HORMONAL FACTORS 



825 



several passages through hosts without thyroid glands (Furth et al., 1952). Such 

 transplants secrete thyrotrophic hormone, as evidenced by hyperplasia of the host 

 thyroid gland (Fig. 4). 



In this instance a factor necessary for induction has been found essential for the 

 continued growth of a neoplasm. Such new growths have been termed "con- 

 ditional" (Furth, 1953; Foulds, 1954) or "dependent" (hormone responsive, 

 Foulds). The pituitary adenomas induced by thyroidectomy are "dependent", 

 but during transplantation "autonomy" is acquired, that is, progressive growth 

 occurs in intact as well as thyroidectomized hosts. 



The genesis of TSH-secreting pituitary neoplasms can be prevented by the 

 administration of thyroid hormone after radiothyroidectomy (Gorbman, 1952; 

 Furth, 1955). Apparently hypothyroidism /)^r se may under specified conditions 

 lead to pituitary tumor formation. In support of this concept is the induction of 

 tumors by propyl-thiouracil (Moore et al., 1953) or surgical thyroidectomy (Dent 

 etal., 1955). In rats fed a low iodine diet both thyroid and pituitary tumors have 

 developed on the basis of the induced hypothyroidism (Axelrad and LeBlond, 

 1955; LeBlond et al., 1957). 



[ THYROID TUMORIGENESIS FOLLOWING HYPOTHYROIDISM [ 



PITUITARY GLAND 



Fig. 2. Sequence of events 

 in experimental thyroid 

 tumorigenesis following hy- 

 pothyroidism. 



(2) 



LOW BLOOD LEVEL OF 

 THYROID HORMONE _ 



(I) 

 THYROID SECRETION 

 LOW AFTER I'S' 

 (OR THIOURACIL) 

 {OR LOW DIETARY IODINE 



(6) (5a) 



TRANSPLANTS TRANSPLANTS 



TO < TO < 



INTACT HYPOTHYROID 



HOSTS HOSTS 



(3) 

 HYPERSECRETION OF TSH 

 TO HYPERSTIMULATE 

 THYROID GLAND 



(4) 



THYROID HYPERPLASIA 



OF REMAINING 



THYROID TISSUE 



(5) 



THYROID NEOPLASM 

 STIMULATED BY TSH 



(GENERAL HYPERPLASIA 

 7 THIOURACIL OR LOW I) 



That factors superimposed on hypothyroidism may be importantly involved 

 has been suggested (Gorbman, 1956). When mice were fed a low iodine diet so 

 that a relatively small dose of radioiodine accomplished thyroidectomy, pituitary 

 tumors were not induced. TSH-secreting tumors resulted, however, if added 

 X-irradiation, not necessarily to the pituitary gland, was given. Although hy- 

 pothyroidism per se may induce pituitary tumor formation, it is likely that ad- 

 ditional factors augment tumorigenesis. 



Hypersecretion of the pituitary gland follows radiothyroidectomy. The in- 

 creased secretory activity leads to adenoma formation which is followed by hor- 

 monally "independent" neoplasia (Gorbman, 1956). The mechanism underlying 

 this sequence of events is completely unknown. Apparently hypothyroidism is the 

 stimulus to tumor formation in the anterior pituitary. These pituitary tumors are 

 dependent, growing only in thyroidectomized hosts which duplicate the environ- 

 ment required for tumor development. The specificity of the altered interrelation, 



Literaiure p. 870 



