Although much controversy continues to rage in regard to what constitutes the normal upper limit for TSH in the context of subclinical hypothyroidism, it is generally accepted thata stateofmildhyperthyroidismexistswhen the TSH level is less than 0.3 mIU/liter. The term “subclinical” hyperthyroidism has been applied when such low TSH levels are accompanied by normal to high normal reference range values for T4 and T3. The laboratory results indicating this diagnosis may have been obtained during routine physical examination or because some signs or symptoms suggested the possibility of hyperthyroidism to the physician. Because TSH may be suppressed transiently for various reasons, confirmationof theresult is important.Onceresultsareobtained with a subsequent repeat test, the clinician should deal next with a determination of the cause of the low TSH and whether or not a remedy may need to be applied (1). Other causes of a low TSH level are excluded as we look for a cause of subclinical hyperthyroidism with a focus on disease of the thyroid gland. Thus, in the differential diagnosis for a low serum TSH level, we can exclude pituitary or hypothalamic disease, the euthyroid sick syndrome, or drugs that suppress TSH such as dobutamine, dopamine, and steroids because these entities do not reflect thyroid disease per se and would be associated with low or low normal serum T4 and T3. The low TSH usually seen in the first trimester of pregnancy is a physiological change, although a degree of subclinical hyperthyroidism may exist with human chorionic gonadotropin stimulation of the thyroid causing augmented hormone secretion, and total T3 and T4 levels rising to or above the reference range enhanced by estrogen-mediated increases in thyroid hormone binding proteins. Factitial or unintentional iatrogenic TSH suppression due to excessive thyroid hormone ingestion as a cause of low TSH can also be excluded by history, and of course its management is not rocket science, merely being dosage adjustment as required. Having excluded these various nonthyroidal causes of a low TSH value, we are left with the likelihood of subclinical hyperthyroidism due to either transient or longterm endogenous thyroid hormone excess usually on the basis of Graves’ disease or nodular goiter. The compelling imperative to make the diagnosis is based upon the consequences of long-term untreated subclinical hyperthyroidism, which may include atrial fibrillation (2–4), diastolic dysfunction (5), a suggestion of higher rates of death due to cardiovascular disease (6), and osteopenia, osteoporosis, and increased fracture rate, especially in postmenopausal women (7, 8). Given these potential consequences of untreated subclinical hyperthyroidism, it would seem logical to implement treatment. However, the necessity for treatment may be arguable depending upon factors such as the degree of TSH suppression ( 0.1 vs. between 0.1–0.4 mIU/liter) (9), the patient’s age, and the presence of comorbid conditions. Moreover, it is possible that the TSH suppression may not be “permanent,” that the subclinical state will not progress to overt hyperthyroidism, and therefore that intervention would not be required. In this issue of the JCEM, Vadiveloo et al. (10) report epidemiological data on the prevalence, incidence, and natural history of 2024 subjects with subclinical hyperthyroidism with data up to 7 yr after diagnosis. In brief, most of the subjects continued to maintain a low TSH level over the course of follow-up, about a third had reverted to normal values by 5–7 yr, and very few ( 1%) actually progressed to overt hyperthyroidism. This experience is very similar to that reported by Rosario (11), but it differs from that reported by Diez and Iglesias (12), who observed that 45% of patients progressed to overt disease during the course of follow-up.
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