What is the diagnosis and treatment for a patient with suppressed Thyroid-Stimulating Hormone (TSH), elevated free Triiodothyronine (T3), and elevated free Thyroxine (T4)?

Diagnosis: Overt Hyperthyroidism (Thyrotoxicosis)

This patient has overt hyperthyroidism, characterized by suppressed TSH (0.00 mIU/L), elevated free T3 (5.5), and elevated free T4 (1.59), requiring immediate diagnostic workup to determine the underlying cause before initiating appropriate treatment. 1, 2, 3

Diagnostic Workup Required

The combination of suppressed TSH with elevated thyroid hormones represents thyrotoxicosis, where excess thyroid hormone suppresses pituitary TSH production through negative feedback. 1 Before treatment, you must establish the specific etiology:

Essential Laboratory Tests

• Measure TSH-receptor antibodies (TSH-R-Ab) to identify Graves' disease, which accounts for 70% of hyperthyroidism cases. 2, 4
• Check thyroid peroxidase (TPO) antibodies to evaluate for autoimmune thyroid disease. 1, 2
• Obtain complete thyroid function panel including total T3 if not already measured, as some patients have isolated T3 toxicosis. 3

Imaging Studies

• Thyroid ultrasound to assess for nodular disease, goiter size, and vascularity—a hypervascular, hypoechoic gland suggests Graves' disease. 4
• Thyroid scintigraphy (radioactive iodine uptake scan) if nodules are present or etiology remains unclear—high uptake indicates Graves' disease or toxic nodular goiter, while low/absent uptake indicates thyroiditis. 1, 3

Differential Diagnosis by Etiology

Most Likely Causes

• Graves' disease (70% of cases): Positive TSH-R-Ab, diffusely enlarged thyroid, high radioiodine uptake, possible eye findings (stare, exophthalmos). 2, 3
• Toxic nodular goiter (16% of cases): Palpable nodules, possible compressive symptoms (dysphagia, orthopnea), high radioiodine uptake in nodules. 2, 3
• Thyroiditis (3% of cases): Painless or painful thyroid, low radioiodine uptake, self-limited course. 1, 2
• Drug-induced (9% of cases): Recent exposure to amiodarone, tyrosine kinase inhibitors, or immune checkpoint inhibitors. 2

Immediate Symptomatic Management

While awaiting diagnostic workup results:

Beta-Blocker Therapy

• Initiate non-selective beta-blocker (preferably with alpha-receptor blocking capacity like carvedilol) to control heart rate, tremor, anxiety, and palpitations. 1
• Propranolol or atenolol are acceptable alternatives for symptomatic relief. 5
• This provides immediate symptom control regardless of underlying etiology. 1

Critical Assessment

• Evaluate for thyroid storm if patient has fever, tachycardia out of proportion to fever, altered mental status, or cardiac arrhythmia—this is a medical emergency requiring immediate hospitalization. 5
• Screen for atrial fibrillation as untreated hyperthyroidism causes cardiac arrhythmias and heart failure. 3
• Assess for osteoporosis risk especially in postmenopausal women and elderly patients. 3

Definitive Treatment Based on Etiology

For Graves' Disease (if TSH-R-Ab positive)

• First-line: Methimazole (MMI) 10-30 mg daily for 12-18 months, as it is the preferred antithyroid drug. 4
• Alternative: Propylthiouracil (PTU) only if patient is pregnant (first trimester), planning pregnancy, or has MMI allergy. 5, 4
• Monitor TSH-R-Ab levels at 12-18 months—persistently elevated antibodies predict 50% recurrence risk after stopping medication. 2, 4
• Consider definitive therapy (radioactive iodine or thyroidectomy) if recurrence occurs after completing antithyroid drug course. 4

For Toxic Nodular Goiter

• Radioactive iodine (I-131) ablation is the preferred treatment for most patients. 2
• Total thyroidectomy by high-volume thyroid surgeon if surgery preferred or RAI contraindicated. 4
• Antithyroid drugs are not curative but can be used for preoperative preparation. 2

For Thyroiditis

• Conservative management during thyrotoxic phase—no antithyroid drugs needed as this is destructive thyrotoxicosis, not increased hormone synthesis. 1, 2
• Beta-blockers for symptoms if needed. 1
• Anticipate hypothyroidism developing approximately 1 month after thyrotoxic phase, requiring levothyroxine replacement. 1

Special Populations Requiring Modified Approach

Pregnancy

• Switch from methimazole to propylthiouracil immediately if pregnant or planning pregnancy, especially during first trimester to avoid methimazole teratogenicity. 5, 4
• Radioactive iodine is absolutely contraindicated in pregnancy. 5
• Thyroidectomy can be performed in second trimester if necessary. 5

Elderly or Cardiac Disease

• Treatment is mandatory in patients >65 years due to increased risk of atrial fibrillation, osteoporosis, and cardiovascular mortality. 6
• More aggressive beta-blockade may be needed to prevent cardiac complications. 3
• Consider earlier definitive therapy rather than prolonged antithyroid drug course. 6

Patients on Immune Checkpoint Inhibitors

• Thyroiditis is most common cause in this population, occurring in 6-9% with anti-PD-1/PD-L1 therapy. 1
• Continue immunotherapy in most cases—high-dose corticosteroids rarely required for thyroid dysfunction. 5, 1
• Monitor for progression to hypothyroidism which typically occurs 1-2 months after thyrotoxic phase. 1

Critical Pitfalls to Avoid

• Never start treatment without confirming etiology—thyroiditis requires observation while Graves' disease requires antithyroid drugs. 1, 2
• Do not use radioactive iodine in patients with active Graves' orbitopathy without steroid prophylaxis, as it can worsen eye disease. 4
• Avoid propylthiouracil as first-line except in pregnancy/first trimester due to higher hepatotoxicity risk compared to methimazole. 4
• Do not delay treatment in severe cases—untreated hyperthyroidism causes atrial fibrillation, heart failure, osteoporosis, and increased mortality. 3
• Rule out pregnancy before radioactive iodine as it causes fetal hypothyroidism if given after 10 weeks gestation. 5

Monitoring During Treatment

• Recheck thyroid function tests (TSH, free T4, free T3) every 4-6 weeks while titrating antithyroid drugs. 5
• Target euthyroid state with TSH 0.5-4.5 mIU/L and normal free T4/T3 levels. 7
• Monitor for antithyroid drug side effects including agranulocytosis (fever, sore throat), hepatotoxicity, and rash. 4
• Assess for atrial fibrillation at each visit, especially in elderly patients. 3, 6