Tiroiditis Hashimoto

01Pathophysiology

Hashimoto thyroiditis is the most common cause of primary hypothyroidism in iodine-sufficient areas. The PNPK Hipotiroid Dewasa 2026 identifies autoimmune thyroiditis (tiroiditis autoimun) as the leading etiology of primary hypothyroidism, where the thyroid gland cannot produce adequate hormone due to destruction of thyroid tissue or ineffective biosynthesis.

The pathogenesis is driven by a loss of immune tolerance to thyroid self-antigens. CD4+ T-helper cells become sensitized to thyroid antigens such as thyroid peroxidase (TPO) and thyroglobulin (Tg). This triggers two parallel destructive pathways. First, cytotoxic CD8+ T cells directly infiltrate the thyroid parenchyma and destroy follicular cells through perforin-granzyme and Fas-FasL mechanisms. Second, B lymphocytes produce anti-TPO and anti-Tg antibodies. Anti-TPO antibodies are particularly important because they fix complement and mediate antibody-dependent cell-mediated cytotoxicity (ADCC), amplifying glandular destruction.

As follicular cells are destroyed, the thyroid's capacity to synthesize T4 and T3 declines. The hypothalamic-pituitary axis senses the falling peripheral hormone levels and responds by increasing thyrotropin-releasing hormone (TRH) secretion, which in turn drives TSH production upward. This compensatory TSH elevation is the earliest laboratory abnormality and defines the subclinical phase of the disease. The PNPK document defines this phase as elevated TSH with a still-normal FT4. Over time, as destruction continues, FT4 falls below the reference range, and the patient enters overt (clinical) hypothyroidism with both elevated TSH and low FT4.

The progressive nature of the disease explains the clinical observation noted in the PNPK that disease progression is most likely in patients with positive anti-TPO antibodies (progresivitas penyakit biasanya terjadi pada pasien dengan antibodi antitiroid peroksidase yang positif). Histologically, the gland shows dense lymphocytic and plasma cell infiltration, germinal center formation, follicular atrophy, and the characteristic Hurthle cells (oncocytic metaplasia of follicular epithelium), which are large eosinophilic cells with abundant mitochondria representing a degenerative response.

The sustained TSH stimulation early in the disease causes goiter formation (diffuse thyroid enlargement). However, in late-stage disease, extensive fibrosis and atrophy can replace the glandular tissue, resulting in a small, shrunken gland. This explains why some patients present with goiter while others present with thyroid atrophy, both under the same diagnosis.

02Classification and Clinical Manifestation

By Anatomic Level

Clinical Manifestations

03Diagnostic Workup

The PNPK Hipotiroid Dewasa 2026 establishes that TSH is the single best initial screening test for primary hypothyroidism. It is the most sensitive marker because TSH rises before FT4 falls, making it the earliest detectable abnormality. A normal TSH effectively rules out primary hypothyroidism (though not central hypothyroidism, where TSH may be low or inappropriately normal).

Once TSH is found to be elevated, FT4 is ordered for confirmation and classification. An elevated TSH with a normal FT4 defines subclinical hypothyroidism. An elevated TSH with a low FT4 defines overt hypothyroidism. The PNPK notes that in suspected central (secondary/tertiary) hypothyroidism, TSH and FT4 should be checked simultaneously, because TSH alone is unreliable in that setting.

To establish the autoimmune etiology (i.e., to confirm Hashimoto as the cause), anti-TPO antibodies are ordered as a follow-up test. The PNPK lists this as a "pemeriksaan lanjutan" (follow-up investigation) for patients with confirmed hypothyroidism and suspected autoimmune etiology. A positive anti-TPO result carries prognostic value: it predicts a higher likelihood of progression from subclinical to overt disease, which directly influences treatment decisions.

Ultrasound of the thyroid is used to evaluate the morphology of the gland. The PNPK instructs clinicians to assess for changes in thyroid size (diffuse goiter, hypertrophy, or atrophy), focal lesions (nodules), parenchymal echogenicity, homogeneity, and vascularity. In Hashimoto, the classic ultrasound pattern is a diffusely hypoechoic and heterogeneous gland, sometimes with fibrous septations creating a pseudolobulated appearance.

For FPKTP settings (primary care facilities with limited laboratory access), the PNPK recommends using the Billewicz Index as a clinical screening score. A score above +25 indicates high likelihood of hypothyroidism and mandates referral for TSH testing. A score below -30 makes hypothyroidism unlikely. This scoring system relies purely on symptoms and physical signs and serves only for screening, not for diagnosis or treatment initiation.

04Management and Treatment

Non-pharmacologic therapy applies to all patients, at both FPKTP and FPKTL levels. The PNPK recommends a balanced diet with attention to limiting high-fat and high-sugar intake in patients who have dyslipidemia or excess weight. Selenium, zinc, and vitamin D supplementation may have a positive effect in autoimmune hypothyroidism. Physical activity should follow the WHO general population recommendation of 150 minutes per week of moderate-to-vigorous exercise combining aerobic and resistance training. Adequate sleep of at least 8 hours per night is also recommended to manage stress and anxiety.

Pharmacologic therapy is the cornerstone of management. Levothyroxine (LT4) is the first-line and standard treatment. The PNPK explicitly states that pharmacologic therapy is not initiated at the FPKTP level due to limitations in laboratory access and drug availability. Treatment is initiated at the FPKTL by internists or endocrinologists.

For uncomplicated adults, the starting dose is 1.6 mcg/kg/day, titrated by TSH measured every 4-8 weeks. Once stable, the monitoring interval extends to 6 months, and then to 12 months.

For elderly patients or those with suspected coronary artery disease, a cautious start at 25 or 50 mcg/day with incremental increases of 25 mcg every 3-4 weeks is required. The target TSH in this population is the upper-normal range to avoid cardiac complications from overreplacement.

For subclinical hypothyroidism, not all patients require treatment. The PNPK adopts a "wait and see" approach for mild cases (TSH 4-10 mU/L) with minimal or no symptoms. Treatment is initiated when any of the following apply: TSH >=10 mU/L, pregnancy or planned pregnancy, clear symptoms of hypothyroidism, positive anti-TPO (indicating progression risk), or presence of cardiovascular comorbidity.

Administration instructions are critical for exam purposes. Levothyroxine must be taken on an empty stomach, at least 60 minutes before breakfast or >=3 hours after dinner. It should not be taken with other medications. Products containing iron, calcium, proton pump inhibitors, sucralfate, and bile acid sequestrants interfere with absorption and require dose adjustment or timed separation.

Avoiding overtreatment is emphasized in the PNPK. Levothyroxine should not be dosed to suppress TSH below 0.1 mU/L because this creates iatrogenic hyperthyroidism, increasing the risk of atrial fibrillation, osteoporosis, fractures, stroke, and dysrhythmia. Patients on long-term replacement should be monitored for cardiac and bone health.

For pregnancy, the PNPK provides trimester-adjusted TSH targets: 0.1-2.5 mU/L in the first trimester, 0.2-3.0 mU/L in the second, and 0.3-3.0 mU/L in the third. Women already on levothyroxine should increase their dose by two extra tablets per week as soon as pregnancy is confirmed. Data show that approximately 70% of pregnant women require about a 30% dose increase. Women newly diagnosed with overt hypothyroidism during pregnancy should start 1.6 mcg/kg/day immediately, given the risks of miscarriage, preterm birth, preeclampsia, postpartum hemorrhage, low birth weight, and impaired cognitive development of the child.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The single most common trap on this topic is confusing subclinical hypothyroidism with overt hypothyroidism and reflexively starting levothyroxine in every patient with an elevated TSH. The PNPK is explicit: subclinical hypothyroidism with TSH between 4 and 10 mU/L and minimal symptoms can be managed with observation alone. Treatment is only indicated when TSH reaches 10 or above, or when the patient is pregnant, planning pregnancy, symptomatic, anti-TPO positive, or has cardiovascular disease. Picking "start levothyroxine" as the answer for a mildly elevated TSH in an asymptomatic patient with no risk factors is a classic wrong answer.

A second frequently tested trap involves the elderly or cardiac patient. Giving a full replacement dose (1.6 mcg/kg/day) to a 75-year-old with known coronary artery disease can precipitate angina, myocardial infarction, or arrhythmia. The correct answer is always to start low (25-50 mcg/day) and titrate slowly.

Third, be wary of the "TSH is suppressed, so reduce the dose" trap. During treatment of primary hypothyroidism, FT4 may rise above the reference range, but if TSH remains within normal limits, do not reduce the dose. The PNPK states clearly that TSH is the primary monitoring parameter for primary hypothyroidism, not FT4. However, for secondary hypothyroidism, FT4 becomes the primary parameter because the pituitary-TSH axis is unreliable.

Fourth, remember that anti-TPO positivity has prognostic value beyond diagnosis. It predicts a higher rate of conversion from subclinical to overt hypothyroidism. A vignette may present a patient with mildly elevated TSH, normal FT4, and positive anti-TPO, asking whether to treat or observe. The anti-TPO positivity tips the scale toward treatment.

Finally, in pregnancy-related questions, note that isolated hypothyroxinemia (low FT4 with normal TSH for the trimester) does not require levothyroxine treatment according to the PNPK and current international guidelines. This is a commonly tested distinction: the vignette may show a pregnant woman with low FT4 but normal trimester-adjusted TSH, and the correct answer is reassurance, not levothyroxine.

The core competency being tested across all these scenarios is the ability to match the treatment intensity to the clinical context: the right drug, the right dose, the right patient, and the right time to start or withhold therapy.