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Suppression of Human Thyroid Function by Antibodies to Bovine Thyrotropin

Departments of Medicine, UCLA and Harbor General Hospital Los Angeles and Torrance, California

Bovine thyrotropin (TSH), in the minimal dose which increased thyroidal ¹³²I uptake, was given repeatedly to 2 normal young men. Both subjects developed resistance to TSH effects, which was only temporarily overcome by doubling the dose. As resistance occurred, their serum acquired hemagglutinating antibodies to bovine TSH and neutralizing antibodies to both bovine and human TSH. Rapidity of the occurrence of TSH resistance and the speed and intensity of antibody formation were considerably greater in Subject D than in Subject S. After a series of 22 or 23 TSH injections (maximal dose of each injection 100 mU/kg), PBI values had decreased compared to pretreatment controls in both subjects, and Subject D's ¹³²I uptake had decreased. After a recovery period of 8 months, plasma, which had been collected by plasmaphoresis at the end of the series of TSH injections, was reinfused into the same subjects (17% plasma volume for Subject S and 24% for Subject D). Passive transfer of hemagglutinating antibodies could be demonstrated in Subject D, and transfer of neutralizing antibodies against human TSH occurred in both subjects. Both subjects had a decrease in ¹³²I uptake over the next 2 weeks, most pronounced at the end of the series of observations. Subject D's PBI fell, as did his rate of appearance of PB¹²⁵I in the circulation after a dose of ¹²⁵iodide. It is concluded that antibodies formed to bovine TSH are inhibitory not only to bovine TSH, but also to human TSH, and that they partially inhibit the effects of endogenous TSH. It would appear from these data that the clinical use of repeated doses of bovine TSH to stimulate the thyroid or thyroactive tissues requires re-evaluation, since it may possibly lead to suppression of spontaneous thyroid activity.

Received May 8, 1967.

Accepted July 14, 1967.

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