Slow growth but intense hypertrophy of thyrocytes in long-standing Grave's goitres

In order to evaluate the relative contribution of true cell replication, in comparison to mere cell hypertrophy, to the notoriously slow growth of toxic Graves' goitres persistently exposed to TSH receptor antibodies and requiring continuous thyrostatic treatment for more than one year, we have determined the fraction of dividing cells in 8 such goitres, using the monoclonal antibody Ki-67. This antibody identifies cells in late G1-, S-, G2- and M-phase. The fraction of Ki-67 positive cells ranged from 0.1 to 4.1% with a mean of 2.3 +/- 1.6. The apparently low absolute number of dividing cells is in full accordance with growth rates observed in multinodular goitres and in benign tumours of thyroidal and non-thyroidal origin. It is compatible with continuous, intense growth stimulation of the gland, particularly since thyrocytes may down-regulate their growth response when exposed to chronic stimulation. The observations account for the clinical observation that goitres, and in particular Graves' goitres, may take years to double their total mass of thyrocytes, whereas cell hyperplasia and functional overactivity (if untreated) continue unabated.