SUBCLINICAL CUSHING'S SYNDROME
Section snippets
EPIDEMIOLOGY
The prevalence of classic overt Cushing's syndrome in the general population is not known with certainty.32 Approximately 85% of cases are adrenocorticotropic hormone (ACTH)–dependent, mainly as a result of pituitary-dependent Cushing's syndrome (Cushing's disease). ACTH-independent, adrenal Cushing's syndrome accounts for 15% of all cases of Cushing's syndrome, with 50% of these cases caused by adrenal adenomas and carcinomas, respectively, whereas bilateral adrenal disease is extremely rare.
CLINICAL PRESENTATION
By definition, no clinical signs or symptoms of Cushing's syndrome should be present in patients with incidentally detected adrenal tumors; however, more detailed questioning and careful second physical examination may reveal subtle evidence of hormone excess (e.g., recent weight gain, skin atrophy, increased facial fullness) (Fig. 1). Arterial hypertension and obesity are significantly more prevalent in patients with incidentally detected adrenal masses than in the general population.
BIOCHEMICAL EVALUATION
The rationale for screening patients with adrenal incidentalomas for the presence of subclinical Cushing's syndrome is twofold. First, early detection of subclinical Cushing's syndrome holds the potential of early prevention of disease. Second, subclinical Cushing's syndrome must be ruled out in every patient with adrenal incidentaloma scheduled for unilateral adrenalectomy because a postoperative adrenal crisis (in some cases, with fatal outcome20, 25 has been reported in patients with
ADRENAL SCINTIGRAPHY
Visualization of the adrenal mass by means of 131I-norcholesterol scintigraphy has been advocated by several groups to screen for subclinical Cushing's syndrome.21 The rationale of this approach is based on the observation that significant glucocorticoid production by the tumor will lead to unilateral tracer uptake, whereas the contralateral adrenal will be scintigraphically silent owing to atrophy. Moreover, adrenal scintigraphy seems to allow a differentiation between benign and malignant
PROSPECTIVE STUDIES AND THERAPEUTIC CONSIDERATIONS
As a general rule, hormonally active incidentally detected adrenal masses are surgically removed to prevent serious morbidity.12, 19, 21, 24, 25, 29, 31 This strategy is undisputed for aldosterone-producing adrenal tumors and pheochromocytoma31; however, it remains doubtful whether patients with subclinical Cushing's syndrome benefit from adrenal surgery because the progression from subclinical disease to overt Cushing's syndrome occurs in a minority of cases. Long-term follow-up studies of
SUMMARY
Classic Cushing's syndrome is a rare disease with an estimated incidence of 1 case per 100,000 persons. With routine use of imaging techniques such as ultrasound and CT, adrenal masses are being detected with increased frequency. A substantial percentage of these incidentalomas are hormonally active, with 5% to 20% of the tumors producing glucocorticoids.
Autonomous glucocorticoid production without specific signs and symptoms of Cushing's syndrome is termed subclinical Cushing's syndrome. With
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Approach to the Patient with an Incidental Adrenal Mass
2021, Medical Clinics of North AmericaIntratumoral steroid profiling of adrenal cortisol-producing adenomas by liquid chromatography- mass spectrometry
2021, Journal of Steroid Biochemistry and Molecular BiologyCitation Excerpt :Conversely, MACE affects 0.2–2% of the adult population and is the most common form of hormonal excess associated with adrenal incidentalomas. Patients with MACE display hormonal evidence for cortisol excess, but only subtle physical signs of disease [13,15–18]. Nevertheless, the diagnosis of MACE is associated with an increased risk of adverse cardiovascular events [2,19].
Functional imaging of adrenal cortex
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Address reprint requests to Martin Reincke, MD, Medical Department, University of Freiburg, Hugstetter-Strasse 55, D-79106 Freiburg, Germany, e-mail: [email protected]
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Medical Department, University of Freiburg, Freiburg, Germany