Hyperthyroidism and goiter have been reported frequently in association with the McCune-Albright syndrome (MAS). To assess the prevalence and extent of thyroid abnormalities in girls with MAS, we studied 19 patients [mean age, 6.6 +/- 1 (+/- SE) yr; mean bone age, 9.5 +/- 1 yr] and 18 normal control girls (mean age, 10.3 +/- 0.5 yr). All patients appeared euthyroid when examined; 1 was taking antithyroid medication. Ultrasonography revealed thyroid abnormalities in 7 patients, including generalized inhomogeneity, small (2-4 mm) and large (greater than 10 mm) hypoechoic regions, and echogenic nodule-like regions. Repeat ultrasonography after intervals of 9-18 months showed enlargement of large hypoechoic regions in 2 patients. In the patients with abnormal ultrasound findings, serum TSH was uniformly low or suppressed both at baseline and after administration of 7 micrograms/kg TRH. The mean serum T3 level in this group was significantly higher than that in controls (2.9 +/- 0.2 vs. 2.3 +/- 0.1 nmol/L; P less than 0.05), whereas mean serum T4, free T4, and T4-binding globulin levels did not differ from those of controls. In the remaining 11 patients, thyroid ultrasonography was normal, and the serum levels of T3, T4, free T4, and TSH were normal. Bioassay showed no detectable thyroid-stimulating activity in the plasma of the MAS patients with suppressed TSH levels. None of the patients became overtly thyrotoxic over 3-6 yr of observation, and their serum iodothyronine levels remained stable. We conclude that thyroid dysfunction is common in girls with MAS, but that it may be clinically occult and not rapidly progressive. The thyroid dysfunction, like that of the ovaries, is associated with structural abnormalities in the gland itself, together with suppressed levels of the respective stimulating hormones.