The pathogenesis of the goiter that is frequently found in patients with acromegaly is not known. Using ultrasonic scanning, we measured thyroid volume in 17 euthyroid patients with acromegaly and examined the relationships among thyroid size, plasma GH and insulin-like growth factor (IGF-I) levels, and serum thyroglobulin (TG) levels. The mean estimated thyroid volume in these 17 patients was 32.8 +/- 15.5 (+/- SD) mL, significantly larger than that in normal subjects (15.4 +/- 3.1 mL), and 64.7% of the patients had multinodular goiter, as identified by ultrasonography. Thyroid volume was positively correlated with plasma GH and IGF-I levels and heel-pad thickness, but not with the serum TSH level. In 7 patients, thyroid volume decreased in association with a decline in plasma GH and IGF-I levels after surgical treatment. The serum TG level was elevated in 7 of the 15 patients in whom it was measured, and the mean value was 51.7 +/- 62.7 (+/- SD) micrograms/L (normal, 12.6 +/- 6.4 micrograms/L). We found no correlations among the serum TG and TSH levels, plasma GH and IGF-I concentrations, and/or thyroid volume. However, serum TG decreased after surgical treatment, just as did plasma IGF-I. These observations together with the results of recent in vitro studies by others suggest that IGF-I is one of the factors involved in goiter formation, but the elevated serum TG levels in acromegaly are controlled not only by IGF-I but also by other factors.