Jane A. Russell 5 1 y 



suggested by Wells and Kendall, that the activity of the thyroid places always 

 a limit upon such manifestations as gluconeogenesis, and this factor may be 

 of importance when replacement therapy is attempted. 



Hypersensitivity to insulin has often been reported to be present after 

 thyroidectomy. However, when thyroidectomized and hy}iophysectomized 

 rats are compared in this respect under comparable conditions, it appears that 

 the hypersensitivity after thyroidectomy is much more slowly developed after 

 the operation than is that after hypophysectomy (table 6). Thyroid atrophy 

 therefore probably is not the cause of the sensitivity in the latter condition 

 In addition, the hypersensitivity seems not to be so extreme after thyroidec- 

 tomy as after hypophysectomy (Goldblatt"' and table 6). Gonadectomy does 

 not add to the sensitivity of the thyroidectomized animal, so the gonadal 

 atrophy after hypophysectomy cannot contribute to the hypersensitivity. The 

 cause of the hypersensitivity to insulin after thyroidectomy is not known; quite 

 possibly it is the result of hypofunction of the anterior lobe consequent to 

 thyroidectomy, for even very slight damage to the hypophysis may noticeably 

 affect the response to insulin and it is well known that cytological changes 

 of a degenerative nature occur there after thyroidectomy. In any case, the 

 abnormal response to insulin of hypophysectomized animals is probably due 

 only in part, if at all, to thyroid atrophy. 



If the thyroid were an important intermediary in the action of the pituitary 

 on carbohydrate metabolism, it would be expected that APE would have less 

 than its usual activity in the absence of the thyroid. However, practically all 

 of the known metabolic effects of these extracts have been observed in thyroid- 

 ectomized animals. Growth occurs, as shown by Evans and others; nitrogen 

 retention was observed by Gaebler^ and ketogenic effects were shown to occur 

 normally when APE was given to thyroidectomized rats by Fry.^' The contra- 

 insulin effect has been found in rabbits by Himsworth and Scott."^ Houssay, 

 Gaebler, and others have reported diabetogenic effects of APE in the absence 

 of the thyroid, and phlorizin diabetes is restored to normal in thyroidecto- 

 mized-phlorizinized animals. Lastly, in some experiments on glucose-fed rats, 

 APE reduced the RQ and increased mtiscle-glycogen deposition in thyroidecto- 

 mized rats just as in normal animals (tables 4 and 5). 



Finally, replacement of the pituitary by thyroid hormone has been at- 

 tempted. Thyroid hormone is not diabetogenic in hypophysectomized-de- 

 pancreatized animals. It has been stated"' to raise the blood sugar of fasted 

 hypophysectomized dogs; this fact may or may not have physiological signifi- 

 cance, for a very large amount of the hormone was given, and no record was 

 made of its effect on the metabolic rate to determine whether there may have 

 been overdosage (hypophysectomized animals are very sensitive to thyroxin, 

 and glycogenolysis commonly accompanies overdosage of thyroid hormone). 

 In hypophysectomized rats thyroid hormone, given in amounts sufficient just 

 to raise the metabolic rate to the normal range, did not affect fasting glycogen 



