There have been a number of discussion about unusual side effects of TKI drugs over the years. Information is coming together which may shed some light on the issues involved. It is possible that numerous unusual side effects from TKI drugs are related interference with hypothalamus, pituitary, adrenal, thyroid gland function. These are the glands which are at the center of controlling many body functions. One study found that more than half of Gleevec patients experienced glucocorticoid deficiency, meaning the adrenal glands are not producing enough cortisol, and this has downstream impact on the thyroid. See link at bottom.
This imbalance in the hypothalamus-pituitary-adrenal-thyroid axis (meaning these glands are tied together in function) can lead to a host of side effects we have complained about, including brain fog, fatigue, how the body deals with internal temperature (both feeling cold and night sweats, which are opposite extremes), and even sunken eyes or puffy face, just to name a few of the side effects. A cortisol (glucocorticoid) deficiency and resulting hypothyroidism (low thyroid function) is an under-appreciated side effect which more than half of TKI drug patients have experienced according to the study cited below. Since the production of cortisol is stimulated by the hypothalamus and pituitary, it is difficult to know where this imbalance originates. The feedback loop among these glands means that a dysfunction at one point can upset the entire system.
There has been little appreciation for this issue among Oncs and GP doctors. Maybe more of us should have an ACTH Stimulation Test, which tests pituitary stimulation of the adrenals, along with the more common thyroid test. It is possible that the dysfunction in both the hypothalamus or pituitary can be causing the downstream effects of low cortisol and low thyroid function, which in turn result in a host of side effects.
To help understand the interaction among the glands: