Pituitary-directed medical treatment of Cushing’s disease

Abstract

The treatment of Cushing’s disease is very complex and represents a challenge for clinicians. Transphenoidal surgical excision of adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma remains the treatment of choice but, unfortunately, the rate of cure at long-term follow-up is suboptimal and recurrences are high, even in the hands of skilled neurosurgeons. Other treatment options, such as bilateral adrenalectomy and pituitary radiotherapy, are currently in use but no treatment has proven fully satisfactory during the lengthy progress of this chronic and devastating disease. Nelson’s syndrome and hypopituitarism are of particular concern as affected patients need lifelong hormone-replacement therapy and have notably increased mortality. Although medical treatment represents a second-line treatment option in patients with Cushing’s disease, so far pharmacological therapy has been considered a transient and palliative treatment. Many drugs have been employed: they may act at the hypothalamic–pituitary level, decreasing ACTH secretion; at the adrenal level, inhibiting cortisol synthesis (steroidogenesis inhibitors); or at the peripheral level by competing with cortisol (glucocorticoid receptor antagonists). Recently, there has been renewed interest in the medical therapy of Cushing’s disease and pituitary-directed drugs include old compounds commercially available for other diseases, such as cabergoline, and new promising compounds, such as pasireotide (SOM230) or retinoic acid. This review focuses on the tumor-directed pharmacological approaches for the management of Cushing’s disease based on the recent identification of possibile targets at a pituitary level.

Keywords::

• cabergoline
• Cushing’s disease
• dopaminergic receptors
• medical therapy
• pasireotide (SOM230)
• pituitary-directed drug
• retinoid acid
• somatostatin receptor
• thiazolidinediones

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing assistance was utilized in the production of this manuscript.