Update on medical treatment for Cushing’s disease

Abstract

Cushing’s disease (CD) is the most common cause of endogenous Cushing’s syndrome (CS). The goal of treatment is to rapidly control cortisol excess and achieve long-term remission, to reverse the clinical features and reduce long-term complications associated with increased mortality.While pituitary surgery remains first line therapy, pituitary radiotherapy and bilateral adrenalectomy have traditionally been seen as second-line therapies for persistent hypercortisolism. Medical therapy is now recognized to play a key role in the control of cortisol excess. In this review, all currently available medical therapies are summarized, and novel medical therapies in phase 3 clinical trials, such as osilodrostat and levoketoconazole are discussed, with an emphasis on indications, efficacy and safety. Emerging data suggests increased efficacy and better tolerability with these novel therapies and combination treatment strategies, and potentially increases the therapeutic options for treatment of CD. New insights into the pathophysiology of CD are highlighted, along with potential therapeutic applications. Future treatments on the horizon such as R-roscovitine, retinoic acid, epidermal growth factor receptor inhibitors and somatostatin-dopamine chimeric compounds are also described, with a focus on potential clinical utility.

SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors

“…However, recurrence occurs in 15 to 66% of patients and some patients either refuse or do not benefit from the surgery (7). Alternative treatments include additional pituitary surgery, radiation therapy or medical treatment (9,10). Medical treatments can be divided into the use of drugs that block cortisol production (anticortisolic drugs) or block cortisol action (glucocorticoid receptor blockers), which do not control pituitary tumor growth and secretion, and those treatments that target the corticotroph tumor (cabergoline or pasireotide).…”

Canagliflozin improves obesity and insulin resistance in a diabetic patient with Cushing's disease undergoing postoperative steroid therapy: A case report

“…However, the blood glucose levels measured during follow-up at the outpatient department are usually variable depending on the time from the last meal. Pasireotide has become available for the treatment of CD caused by pituitary adenoma (28). Pasireotide was not used in the present case since this medication has not been officially approved in Japan and the tumor was completely removed.…”

Current management of Cushing's disease

“…Hypoadrenalism, headache, nausea, diarrhoea, dizziness, mineralocorticoid (oedema, hypertension, hypokalaemia) and hyperandrogenic (hirsutism, acne) adverse events have been reported. Levoketoconazole is an enantiomer (2S, 4R) of ketoconazole that is more potent in inhibiting several steroidogenic enzymes than its enantiomer (2R, 4S) . Based on theoretical considerations, it has been proposed that levoketoconazole may be less likely to result in hepatotoxicity than ketoconazole.…”

“…A study of abiraterone acetate in adrenocortical carcinoma is under way; however, there are currently no published data on the efficacy of abiraterone acetate in CD. Other agents in early stages of development include a monoclonal antibody (ALD1613) that neutralizes ACTH and peptides acting as antagonists of the melanocortin 2 receptor, which aim at inhibiting ACTH action .…”