From the Guidelines
The workup for subclinical hyperthyroidism should begin with confirming the diagnosis through repeat thyroid function tests, including TSH, free T4, and free T3, typically 2-3 months after the initial abnormal result. Once confirmed (low TSH with normal free T4 and T3), additional testing should include:
- Thyroid antibodies (TSI, TPO, and TRAb) to determine etiology
- A thyroid ultrasound to evaluate for nodules or structural abnormalities
- A radioactive iodine uptake scan may be necessary to distinguish between Graves' disease and toxic nodular disease, especially if the cause remains unclear after initial testing
- Bone density testing should be considered in postmenopausal women and men over 50 years due to increased fracture risk
- Cardiovascular assessment including ECG is important, particularly in older patients or those with cardiac symptoms, as subclinical hyperthyroidism increases the risk of atrial fibrillation and other cardiac complications 1. The urgency and extent of workup depends on the degree of TSH suppression, patient age, and presence of comorbidities, with more aggressive evaluation recommended for those with TSH <0.1 mIU/L, older adults, and patients with cardiovascular disease or osteoporosis risk factors. Subclinical hyperthyroidism has been associated with atrial fibrillation; dementia; and, less clearly, osteoporosis 1. However, progression from subclinical to clinical disease in patients without a history of thyroid disease is not clearly established 1. It is essential to weigh the benefits and potential harms of screening and treatment for subclinical hyperthyroidism, considering the risk of false-positive results, labeling, and overdiagnosis and overtreatment 1.
From the Research
Definition and Diagnosis of Subclinical Hyperthyroidism
- Subclinical hyperthyroidism is a laboratory diagnosis defined by a serum thyrotropin (TSH) concentration below the reference range, and a free thyroxine (FT4) and 3,5,3'-triiodothyronine levels (FT3) in the reference range 2.
- It is characterized by a decreased serum thyroid-stimulating hormone (TSH) and normal serum thyroxine (T4) and triiodothyronine (T3) concentrations 3.
- The normal laboratory reference range for TSH is 0.3-5.0 mIU/l, and subclinical hyperthyroidism occurs when TSH levels are less than normal 4.
Evaluation and Risk Assessment
- Evaluation should include repeat thyroid function tests to document persistent TSH suppression, investigation of the underlying cause, as well as evaluation of the patient's risk of adverse outcomes in the setting of a subnormal TSH 2.
- Patient factors such as age, symptoms, and underlying heart and bone disease are used to stratify patients for the risk of adverse outcomes and determine the appropriate treatment 2.
- Proposed grading systems distinguish between mild (TSH, 0.1-0.4 mIU/L) and severe subclinical hyperthyroidism (TSH, <0.1 mIU/L) and are used alongside patients' age and the presence of risk factors and symptoms to guide treatment 3.
Treatment Options
- Management options include observation without active therapy, radioactive iodine ablation of the thyroid, antithyroid medication, thyroid surgery, or radiofrequency ablation, as appropriate for the patient and clinical setting 2.
- Treatment may include observation without therapy, initiation of antithyroid medications, or pursuit of radioiodine therapy or thyroid surgery 3.
- The American Thyroid Association and the American Association of Clinical Endocrinologists recommend treating patients with TSH levels less than 0.1 mIU per L if they are older than 65 years or have comorbidities such as heart disease or osteoporosis 5.
Associated Risks and Considerations
- Subclinical hyperthyroidism has been associated with an increased risk of cardiovascular events such as atrial fibrillation and heart failure, bone loss and fracture, and in some studies, cognitive decline 2, 3, 5.
- The effectiveness of treatment in preventing these conditions is unclear, and the U.S. Preventive Services Task Force found insufficient evidence to assess the balance of benefits and harms of screening for thyroid dysfunction in asymptomatic persons 5.