Management of Overt Graves’ Disease

Diagnosis and Confirmation

Overt hyperthyroidism is defined by a suppressed thyroid‑stimulating hormone (TSH) together with elevated free T3 and free T4 levels【2】.
Measurement of thyroid‑stimulating hormone‑receptor antibodies (TRAb) provides near‑100 % sensitivity and specificity for Graves’ disease and can obviate the need for radioactive iodine uptake scanning【2】.
When TRAb testing is unavailable or negative, radioactive iodine uptake (RAIU) and thyroid scintigraphy should be performed; diffuse uptake is characteristic of Graves’ disease, whereas focal or heterogeneous uptake suggests toxic nodular disease【2】.

Initiate methimazole at a dose of 10–30 mg once daily, titrated to the degree of T3 elevation (e.g., 15–20 mg daily for T3 2–3 × the upper limit of normal)【1】.
Methimazole is the preferred first‑line antithyroid drug for virtually all adults with newly diagnosed Graves’ disease, except in first‑trimester pregnancy, thyroid storm, or when the patient declines radioactive iodine or surgery due to severe methimazole intolerance【1】.
Propylthiouracil should not be used as first‑line therapy because it carries a higher risk of hepatotoxicity, including rare fatal hepatic necrosis【1】.
Begin a beta‑adrenergic blocker immediately if the resting heart rate exceeds 90 bpm, if cardiovascular disease is present, or if the patient has symptomatic hyperthyroid features (palpitations, tremor, heat intolerance)【1】.
Beta‑blockers provide symptomatic relief but do not treat the underlying hyperthyroidism【1】.
Obtain a baseline complete blood count with differential and liver function tests (bilirubin and transaminases) before starting methimazole【1】.
Routine white‑blood‑cell monitoring is not required; obtain a differential only during febrile illness or pharyngitis because agranulocytosis can develop rapidly and most patients have normal counts within two weeks of symptom onset【1】.

At week 4, measure free T4 and total T3 (total T3 assays have superior methodological reliability) and adjust the methimazole dose accordingly【1】.
Repeat thyroid function tests every 4–8 weeks until euthyroidism is achieved on the minimal effective methimazole dose【1】.
After euthyroidism, monitor free T4 and TSH every 2–3 months【1】.
TSH may remain suppressed for 1–3 months after free T4 and T3 have normalized; persistent TSH suppression during this period should not be interpreted as treatment failure【3】.

A single dose of 10–15 mCi of RAI typically induces hypothyroidism within 4–8 weeks, providing definitive disease control【1】.
Absolute contraindications include pregnancy, breastfeeding, or planning pregnancy within the next 4–6 months【1】.
Pre‑treatment steps: obtain a negative pregnancy test within 48 hours (if applicable), provide written radiation‑safety instructions, and continue methimazole until 3–7 days before RAI administration【1】.
Post‑RAI follow‑up: check free T4 and total T3 at 1–2 months, then every 4–6 weeks while thyrotoxic; consider retreatment if hyperthyroidism persists at 6 months (or if minimal response is seen at 3 months)【3】.
Lifelong annual thyroid function testing is required after RAI therapy【3】.

Continue methimazole for 12–18 months, then taper or discontinue if TSH is within the normal range【1】.
This approach offers the only potential cure without lifelong thyroid‑hormone replacement, with an approximate 50 % remission rate after the treatment course【1】.
Measure TRAb before stopping therapy; a TRAb level > 6 U/L predicts a higher relapse risk (≥ 50 %)【1】.
After discontinuation, monitor TSH and free T4 every 1–3 months for 6–12 months to detect early relapse【1】.
Relapse after short‑term therapy occurs in about 50 % of patients; risk factors include male gender, smoking, severe hyperthyroidism, large goiter (> 80 mL), and persistently elevated TRAb【1】.

Thyroidectomy provides rapid definitive disease control and avoids radiation exposure【1】.
Indications include large goiters (≥ 80 g) or compressive symptoms, women planning pregnancy within < 4–6 months, coexisting suspicious or malignant nodules, and patients refusing radiation or antithyroid drugs【1】.
Pre‑operative preparation: achieve euthyroidism with methimazole ± beta‑blockers and administer potassium iodide (Lugol’s solution or saturated solution of potassium iodide) for 10 days before surgery to reduce thyroid vascularity【1】.
Surgery should be performed by a high‑volume thyroid surgeon (≥ 30 thyroidectomies per year; ideally > 100) to minimize complications【1】.
Post‑operative management: monitor serum calcium or intact PTH, start levothyroxine at approximately 0.8 µg per lb (≈ 1.7 µg kg⁻¹) daily, and check TSH at 6–8 weeks after surgery【1】.
Lifelong annual thyroid function testing is required after thyroidectomy【1】.

For patients who relapse after short‑term therapy or have high‑risk features, long‑term methimazole (5–10 years) is feasible and is associated with a 15 % recurrence rate, markedly lower than the ≈ 50 % recurrence after short‑term therapy【1】.
This strategy requires monitoring every 2–3 months and patient willingness to remain on indefinite medication【1】.