What causes Cushing Syndrome due to long-term therapy?

Cushing Syndrome resulting from long-term therapy is primarily caused by high cortisol levels due to glucocorticoid therapy. When patients receive glucocorticoids for an extended period, either for managing autoimmune diseases, inflammatory conditions, or to suppress the immune system, the body is exposed to an artificial source of cortisol. This leads to an excess of circulating cortisol levels, mimicking the effects of Cushing Syndrome, which include symptoms such as weight gain, hypertension, and changes in skin appearance.

This situation arises because the body’s feedback system is disrupted; the exogenous glucocorticoids inhibit endogenous cortisol production through negative feedback on the hypothalamus and pituitary gland. As a result, the adrenal glands reduce their own cortisol production, but the administered glucocorticoids override that control mechanism, leading to elevated cortisol levels that create the clinical picture of Cushing Syndrome.

The other choices either pertain to different mechanisms or hormones that do not specifically contribute to Cushing Syndrome as a result of glucocorticoid therapy.