Classical overt Cushing's syndrome, the consequence of longstanding excess of circulating glucocorticoids, is characterized by typical signs and symptoms of hypercortisolism, such as plethora, a moon face, buffalo hump, and central obesity, easy bruising, deep purple striae, proximal muscle weakness, menstrual irregularities, acne, hirsutism, osteoporosis, and glucose intolerance. Classic Cushing's syndrome is a rare disease with an estimated incidence of 1 case per 500,000 persons.<sup>32References 1,2,5,6,7,8,10,12,13,16,19,20,24,25,26,27,29,30,31, and 34,35,36,37.

Cliccare qui per andare alla sezione Riferimenti</sup> With the routine use of imaging techniques such as ultrasound and CT, adrenal masses are being detected with increased frequency.<sup>21References 1,2,5,6,7,8,10,12,13,16,19,20,24,25,26,27,29,30,31, and 34,35,36,37.

Cliccare qui per andare alla sezione Riferimenti</sup> A substantial percentage of these incidentally detected adrenal tumors are hormonally active, with as many as 20% of the tumors producing glucocorticoids. Generally, autonomous glucocorticoid production without specific signs and symptoms of Cushing's syndrome is termed subclinical or preclinical Cushing's syndrome. It is assumed that glucocorticoid production in these patients is insufficient to cause a clinically recognizable syndrome. Preclinical or subclinical Cushing's syndrome was first described by Charbonnel and co-workers<sup>11References 1,2,5,6,7,8,10,12,13,16,19,20,24,25,26,27,29,30,31, and 34,35,36,37.

Cliccare qui per andare alla sezione Riferimenti</sup> in 1981 and has become the focus of a steadily increasing number of studies.^{*References 1,2,5,6,7,8,10,12,13,16,19,20,24,25,26,27,29,30,31, and 34,35,36,37.} The terms preclinical and subclinical Cushing's syndrome have often been used interchangeably in the literature; however, subclinical Cushing's syndrome relates to a biochemical abnormality that most likely will not become clinically manifest, whereas preclinical Cushing's syndrome implicates a general progression to overt Cushing's syndrome. Long-term prospective studies evaluating the outcome of patients with this condition are lacking. The progression to overt Cushing's syndrome seems to occur in a low percentage of patients<sup>5References 1,2,5,6,7,8,10,12,13,16,19,20,24,25,26,27,29,30,31, and 34,35,36,37.

Cliccare qui per andare alla sezione Riferimenti</sup>; therefore, the term subclinical Cushing's syndrome better describes the metabolic consequences of this condition and is used throughout this article.