This condition affects the skeleton and the cardiovascular system adversely, and abnormalities in other organ systems have also been reported ( 11 , 12 ). There is no evidence that patients with subclinical hyperthyroidism have an increase in fractures ( 225 , 226 ), but a significant reduction in bone density in postmenopausal women is seen ( 227 , 228 ). In addition, there is a documented risk of atrial fibrillation in patients with subclinical hyperthyroidism, and the cumulative incidence is inversely related to the TSH concentration ( 229 , 230 ). Low serum TSH in individuals aged 60 yr or older is associated with increased mortality from all causes, and in particular mortality due to circulatory and cardiovascular diseases ( 11 , 12 ). Because lifelong therapy is probably needed to avoid goiter recurrence ( 69 ) and the natural history of the disease is progression toward hyperthyroidism due to autonomous function of the thyroid nodules ( 77 , 78 ), l-T4 treatment is unfeasible in many patients. The incidence of permanent hypothyroidism after 131I therapy in moderately enlarged multinodular nontoxic goiters ranges from 22% to 58% within 5-8 yr ( 253 , 254 ), occurring more commonly in those patients with an initially smaller goiter size and with the presence of anti-TPO antibodies ( 254 ). The cumulated risk of hypothyroidism after treating large goiters is theoretically the same as in smaller goiters, because the administered radioactivity is targeted at the same absorbed dose. Many disregard thyroid scintigraphy in the initial evaluation of patients with nontoxic nodular goiter ( 16 , 126 ). Nevertheless, more than two thirds of ETA members ( 6 , 8 ) routinely use scintigraphy, www.agenqncjellygamat.com/ whereas less than 25% of ATA members prefer such a strategy in this condition ( 7 , 9 ). Indisputable indications for scintigraphy in the setting of a nodular goiter are hyperthyroidism (to visualize hot nodules suitable for 131I therapy) and a follicular neoplasm shown by FNAB, because warm nodules with great certainty are benign ( 163 ). If there is a suspicion of the nodules harboring cancer, the goiter is growing quickly, or if the goiter's large size is causing compressive symptoms, such as hoarseness, difficulty swallowing, or difficulty breathing, use of thyroid hormone to attempt to "suppress" and shrink MNG is not used because it puts patients at risk for hyperthyroidism.
If autonomously functioning nodules within these nontoxic multinodular goiters produce thyroid hormones in excess, the serum hormone level increases and causes thyrotoxicosis. Thyroxine (reduces TSH and size of diffuse simple goiters, less effective for multinodular goiter), radioactive iodine (safe and effective but may cause hypothyroidism), total thyroidectomy eliminates recurrences except for rare cases due to growth in embryonic remnants outside thyroid gland ( World J Surg 2007;31:593 ), near total thyroidectomy reduces hypoparathyroidism ( Langenbecks Arch Surg 2006;391:567 ) Indeed, a beneficial effect of thyroid hormones in diffuse goiters has been demonstrated in several controlled trials ( 211 , 215 - 221 ). In general, a goiter reduction of 15-40% can be expected within 3 months, but the gland returns to the pretreatment size just as soon after withdrawal ( 215 , 216 ). Treatment effect with T3 or in combination with l-T4 does not differ from that of l-T4 alone ( 216 , 217 ), but the effect may be more sustained after cessation of T3 therapy ( 216 ). The efficacy of thyroid hormones is shown to depend on the degree of TSH suppression ( 216 , 217 ), although results have been conflicting ( 218 ). In some of the studies in which l-T4 was compared ( 211 , 218 , 220 ) or combined ( 211 , 220 , 221 ) with iodine supplementation, no substantial differences were found between the regimens, but l-T4 resulted in a more pronounced depression of serum TSH than did iodine ( 211 , 218 , 221 ). It has been recommended that diffuse euthyroid endemic goiters are treated with 200 μg iodine combined with 100 μg l-T4 for at least 6 months, followed by iodine alone ( 222 ). Comparing nodular and diffuse goiters, the effect of l-T4 is clearly more convincing in diffuse glands ( 219 ).