Cushing syndrome은 글루코코르티코이드의 조직 노출을 반영한 임상 증후군이며 ACTH-dependent이냐 ACTH-independent이냐로 구분하는데 이 중에서 pituitary adenoma에서 분비되는 ACTH로 인한 과도한 글루코코르티코이드 상태를 Cushing disease라고 합니다. 이것이 쿠싱증후군의 가장 흔한 원입니다.
Cushing syndrome is a clinical syndrome that reflects excessive tissue exposure to glucocorticoids. The diagnosis depends on a suspicion and definitive laboratory testing. The syndrome can be ACTH-dependent and ACTH-independent, but the most common cause is when excess cortisol is produced by the unmitigated release of ACTH from a pituitary adenoma; the term Cushing disease is reserved for this specific cause of Cushing syndrome . Other causes of ACTH-dependent Cushing syndrome are ectopic ACTH secretion, ectopic CRH secretion, and exogenous administration of ACTH. ACTH- in dependent causes of Cushing syndrome are adrenal adenomas, adrenal carcinomas, primary pigmented nodular adrenal disease, ACTH-independent bilateral macronodular hyperplasia, and the exogenous administration of glucocorticoids.
쿠싱증후군의 진단
FIGURE 214-4
Algorithm for testing of patients suspected of having Cushing syndrome (CS).
All statements are recommendations except for those prefaced by “suggest.” Diagnostic criteria that suggest Cushing syndrome are urine free cortisol (UFC) greater than the normal range for the assay, serum cortisol greater than 1.8 µg/dL (50 nmol/liter) after 1 mg dexamethasone (1-mg DST), and late-night salivary cortisol greater than 145 ng/dL (4 nmol/liter). Dex-CRH = dexamethasone–corticotropin-releasing hormone test; DST = dexamethasone suppression test.
(Reprinted with permission from Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:1526-1540.)
Endocrine Society clinical guidelines에 따른 Cushing syndrome 진단 가이드라인은 다음과 같습니다. 처음에는 아주 민감한 다음 4가지 screening tests 중의 하나를 시행합니다.
㉮Urinary free cortisol(≥ 2 tests)
㉯Late-night salivary cortisol(≥2 tests)
㉰Long overnight dexamethasone
㉱ 2-mg/48-hour dexamethasone screening test.
임상적으로 Cushing syndrome이 의심되는 환자에서 어느 한 검사가 비정상이라면 나머지 검사들 중의 하나를 시행하고 두 검사 모두 비정상이라면 Cushing syndrome 원인을 확인하기 위한 검사를 시행해야 합니다.
Diagnostic criteria
㉮Urinary free cortisol (UFC) value > normal range for the assay
㉯Late-night salivary cortisol concentration > 145 ng/dL (>4 nmol/L)
-- 해리슨20판에 언급되어 있는 midnight plasma cortisol > 130 nmol/L는 > 4.7 ㎍/dL에 해당
㉰Serum cortisol level > 1.8 ㎍/dL (>50 nmol/L) (1-mg DST)
㉱Serum cortisol level > 1.8 ㎍/dL (>50 nmol/L) (Two day, 2 mg DST)
임상적으로, 생화학 검사로 Cushing syndrome이 확진되었으므로 다음 단계는 원인을 찾는 검사입니다.
Plasma ACTH로 ACTH dependent한 것인지 independent한 것인지 구분합니다. Primary adrenal disorders인 경우는 ACTH가 10 pg/mL보다 작습니다. 해리슨 20판에서는 5 pg/mL보다 작다고 되어 있습니다. 어찌하였든 억제되어 있습니다. 이러한 경우는 부신 이상 여부를 확인하기 위한 부신 영상 검사가 필요합니다.
Differential Diagnosis
The causes of endogenous Cushing syndrome can be divided broadly into ACTH-dependent (80%) and ACTH-independent (20%) forms ( Table 214-2 ). Hypercortisolism from autonomously functioning adrenal tumors suppresses ACTH, whereas in primary disorders of ACTH excess, the adrenal glands respond to tumor-derived ACTH. Plasma ACTH concentration distinguishes between these causes. ACTH is usually less than 10 pg/mL in primary adrenal disorders but is also suppressed by exogenous steroids, whether they are prescribed intentionally (iatrogenic Cushing syndrome) or taken factitiously. Patients in the latter group often have had multiple surgical procedures and do not reveal that they are self-administering steroids. As a result, patients must be queried closely about exogenous steroid administration, recognizing that parenteral, inhaled, and topical steroids can all cause glucocorticoid excess. Patients with endogenous Cushing syndrome and low ACTH concentrations should undergo adrenal imaging to identify the site of adrenal abnormality. Nonautonomous adrenal tissue atrophies when ACTH support is subnormal. Because of this, the common ACTH-independent forms of Cushing syndrome—adrenal adenoma and carcinoma—are manifested as a unilateral adrenal mass, with atrophy of the adjacent and contralateral tissue on magnetic resonance imaging or computed tomography.
REF. Goldman-Cecil 26th edition
