Adrenocortical hormone
1. ÇÕ¼º
ACTH-secreting corticotrope cells : pituitary cellÀÇ 20%
POMC precursor protein¿¡¼ »ý¼º
cf. POMC precursor -> ¥â-endorphin, ¥â-lipotropin, met-enkephalin, ¥á-MSH,
corticotropin-like intermediate lobe protein, CLIP
POMC gene = chr 2¿¡ À§Ä¡
CRH : higher brain center»Ó¸¸ ¾Æ´Ï¶ó paraventricular nucleus¿¡¼µµ ÇÕ¼º
predominant stimulator of ACTH synthesis & release
CRH receptor = GPCR -> POMC transcription(cAMP, MAP kinase-activator
protein-1(AP-1) cascades)
2. ºÐºñ
6AM - peak, midnight - nadir
AVP, physical stress, exercise, acute illness, insulin-induced hypoglycemia
-> ACTH levelÁõ°¡
ACTH inducing cytokines: TNF, IL-1, 2, 6, leukemia inhibitory factor
=> hypothalamic CRH & AVP secretion activation
pituitary POMC gene expression
local paracrine pituitary cytokine networks activation
3. ÀÛ¿ë
ACTH receptor(melanocortin-2 receptor)´Â GPCR·Î cAMP & MAP(mitogen activated
protein) kinase pathway¸¦ Ȱ¼ºÈ½ÃÄÑ steroidogenesis¸¦ ÀÏÀ¸Å²´Ù.
4. ACTH deficiency
1) ¹ßÇö ¹× Áø´Ü
primary adrenal failure¿Í ´Þ¸® pituitary failure¿¡¼´Â hyperpigmentation or
mineralocorticoid deficiency°¡ µ¿¹ÝµÇÁö ¾Ê´Â´Ù.
2) Lab
ACTH, cortisol¸ðµÎ °¨¼Ò
insulin-induced hypoglycemia, metyrapone or CRH test
3) Ä¡·á
glucocorticoid replacement
hydrocortisone¿ë·®ÀÌ ÇÏ·ç 30mgÀ» ³ÑÁö ¾Êµµ·Ï ÇÑ´Ù.
(5mg ¾ÆÄ§, 2.5mg Àú³á)
5. Cushing's disease(ACTH-producing adenoma)
1) ¿øÀÎ ¹× ºóµµ
iatrogenic hypercortisolismÀÌ Cushing's syndromeÁß °¡Àå ¸¹Àº ¿øÀÎ
endogenous Cushing's syndromeÁß¿¡¼´Â Cushing's disese°¡ °¡Àå ¸¹´Ù(70%).
ACTH-producing adenoma´Â Àüü pituitary tumorÀÇ 10-15%
´ëºÎºÐÀº microadenoma, ±×·¯³ª macroadenomaµµ º¼¼ö ÀÖ´Ù.
¿©ÀÚ°¡ ³²ÀÚº¸´Ù 5-10¹è ¸¹´Ù.
2) ¹ßÇö ¹× Áø´Ü(Tab 328-12)
hypercortisolismÀÌ ºü¸£°Ô »ý±â°í skin hyperpigmentation, severe myopathy°¡ µ¿¹ÝµÈ´Ù
¸é ectopic ACTH °¡´É¼ºÀ» ½Ã»çÇÑ´Ù. hypertension, hypokalemic alkalosis, glucose
intolerance, edema ¿ª½Ã ectopic ACTH¿¡¼ ´õ µÎµå·¯Áø´Ù.
serum K+<3.3 mmol/L´Â ectopic ACTH secretionÀÇ °æ¿ì ¡70%¿¡¼ ³ªÅ¸³ªÁö¸¸
pituitary-dependent Cushing's disease¿¡¼´Â 10%¿¡¼¸¸ º¼¼ö ÀÖ´Ù.
3) Lab
¨ç screening test
i) 24hr urine free cortisol
ii) overnight 1mg dexamethasone suppression test
ÀÚÁ¤¿¡ cortisol levelÀº ÃÖÀúÄ¡¸¦ º¸À̹ǷΠÀÚÁ¤¿¡ sampleÇÏ¿©
high cortisol levelÀ» º¸À̸é Cushing's syndromeÀ» ÀǽÉÇØ º¼¼ö ÀÖ´Ù.
¨è basal plasma ACTH level
ACTH-dependent(pituitary, ectopic ACTH)¿Í ACTH-independent(adrenal or exogenous
glucocorticoid)¸¦ ±¸º°ÇÒ¼ö ÀÖ´Ù.
ACTH-dependent Áß¿¡¼µµ ectopic ACTH secretionÀÌ pituitary ACTH-secreting
adenomaº¸´Ù mean basal ACTH°¡ 8¹è ´õ ³ô´Ù.
±×·¯³ª µÎ Áúȯ»çÀÌ¿¡ ACTH ¼öÄ¡°¡ °ãÄ¡´Â ºÎºÐÀÌ ¸¹¾Æ¼ ACTH¸¦ ÀÌ¿ëÇÏ¿© µÎ ÁúȯÀ»
±¸º°ÇÒ ¼ö´Â ¾ø´Ù.
¨é Dynamic test: CRH stimulation test
4) Inferior petrosal venous sampling
pituitary MRI with Gad enhance´Â 2mm¹Ì¸¸ÀÇ pituitary ACTH-secreting adenoma¸¦
Áø´ÜÇÏ±â ¾î·Æ´Ù. ÀÌ·² ¶§ CRHÅõ¿© ÀüÈÄ·Î ÇØ¼ bilateral inferior petrosal sinus ACTH
samplingÀÌ ÇÊ¿äÇÏ´Ù.
IV CRH(1ug/kg)ÈÄ baseline, 2, 5, 10min samplingÇÏ¿© inferior petrosal/peripheral venous
ACTH ratio°¡ 2ÀÌ»óÀ̸é pituitary Cushing's disease·Î È®ÁøÇÒ¼ö ÀÖÀ¸¸ç 3ÀÌ»óÀÏ ¶§´Â
pituitary ACTH-secreting tumor°¡ ÀÖÀ½À» È®½ÅÇÒ¼ö ÀÖ´Ù. ¹Î°¨µµ°¡ 99%¿¡ ´ÞÇϸç
false-positive´Â ¸Å¿ì µå¹°´Ù. false-negative result°¡ ³ª¿À´Â °æ¿ì´Â aberrant venous
anatomic drainage µÉ¶§ÀÌ´Ù.
±×·¯³ª ±â¼úÀûÀ¸·Î ¾î·Á¿ì¸ç 0.05%¿¡¼ neurovascular complicationÀÌ ¹ß»ýÇÑ´Ù.
°íÇ÷¾ÐÀ̳ª MRI»ó pituitary adenoma°¡ Àß °üÂûµÇ´Â °æ¿ì¿£ ½ÃÇàÇØ¼± ¾ÈµÈ´Ù.
5) Ä¡·á
¨ç selective transsphenoidal resectionÀÌ choice(Fig 328-12)
remission rate: microadenoma ¡80%, macroadenoma <50%
¼ö¼úÈÄ ´ëºÎºÐ postop adrenal insufficiency°¡ »ý°Ü 12°³¿ù±îÁö Áö¼ÓÇÑ´Ù.
µû¶ó¼ ÈçÈ÷ low-dose cortisol replacement°¡ ÇÊ¿äÇÏ´Ù.
¼ö¼úÀÌ ¼º°øÀûÀ̾ú´õ¶óµµ 5%¿¡¼´Â biochemical recurrence°¡ »ý±ä´Ù.
¨è pituitary irradiation
unsuccessful surgeryÈÄ ½ÃÇàÇÒ¼ö ÀÖÀ¸³ª cure´Â 15%¿¡ ºÒ°úÇÏ´Ù.
¨é steroidogenic inhibitors
radiationÀÌ ´À¸®°í ¼ºÀο¡¼ ºÎºÐÀûÀ¸·Î¸¸ È¿°ú°¡ ÀÖÀ¸¹Ç·Î pituitary irradiation°ú
steroidogenic inhibitor¸¦ ÇÔ²² »ç¿ëÇÑ´Ù.
i) mitotane(o,p'-DDD)
11¥â-hydroxylase & cholesterol side-chain cleavage enzymesÀ» ¾ïÁ¦Çϰí
adrenocortical cellÀ» ÆÄ±«ÇÑ´Ù.
ºÎÀÛ¿ëÀ¸·Î GI sx, dizziness, gynecomastia, hyperlipidemia, skin rash, hepatic enzyme
elevationÀÌ ³ªÅ¸³¯ ¼ö ÀÖ´Ù. ¶ÇÇÑ hypoaldosteronismÀ» ÀÏÀ¸Å³¼öµµ ÀÖ´Ù.
ii) ketoconazole 600-1200 mg/d #2
P450 enzyme inhibitionÇÏ¿© ´ëºÎºÐÀÇ È¯ÀÚ¿¡¼ cortisolÀ» ³·Ãá´Ù.
elevated hepatic transaminases, gynecomastia, impotence, GI upset, edema°¡
ÈçÇÑ ºÎÀÛ¿ëÀÌ´Ù.
iii) metyrapone(2-4 g/d)
11¥â-hydroxylase inhibitionÇÏ¿© 75%ÀÇ È¯ÀÚ¿¡¼ plasma cortisolÀ» Á¤»óȽÃŲ´Ù.
ºÎÀÛ¿ëÀ¸·Î´Â N/V, rash, acne or hirsutism exacerbation
iv) aminoglutethimide(250mg tid)
v) trilostane, cyproheptadine, IV etomidate
¨ê bilateral adrenalectomy
hypercortisolismÀ» ±³Á¤ÇÒ ¼ö´Â ÀÖÀ¸³ª Æò»ý glucocorticoid & mineralocorticoid
replacement¸¦ ¹Þ¾Æ¾ß Çϸç Nelson's syndrome(pituitary tumor + skin pigmentation)ÀÌ
»ý±æ¼ö ÀÖ´Ù. adrenalectomyÈÄ Nelson's syndromeÀ» ¿¹¹æÇϱâ À§Çؼ radiation therapy
¸¦ ½ÃÇàÇÒ¼ö ÀÖ´Ù.