Management of Low TSH with Goiter
For a patient presenting with low TSH and goiter, immediately obtain thyroid ultrasound and radionuclide uptake scan to distinguish between toxic multinodular goiter, toxic adenoma, and Graves' disease, as these conditions require different treatment approaches. 1
Initial Diagnostic Workup
Confirm biochemical hyperthyroidism by measuring free T4 and free T3 alongside the suppressed TSH—this distinguishes overt hyperthyroidism (elevated thyroid hormones) from subclinical hyperthyroidism (normal thyroid hormones) 2, 3. The combination of low TSH with goiter most commonly indicates toxic multinodular goiter (16% of hyperthyroidism cases) or Graves' disease (70% of cases) 2.
Obtain thyroid ultrasound as the first-line imaging modality to confirm the goiter originates from thyroid tissue, characterize its size and morphology, and identify nodules that may require biopsy if hypofunctioning or isofunctioning 1. Ultrasound also evaluates for suspicious features of malignancy in any nodules present 1.
Perform radionuclide uptake and scan with I-123 (preferred over I-131 for superior imaging quality) when goiter is associated with thyrotoxicosis 1. This confirms the entire goiter consists of thyroid tissue and distinguishes between:
- Diffuse increased uptake: Graves' disease
- Focal hot nodules with suppressed surrounding tissue: Toxic adenoma or toxic multinodular goiter
- Decreased uptake: Destructive thyroiditis (subacute or lymphocytic) 1
Measure TSH receptor antibodies to diagnose Graves' disease, particularly in ambiguous cases 1, 2. Low TSH levels occur in 29% of clinically euthyroid patients with multinodular goiter and normal iodine uptake, indicating these patients are at risk of developing overt hyperthyroidism 4.
Treatment Based on Etiology
For Toxic Multinodular Goiter or Toxic Adenoma
Radioactive iodine (RAI) is the treatment of choice for toxic nodular goiter, as antithyroid drugs will not cure hyperthyroidism associated with autonomous nodules 5, 6. Surgery (subtotal or near-total thyroidectomy) is indicated for large goiters causing compression symptoms (dysphagia, orthopnea, voice changes, dyspnea) or when RAI is refused 3, 5, 6.
Antithyroid drugs (methimazole) are used short-term to render the patient euthyroid before definitive therapy with radioiodine or surgery 7, 5. Methimazole is FDA-approved for toxic multinodular goiter when surgery or radioactive iodine is not appropriate, or to ameliorate symptoms before definitive treatment 7.
CT imaging is superior to ultrasound for evaluating substernal extension, deep extension to retropharyngeal space, and degree of tracheal compression when obstructive symptoms are present 1. This information guides surgical planning if compression symptoms warrant intervention 1.
For Graves' Disease with Goiter
Antithyroid drugs are the preferred initial treatment for Graves' hyperthyroidism, typically given for 12-18 months to induce remission 2, 5. However, recurrence occurs in approximately 50% of patients after this short-term course 2.
Long-term antithyroid drug treatment (5-10 years) is associated with fewer recurrences (15%) compared to short-term treatment 2. Risk factors for recurrence include age <40 years, FT4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, and goiter size ≥WHO grade 2 2.
Radioiodine or surgery are definitive treatments when antithyroid drugs fail, recurrence occurs, or the patient has a large goiter causing compression symptoms 2, 3, 5. Ultrasound provides thyroid dimensions for planning RAI treatment 1.
For Destructive Thyroiditis
Doppler ultrasound can distinguish thyrotoxicosis from overactive thyroid (Graves' disease, toxic adenoma—showing increased blood flow) versus destructive causes (subacute or lymphocytic thyroiditis—showing decreased blood flow) 1. Destructive thyrotoxicosis is usually mild and transient, requiring steroids only in severe cases 2.
Critical Monitoring and Complications
Untreated hyperthyroidism causes cardiac arrhythmias, heart failure, osteoporosis, adverse pregnancy outcomes, and increased mortality 3. Patients with low TSH and normal free T3/T4 levels remain at risk of developing overt hyperthyroidism and require close monitoring 4.
Avoid iodinated contrast CT unless evaluating for infiltrative neoplasm, as iodine exposure can exacerbate hyperthyroidism in patients with nodular thyroid disease 1. MRI is an alternative to CT but has more respiratory motion artifact 1.
Common Pitfalls
- Do not rely on TSH alone—29% of euthyroid patients with multinodular goiter have low TSH with normal free T3, indicating subclinical hyperthyroidism that may progress 4
- Do not use levothyroxine suppression therapy in patients with suppressed TSH levels, as this risks toxic symptoms 6
- Do not assume antithyroid drugs will cure toxic nodular goiter—these patients require definitive treatment with RAI or surgery 5, 6
- Do not skip radionuclide scanning when the etiology is unclear or nodules are present, as this directly measures thyroid activity rather than inferring it from blood flow 1