What is the initial workup for a patient with hyperthyroxinemia (elevated T4) and secondary hypothyroidism (low Thyroid-Stimulating Hormone (TSH))?

From the Guidelines

The initial workup for someone with elevated T4 and low TSH should include a comprehensive evaluation and treatment of hyperthyroidism, as indicated by the presence of suppressed TSH and elevated T4 levels. This approach is supported by the American Diabetes Association's statement on the care of children and adolescents with type 1 diabetes, which recommends comprehensive evaluation and treatment of hyperthyroidism in patients with suppressed TSH and elevated T4/T3 levels 1.

Key Components of the Initial Workup

• A comprehensive history and physical examination to identify symptoms and signs of hyperthyroidism, such as weight loss, heat intolerance, palpitations, tachycardia, tremor, or exophthalmos
• Laboratory testing, including free T4 and free T3 levels to confirm true hyperthyroidism, as well as thyroid autoantibodies (particularly TSI and anti-TPO antibodies) to evaluate for Graves' disease
• A radioactive iodine uptake scan (RAIU) with I-123 to differentiate between causes with increased uptake (Graves' disease, toxic nodular goiter) versus decreased uptake (thyroiditis, exogenous thyroid hormone)
• Thyroid ultrasound to identify nodules and assess thyroid size and vascularity

Additional Considerations

• Symptomatic patients may benefit from beta-blockers, such as propranolol, to control adrenergic symptoms
• The workup should be expedited in elderly patients or those with significant cardiac symptoms, as untreated hyperthyroidism can lead to serious complications, including thyroid storm, atrial fibrillation, and heart failure
• Patients with previously normal TSH levels may be rechecked every 1–2 years or obtained at any time the growth rate is abnormal, as recommended by the American Diabetes Association 1

From the Research

Initial Workup for Elevated T4 and Low TSH

The initial workup for someone with elevated T4 and low TSH involves several steps to determine the underlying cause of hyperthyroidism.

• Clinical presentation and medical history: Assessing symptoms such as nervousness, heat intolerance, weight loss, and fatigue 2, 3.
• Thyroid function tests: Measuring TSH, T3, and T4 levels to confirm hyperthyroidism 2, 3, 4.
• Thyrotropin-receptor antibody status: Checking for the presence of thyrotropin-receptor antibodies to help diagnose Graves' disease 3.
• Thyroid scintigraphy: Recommended if thyroid nodules are present or the etiology is unclear 3.

Diagnostic Considerations

The diagnosis of hyperthyroidism can be overt or subclinical.

• Overt hyperthyroidism is defined as a low or undetectable TSH level with elevated T3 or T4 values 2, 3.
• Subclinical hyperthyroidism is defined as low or undetectable TSH with normal T3 and T4 levels 2, 3.
• The choice of treatment depends on the underlying diagnosis, the presence of contraindications to a particular treatment modality, the severity of hyperthyroidism, and the patient's preference 4.

Treatment Options

Treatment options for hyperthyroidism include:

• Antithyroid drugs (e.g., propylthiouracil, methimazole) 2, 3, 4.
• Radioactive iodine ablation 2, 3, 4.
• Surgery (thyroidectomy) 2, 3, 4.
• Beta-blockers (e.g., propranolol) may be used to control symptoms such as palpitations and tremors 5.