Evaluation of Diagnostic Tests for ACTH-Dependent Cushing’s Syndrome

Abstract

because of the Cushingoid appearance, with the characteristic features of central obesity, moon face, skin atrophy, purple striae and buffalo hump, and the clinical criteria are clear, a debate exists in the literature over the biochemical diagnosis of this disease [3]. Recently, the diagnostic criteria for Cushing's disease have been reported by the Ministry of Health, Labour, and Welfare of Japan [4]. In the guideline, the following endocrinological findings were considered as diagnostic criteria: 1) The presence of a Cushingoid appearance; 2) Evidence of autonomic or abnormal secretion of ACTH, such as (a) normal-high ACTH and cortisol levels, and (b) high levels of urinary excretion of free cortisol; 3) Screening tests show (a) incomplete suppression of cortisol (> 5 µg/dl) by a lowdose (0.5 mg) overnight dexamethasone suppression test (DST), (b) high cortisol levels (> 5 µg/dl) during night time sleeping, and (c) response of plasma ACTH levels to the desmopressin (DDAVP) test; 4) The dif- Abstract. We evaluated the usefulness and accuracy of diagnostic tests for adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, based on our experience of 88 cases, including 73 cases with Cushing's disease, and 15 cases with ectopic ACTH syndrome (EAS). In our study, 0.5 mg of dexamethasone failed to suppress the morning cortisol secretion in 100% of cases with Cushing's disease and EAS. Plasma ACTH levels were significantly increased by desmopressin (DDAVP) in 86% of cases with Cushing's disease, especially in microadenomas (90%), while these levels were not affected in normal subjects. In EAS, 44% responded to DDAVP. Plasma ACTH levels were increased in response to the human corticotropin-releasing hormone (CRH) test in 100% of microadenomas and 73% of macroadenomas with Cushing's disease, but only in 27% of cases with EAS. A high dose (8 mg) of dexamethasone suppressed the morning cortisol secretion in 89% of microadenomas with Cushing's disease, and in 82% of all cases with Cushing's disease, while it did in only 20% of cases with EAS. Taken together, the 0.5 mg dexamethasone suppression test (DST) and DDAVP test are considerably useful for the screening of ACTH-dependent Cushing's syndrome. The CRH test and 8 mg DST would be effective for the diagnosis of Cushing's diseases, because our study shows a sensitivity of 81% in cases with Cushing's disease when these tests are considered together. These data were submitted to prepare the diagnostic criteria for Cushing's disease, suggested by the working group of the Ministry of Health, Labour, and Welfare of Japan.

ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's syndrome: a proposal for a short and simple CRH test

“…The combined analysis of the CRH and the HDDS test did not increase diagnostic precision in the ROC analysis. These results are in accordance with previous data that showed that the HDDS test in combination with the CRH test was not superior to the CRH test alone (13,19,22) or the CRH test in combination with the 48 h low-dose dexamethasone suppression test (16). Nevertheless we believe that the HDDS test can still have some impact in the differential diagnosis of (11).…”

“…We decided not to follow this approach, because we believe that 100% specificity is difficult to obtain with the CRH test. It has been well documented that a small number of patients with ECS show a clear cortisol and ACTH response to CRH, especially patients with carcinoids (13,14,15,16,17,18,19). Presetting specificity to 100% will always lead to a pronounced reduction in sensitivity.…”

Evaluation of Plasma, Salivary, and Urinary Cortisol Levels for Diagnosis of Cushing’s Syndrome

“…The first diagnostic criteria for Cushing's disease were reported by the working group of the Ministry of Health, Labour, and Welfare of Japan in 2003, and screening tests were renewed in 2007 [4,15]. In discussing the present diagnostic criteria, we refer to our extensive data on plasma, salivary, and urinary cortisol levels.…”

ACTH response to desmopressin in a patient with acromegaly; Expression of corticotropin-releasing factor, urocortins and vasopressin V1b receptor in GH-producing pituitary adenoma

“…In the patient with ACTH-producing adenoma, DDAVP stimulates ACTH via V1b receptors which exist abundantly in corticotroph adenoma [6]. DDAVP test is included in the initial screening procedure of the diagnostic criteria for Cushing's disease reported by the Ministry of Health, Labour, and Welfare of Japan, which is not available in English, but reported in two articles [7,8].…”

“…4A, B, C). Particularly, Ucn1 immunostaining in the tumor ing tests for (subclinical) Cushing's disease [7,8].…”