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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¤»óÈ­½ÃŲ´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.