ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 S24.2

Medical therapy of Cushing's disease

Rosario Pivonello

Department of Molecular and Clinical Endocrinology and Oncology, ‘Federico II’ University, Naples, Italy.

The first-line therapy of Cushing’s disease (CD) is pituitary surgery, whereas pituitary radiotherapy and bilateral adrenalectomy represent alternative treatments for patients not cured by surgery. Medical therapy has a minor role in the management of CD, and it is mainly based on the use of two different categories of drugs, the adrenal-blocking drugs, which act at the adrenal level, and the neuromodulatory drugs, which act at the pituitary level. These drugs are not usually effective as sole long-term treatment of the disorder, and are used mainly either in preparation for surgery or as adjunctive treatment after surgery and/or radiotherapy, waiting for their definitive effectiveness. Among the adrenal-blocking drugs, the most commonly used agent is ketoconazole, which has a rapid onset of action, but it is frequently associated with loss of control of hypercortisolism, a phenomenon known as escape, and is affected by gastrointestinal side-effects, including a liver dysfunction, which rarely induce a severe hepatitis with acute liver failure. The neuromodulatory drugs include a long series of agents which, however, have been never demonstrated a great effectiveness to be routinely used in the management of CD. Recently, the peroxisome proliferators activated receptor γ agonists were demonstrated to induce short-term control of cortisol, with later escape. The possible role of dopamine agonists has been reconsidered in the treatment of CD as short-term treatment with cabergoline was demonstrated to normalize cortisol secretion in 40% of patients with CD. Preliminary data on long-term treatment suggested that more than one third of patient is controlled by cabergoline. The possible role of somatostatin analogues has been also re-evaluated in the treatment of CD as a newer somatostatin analogue, pasireotide has been demonstrated to inhibit cortisol secretion in a subgroup of patients with CD. Combination treatments with dopamine agonists and specific somatostatin analogues or low-dose ketoconazole might represent effective treatment for CD.

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