Endocrine Abstracts

Endogenous hypercortisolism and chronic glucocorticoid (GC) therapy reduce bone mass, increase central fat mass, alter adipokines and enhance cardiovascular risk. Surgery (pituitary, adrenal or for ectopic ACTH) can control hypercortisolism in 90% of patients in experienced hands, and is often followed by inhibition of the adrenal axis, requiring substitution therapy with GC for months or years. We have been interested in learning on long-term outcome of ‘cured’ CS patients, since recent evidence suggests that specific morbidity is not always reversible.

Duration of both exogenous GC replacement therapy after successful surgery and endogenous hypercortisolism both negatively affect bone mineral density (BMD) in women in long-term remission after successful therapy for CS, when compared to controls; furthermore, an unfavorable lipid profile is seen in these cured CS. Persistent accumulation of central fat not only in active hypercortisolism but also in ‘cured’ patients, with an unfavorable adipokine profile (low adiponectin, elevated plasma sTNF-R1 and IL-6), leading to a state of low-grade inflammation have been found. This ‘inflammatory state’ may determine vascular damage, atherosclerosis and cardiovascular disease in patients with long-term cured CS. Moreover, hypercortisolism affects behavior, mood, neural activity, memory and other functions of the central nervous system. Brain volume reduction appears to be partly reversible when hypercortisolism is controlled; psychopathology (mainly atypical depression) highly prevalent at baseline improves 1 year after treatment, but often with residual symptoms; cognition and impaired health-related quality of life (HRQoL) do not appear to normalize after endocrine cure, strongly suggesting that all these changes are not fully reversible.

In conclusion, having suffered CS even if hypercortisolism is controlled confers a premature increase in cardiovascular risk and impaired HRQoL; clinical management of these patients should be particularly careful in identifying these long-term consequences of chronic hypercortisolism, to improve prognosis and offer the patient a realistic expectation with respect to the results of treatment.