Part of “CHAPTER 38 – NONTOXIC GOITER“

The approach to managing nontoxic goiter involves (a) prevention of progressive enlargement of the thyroid gland; (b) anticipation, where appropriate, of hyperthyroidism or hypothyroidism; (c) reduction of the risk of carcinoma in the gland; and (d) relief of local symptoms attributable to goiter. Annual clinical evaluation of the patient with nontoxic goiter is a cornerstone of management, as is routine instruction of the patient to contact the treating physician if local symptoms emerge or change, or if systemic symptoms develop that are consistent with hypothyroidism or hyperthyroidism.

Because nontoxic goiter is a state in which the permissive or directorial role of TSH is expressed, suppression of endogenous TSH secretion with exogenous thyroid hormone (L-thyroxine, T₄) prevents further enlargement of the gland.58 Two-thirds of sporadic nontoxic goiters shrink when endogenous TSH is suppressed by exogenous thyroid hormone.59 This rate of success is less likely for nodular goiters than for diffuse goiters.59 Modest goiter, particularly that associated with Hashimoto thyroiditis, predictably responds to TSH suppression with a return of the gland to normal or near-normal size. Nodular goiter responds to suppression therapy in a nonpredictable manner. Sometimes normal thyroid tissue located between multiple nodules atrophies when endogenous TSH is suppressed, bringing the nodules into greater relief. This change can be misinterpreted as an increase in nodule size in the face of suppression. The effectiveness of the strategy of TSH suppression in management of nodular goiter is under review by several groups. Nodular or nonnodular, very large nontoxic goiters are unlikely to respond to suppressive treatment, and aggressive suppression of TSH places such patients at risk for iatrogenic hyperthyroidism.

Although the suggestion has been made that T₃ may be more effective than T₄ in reducing goiter size,60 use of T₄ is preferable because T₄ has a long half-life and it does not lead to the transient episodes of elevated circulating T₃ levels that occur with daily T₃ therapy. TSH is suppressed in hypothyroid patients by 1.8 μg/kg body weight per day, and by 2.2 to 2.5 μg/kg per day in thyroid cancer patients.61 Although a definitive study of the suppressibility by T₄ of TSH in nontoxic goiter patients using a sensitive TSH assay has not been conducted, a dose of 2 to 2.5 μg/kg per day suffices in these patients.

Avoidance of overtreatment with exogenous thyroid hormone is desirable, particularly in the elderly. The increasing availability of sensitive TSH assays that readily distinguish
between suppressed and normal levels of TSH should help in determining the lowest suppressive dose of T₄.62 The risk of bone demineralization in the course of T₄ administration to suppress endogenous TSH secretion has been widely discussed, although its clinical impact, particularly in the setting of treatment of nontoxic goiter, is not clear.63 Another apparent complication of long-term T₄ treatment of nontoxic goiter patients may be increased left ventricular cardiac mass and diastolic dysfunction.64 The frequency and significance of these echocardiographic findings have not yet been determined. Autonomous nodular goiter should not be treated with T₄; the additional hormonal load may result in clinical hyperthyroidism.