Nuevas perspectivas en el tratamiento farmacologico de la enfermedad de Cushing / New prospects for drug treatment in Cushing disease

Los farmacos que en la actualidad estan mereciendo mas atencion son aquellos con accion directa sobre el tumor inhibiendo la secrecion de ACTH: analogos de la somatostatina (..) (AU)

Hypercortisolism induced by Cushing disease causes high morbidity and mortality.The treatment of choice is pituitary surgery, but it often fails to achieve cure, and othertreatment modalities (radiotherapy, bilateral adrenalectomy) may therefore be required. Ifthese treatments are not effective or while waiting for their results, hypercortisolism shouldbe controlled with drugs.The classical drug treatments are those that act by inhibiting cortisol secretion by the adrenalgland (ketoconazole, metyrapone, mitotane, etomidate). The preliminary results of a new drug (LCI699) which is a potent enzyme inhibitor of cortisolsecretion have been reported.A clinical trial of the safety and efficacy of mifepristone, a glucocorticoid receptor antagonist,has just been published.The drugs deserving more attention today are those with a direct action on the tumor by inhibiting ACTH secretion: somatostatin analogues (pasireotide), dopamine agonists (cabergoline),PPAR- , and retinoic acid.A special review is made of the available clinical trials with pasireotide and cabergoline (AU)

New prospects for drug treatment in Cushing disease.

Hypercortisolism induced by Cushing disease causes high morbidity and mortality. The treatment of choice is pituitary surgery, but it often fails to achieve cure, and other treatment modalities (radiotherapy, bilateral adrenalectomy) may therefore be required. If these treatments are not effective or while waiting for their results, hypercortisolism should be controlled with drugs. The classical drug treatments are those that act by inhibiting cortisol secretion by the adrenal gland (ketoconazole, metyrapone, mitotane, etomidate). The preliminary results of a new drug (LCI699) which is a potent enzyme inhibitor of cortisol secretion have been reported. A clinical trial of the safety and efficacy of mifepristone, a glucocorticoid receptor antagonist, has just been published. The drugs deserving more attention today are those with a direct action on the tumor by inhibiting ACTH secretion: somatostatin analogues (pasireotide), dopamine agonists (cabergoline), PPAR-γ, and retinoic acid. A special review is made of the available clinical trials with pasireotide and cabergoline.

[The OASIS study: therapeutic management of acromegaly in standard clinical practice. Assessment of the efficacy of various treatment strategies]. / Estudio OASIS: manejo terapéutico de la acromegalia en un escenario de práctica clínica habitual. Evaluación de la eficacia de las diversas estrategias de tratamiento aplicadas.

BACKGROUND AND OBJECTIVES: The reported efficacy of treatments for acromegaly varies depending on reference centers and national registries. The aim of this study was to describe clinical management of this disease and to assess the efficacy of treatments used in standard clinical practice. MATERIAL AND METHODS: An epidemiological, observational, longitudinal, multicenter study was performed in adult patients with newly diagnosed acromegaly (n = 74) seen by 38 Spanish endocrinologists who collected during routine clinic visits data on disease treatment and control during 2 years of follow-up. RESULTS: Pituitary surgery and treatment with somatostatin analogs were the first choice therapies in 76% and 24% of patients respectively, with no differences related to tumor size. Surgery achieved disease control in 27% of operated patients. After surgery failure, the preferred therapeutic option were somatostatin analogs, which normalized insulin-like growth factor-1(IGF-I) in 52% of patients and achieved disease control criteria in more than 40% of patients. At the end of follow-up, normal IGF-I levels were found in 63% and 53% of patients with microadenomas and macroadenomas respectively. Only 19% of patients with macroadenoma met disease control criteria without requiring drug treatment, which was required by 85% of them at some time during follow-up. CONCLUSIONS: Surgery is the preferred initial treatment for patients with acromegaly, regardless of tumor size. Treatment efficacy in actual clinical practice is far from the success rates reported by reference centers.

Clinical practice guideline for hypotalamic-pituitary disturbances in pregnancy and the postpartum period.

During pregnancy, the body undergoes a major adaptation process as a result of the interaction between mother, placenta and fetus. Major anatomical and histological changes are produced in the pituitary, with an increase of up to 40% in the size of the gland. There are wide variations in the function of the hypothalamus-pituitary-thyroid axis that effect iodine balance, the overall activity of the gland, as well as transport of thyroid hormones in plasma and peripheral metabolism of thyroid hormones. The incidence of goiter and thyroid nodules increases throughout pregnancy. The management of differentiated thyroid carcinoma should be individually tailored according to tumoral type and pregnancy stage. Given the effects of hypothyroidism on fetal development, both the diagnosis and appropriate therapeutic management of thyroid hypofunction are essential. The most important modification to the hypothalamus-pituitary-adrenal axis during pregnancy is the rise in serum cortisol levels due to an increase in cortisol-binding proteins. Although Cushing's syndrome during pregnancy is infrequent, both diagnosis and treatment of this disorder are especially difficult. Adrenal insufficiency during pregnancy does not substantially differ from that occurring outside pregnancy. However, postpartum pituitary necrosis (Sheehan's syndrome) is a well-known complication that occurs after delivery and, together with lymphocytic hypophysitis, constitutes the most frequent cause of adrenal insufficiency. The management of prolactinoma during pregnancy requires suppression of dopaminergic agonists and their reintroduction if there is tumoral growth. Notable among the neuropituitary disorders that can occur throughout pregnancy is diabetes insipidus, which occurs as a consequence of increased vasopressinase activity.

Clinical practice guideline for the diagnosis and treatment of hypophysitis.

Hypophysitis are a group of inflammatory lesions affecting the pituitary gland and pituitary stalk. These lesions should be included in the differential diagnosis of sellar masses. There are three types of primary hypophysitis: lymphocytic, granulomatous and xanthomatous. Lymphocytic hypophysitis is the most frequent form of chronic pituitary inflammation and is believed to have an autoimmune origin. This form characteristically affects women during the peripartum, with diverse types of pituitary deficiency, especially ACTH deficiency, and frequently there are other associated autoimmune processes. Lymphocytic hypophysitis can affect the anterior pituitary only, the infundibular stalk and posterior lobe of the pituitary (infundibuloneurohypophysitis), or the entire pituitary (panhypophysitis). Clinically, lymphocytic hypophysitis can manifest with compression symptoms, hypopituitarism, diabetes insipidus or hyperprolactinemia. The imaging technique of choice is magnetic resonance imaging, which helps to characterize the sellar lesion. Treatment includes replacement of the functional pituitary deficiency and the use of corticosteroids, generally at high doses. Surgical treatment is reserved for patients unresponsive to conservative therapy. Granulomatous hypophysitis can be of known etiology, whether infectious (currently highly infrequent) or non-infectious (ruptured Rathke's cyst, etc.). Granulomatous hypophysitis of unknown etiology is manifested by the presence of idiopathic granulomas. Xanthomatous hypophysitis is characterized by a histiocytic infiltrate with cystic characteristics on imaging. Secondary hypophysitis is due to pituitary inflammation caused by surrounding lesions or can form part of systemic diseases.