Production and measurement of exophthalmos-producing factor in guinea pigs

Although the extent of proptosis in exophthalmic Graves' disease has been measured directly and shown to correlate with serum content of a bioassayable exophthalmus-producing factor (EPS;1), a comparable relationship in an experimental model has not been reported. Progressive exophthalmos, measured from photographs and expressed as a ratio of intercorneal distance to intersupraorbital ridge distance, was produced in male guinea pigs when thyroid status was altered either by surgical thyroidectomy supplemented with 131-I treatment or by the administration of 6-propyl-2 thiouracil (0.1% in chow). In both groups, at time of sacrifice, serum content of EPF estimated by a modified goldfish bioassay using a known exophthalmogeric TSH preparation (Ambinon, Organon-Oss) as standard was positively correlated (r equals 0.804) with the terminal degree of exophthalmos. Daily replacement therapy with T4 (15mug/kg body wt) failed to alter significantly the exophthalmos which developed, even when replacement was initiated prior to the alterations of thyroid gland function; this observation tends to eliminate thyroid hormone deficiency per se as the causal event in exophthalmos. T4 treatment did, however, reverse or prevent the rises in serum TSH levels (McKenzie bioassay) thus dissociating TSH activity from EPF activity in the guinea pig. Treatment of guinea pigs with synthetic TRH (0.5, 1.0 OR 10 mug/kg body wt) for 21 days failed to produce demonstrable exophthalmos or assayable EPF levels although plasma TSH was significantly elevated.