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Endocrine Abstracts (2008) 16 S24.2

State of the art in the therapy of pituitary disease

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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