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