Production of Goiter and Exophthalmos in Rabbits by Administration of Cyanide

We have shown that several of the organic cyanides 1 when injected subcutaneously into rabbits daily for 3 or more weeks produce thyroid hyperplasia. Methyl cyanide produces the greatest thyroid reactions, and young rabbits (3 to 4 months) are more reactive than adults to the same doses per kg.

Chronic bilateral exophthalmos has occurred in a significant number of prepubertal rabbits after methyl cyanide has been given for varying lengths of time. Exophthalmos has developed as early as the 20th day after beginning daily injections of 0.1 cc. of methyl cyanide in 3 months old rabbits. Of the 2 breeds used (Dutch and Belgian) we have observed it most frequently in young Dutch rabbits. It has not been detected in adults (6 months and over) in either strain. Representative instances are given in Table I.

So far we have observed only moderate degrees of exophthalmos. It occurs earliest in those rabbits which develop thyroid hyperplasia the quickest and appears to be proportional to the degree of thyroid hyperplasia. Rabbits that have failed to develop thyroid hyperplasia, or rabbits in which the hyperplasia has been slight have not developed exophthalmos. When exophthalmos is developing the rabbits become nervous and fidgety. This is frequently associated with soft feces and an increase in the volume of urine.

No attempt has been made to determine what rôle the hormones of the posterior pituitary and chromaffin tissue may play in the production and maintenance of the exophthalmos. There is, however, some hypertrophy and great hyperemia of the medulla of the suprarenals in these animals.