Preclinical or subclinical Cushing's syndrome is caused by autonomous glucocorticoid secretion in patients who may have no overt, or only minimal, clinical signs and symptoms of full-blown Cushing's syndrome. Subclinical hypercortisolism has been reported in 5 to 20% of patients with adrenal inci-dentalomas. Depending on the amount of glucocor-ticoid secreted by the tumor, the clinical spectrum can vary considerably. Diagnostically, patients often have a slightly attenuated diurnal rhythm of cortisol secretion. They may also have a suppressed contralateral adrenal gland. Removing the hypersecret-ing adrenal gland, even without removing the normal gland, may result in life-threatening acute adrenal insufficiency. The natural history of this condition is unclear because long-term prospective studies are lacking. Subclinical Cushing's syndrome may progress to overt Cushing's syndrome. Some patients with subclinical Cushing's syndrome have subtle biochemical abnormalities that are reversed by adrenalectomy. Therefore, surgery should be considered in young or symptomatic patients and in those who have significant comorbidities, such as diabetes, hypertension, and osteopenia.113116 Close follow-up is required for other patients.80117118 This includes 24-hour urinary free cortisol levels, overnight dexamethasone suppression test, and serum electrolyte levels at 6-month intervals to detect progression of endocrine function. Serial imaging studies are also needed to detect tumor growth for the risk of malignancy.
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