chronic autoimmune thyroiditis (CAIT)

In children, in most cases, there is an enlargement of the thyroid gland in the absence of clinical symptoms of its functional impairment. At the time of diagnosis, 52.1% of children are in a euthyroid state, 22.5% have hypothyroidism, and in 19.2% of cases, subclinical hypothyroidism is present. Other changes in thyroid function (6.5%), namely subclinical and overt hyperthyroidism (hashitoxicosis), may not be recorded by the pediatrician [13]. It is also noted that in at least 3–4% of children with Graves' disease (GD), the manifestation of thyrotoxicosis is preceded by chronic autoimmune thyroiditis, which indicates the existence of a continuous spectrum between autoimmune thyroiditis and Graves' disease within a broad range of autoimmune thyroid disorders [13,14,15]. As a rule, hashitoxicosis manifests as subclinical thyrotoxicosis (isolated suppression of TSH levels with normal _T4 and _T3). Patients complain of weakness, malaise, and irritability. Very rarely, the disease in its initial stage manifests as dysphagia, sore throat, hoarseness, and a feeling of pressure in the neck. In the hypertrophic form, a goiter is detected. On palpation, the gland is soft or elastic in consistency with a granular surface. In later stages, the glandular tissue becomes dense and the surface nodular, mimicking nodular formations. Sometimes several nodular formations can be palpated, which become more prominent during levothyroxine replacement therapy when hyperplastic tissue regresses against the background of TSH suppression. These nodules are represented by lymphoid follicles against a background of diffuse lymphocytic infiltration of the glandular tissue.

In cases where the disease debuts with pronounced symptoms of hypothyroidism, the presence of the atrophic form of autoimmune thyroiditis should be suspected. On palpation, the thyroid gland is not enlarged or is palpated as a dense, small-volume formation.

The features of the clinical presentation in autoimmune thyroiditis in childhood and adolescence are due to the short duration of the disease and minimal morphological and functional changes of the thyroid gland in the early stages of the immunopathological process.

AIT in early childhood and preschool age manifests predominantly with hypothyroidism. Over the course of the disease in childhood and adolescence, an increase in the frequency of overt hypothyroidism is noted, most significantly in the first 3 years of the disease. The possibility of transient thyroid function disorders in AIT has been revealed. At the same time, it is noted that in subclinical hypothyroidism and hyperthyroidism, thyroid function is capable of spontaneous recovery in half of the cases. There are no differences in the main clinical, instrumental, and biochemical parameters between patients with AIT in a euthyroid state and those with subclinical hypothyroidism [16,17,18].

The long-term prognosis of thyroid function in children and adolescents with chronic autoimmune thyroiditis differs significantly between patients with euthyroid thyroid function or subclinical hypothyroidism at the time of diagnosis and those who had overt hypothyroidism or subclinical hyperthyroidism.

The long-term 5-year prognosis of thyroid function is presented in a study by Aversa et al. [19].

1. With a euthyroid onset of chronic autoimmune thyroiditis, 57.1% of patients remain euthyroid 5 years after manifestation, subclinical hypothyroidism develops in 30.6% of cases, and overt hypothyroidism in 12.3%. The presence of goiter and elevated levels of antithyroglobulin antibodies can serve as predictors of future hypothyroidism development.

2. In the presence of subclinical hypothyroidism at the time of chronic autoimmune thyroiditis diagnosis, overt hypothyroidism developed in 30.5% of patients after 5 years. However, the long-term prognosis for this cohort of patients was not uniformly unfavorable: 40.6% showed spontaneous normalization of TSH and free T4 levels by the end of the follow-up period.

3. When a clinical and laboratory picture of thyrotoxicosis (hashitoxicosis) is present at the time of chronic autoimmune thyroiditis diagnosis, which is infrequent in pediatric practice, dynamic monitoring is indicated, and antithyroid drug therapy is performed only in selected cases. Spontaneous resolution of hyperthyroidism in chronic autoimmune thyroiditis is noted on average 5 months after the manifestation of chronic autoimmune thyroiditis, although considerable individual variability is noted.

4. Subclinical thyrotoxicosis (Hashitoxicosis) at the time of chronic autoimmune thyroiditis diagnosis (blood TSH concentration below the lower limit of normal, free T4 within reference ranges). According to prospective studies, subclinical hyperthyroidism due to AIT resolves spontaneously within 1–24 months from the detection of AIT.

Riedel's chronic fibrous thyroiditis.

The thyroid gland is enlarged, of "stony" density, with an uneven surface, and does not move during swallowing. Breathing difficulties, cough, hoarseness, and dysphagia are possible. In some cases, enlargement of the goiter is accompanied by progressive hypothyroidism. Much less frequently, phenomena of hypoparathyroidism (tetany syndrome) are noted as a consequence of the spread of the fibrous process to the parathyroid glands. When the muscles of the eyeball and retrobulbar tissues are involved, secondary exophthalmos develops [9].

Specific thyroiditis.

The clinical presentation of chronic specific thyroiditis is determined by the underlying disease. The thyroid gland is typically dense, painless, and mobile [1].

2. Diagnostics, medical indications and contraindications for diagnostic methods

2.1 Complaints and Anamnesis

2.1.1. Acute thyroiditis

The diagnosis is established on the basis of:

1. Anamnestic data: previous manifestations of acute thyroiditis, inflammatory diseases of the upper respiratory tract;

2. Physical examination: pain syndrome radiating to the jaw, ear, shoulder on the affected side; local signs of inflammation (redness, edema) and abscess formation in the thyroid gland;

3. Laboratory testing – results of a complete blood count (CBC): leukocytosis, neutrophilic left shift, elevated ESR;

4. Instrumental examinations: characteristic ultrasound and scintigraphic pattern of the thyroid gland – hypoechoic area of inflammation on ultrasound, "cold" on scintigraphy;

5. Fine-needle aspiration biopsy of the inflammatory focus with fluctuation: purulent discharge; pathological examination of the biopsy material: infiltration of the thyroid tissue by polymorphonuclear leukocytes and lymphocytes; presence of epithelial cells with varying degrees of damage (dystrophy and necrosis).

• Diagnosis of acute thyroiditis in accordance with the criteria proposed above is recommended for all patients to establish a diagnosis [2,3,4,12].

LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)

2.1.2. Subacute thyroiditis

The diagnosis is established on the basis of:

1. anamnestic data: previous manifestations of subacute thyroiditis following an epidemic of viral diseases: measles, influenza, adenoviral infection, Coxsackie virus infection, infectious mononucleosis. Subacute thyroiditis also occurs against the background of sarcoidosis, Q fever, malaria, streptococcal infection, invasive medical procedures, after antibiotic therapy, emotional stress.

2. physical examination: swelling and tenderness upon palpation in the thyroid area, enlargement of the thyroid gland; pain in the thyroid area increases with neck extension and swallowing;

3. laboratory testing – results of a complete blood count (CBC): normal blood formula with elevated ESR;

4. assays of TSH and thyroid hormone levels: changes in TSH and thyroid hormone levels depending on the phase of the disease;

instrumental examinations: characteristic ultrasound (enlarged thyroid gland, diffuse heterogeneity or focal "cloud-like" zones of decreased echogenicity in one or both lobes) and scintigraphic picture of the thyroid gland (decreased thyroid iodine uptake in the acute phase).Diagnosis of subacute thyroiditis in accordance with the criteria proposed above is recommended for all patients to establish a diagnosis [5,6].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

- previous manifestations of subacute thyroiditis following an epidemic of viral diseases: measles, influenza, adenoviral infection, Coxsackie virus infection, infectious mononucleosis;

- presence of associated subacute thyroiditis conditions such as sarcoidosis, Q fever, malaria, streptococcal infection, invasive medical procedures, antibiotic therapy, emotional stress;

- complaints of malaise, low-grade fever, fatigue;

- complaints of sore throat, moderate to severe pain in the thyroid gland, often radiating to the ear and jaw [6].

LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)

2.1.3. Chronic autoimmune thyroiditis

The diagnosis is established on the basis of:

1. Presence of antibodies to thyroid peroxidase (TPO);

2. Characteristic ultrasound changes in the structure of the thyroid gland.

• Diagnosis of subacute thyroiditis in accordance with the criteria proposed above is recommended for all patients to establish a diagnosis [8].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: traditionally, diagnostic criteria included the presence of goiter, elevated levels of antithyroid antibodies in the blood, and characteristic ultrasound changes in the thyroid structure (diffuse heterogeneity and decreased echogenicity) [20, 21,22]. At present, the presence of goiter is no longer considered a mandatory diagnostic sign [8], since screening for Hashimoto's thyroiditis can be performed even in the absence of clinical symptoms, for example, if the patient has other autoimmune diseases, in order to rule out concomitant thyroid involvement. Thyroid ultrasound is the most reliable diagnostic method; at the same time, a normal ultrasound finding is extremely rare in the presence of elevated antithyroid antibody levels.

- thyroid disorders in parents and siblings;

- presence of other autoimmune diseases;

- complaints of neck enlargement; sensation of pressure in the neck area [1].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

2.1.4. Chronic fibrous Riedel's thyroiditis

The diagnosis is established on the basis of:

1. Complaints of dysphagia, cough, voice huskiness, breathing impairment;

2. Physical examination: the thyroid gland is usually enlarged; painless on palpation, woody consistency, with a smooth surface. Thyroid mobility is limited or completely lost due to adhesions to surrounding tissues. The skin over the thyroid gland is not adherent to it and is easily gathered into a skin fold. Lymph nodes are not enlarged.

3. Laboratory testing: results of a complete blood count (CBC) – no peripheral blood changes; an increase in ESR is sometimes observed;

4. Assays of TSH and FT4 levels: FT4 level is normal or decreased, TSH level is normal or increased;

5. Instrumental examinations: ultrasound picture of the thyroid gland and thyroid scintigraphy data.

6. Fine-needle aspiration biopsy of the thyroid gland.

7. esophageal x-ray or computed tomography of the esophagus with oral contrast often reveals displacement or compression of the esophagus or trachea [9,23].

2.1.5. Specific thyroiditis

The diagnosis is established on the basis of:

1. Anamnestic data on the presence of an underlying disease (tuberculosis, syphilis, actinomycosis, sarcoidosis, etc.);

2. Visual and palpation examination of the thyroid gland assessing size, consistency, and presence of nodular formations;

3. Characteristic ultrasound changes in the structure of the thyroid gland;

4. Changes on thyroid scintigraphy;

5. Fine-needle aspiration biopsy of the thyroid gland followed by culture of the contents.

- concomitant conditions (tuberculosis, syphilis, actinomycosis, sarcoidosis, etc.);

- complaints of neck enlargement; sensation of pressure in the neck area [1].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

2.2 Physical Examination

- external examination of the neck area with surrounding tissues (presence of redness, edema, neck deformity);

- palpation of the neck area with surrounding tissues (presence of areas of induration and fluctuation) [12].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

- external examination of the neck area with surrounding tissues - palpation of the neck area with surrounding tissues [6].

GCR C LoE 4 Grade of Recommendation C (Level of Evidence – 4)

- external examination of the patient's neck area;

- palpation of the patient's neck area [1].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

- external examination of the neck area with surrounding tissues to visualize the size of the thyroid gland and its mobility during swallowing;

- palpation of the neck area with surrounding tissues to determine thyroid density;

- registration of obstructive symptoms: dyspnea (respiratory rate count), dysphagia, hoarseness due to involvement of structures surrounding the thyroid gland

- visual assessment of the presence of exophthalmos;

- testing for Chvostek's and Trousseau's signs [9,23,24].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Dyspnea occurs due to tracheal involvement, dysphagia is associated with esophageal involvement, stridor develops when the recurrent laryngeal nerve is affected, and venous sinus thrombosis occurs due to involvement of the vascular network. Involvement of the extraocular muscles and retrobulbar tissues leads to secondary exophthalmos. Positive Chvostek's and Trousseau's signs indicate the development of secondary hypoparathyroidism.

- external examination of the patient's neck area;

- palpation of the patient's neck area to assess thyroid enlargement,

- determination of thyroid density and its mobility [1].

GCR CLeveI of recommendation C (level of evidenceComments: The thyroid gland is firm, painless, and mobile.

2.3 Laboratory Diagnostics

Comments: The complete blood count (CBC) reveals leukocytosis, a neutrophil shift to the left, and an elevated ESR [12]. Assessment of thyroid hormonal function (blood TSH level testing) is performed only if clinical signs of thyrotoxicosis are present.

- complete blood count (CBC) with erythrocyte sedimentation rate (ESR) determination;

- blood TSH level testing, and serum free T4 (fT4) and free T3 (fT3) levels testing [6,7].

LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)

Comments: An elevated ESR > 50 mm/h is noted. At the same time, the leukocyte count and leukocyte differential are typically normal.

About 50% of patients with subacute thyroiditis have an initial thyrotoxic phase due to the unregulated release of thyroid hormones from damaged thyroid follicles. In thyrotoxicosis, a decreased TSH level is detected in combination with elevated free T3 and free T4 levels. In the early stages of the disease, the TSH level may be normal.

- detection of blood anti-thyroperoxidase antibodies to verify the diagnosis;

- blood TSH level testing and serum free T4 (fT4) level testing to assess the functional state of the thyroid gland [8].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

- blood TSH level testing and serum free T4 (fT4) levels testing to assess the functional state of the thyroid gland [9,23,24];

- blood calcitonin level testing in the presence of nodular formations to rule out medullary thyroid carcinoma [5].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

- blood TSH level testing and serum free T4 (fT4) level testing to assess thyroid function [5].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

2.4 Instrumental Diagnostics

Comments: in the early stage of the disease, a decrease in tissue echogenicity and blurred contours of the thyroid lobe are detected due to local edema. In later stages, an abscess pattern is observed (a hypoechoic mass with fluid content).

Comments: A decrease in radiopharmaceutical (RP) uptake on the affected side («cold spot») is noted.

• Spiral computed tomography of the neck in patients with acute thyroiditis is recommended in rare cases with massive involvement to diagnose complications: mediastinitis, neck phlegmon, and tracheal fistulas [12].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• Neck MRI is recommended for patients with acute thyroiditis for differential diagnosis only if there are contraindications to radiation diagnostic methods [12].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Ultrasound examination of the thyroid and parathyroid glands may reveal thyroid enlargement, diffuse heterogeneity, or focal «cloud-like» zones of decreased echogenicity in one or both lobes. Migration of these zones has been described. Doppler sonography shows decreased or normal blood flow, in contrast to increased vascularization in Graves' disease.

Comments: A decrease and sometimes absence of radiopharmaceutical uptake is noted during the thyrotoxic phase of subacute thyroiditis.

Comments: Ultrasound changes characteristic of autoimmune thyroiditis may appear before an elevation in blood antibodies to thyroid tissue is detected. Classic signs of autoimmune thyroiditis are determined by ultrasound at the stage of full-blown clinical presentation. Such late ultrasound signs form the following diagnostic triad:

- thyromegaly (more frequently) or thyroid hypoplasia (much less frequently);

- echogenicity of thyroid tissue: moderately or slightly diffusely decreased;

- against this background, in varying proportions and with varying intensity, depending on the duration and activity of the process, irregular-shaped areas with blurred, uneven margins are detected, changing their direction and contrast when changing the position of the probe and the direction of the ultrasound beam in the area under study, and having some areas with a more pronounced decrease in density (maximum severity of autoaggression), others isoechoic to the tissue of the salivary glands (not yet involved in inflammation), and the rest being hyperechoic rounded foci or linear strands of connective tissue (replacement fibrosis).

Such changes correspond to the heterogeneous tissue of the thyroid gland and the clearly heterogeneous nature of its echographic structure.

Other signs of the disease should be described, giving them only a facultative value (nodular contours of the lobes, blurred, uneven, and interrupted character of the thickened and edematous capsule). Various visual-figurative word forms frequently mentioned as signs of autoimmune thyroiditis («honeycomb», «patches of cotton wool on wet asphalt», «plowed field», «cobblestone pavement», «aurora», «black hole») are unacceptable due to subjectivity and irreproducibility even upon re-evaluation by the same specialist.

Doppler sonography shows decreased or normal blood flow, in contrast to increased vascularization in Graves' disease.

Comments: Ultrasound reveals hypoechoic, hypovascular tissue involving adjacent tissues and sometimes the carotid arteries; on scintigraphy, these lesions are most often detected as «cold» thyroid nodules.

Comments: CT reveals a hypodense mass that does not accumulate contrast media. Narrowing of the esophagus or trachea is frequently detected.

2.5 Other Procedures

• Pathoanatomical examination of biopsy (surgical) material of thyroid tissues is recommended for patients with acute thyroiditis only for differential diagnosis [3,4].

GCR CLE 4Level of recommendation C (level of evidence – 4)

Comments: In acute thyroiditis, infiltration of the thyroid tissue by polymorphonuclear leukocytes and lymphocytes is noted; epithelial cells with varying degrees of damage (dystrophy and necrosis) are present.

Comments: Treatment of a branchial cleft cyst of the neck is generally surgical and involves excision of the cyst and its tract up to the pyriform sinus, which prevents the recurrence of the branchial cleft cyst of the neck.

Comments: FNA is primarily performed as part of the diagnostic workup for nodular goiter.

Comments: Fine-needle aspiration biopsy of the thyroid gland reveals areas of fibrosis with elements of lymphocytic infiltration. Due to the difficulties encountered in obtaining puncture material (significant density of the thyroid gland) and interpreting the obtained data (histological picture similar to thyroid cancer), it is advisable to perform an open biopsy and obtain ad oculos a specific amount of tissue for histological examination.

Comments: following the puncture, a cytological examination of the thyroid tissue smear and a microbiological (culture) examination of the punctate are performed. The diagnosis of Pneumocystis thyroiditis can be confirmed only by fine-needle aspiration biopsy of the thyroid gland with Grocott-Gomori's methenamine silver stain of the obtained material for the pathogen, as Pneumocystis thyroiditis is clinically and laboratory-wise similar to typical subacute granulomatous thyroiditis.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1. Acute thyroiditis

3.1.1. Conservative treatment

Comments: antibacterial therapy is carried out with broad-spectrum drugs (third-generation, fourth-generation, fifth-generation cephalosporins (ATX group Other cephalosporins and penems), penicillin combinations, including combinations with beta-lactamase inhibitors, macrolides).

• Also, at the conservative treatment stage, all patients with acute thyroiditis are recommended to use nonsteroidal anti-inflammatory and antirheumatic drugs (ATX - M01A) to achieve an anti-inflammatory effect [1].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

3.1.2. Surgical treatment

Comments: when the process is localized in one of the lobes, lobectomy is the method of choice. If the infection spreads beyond the capsule into adjacent tissues, drainage is required. Puncture drainage combined with antibacterial therapy is performed in case of abscess formation. The patient should be carefully examined for the presence of a pyriform sinus fistula into the pharyngeal cavity (hypopharynx). For this purpose, fistulography with barium sulfate** is performed. If such a fistula forms, its excision and adequate antimicrobial therapy are necessary to avoid disease recurrence.

3.1.3. Other treatment

Comments: Searching for and identifying the recurrent laryngeal nerve on the affected side may be complicated by inflammatory infiltration. The use of continuous neuromonitoring reduces the likelihood of recurrent laryngeal nerve palsy.

3.2. Subacute thyroiditis (viral, granulomatous, de Quervain's thyroiditis)

Since subacute thyroiditis in children is characterized by a mild course with spontaneous resolution, only symptomatic therapy is administered.

3.2.1. Conservative treatment

Comments: The nature of thyrotoxicosis in PT is destructive; prescribing thionamide therapy is not justified, but careful monitoring is required.

Comments: Antibiotic therapy is ineffective, as the etiology of the disease is presumed to be viral.

3.3. Chronic autoimmune thyroiditis

3.3.1. Conservative treatment

Decreased thyroid function in children and adolescents with AIT is not an obligatory symptom of the disease. However, the presence of acquired primary hypothyroidism should be regarded as a result of AIT, necessitating replacement therapy with levothyroxine sodium** preparations.

- at an adequate dose of 100 mcg/m² or

- at the age of 1 to 5 years at a dose of 4–6 mcg/kg/day;

- at the age of 6 to 10 years at a dose of 3–4 mcg/kg/day;

- at the age of 11 years and older at a dose of 2–3 mcg/kg/day [1,7].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: in patients with goiter, the dose of levothyroxine sodium** may be somewhat higher to maintain a low-normal TSH level (from 0.3 to 1.0 IU/L), minimizing its goitrogenic effect. Assessment of TSH and free T4 levels should be performed every 6–8 weeks from the start of therapy. Once the euthyroid state is achieved, every 6–12 months.

1. To confirm that AIT is indeed present.

2. To recheck blood TSH levels to rule out laboratory error and the influence of other factors (stress, hypothermia, etc.).

3. For patients under 3 years of age — treatment with levothyroxine sodium** if TSH levels are between 5 and 10 IU/L with normal free T4.

4. For patients over 3 years of age — watch-and-wait approach / observation if TSH levels are between 5 and 10 IU/L with normal free T4.

5. For patients with TSH levels above 10 IU/L — treatment with levothyroxine sodium**, if it has not been initiated previously [8, 27, 28].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

3.4. Chronic fibrous Riedel's thyroiditis

3.4.1. Conservative treatment

Comments: GCs are considered the basis of conservative therapy, and their anti-inflammatory effect is most effective when used in the early stages of the disease. An effective dose currently does not exist.

3.4.2. Surgical treatment

• Minimal surgical intervention is recommended for patients with RT only when signs of compression syndrome are present [23,24].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: due to the absence of a clear boundary between fibrous and normal thyroid tissue, the risk of perioperative complications is high: even with limited surgical interventions, it reaches 39%. Minimal surgical intervention is intended to relieve compression symptoms.

3.5. Specific thyroiditis

Treatment of chronic specific thyroiditis should not be limited to thyroid hormone replacement therapy; treatment of the underlying disease is required.

3.5.1. Conservative management

3.5.2. Surgical treatment

Comments: when the process is localized in one of the lobes, lobectomy is the method of choice. If the infection spreads beyond the capsule into adjacent tissues, drainage is required. Surgical removal of the affected lesion carries a risk of postoperative hypothyroidism.

3.5.3. Other treatment

Comments: locating and identifying the recurrent laryngeal nerve on the affected side may be complicated by inflammatory infiltration. The use of continuous neuromonitoring helps reduce the likelihood of recurrent laryngeal nerve palsy.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

1. There is no medical rehabilitation for acute thyroiditis. In most cases, the outcome of the disease is a complete recovery. Thyroid function is not impaired.

2. There is no medical rehabilitation for subacute thyroiditis . In most cases, the outcome of the disease is a complete recovery.

3. For specific thyroidites, approaches to medical rehabilitation are determined by the nature of the underlying disease that caused the specific thyroiditis.

• Patients with Riedel's thyroiditis are recommended social adaptation involving specialists and social workers. Rehabilitation measures in patients with Riedel's thyroiditis can be carried out in specialized sanatoriums [24].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

5. Prevention and Dispensary Observation

Acute thyroiditis

Subacute thyroiditis

Comments: The recommendation is due to the etiopathogenesis of subacute thyroiditis.

Follow-up monitoring depends on the severity of the patient's condition and the duration of the specific phase of the disease.

Chronic autoimmune thyroiditis

No preventive measures have been developed for autoimmune thyroiditis.

Dispensary follow-up (Active surveillance)

Follow-up monitoring is recommended to be carried out in accordance with the methodology proposed below.

Table 2. Follow-up monitoring of children with chronic autoimmune thyroiditis.

Riedel's thyroiditis

There is currently no prevention for Riedel's thyroiditis; however, attention should be paid to provoking factors and conditions that exacerbate obstruction symptoms (smoking, upper respiratory tract infections, air pollution, climatic conditions).

Follow-up monitoring depends on the severity of the patient's condition and the involvement of surrounding organs and tissues in the pathological process; the frequency of follow-up examinations and specialist consultations is determined individually.

6. Organization of Medical Care

Acute thyroiditis

1. Indications for emergency hospitalization in a medical organization (inpatient facility) for acute thyroiditis — in all cases.

2. Indications for discharging a patient from a medical organization in acute thyroiditis:

- after surgical treatment with radical elimination of the lesion;

- following conservative treatment after completed antibacterial therapy with a positive treatment outcome and elimination of the threat of recurrence and disease persistence.

Subacute thyroiditis

1. Indications for emergency hospitalization in a medical organization (inpatient facility) for subacute thyroiditis are present if the patient has:

1) severe pain syndrome;

2) pronounced symptoms of thyrotoxicosis.

2. Indications for discharging a patient from a medical organization in subacute thyroiditis:

1) relief of pain syndrome;

2) elimination of pronounced symptoms of thyrotoxicosis.

Chronic autoimmune thyroiditis

In most cases, hospitalization is not required.

1. Indications for elective hospitalization:

1) thyroid dysfunction refractory to correction in an outpatient setting;

2) presence of nodular lesions in the thyroid gland requiring inpatient evaluation.

Riedel's thyroiditis

1. Indications for elective hospitalization:

1) thyroid dysfunction refractory to correction in an outpatient setting

2. Indications for emergency hospitalization:

1) development of tracheal and esophageal compression syndrome.

3. Indications for discharging a patient from the inpatient facility:

1) improvement in condition when the patient can continue treatment in an outpatient clinic or at home without prejudice to health.

Common to all diseases.

1. If it is necessary to transfer the patient to another healthcare organization.

2. Gross violation of hospital regulations.

3. Upon the written request of the patient or their legal representative, provided that discharge does not threaten the patient's life and is not dangerous to others. In this case, discharge may be carried out only with the permission of the head physician of the medical organization or their deputy for medical work.

7. Additional Information

No.

Criteria for Evaluating the Quality of Medical Care

1. Acute thyroiditis

2. Subacute thyroiditis

3. Chronic autoimmune thyroiditis

4. Riedel's thyroiditis.

References

Appendix A1. Working Group Composition

LEADERS:

Peterkova Valentina Alexandrovna – Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, Scientific Director of the Institute of Pediatric Endocrinology, Federal State Budgetary Institution "National Medical Research Center for Endocrinology" of the Russian Ministry of Health, Head of the Department of Pediatric Endocrinology-Diabetology, Institute of Higher and Additional Professional Education, Federal State Budgetary Institution "National Medical Research Center for Endocrinology" of the Russian Ministry of Health, Chief freelance pediatric specialist endocrinologist of the Russian Ministry of Health.

Bezlepkina Olga Borisovna – Doctor of Medical Sciences, Deputy Director of the Center – Director of the Institute of Pediatric Endocrinology, Federal State Budgetary Institution "National Medical Research Center for Endocrinology" of the Russian Ministry of Health, Professor of the Department of Pediatric Endocrinology-Diabetology, Institute of Higher and Additional Professional Education, Federal State Budgetary Institution "National Medical Research Center for Endocrinology" of the Russian Ministry of Health.

TEXT AUTHORS:

Tatiana Yu. Shiryaeva – Candidate of Medical Sciences, Associate Professor, Leading Researcher at the Department of Thyroidology, Somatic and Reproductive Development, Institute of Pediatric Endocrinology, National Medical Research Center for Endocrinology of the Russian Ministry of Health.

Elena V. Nagaeva – Doctor of Medical Sciences, Head of the Department of Thyroidology, Reproductive and Somatic Development, Institute of Pediatric Endocrinology, National Medical Research Center for Endocrinology of the Russian Ministry of Health, Associate Professor at the Department of Pediatric Endocrinology and Diabetology, Institute of Higher and Continuing Professional Education, National Medical Research Center for Endocrinology of the Russian Ministry of Health.

Vadina Tatiana Alekseevna – Candidate of Medical Sciences, Physician at the Institute of Pediatric Endocrinology, Federal State Budgetary Institution "National Medical Research Center for Endocrinology" of the Russian Ministry of Health.

Chikulaeva Olga Alexandrovna – Candidate of Medical Sciences, Leading Researcher at the Department of Thyroidology, Somatic and Reproductive Development, Institute of Pediatric Endocrinology, Federal State Budgetary Institution "National Medical Research Center for Endocrinology" of the Russian Ministry of Health, Associate Professor at the Department of Pediatric Endocrinology-Diabetology, Institute of Higher and Additional Professional Education, Federal State Budgetary Institution "National Medical Research Center for Endocrinology" of the Russian Ministry of Health.

EXPERTS:

Bashnina Elena Borisovna — Doctor of Medical Sciences, Professor at the Department of Endocrinology named after Academician V.G. Baranov, North-Western State Medical University named after I.I. Mechnikov, Chief freelance pediatric endocrinologist of the North-Western Federal District.

Bolotova Nina Viktorovna — Doctor of Medical Sciences, Professor at the Department of Propaedeutics of Childhood Diseases, Pediatric Endocrinology, and Diabetology, Saratov State Medical University named after V.I. Razumovsky of the Russian Ministry of Health.

Galkina Galina Aleksandrovna — Doctor of Medical Sciences, Head of the Pediatric Endocrinology Department, Research Institute of Obstetrics and Pediatrics, Rostov State Medical University of the Russian Ministry of Health, Chief freelance pediatric endocrinologist of the Rostov Region, Chief freelance pediatric endocrinologist of the Southern Federal District.

Kiyaev Alexey Vasilievich — Doctor of Medical Sciences, Professor at the Department of Hospital Pediatrics, Ural State Medical University of the Russian Ministry of Health, Head of the Center for Pediatric Endocrinology, Regional Children's Clinical Hospital, Chief freelance pediatric endocrinologist of the Sverdlovsk Region, Chief freelance pediatric endocrinologist of the Ural Federal District.

Kolodkina Anna Aleksandrovna — Head of the Department of Hereditary Diseases and Early-Onset Endocrinopathies, Institute of Pediatric Endocrinology, National Medical Research Center for Endocrinology of the Russian Ministry of Health, Candidate of Medical Sciences.

Kostrova Irina Borisovna — Head of the Pediatric Endocrinology Department, Children's Republican Clinical Hospital named after N.M. Kuraev, Chief freelance pediatric endocrinologist of the Republic of Dagestan, Chief freelance pediatric endocrinologist of the North Caucasian Federal District.

Malievsky Oleg Arturovich, Doctor of Medical Sciences, Professor at the Department of Hospital Pediatrics, Bashkir State Medical University of the Russian Ministry of Health, Chief freelance pediatric endocrinologist of the Volga Federal District.

Petryaikina Elena Efimovna — Doctor of Medical Sciences, Director of the Russian Children's Clinical Hospital, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Chief freelance pediatric endocrinologist of Moscow, Chief freelance pediatric endocrinologist of the Central Federal District.

Samsonova Lyubov Nikolaevna — Doctor of Medical Sciences, Head of the Department of Pediatric Endocrinology, Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health.

Svetlova Galina Nikolaevna — Deputy Chief Physician, National Medical Research Center for Endocrinology of the Russian Ministry of Health, Pediatric Endocrinologist, Candidate of Medical Sciences.

Tatyana E. Taranushenko – D.Sc. in Medicine, Head of the Department of Pediatrics, Institute of Postgraduate Education, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University of the Russian Ministry of Health, Chief freelance pediatric endocrinologist of Krasnoyarsk Krai, Chief freelance pediatric endocrinologist of the Siberian Federal District.

Chugunov Igor Sergeevich — Head of the Pediatric Endocrine Tumor Department, Institute of Pediatric Endocrinology, National Medical Research Center for Endocrinology of the Russian Ministry of Health, Candidate of Medical Sciences

Conflict of interest: Members of the working group declare no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Pediatrician.

2. Pediatric endocrinologist.

Table 1. Scale for assessing levels of reliable evidence (LRE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing the levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for assessing levels of recommendation persuasiveness (LRP) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix B. Physician Action Algorithms

Chronic autoimmune thyroiditis

Appendix C. Patient Information

Acute thyroiditis is an inflammation of the thyroid gland that occurs due to a bacterial infection (suppurative thyroiditis) or non-suppurative thyroiditis caused by trauma. Both conditions are extremely rare and have a favorable prognosis. In the first case, treatment with antibacterial drugs in a hospital setting is required; in the second case, treatment at home under medical supervision is possible.

Subacute thyroiditis occurs extremely rarely, the disease is of viral origin and is characterized by a mild course in childhood. Treatment at home under medical supervision is possible. Anti-inflammatory drugs are prescribed only upon a doctor's recommendation.

The most common thyroid disease in childhood is chronic autoimmune thyroiditis. There can be two forms of the disease: with an increase in the size of the thyroid gland above the upper limit of normal, and with a decrease (atrophy) of the gland. The cause of the disease is unknown. The marker of the disease is autoantibodies to thyroid tissue, which destroy the gland itself. In the first phase of the disease, signs of increased thyroid function are possible (increased heart rate, increased appetite against the background of weight loss, irritability). For a long time in children, the disease may not cause discomfort, be accompanied by normal values of TSH and free T4, and be detected only during examination (by the presence of anti-TPO antibodies and a characteristic ultrasound picture). In this case, treatment is not required; it is necessary to visit a pediatric endocrinologist regularly (on average 1 time in 6 months). The pediatric endocrinologist will prescribe regular monitoring of TSH, free T4 in the blood, and an ultrasound examination of the thyroid gland. If hypothyroidism occurs, the doctor will prescribe effective treatment and regularly conduct dynamic examinations.

Chronic fibrous Riedel's thyroiditis is an extremely rare disease of the thyroid gland; during this period, the thyroid gland is enlarged, immobile during swallowing because it is fused with surrounding tissues. Difficulties in swallowing occur. Surgical treatment is necessary.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Not required.