a De Martin
University of Milan
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Clinical Endocrinology | 2006
Francesca Pecori Giraldi; Carla Scaroni; Emanuela Arvat; Martina De Martin; Roberta Giordano; Nora Albiger; Adriana A. S. Leao; Andreea Picu; Franco Mantero; Francesco Cavagnini
Objectiveu2002 Cushings disease, hypercortisolism due to a pituitary ACTH‐secreting tumour, is a highly morbid illness as yet without effective medical therapy. Recent studies have demonstrated that peroxisome proliferator‐activated receptor gamma (PPARγ) agonists effectively suppress ACTH secretion in a murine tumoral corticotroph cell line, but the few studies conducted so far in patients with ACTH‐secreting pituitary adenomas have yielded variable results.
Clinical Endocrinology | 2006
Letizia Maria Fatti; Massimo Scacchi; Elisabetta Lavezzi; Francesca Pecori Giraldi; Martina De Martin; Paola Toja; Georgios Michailidis; Marco Stramba-Badiale; Francesco Cavagnini
Objectiveu2002 Cardiovascular disease is a major contributor to the increased mortality of acromegalic patients. Prolongation of the QT interval is considered an established risk factor for potentially fatal cardiac arrhythmias, an event frequently observed in acromegaly. Changes in ventricular repolarization have been observed with the use of octreotide, one of the somatostatin analogues (SSA) currently used for the medical treatment of this disease. Furthermore, octreotide is listed among the drugs able to prolong the QT interval. Thus, we elected to study the effects of long‐term SSA administration on QT duration and left ventricular mass (LVM) in a group of acromegalic patients.
Clinical Endocrinology | 2012
Paola Toja; Giovanna Branzi; Francesca Ciambellotti; Piero Radaelli; Martina De Martin; Laura Lonati; Massimo Scacchi; Gianfranco Parati; Francesco Cavagnini; Francesca Pecori Giraldi
Objectivesu2002 Sustained hypercortisolism impacts cardiac function, and, indeed, cardiac disease is one of the major determinants of mortality in patients with Cushing’s syndrome. The aim of this study was to assess the clinical relevance of cardiac structure and function alterations by echocardiography in patients with active Cushing’s syndrome and after disease remission.
Pituitary | 2006
Martina De Martin; Francesca Pecori Giraldi; Francesco Cavagnini
Cushing’s disease, i.e., pituitary ACTH-secreting adenoma causing excess glucocorticoid secretion, is a rare disease with significant mortality and morbidity. Timely diagnosis and appropriate treatment can alter the course of the disease and are therefore mandatory. First step of the diagnostic work-up is the endogenous glucocorticoid excess by measurement of urinary free cortisol, cortisol circadian rhythmicity or suppression by low doses of dexamethasone. In patients with equivocal results, second line tests, such as the dexamethasone-suppressed CRH test and desmopressin stimulation, usually enable the diagnosis to be confirmed. Measurement of plasma ACTH then allows the distinction between ACTH-dependent (e.g., pituitary or extrapituitary neuroendocrine tumors) and ACTH-independent causes (e.g., adrenal tumors). The last step in the diagnostic algorhythm is often the most fraught with problems as the distinction between Cushing’s disease and ectopic ACTH secretion relies on judicious interpretation of several diagnostic procedures. Positive responses to stimulation with CRH and inhibition by high doses of dexamethasone, if concurrent, enable a pituitary origin to be established whereas conflicting results call for inferior petrosal sinus sampling, the latter to be performed in experienced centres only. Visualisation of the tumor at pituitary imaging is helpful but not required for the diagnosis, as microadenomas often remain undectected by MRI and/or CT scan and, on the other hand, visualisation of a non-secreting incidentaloma may be misleading. Surgical removal of the pituitary tumor is the optimal treatment choice and should be attempted in every patient. Surgical failures as well as relapses can be treated by radiotherapy, medical therapy or, if necessary, bilateral adrenalectomy. Finally, patients cured of Cushing’s disease require long-term monitoring given the risk of relapse and clinical burden of associated ailments.
Pituitary | 2009
Massimiliano Andrioli; Francesca Pecori Giraldi; Martina De Martin; Agnese Cattaneo; Chiara Carzaniga; Francesco Cavagnini
Differential diagnosis of ACTH-dependent Cushing’s syndrome often presents major difficulties. Diagnostic troubles are increased by suboptimal specificity of endocrine tests, the rarity of ectopic ACTH secretion and the frequent incidental discovery of pituitary adenomas. A 43-year-old female reported with mild signs and symptoms of hypercortisolism, and initial hormonal tests and results of pituitary imaging (7-mm adenoma) were suggestive for Cushing’s disease. However, inadequate response to corticotrophin-releasing hormone and failure to suppress after 8xa0mg dexamethasone pointed towards an ectopic source. Total body CT scan visualized only a small, non-specific nodule in the right posterior costophrenic excavation. Inferior petrosal sinus sampling revealed an absent center:periphery ACTH gradient but octreoscan and 18F-FDG-PET-CT failed to detect abnormal tracer accumulation. We weighed results of the laboratory with those of imaging and decided to remove the lung nodule. Pathology identified a typical, ACTH-staining carcinoid and the diagnosis was confirmed by postsurgical hypoadrenalism. In conclusion, imaging may prove unsatisfactory or even misleading for the etiologial diagnosis of ACTH-dependent Cushing’s syndrome and should therefore be interpreted only in context with results of hormonal dynamic testing.
Basic & Clinical Pharmacology & Toxicology | 2016
Martina De Martin; Paola Toja; Karine Goulene; Piero Radaelli; Francesco Cavagnini; Marco Stramba-Badiale; Francesca Pecori Giraldi
Ketoconazole is listed among drugs that prolong QT interval and may increase the risk of torsade de pointes, a severe ventricular arrhythmia. This compound has recently been approved for treatment of Cushings syndrome, a severe endocrine disorder. These patients harbour several risk factors for prolonged QT interval, for example hypokalaemia and left ventricular hypertrophy, but no study has evaluated whether administration of ketoconazole affects their QT interval. The aim of this study was to assess the QT interval in patients with Cushings disease during long‐term administration of ketoconazole. Electrocardiograms from 15 patients with Cushings disease (12 women, 3 men, age: 37.8 ± 2.66 years) on ketoconazole treatment (100 mg–800 mg qd) for 1 month to 12 years were reviewed retrospectively. QT interval was measured and corrected for heart rate (QTc). Measurements before and during ketoconazole treatment were compared and any abnormal QTc value recorded. Concurrent medical therapies were also documented. On average, QTc was superimposable before and during ketoconazole treatment (393.2 ± 7.17 versus 403.3 ± 6.05 msec. in women; 424.3 ± 23.54 versus 398.0 ± 14.93 msec. in men, N.S.). QTc normalized on ketoconazole in one man with prolonged QTc prior to treatment; no abnormal QTc was observed in any other patient during the entire observation period, even during concurrent treatment with other QT‐prolonging drugs. In conclusion, long‐term ketoconazole administration does not appear to be associated with significant prolongation of QT interval in patients with Cushings disease. ECG monitoring can follow recommendations drawn for other low‐risk QT‐prolonging drugs with attention to specific risk factors, for example hypokalaemia and drug interactions.
European Journal of Endocrinology | 2014
Alberto Giacinto Ambrogio; Martina De Martin; Paola Ascoli; Francesco Cavagnini; Francesca Pecori Giraldi
OBJECTIVEnGlucocorticoids stimulate several steps in red blood cell (RBC) development; however, little is known on changes in erythroid parameters in patients with Cushings disease. The aim of this study was to assess both RBC and white blood cell (WBC) parameters in a large cohort of patients with Cushings disease and report on alterations in the active phase and after surgical remission.nnnDESIGN AND METHODSnA total of 80 patients with Cushings disease (63 women and 17 men) were studied before and for up to 254 months follow-up (mean follow-up 65.8 ± 6.71 months) after pituitary/adrenal surgery. Details of blood counts were reviewed and compared with data obtained from a database of healthy subjects.nnnRESULTSnThe RBC counts and haemoglobin levels were low in men with active Cushings disease (over 80% of values in the lowest quartile) and four patients were overtly anaemic, whereas erythrocyte counts and haemoglobin levels were evenly distributed across the normal range in women with active Cushings disease. Low erythroid parameters were linked to hypogonadism in men with Cushings disease. Recovery in erythroid parameters occurred slowly after remission of hypercortisolism in men, in parallel with improvements in testosterone levels. Over 50% of patients with active disease presented increased WBC counts, irrespective of gender, and prompt normalisation within 1 month after surgery.nnnCONCLUSIONSnMale patients with Cushings disease present reduced RBC counts and haemoglobin levels, associated with low testosterone concentrations, which resolve over time after remission of hypercortisolism. Anaemia should therefore be regarded as another unfavourable feature in men with Cushings disease.
Endocrine Pathology | 2012
Maria Francesca Cassarino; Alberto Giacinto Ambrogio; Luca Pagliardini; Martina De Martin; Valeria Barresi; Francesco Cavagnini; Francesca Pecori Giraldi
Since 1955, when Roux [1] published the first association between pheochromocytoma and Cushing’s syndrome, we have come to appreciate the unique features of this unusual clinical entity. Pheochromocytoma represents a rare cause of hypercortisolism, accounting for less than 5 % of ectopic Cushing’s syndrome [2, 3] while less than 1 % of pheochromocytomas is accompanied by Cushing’s syndrome [4]. Pheochromocytomas are known to be heterogeneous, both functionally and clinically, a likely consequence of their ability to synthesize and secrete peptides in addition to catecholamine, such as vasoactive intestinal polypeptide, somatostatin, and calcitonin [5]. As regards hypothalamo– pituitary–adrenal axis peptides, both adrenocorticotropin (ACTH) and other proopiomelanocortin (POMC)-derived peptides [6, 7] as well as, occasionally, corticotropinreleasing hormone (CRH) [8] have been demonstrated in pheochromocytomas associated with ectopic Cushing’s syndrome. The diagnosis of ectopic Cushing’s syndrome is known to be fraught, as the most common cause of ACTHdependent hypercortisolism, i.e., pituitary Cushing’s disease, must first be excluded. This is accomplished by extensive diagnostic procedures, such as stimulation with CRH, suppression with high dose dexamethasone and inferior petrosal sinus sampling [9]. Imaging does not play a pivotal role in the diagnostic work-up as both pituitary and ectopic ACTH-secreting pituitary tumors may prove elusive and, conversely, false-positive imaging may lead to erroneous tumor localization [10–12]. The diagnosis of ectopic ACTH-secreting Cushing’s syndrome is therefore confirmed by remission of hypercortisolism after removal of the causative lesion and positive ACTH immunostaining in surgical specimens. We here present a thought-provoking ACTH-secreting pheochromocytoma with negative immunostaining for ACTH.
Endocrine connections | 2017
Alberto Giacinto Ambrogio; Massimiliano Andrioli; Martina De Martin; Francesco Cavagnini; Francesca Pecori Giraldi
Recurrence of Cushing’s disease after successful transsphenoidal surgery occurs in some 30% of the patients and the response to desmopressin shortly after surgery has been proposed as a marker for disease recurrence. The aim of the present study was to evaluate the response to desmopressin over time after surgery. We tested 56 patients with Cushing’s disease in remission after transsphenoidal surgery with desmopressin for up to 20 years after surgery. The ACTH and cortisol response to desmopressin over time was evaluated in patients on long-term remission or undergoing relapse; an increase by at least 27u2009pg/mL in ACTH levels identified responders. The vast majority of patients who underwent successful adenomectomy failed to respond to desmopressin after surgery and this response pattern was maintained over time in patients on long-term remission. Conversely, a response to desmopressin reappeared in patients who subsequently developed a recurrence of Cushing’s disease, even years prior to frank hypercortisolism. It appears therefore that a change in the response pattern to desmopressin proves predictive of recurrence of Cushing’s disease and may indicate which patients require close monitoring.
Expert Opinion on Therapeutic Patents | 2007
Massimiliano Andrioli; Francesca Pecori Giraldi; Martina De Martin; Francesco Cavagnini
Adrenal insufficiency is a rare disorder in which the adrenal cortex fails to secrete sufficient amounts of steroid hormones. All adrenal hormones are affected in primary adrenal insufficiency, whereas only glucocorticoid secretion is deficient in secondary adrenal insufficiency. Low doses of hydrocortisone/cortisone acetate (20 mg and 25 mg daily, respectively) subdivided in thrice-daily administration approach the physiological cortisol profile and resolve clinical features. Clinical assessment is the mainstay for establishing adequacy of corticosteroid replacement therapy as no biochemical/hormonal marker is fully reliable. Glucocorticoid replacement has to be potentiated during stressful events (e.g., surgery, infection, delivery and trauma). Fludrocortisone (0.05 – 0.2 mg daily) is administered in order to normalise blood pressure and potassium levels, aiming for plasma renin activity in the upper normal range. Dehydroepiandrosterone (20 – 50 mg daily) may prove beneficial, but cannot as yet be recommended for routine clinical use.