Glucocorticoids are not soluble in water, so most cortisol in the blood is bound to a special carrier protein, called cortisol-binding globulin, and only about 5% is unbound or free.
Diagnosis of Cushing syndrome is initially based on measuring the free, or unbound cortisol in a 24-hour urine sample, in order to assess the total amount of cortisol excreted in the urine over a 24-hour period.
After the neurotransmitters have done their job, they unbind from the receptors, and can just diffuse away, get degraded by enzymes, or get picked up by proteins and returned to their release site in a process called reuptake.