Evaluation of the diagnostic criteria for Cushing’s disease in Japan [Review]

Abstract

Abstract. Adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome is caused by an ACTH-producing tumor, as is the case with Cushing's disease and ectopic ACTH syndrome (EAS). Diagnosis and differential diagnosis of Cushing's disease from EAS in ACTH-dependent Cushing's syndrome are thus challenging problems in clinical endocrinology. The diagnostic criteria for Cushing's disease in Japan, established by the working group of the Japan Ministry of Health, Labour and Welfare, were originally reported in 2003 and revised in 2007 and 2010. In addition, criteria for subclinical Cushing's disease were established in Japan in 2010. In this review, we evaluate the usefulness and accuracy of the most recent diagnostic criteria. Previous data suggest that as an initial test of Cushing's syndrome, 0.5 mg dexamethasone is more sensitive than 1 mg in the overnight dexamethasone suppression test (DST). Here, we recommend 0.5 mg plus a plasma cortisol cut-off level of 3 µg/dL as a suitable low-dose overnight DST for screening of all cases of ACTH-dependent Cushing's syndrome in Japan. Recently, standardization of cortisol measurements by the ID-LC/MS/MS method using seven assay kits with standard plasma material containing synthetic hydrocortisone-d4 was carried out in Japan. The resulting relative standard deviation was within 10%. The cut-off value remains valid even after standardization of plasma cortisol measurements. Although the recent diagnostic criteria achieve higher diagnostic specificity, care should be taken since data for Cushing's disease partially overlaps with some cases of EAS. Overall, therefore, this review suggests that the accuracy of each diagnostic test should be considered.

Clinical significance of screening for subclinical Cushing’s disease in patients with pituitary tumors

“…They defined subclinicalmild AH by criteria similar to those of the Japanese guideline [12]. The prevalence of SCD in our cohort is similar to those estimated in the above study.…”

“…However 7 of 10 patients were excluded from the diagnosis of SCD. The reason is that one patient was suffering from depression causing the pseudo-Cushing's syndrome [12] and the rest 6 patients have taken the medicines that were reported to affect dexamethasone metabolism (e.g. atorvastatin, clonazepam or terbinafine) [18].…”

A somatotropin-producing pituitary adenoma with an isolated adrenocorticotropin-producing pituitary adenoma in a female patient with acromegaly, subclinical Cushing’s disease and a left adrenal tumor

“…A lack of characteristic physical findings of Cushing's disease, a loss of circadian rhythmicity of ACTH and cortisol secretion, non-suppressable cortisol by the low-dose dexamethasone suppression test and the response of ACTH to CRH stimulation were all compatible with subclinical Cushing's disease [13,14]. A left adrenal tumor was also detected, nevertheless, the endocrine data were compatible with a diagnosis of subclinical Cushing's disease preoperatively.…”

“…Taken together with the clinical findings described above, we made a diagnosis of acromegaly with subclinical Cushing's disease based on the diagnostic criteria published by the Japan Endocrine Society [13,14] and a left adrenal incidentaloma. Transsphenoidal surgery was performed.…”

The diagnostical importance of steroid profiles of biological fluids of patients with Cushing’s syndrome

“…Определение экс-креции свободного кортизола с мочой (CКМ), сво-бодного кортизола в слюне в 23 ч (СКС), уровней кортизола (К) и адренокортикотропного гормона (АКТГ) в плазме в ходе пробы с дексаметазоном яв-ляются стандартными тестами, используемыми в диагностике СИК [5][6][7][8]. Специфичность и чув-ствительность перечисленных тестов составляет 85-95%.…”