Preclinical Cushing’s syndrome: Report of seven cases and a review of the literature

Abstract

Background: Adrenal adenomas showing autonomous cortisol secretion without specific endocrine symptoms are sometimes discovered in patients with adrenal incidentalomas. This entity has been described as subclinical or preclinical Cushing's syndrome (PCS), but the endocrine data of reported cases have varied and the diagnostic criteria of PCS have been uncertain. Methods:We report seven Japanese cases of PCS due to a unilateral, solitary adrenal adenoma with examination of the endocrine data of these patients. The diagnostic parameters of subtle hypercortisolism and the risk of postoperative adrenal insufficiency and surgical indications are discussed and reviewed. Results: In the present cases, the most frequently found biochemical parameters of autonomous cortisol secretion were a low adrenocorticotropic hormone (ACTH) level (100%) and insufficient suppression of cortisol by low-dose dexamethasone (85.7%). Unilateral accumulation of radiopharmaceuticals in tumors was also frequently observed (100%). A postoperative hydrocortisone supplement was given to six of the seven patients for 5-122 days. It was not given to case 4, because a moderate response of 11-deoxycortisol to metyrapone was identified. Plasma ACTH levels and the diurnal rhythm of plasma cortisol rapidly recovered within 3 weeks postoperatively in six of the seven cases. Conclusion:This entity is heterogeneous and various degrees of cortisol excess have been observed. It should be diagnosed in the wide spectrum and the risk of adrenal insufficiency after surgery should be evaluated by dynamic tests such as the corticotropin-releasing hormone (CRH) test. Based on the results of the present study and a review of the literature, PCS patients may not require hydrocortisone supplement therapy for a long period.

Prevalence and natural history of adrenal incidentalomas

“…Whether these features, which are typical of the metabolic syndrome, will have an impact on the long-term morbidity of patients with subclinical Cushing's syndrome remains to be determined. Long-term perspective studies are lacking; however, an amelioration of clinical or biochemical abnormalities in patients with subclinical hypercortisolism after surgery has been reported (42,51,53,66,67,(88)(89)(90). Improvement of blood pressure, obesity, metabolic abnomalities, collagen and bone turnover markers was observed after adrenalectomy in patients with subclinical Cushing's syndrome (51,66,67).…”

THERAPY OF ENDOCRINE DISEASE: Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing’s syndrome: a systematic review and meta-analysis

“…The search yielded 854 references for abstract screening of which 26 studies (19,20,21,22,23,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49) were included in this systematic review (Fig. 1).…”

The Diagnostic Standard of Preclinical Cushing's Syndrome: Evaluation of the Dexamethasone Suppression Test Using Various Cortisol Kits

“…Low-dose as well as high-dose DEX suppression tests were also essential for the diagnosis of preCS in other studies [6][7][8][9][10][11][12][13][14]. However, the method of DEX administration and the diagnostic criteria of the cortisol level after the DEX dose have yet to be fixed for the diagnosis of preCS (Table 4).…”