• Thyroid hormone speeds up the sinus node, increases the heart's sensitivity to catecholamines, and raises contractility. Excess hormone therefore causes tachycardia and palpitations.
• Lippincott's pharmacology text says toxicity from thyroid hormone replacement is related to T3/T4 levels. It shows up as nervousness, palpitations, tachycardia, heat intolerance, and unexplained weight loss (Lippincott Illustrated Reviews: Pharmacology, Treatment of hypothyroidism section).
• That text also lists palpitations as a sign that a patient may need a lower levothyroxine dose.

• Over-replacement: A TSH that is suppressed (iatrogenic subclinical or overt hyperthyroidism) is the main cause.
• Rapid dose increases or high starting doses: These are riskier in older patients and in people with coronary disease or arrhythmia. Clinicians usually start low and go slow in these groups.
• Intentional TSH suppression: This is done in thyroid cancer (Goodman & Gilman's). It carries a higher cardiac risk.
• Overdose: Tintinalli's Emergency Medicine says propranolol can control the tachycardia and anxiety in thyroxine overdose.
• Long-term over-replacement: This raises the risk of atrial fibrillation and other cardiovascular complications (Swanson's Family Medicine Review).

1. Check TSH and free T4 first. Many cases turn out to be over-replacement.
2. Reduce the dose if TSH is suppressed. Symptoms often settle once TSH is back in range.
3. Look for other causes if TSH is normal. Examples are anemia, caffeine, anxiety, arrhythmia, and interacting drugs.
4. Get an ECG if palpitations are irregular or persistent, to look for atrial fibrillation.
5. A beta-blocker can be used short term for symptoms while the dose is adjusted.

Iatrogenic hyperthyroidism

Main causes

• Levothyroxine over-replacement. This is the most common cause. Tietz says exogenous subclinical hyperthyroidism is the most common type and is reversible by reducing the levothyroxine dose (Tietz Textbook of Laboratory Medicine, 7th Ed, Subclinical Hyperthyroidism).
• Intentional TSH suppression in differentiated thyroid cancer. Goldman-Cecil advises relaxing TSH goals in patients at higher risk of iatrogenic thyrotoxicosis, such as older patients, those with cardiovascular risk factors, and those with osteoporosis (Goldman-Cecil Medicine, Postoperative Thyroid Hormone Treatment).
• Drug and dosing errors, including prescription mistakes and changes in brand or formulation.
• Thyrotoxicosis factitia. Surreptitious ingestion of thyroid hormone, often to lose weight. Frameworks for Internal Medicine notes it causes TSH-independent thyrotoxicosis with low radioiodine uptake.
• Amiodarone and iodine excess. Harrison's says amiodarone is associated with thyrotoxicosis in up to 10% of patients, especially in areas of low iodine intake (Harrison's 22E, Other Causes of Thyrotoxicosis).
• Over-treatment of hyperthyroidism with radioiodine or antithyroid drugs can cause a transient period of subclinical hyperthyroidism.

Clinical features

• Common symptoms: nervousness, palpitations, tachycardia, heat intolerance, tremor, insomnia, and unexplained weight loss. These match the toxicity features in Lippincott's Pharmacology.
• Subclinical form: often has few or no symptoms. It is defined by a low TSH with normal free T4 and T3. Mild is TSH 0.1 to 0.4 mIU/L (Tietz).
• Higher-risk patients: older people, and those with coronary disease or arrhythmia, may present with atrial fibrillation, angina, or heart failure.

Consequences of prolonged TSH suppression

Diagnosis

1. TSH and free T4 (± T3). TSH is suppressed. Free T4 is high in overt cases and normal in subclinical cases.
2. Review the dose, adherence, and timing. Check what was taken before the blood draw, and check for interacting products such as biotin, which can distort assays.
3. If the cause is unclear (suspected factitia or a different cause):
   • Serum thyroglobulin is low or undetectable in factitia. It is high in destructive thyroiditis. Anti-thyroglobulin antibodies can interfere with the assay.
   • Radioiodine uptake is low in factitia, thyroiditis, and iodine-induced disease. It is high in Graves disease and toxic nodules.
   • The Tietz and Rosen's references also note a low T3/T4 ratio in these exogenous or destructive states.

Management

• Reduce the levothyroxine dose, or hold it briefly if toxicity is marked. Recheck TSH in about 6 to 8 weeks.
• Beta-blocker (e.g. propranolol) for symptoms and rate control while TSH normalises.
• In overdose, Tintinalli's mentions cholestyramine to increase fecal elimination, and propranolol for tachycardia and anxiety.
• Check for atrial fibrillation with an ECG if palpitations are irregular or persistent. Assess stroke risk and anticoagulate as for any atrial fibrillation.
• Factitia: address the underlying psychological or weight-related issue. Stop the hormone.
• Amiodarone-induced thyrotoxicosis needs endocrine input, because the type (iodine-induced or destructive) changes treatment.
• Bone health: consider a DEXA scan if suppression has been long-standing, particularly in postmenopausal women.

Prevention

• Start low and go slow in older patients and in those with cardiac disease.
• Target a TSH within the reference range unless there is a specific reason for suppression, such as thyroid cancer.
• Monitor TSH regularly and after any dose or formulation change.
• Take levothyroxine consistently on an empty stomach, and separate it from calcium and iron by at least 4 hours.

Recent literature