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Parathyroid gland & Hyper- & Hypocalcemic disorders

1. PTH

bone¿¡ Á÷Á¢ ÀÛ¿ëÇÏ¿© Ca resorption½Ã۰í

kidney¿¡¼­ Ca reabsorption ¹× 1,25(OH)2D3ÇÕ¼ºÀ» ÀÚ±ØÇϸç

GI Ca Èí¼ö¸¦ ÃËÁøÇÑ´Ù.

serum PTH´Â negative feedback loop¿¡ ÀÇÇØ öÀúÈ÷ Á¶ÀýµÈ´Ù.

CaÀº Ca-sensing receptor¿¡ ÀÛ¿ëÇϰí, VitD´Â nuclear receptor¿¡ ÀÛ¿ëÇÏ¿©

PTHÇÕ¼º ¹× À¯¸®¸¦ ¾ïÁ¦ÇÑ´Ù.

hypercalcemia´Â hyperparathyroidism°ú malignancy¿¡ ÀÇÇØ ÁÖ·Î »ý±ä´Ù.

i) hyperparathyroidism : parathyroid adenoma or hyperplasia

ii) malignancy : cancer cellÀÌ PTH-related peptide(PTH-rP) overproduction

PTH & PTH°è µÑ´Ù G protein-coupled receptor(GPCR)¸¦ ÅëÇØ ÀÛ¿ëÇÑ´Ù.

1) physiology

bone, kidney¿¡ Á÷Á¢ ÀÛ¿ëÇϸç, intestineÀº 1,25(OH)2D3¸¦ ÅëÇÏ¿© °£Á¢ÀûÀ¸·Î ÀÛ¿ëÇÏ¿©

s-Ca ³óµµ¸¦ Áõ°¡½Ã۸ç PTH´Â ionized Ca³óµµ¿¡ ÀÇÇØ Á¶ÀýµÈ´Ù.

osteoblast¿¡´Â PTH receptor°¡ ÀÖÀ¸¸ç PTHÀÇ bone-forming effect¿¡ Áß¿äÇÏ´Ù.

¹Ý¸é osteoclast¿¡´Â PTH receptor°¡ ¾ø´Ù. PTH receptor´Â bone breakdownÀ» Á¶ÀýÇÏ´Â

ÀÛ¿ëÀ» Çϴµ¥ PTH-mediated stimulation of osteoclast´Â osteoblast¿¡¼­ À¯¸®µÇ´Â

cytokineÀ» ÅëÇØ °£Á¢ÀûÀ¸·Î ÀÛ¿ëÇÑ´Ù.

<Á¤¸®> PTH -> osteoblastÀÇ PTH receptorÀÚ±Ø -> osteoblast¿¡¼­ cytokineºÐºñ

-> osteoclast stimulation

cytokines : IGF-1, IL-6, GM-CSF¡¥

2) biosynthesis, secretion, and metabolism

¨ç synthesis

óÀ½¿¡´Â large molecules·Î ÇÕ¼ºµÇ¾ú´Ù°¡(Pre-PTH, 115 a.a) Àß·ÁÁ® Å©±â°¡ °¨¼ÒÇÑ´Ù

(Pro-PTH 90 a.a).

1,25(OH)2D3 -> PTH¸¦ °­ÇÏ°Ô ¾ïÁ¦

¨è secretion Á¶Àý

Ca, Mg -> GPCR -> phospholipase activation -> IP3 & DAG

2. PTH-related protein, PTHrP

malignancyÀÇ hypercalcemiaÀÇ ÁÖ¿øÀÎ

PTH¿Í ±¸Á¶ÀûÀ¸·Î À¯»çÇÏ´Ù. Fig 341-1

1) PTH & PTH°è action

PTH receptor = PTH1, PTH2 receptor

PTH1 receptor(brain, pancreas, several other tissue)´Â µÑ´Ù ¹ÝÀÀÇϳª

PTH2 receptor´Â PTH¿¡¸¸ ¹ÝÀÀÇÑ´Ù.

* Fig 341-2 PTH action

* Fig 341-3 PTH/PTHrP receptorÀÇ dual role

3. Calcitonin

¥á, ¥â gene(chr 11)

blood Ca level¿¡ direct control

Calcitoninº¯È­°¡ ½ÉÇÏ´õ¶óµµ Ca & P metabolismÀº ¶Ñ·ÇÇÏÁö ¾Ê´Ù.

±×·¯³ª bone remodellingÀº ¾ïÁ¦µÈ´Ù.

Paget's disease¿¡¼­ bone resorption¾ïÁ¦, osteoporosisÄ¡·á¿¡´Â Á¦ÇÑÀû,

serum hypercalcemiaÄ¡·á Ãʱ⿡ À¯¿ë

4. Hypercalcemia Tab 341-1 ºÐ·ù

* Áõ»ó: fatigue, depression, mental confusion, anorexia, nausea, vomiting, constipation,

reversible tubular defect, increased urination, short QT interval, cardiac arrhythmia

hypercalcemiaÁ¤µµ¿Í Áõ»óÀÇ Á¤µµ´Â °³Àθ¶´Ù ´Ù¾çÇÏ´Ù.

ÀϹÝÀûÀ¸·Î s-Ca > 11.5-12.0 mg/dLÀÏ ¶§ Áõ»óÀÌ »ý±ä´Ù.

> 13 : kidney, skin, vessel, lung, heart, stomach calcification¹ß»ý

renal insufficiency°¡ »ý±æ¼öµµ ÀÖ´Ù.

(ƯÈ÷ phosphate°¡ Á¤»ó ³»Áö´Â Áõ°¡µÇ¾î ÀÖÀ» ¶§)

¡Ã 15-18 : medical emergency, coma & cardiac arrest

malignancy-associated hypercalcemia¸¦ Á¦¿ÜÇϰí´Â acute management¿¡ Àß

¹ÝÀÀÇÑ´Ù.

1) Primary hyperparathyroidism

(1) ¿øÀÎ

¨ç solitary adenoma

¨è MEN(AD) MEN 1(Wermer's syndrome) - hyperparathyroidism, pituitary,

pancreas(Z-E)

MEN 2A : MCT, pheo, hyperparathyroidism

MEN 2B : MCT, pheo, multiple neuroma

* MEN 2B¿¡´Â hyperparathyroidismÀÌ Æ÷ÇÔµÇÁö ¾Ê´Â´Ù.

(2) pathology

´ëºÎºÐ inferior gland adenoma

carcinoma´õ¶óµµ º¸Åë aggressiveÇÏÁö ¾Ê´Ù.

(3) genetic consideration

MEN1N gene mutation(chr 11q13) -> MEN 1À¯¹ß

Rb gene(chr 13q14) ; tumor suppression gene

óÀ½ retinoblastoma¿¡¼­ ±â¼úµÇ¾úÀ¸³ª parathyroid carcinoma¸¦ Æ÷ÇÔÇÑ

¸¹Àº neoplasm¿¡ Á¸ÀçÇÑ´Ù.

RET protooncogene: MEN 2À¯¹ß