At present, Cushing's disease Is believed to be due to Inappropriate secretion of adrenocorticotropic hormone (ACTH). Associated abnormalities such as disturbed sleep pattern, growth hormone secretion, depressed thyroid hormone levels, and gonadal function are considered by some as manifestations of a generalized central nervous system disturbance, with abnormal ACTH secretion as one of the components. Recognition of microadenomata in Increasing numbers of patients with Cushing's disease, the reversal of hypothalamic abnormalities after adenomectomy, and correction of hypercortisolemia all suggest that the central nervous system disturbances result from Cortisol excess. We hypothesize that the basic abnormality in Cushing's disease is the development of resistance to Cortisol at the level of corticotrophs, due either to abnormal Cortisol receptors or to a postreceptor defect. An increasing number of these abnormal corticotrophs result in the development of hypercortisolemia subsequent to inappropriately elevated ACTH levels.
Zafar, M. Saeed and Mellinger, Raymond C.
"Cushing's Disease, a Pituitary Disorder: A hypothesis,"
Henry Ford Hospital Medical Journal
: Vol. 28
Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol28/iss2/10