Diagnosis and Complications of Cushing’s Syndrome: A Consensus Statement

University of Milan, Milano, Lombardy, Italy
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 01/2004; 88(12):5593-602. DOI: 10.1210/jc.2003-030871
Source: PubMed


In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on the management of Cushing's syndrome. The workshop was organized by the University of Ancona and sponsored by the Pituitary Society, the European Neuroendocrine Association, and the Italian Society of Endocrinology. Invited international participants included almost 50 leading endocrinologists with specific expertise in the management of Cushing's syndrome. The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.

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    • "Untreated or inadequately treated Cushing's disease is associated with cardiovascular disease, central obesity, skeletal fractures, insulin-resistant hyperglycaemia, arterial hypertension, limiting proximal muscle weakness, persistent cognitive defects and increased mortality (Lindholm et al., 2001; Schteingart, 2009; Arnaldi et al., 2003; Newell-Price et al., 2006; Plotz et al., 1952). However, when eucortisolemia is achieved, the observed mortality rate returns to normal over a 10–20 year follow-up period (Clayton, 2010). "
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    ABSTRACT: Cushing's disease, a hypercortisolemic state induced by an ACTH overexpressing pituitary adenoma, causes increased morbidity and mortality. Selective antagonism of the melanocortin type 2 receptor (MC2R) may be a novel treatment modality. Five structurally related peptides with modified HFRW sites but intact putative MC2R binding sites were tested for antagonistic activity at MC1R, MC2R/MRAP, MC3R, MC4R and MC5R. Two of these peptides (GPS1573 and GPS1574) dose-dependently antagonized ACTH-stimulated MC2R activity (IC50s of 66 ±23 nM and 260±1 nM, respectively). GPS1573 and 1574 suppressed the Rmax but not EC50 of ACTH on MC2R, indicating non-competitive antagonism. These peptides did not antagonize α-MSH stimulation of MC1R and antagonized MC3, 4 and 5R at markedly lower potency. GP1573 and GPS1574 antagonize MC4R with IC50s of 950 nM and 3.7 μM, respectively. In conclusion, two peptide antagonists were developed with selectivity for MC2R, forming a platform for development of a medical treatment for Cushing's disease.
    Molecular and Cellular Endocrinology 07/2014; 394(1-2). DOI:10.1016/j.mce.2014.07.003 · 4.41 Impact Factor
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    • "Alternatively, urinary free cortisol (UFC) measurements, the most commonly used test for diagnosis of hypercortisolism, can also be used. Although assessments such as ACTH levels, CRH stimulation test, dexamethasone suppression test, and desmopressin stimulation test may be used, they are less convenient: ACTH degrades quickly and sample collection needs to be handled with great care; CRH and desmopressin stimulation tests require intravenous administration, and the dexamethasone suppression test requires the patient to take a dose of the glucocorticoid late at night and return to the clinic the next morning to have their blood drawn [42]. Although late-night salivary cortisol is useful for the screening and diagnosis of patients with CD [43], it has not been extensively studied in post-surgical patients and is therefore not currently recommended over morning serum cortisol [5]. "
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    ABSTRACT: Transsphenoidal surgery (TSS) is first-line treatment for Cushing's disease (CD), a devastating disorder of hypercortisolism resulting from overproduction of adrenocorticotropic hormone by a pituitary adenoma. Surgical success rates vary widely and disease may recur years after remission is achieved. Recognizing CD recurrence can be challenging; although there is general acceptance among endocrinologists that patients need lifelong follow-up, there are currently no standardized monitoring guidelines. To begin addressing this need we created a novel, systematic algorithm by integrating information from literature on relapse rates in surgically-treated CD patients and our own clinical experiences. Reported recurrence rates range from 3 to 47 % (mean time to recurrence 16-49 months), emphasizing the need for careful post-surgical patient monitoring. We recommend that patients with post-operative serum cortisol <2 µg/dL (measured 2-3 days post-surgery) be monitored semiannually for 3 years and annually thereafter. Patients with post-operative cortisol between 2 and 5 µg/dL may experience persistent or subclinical CD and should be evaluated every 2-3 months until biochemical control is achieved or additional treatment is initiated. Post-operative cortisol >5 µg/dL often signifies persistent disease and second-line treatment (e.g., immediate repeat pituitary surgery, radiotherapy, and/or medical therapy) may be considered. This follow-up algorithm aims to (a) enable early diagnosis and treatment of recurrent CD, thereby minimizing the detrimental effects of hypercortisolism, and (b) begin addressing the need for standardized guidelines for vigilant monitoring of CD patients treated by TSS, as demonstrated by the reported rates of recurrence.
    Journal of Neuro-Oncology 07/2014; 119(2). DOI:10.1007/s11060-014-1508-0 · 3.07 Impact Factor
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    • "CS diagnosis was based on blunted diurnal cortisol circadian rhythm (plasma cortisol at 24.00/8.00 percent ratio > 50%), suppressed ACTH concentrations (morning plasma ACTH < 10 pg/ml) and elevated 24 h urinary free cortisol excretion (24 h urinary free cortisol > 100 mg), combined with an abnormal result of at least one other test of the HePeA axis such as 1 mg dexamethasone, given between 23.00 and 24.00 h, and cortisol measured between 08.00 and 09.00 h the following morning or dexamethasone 2 mg/day orally, 0.5 mg every 6 h for 48 h, plasma cortisol level 1.8 mg/dl with a cut-off value for suppression of 50 nmol/L (1.8 g/dl) [6]. Impaired fasting glucose levels and diabetes were defined according to Alberti et al. [7]. "
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    ABSTRACT: Introduction: In the surgical management of the patients with Cushing syndrome (CS), minimal invasive adrenalectomy (MA) has become the procedure of choice to treat adrenal tumors with a benign appearance ≤6 cm in diameter. Authors evaluated medium- and long-term outcomes of laparoscopic adrenalectomy (LA) for CS or subclinical CS (sCS), performed for ten years in an endocrine surgery unit. Methods: We retrospectively reviewed 21 consecutive patients undergone LA for CS or sCS from 2003 to 2013. Postoperative clinical and cardiovascular status modifications and surgical medium and long-term outcomes were analyzed. Results: In each patient surgery determined a normalization of the hormonal profile. There was no mortality neither major post-operative complications. Mean operative time was higher during the learning curve, there was no conversion, and morbidity rate was 6.3%. Regression of the main clinical symptoms occurred slowly in twelve months. Conclusions: LA is a safe, effective and well-tolerated procedure for the treatment of CS and sCS reducing arterial blood pressure, body weight and fasting glucose levels. Following the learning curve a morbidity rate similar to that reported in the MA series for other adrenal diseases is observed.
    International Journal of Surgery (London, England) 05/2014; 12. DOI:10.1016/j.ijsu.2014.05.036 · 1.53 Impact Factor
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