1,720,999 research outputs found
Different therapeutic options in patients with Cushing's syndrome due to bilateral macronodular adrenal hyperplasia
No full textBilateral macronodular adrenal hyperplasia (BMAH) is a relatively rare cause of Cushing's syndrome (CS). In recent years, growing evidence has shown that steroidogenesis is regulated by aberrant G-protein-coupled receptors (GPCR) expression and their ligands, in a significant proportion of patients with BMAH. The screening of patients with overt or subclinical CS demonstrate the frequent expression of several GPCR that opened the option to potential therapeutic applications. Thus, several studies have demonstrated that targeting the involved receptor with specific antagonists, may result in a more or less effective control of cortisol excess. Bilateral adrenalectomy has traditionally been considered the treatment of choice for BMAH. However, unilateral adrenalectomy has been recently proposed as an alternative in selective patients to avoid the long-term necessity of gluco/mineralocorticoid replacement. Adrenal steroidogenesis inhibitors remains a valid option when medical treatment is needed due to high surgical risk
The pathogenic role of the GIP/GIPR axis in human endocrine tumors: emerging clinical mechanisms beyond diabetes
No full textThe glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone produced in the gastrointestinal tract in response to nutrients. GIP has a variety of effects on different systems, including the potentiation of insulin secretion from pancreatic β-cells after food intake (i.e. incretin effect), which is probably the most important. GIP effects are mediated by the GIP receptor (GIPR), a G protein-coupled receptor expressed in several tissues, including islet β-cells, adipocytes, bone cells, and brain. As well as its involvement in metabolic disorders (e.g. it contributes to the impaired postprandial insulin secretion in type 2 diabetes (T2DM), and to the pathogenesis of obesity and associated insulin resistance), an inappropriate GIP/GIPR axis activation of potential diagnostic and prognostic value has been reported in several endocrine tumors in recent years. The ectopic GIPR expression seen in patients with overt Cushing syndrome and primary bilateral macronodular adrenal hyperplasia or unilateral cortisol-producing adenoma has been associated with an inverse rhythm of cortisol secretion, with low fasting morning plasma levels that increase after eating. On the other hand, most acromegalic patients with an unusual GH response to oral glucose suppression have GIPR-positive somatotropinomas, and a milder phenotype, and are more responsive to medical treatment. Neuroendocrine tumors are characterized by a strong GIPR expression that may correlate positively or inversely with the proliferative index MIB-1, and that seems an attractive target for developing novel radioligands. The main purpose of this review is to summarize the role of the GIP/GIPR axis in endocrine neoplasia, in the experimental and the clinical settings
Haplotypes of Von Willebrand factor promoter predict thrombotic risk in Cushing's syndrome
No full textSindrome di Cushing e rischio cardiovascolare
No full text1° Incontro Italiano sulle Malattie Ipotalamo-Ipofisarie. Firenze, 3-5 febbrai
Temozolomide cytoreductive treatment in a giant cabergoline-resistant prolactin-secreting pituitary neuroendocrine tumor
No full textDopamine agonists (DAs, especially cabergoline) are recommended as first-line treatment in patients with prolactin-secreting pituitary adenomas, to reduce hormone secretion and tumor size. Pituitary surgery, suggested in nonresponsive patients, cannot achieve a gross total resection or is not feasible in some cases. Temozolomide (TMZ) has been proposed in patients with aggressive pituitary neuroendocrine tumors (PitNETs) who do not respond to conventional treatments. We present a 47-year-old man with a giant (70×51×64 mm) prolactin-secreting PitNET. Cabergoline treatment (at first 1.5 mg/week, and then increased to 3.5 mg/week after 3 months) achieved prolactin suppression; however, magnetic resonance revealed a stable mass. After explanation of surgical complications, the patient rejected the procedure. Therefore, a primary neoadjuvant cytoreductive TMZ treatment was discussed during a meeting of the Pituitary Multidisciplinary Team, and added to cabergoline. After 13 cycles of TMZ (1 year of treatment), we observed dramatic reduction of the PitNET (from 18 cm of adenoma to 6 cm of necrotic tissue). MRI performed 4, 12, and 18 months after TMZ discontinuation revealed a stable residual PitNET, and 1.5 mg/week of cabergoline has been continued until today. Recently, the criteria for developing Pituitary Tumors Centers of Excellence have been proposed, indicating that a multidisciplinary team is the best care for patients. Surgery, rejected by the patient, could only achieve a partial resection; therefore, we decided to combine TMZ and cabergoline. An early initiation of TMZ could be considered in selected cases, especially when surgery could be only partially effective
Idiopathic primary hyperaldosteronism: normalization of plasma aldosterone after one month withdrawal of long-term therapy with aldosterone-receptor antagonist potassium canrenoate
No full textWe have re-evaluated 15 patients with idiopathic primary aldosteronism one month after withdrawal of therapy with aldosterone-receptor antagonist potassium canrenoate. Therapy had lasted for 3 to 24 yr. Median blood pressure (BP) in the sitting position at the time of diagnosis was 160/100 (ranges 150-200/95-110 mmHg); while 1 month after withdrawal of therapy median BP was 145/90 (ranges 125-160/80-100 mmHg). One month after withdrawal, the ratio aldosterone (ng/dl)/plasma renin activity (ng/ml/h) in the upright position was increased only in 3 cases (median 18, range 6.1-125). We found a significant inverse correlation between the upright aldosterone/plasma renin activity (aldo/PRA) ratio, 1 month after withdrawal, and the number of years of therapy with potassium canrenoate. We conclude that long-term therapy with the aldosterone-receptor blocker, potassium canrenoate, can normalize the aldo/PRA ratio in many cases of idiopathic primary hyperaldosteronism after one-month withdrawal of the drug. These data are consistent with possible regression of idiopathic primary hyperaldosteronism after long-term therapy with potassium canrenoate, or in alternative to a persistent effect of potassium canrenoate, on aldosterone synthesis
Therapeutic strategies for Cushing's syndrome: An update
No full textntroduction: Endogenous Cushing's syndrome (CS) is a severe clinical condition caused by excess cortisol secretion. The treatment goals (with surgery, radiotherapy or medical therapy) are to normalize cortisol levels, reverse the clinical symptoms and remove the secreting neoplasm.
Areas covered: Medical treatments are increasingly used in CS, especially when surgery fails or is not indicated, or while waiting for radiotherapy to take effect. This review summarizes the different medical approaches for treating CS (adrenal- or pituitary-directed drugs, glucocorticoid receptor antagonist), alone or in combination.
Expert opinion: Adrenal steroidogenesis inhibitors have been the mainstay of medical treatment for CS: the most used are ketoconazole (or fluconazole), which inhibits adrenal steroidogenic enzymatic activities; metyrapone and LCI699 that inhibit 11 beta-hydroxylase (the latter is still an experimental compound); mitotane, used in adrenocortical carcinoma. The available glucocorticoid receptor antagonist is mifepristone, recently approved for use in controlling hyperglycemia secondary to hypercortisolism. There has recently been a lot of interest in using agents directly targeting the pituitary corticotroph cells to reduce Adreno Cortico Tropic Hormone secretion and, if possible, control the volume of pituitary adenomas. This is because corticotroph cells contain dopamine receptors (targets of bromocriptine and cabergoline), retinoic acid receptors, PPAR-gamma or somatostatin receptors, the target of the first drug developed and approved for Cushing's disease (pasireotide)
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