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Thyroid gland

Anatomy & development

* blood supply: ext. carotid a. -> superior thyroid artery

subclavian a. -> inferior thyroid artery

12-20g, highly vascular

medullary C cell : calcitonin»ý»ê

* ¹ß»ý

pharyngeal epitheliumÀÇ evagination

parathyroid gland : 3rd & 4th pharyngeal pouch¿¡¼­ migration

fetal thyroid´Â ÀӽŠ10ÁÖ¿¡ iodine concentration & organification´É·Â ȹµæ

* transcription factor : Tg, TPO, NIS, TSH-R¿Í °°Àº thyroid-specific gene induction

Thyroid axis regulation

ant. pituitary thyrotrope cell¿¡¼­ TSHºÐºñ : ¥á, ¥â subunits

¥á subunit : ´Ù¸¥ glycoprotein hormone(LH, FSH, hCG)¿Í À¯»ç

¥â subunit : TSH¿¡¸¸ À¯ÀÏ

Hormone synthesis, metabolism, and action

1. ÇÕ¼º

I- ----> I- ----> I ----> coupling --> release

(trapping) (organification)

1) Iodine metabolism and transport

iodide uptake normal : 10-25%, Graves' ds: 70-90%

NIS(Na+/I- symporter)¿¡ ÀÇÇØ ¸Å°³µÊ

iodine deficiency area¿¡¼­ goiter, ½ÉÇϸé hypothyroidism, cretinismÀÌ ¹ß»ýÇÒ °¡´É¼ºÀÌ

³ô´Ù.

cf. cretinism : ¾ÆÀÌ¿¡°Ô¼­ thyroid hormone or iodineÀÌ °ø±ÞµÇÁö ¾Ê¾ÒÀ» ¶§ mental &

growth retardationÀÌ ¹ß»ý

* ÇÏ·ç Çʿ䷮: ¼ºÀÎ 150 ug/d, ¾ÆÀÌ 90-120 ug/d, ÀÓ»êºÎ 200 ug/d

2) organification, coupling, storage, release

organification: TPO¿¡ ÀÇÇØ I- ¡æ I·Î oxidation

Tg + iodine => MIT, DIT

coupling: T3, T4

cf. organification & couplingÀ» blockÇÏ´Â antithyroid drug

: PTU, methymazole, mercaptoimidazole

release blocking agent: lithium, dexamethasone

3) TSH action

TSH-R(seven-transmembrane GPCR)À» ÅëÇÏ¿© thyroid functionÀ» Á¶ÀýÇÑ´Ù.

TSH-R´Â stimulatory G proteinÀÇ ¥á subunit(Gs¥á)¿Í ¿¬°áµÇ¾î adenylate cyclase¸¦

Ȱ¼ºÈ­½Ã۰í cAMP»ý»êÀ» Áõ°¡½ÃŲ´Ù.

TSH´Â ¶ÇÇÑ phospholipase C¸¦ activation½ÃÄÑ phosphatidylinositol turnover¸¦ ÀÚ±ØÇÑ´Ù.

4) È£¸£¸ó ÇÕ¼º°ú ºÐºñ¿¡ ¿µÇâÀ» ¹ÌÄ¡´Â ÀÎÀÚ

TSH°¡ dominant hormonal regulatorÁö¸¸ ±× ¿Ü¿¡ ´Ù¾çÇÑ growth factor°¡ thyroid hormone

ÇÕ¼º¿¡ ¿µÇâÀ» ¹ÌÄ£´Ù.

: IGF-I, EGF, TGF-¥â, endothelin, various cytokines

¿¹¸¦ µé¸é, acromegaly¿¡¼­ growth hormone°ú IGF-IÀÇ Áõ°¡´Â goiter¸¦ µ¿¹ÝÇϱ⵵ Çϰí,

multinodular goiterÀÇ ¼±ÇàÀÎÀÚ°¡ µÇ±âµµ ÇÑ´Ù.

¾î¶² cytokineµéÀº autoimmune thyroid disease¿Í °ü·ÃÇÏ¿© thyroid growth¸¦ ÀÏÀ¸Å°±âµµ

ÇÏ°í ¶Ç´Ù¸¥ °ÍµéÀº apoptosis¸¦ ÀÏÀ¸Å²´Ù. iodineÀº thyroid functionÀÇ important

regulatorÀε¥ ¿¹¸¦ µé¾î iodine deficiency¶§ thyroid blood flow°¡ Áõ°¡Çϰí NIS¿¡ ÀÇÇØ

uptake¸¦ ÀÚ±ØÇÑ´Ù.

iodine°ú´Ù½Ã ÀϽÃÀûÀ¸·Î thyroid iodide organificationÀ» ¾ïÁ¦Çϴµ¥ ÀÌ Çö»óÀ»

"Wolff-Chaikoff effect"¶ó Çϸç thyrotoxic crisisÄ¡·á¿¡ À̿밡´ÉÇÏ´Ù.

2. Thyroid hormone transport and metabolism

1) serum binding proteins

T4´Â T3º¸´Ù 20¹è ´õ ¸¹ÀÌ ºÐºñµÈ´Ù. µÑ´Ù TBG, transthyretin(TTR=thyroxine-binding

prealbumin, TBPA)¿Í °°Àº plasma protein°ú °áÇÕÇÏ¿© ¼øÈ¯ÇÑ´Ù.

TBG³óµµ´Â ¸Å¿ì ³·Áö¸¸(1-2mg/dL) high affinity(T4>T3)°¡ ÀÖ¾î hormoneÀº ´ë·« 80%°¡

°áÇյǾî ÀÖ´Ù. AlbuminÀº thyroid hormone¿¡ ´ëÇÑ affinity°¡ ³·Áö¸¸ ³óµµ°¡ ³ô´Ù(¡­3.5

g/dL).

albuminÀº T4ÀÇ 10%, T3¿Í´Â 30%Á¤µµ °áÇյǾî ÀÖ´Ù.

¿©·¯ °¡Áö binding proteinÀÇ È¿°ú°¡ º¹ÇÕÀûÀ¸·Î ÀÛ¿ëÇÒ ¶§ ´ë·« T4ÀÇ 99.98%, T3ÀÇ 99.7%

°¡ protein°ú °áÇÕµÈ ÇüÅ·ΠÀÖ´Ù. T3°¡ T4º¸´Ù ´Ù¼Ò ´À½¼ÇÏ°Ô °áÇÕÇϹǷΠfree T3°¡ free

T4º¸´Ù ¸¹´Ù.

2) dysalbuminemic hyperthyroxinemia

X-linked TBG deficiency¶§ total T4 & T3 levelÀº ¸Å¿ì ³·´Ù. ±×·¯³ª free hormoneÀº Á¤»ó

À̸ç ȯÀÚ´Â euthyroid & normal TSH levelÀ» °®´Â´Ù.

estrogen°ú °°ÀÌ TBG levelÀÌ Áõ°¡µÈ °æ¿ì¿¡µµ free T3, T4´Â Á¤»óÀÌ´Ù.

TBG, TTR, and albuminÀÇ T4 and/or T3 affinity°¡ Áõ°¡ÇÑ °æ¿ì¿¡ euthyroid

hyperthyroxinemia or familial dysalbuminemic hyperthyroixinemia(FDH)¸¦ ÀÏÀ¸Å²´Ù.

À̺´Àº total T4 and/or T3´Â

Áõ°¡µÇ¾î ÀÖÀ¸³ª free hormone levelÀº Á¤»óÀÌ´Ù.

3) deiodinases

¨ç T4 -> T3(30%), rT3(40%), liver¿¡¼­ conjugationµÇ¾î bile·Î ¹è¼³(20%)

¨è T3: thyroid gland¿¡¼­ ÇÕ¼º(20%)

T4·ÎºÎÅÍ Àüȯ(80%)

monodeiodinationµÇ¾î T4->T3·Î ÀüȯµÈ´Ù.

T3´Â rapid clearance(1ÀÏ), T4´Â slow clearance(7ÀÏ)

* T4 -> T3 ¾ïÁ¦

: fasting, systemic illness or acute trauma,

oral contrast agents,

drug(PTU, propranolol amiodarone, glucocorticoid)

3. Thyroid hormone action

1) nuclear thyroid hormone receptors

thyroid hormone receptor(TRs) ¥á,¥â

µÑ´Ù ¸ðµç Á¶Á÷¿¡ ÀÖÀ¸³ª ¾çÀº ´Ù¼Ò Â÷À̰¡ Àִµ¥

TR¥á´Â brain, kidney, gonads, muscle, and heart¿¡ ÁÖ·Î ÀÖ°í

TR¥â´Â pituitary, liver¿¡ ¸¹´Ù.

TRsÀº central DNA-binding domain & C-terminal ligand-binding domainÀ» °¡Áö°í ÀÖ´Ù.

ÀÌ´Â thyroid response elements(TREs)¶ó´Â ƯÁ¤ DNA sequences(target geneÀÇ

promotor regions)¿¡ °áÇÕÇÑ´Ù.

thyroid hormoneÀº TR¥á, TR¥â¿¡ ¸ðµÎ °°Àº Á¤µµÀÇ Ä£È­·ÂÀ¸·Î °áÇÕÇÏÁö¸¸ T3°¡ T4º¸´Ù

10-15¹è ´õ Å« ģȭ·ÂÀ¸·Î °áÇÕÇÏ¿© Áõ°¡µÈ hormonal potency¸¦ ³ªÅ¸³½´Ù.

2) thyroid hormone resistance

autosomal dominant disorder·Î TR¥â receptor gene mutationÀ¸·Î ¹ß»ýÇÑ´Ù.

free thyroid hormone & TSH°¡ ºñÁ¤»óÀûÀ¸·Î Áõ°¡µÇ¾î ÀÖ´Ù.

Ưº°ÇÑ Ä¡·á´Â ÇÊ¿ä¾ø´Ù.

Áø´ÜÀÇ ¸ñÀûÀº hyperthyroidismÀ¸·Î ¿ÀÀÎÇÏ¿© ºÎÀûÀýÇÑ Ä¡·á¸¦ ÇÏ´Â °ÍÀ» ¹æÁöÇϴµ¥

ÀÖ´Ù.

Physical examination

* Pemberton's sign : large retrosternal goiter°¡ ÀÖÀ» ¶§ ÆÈÀ» µé¸é ¸ñÀ§·Î venous

congestion°ú È£Èí°ï¶õÀÌ ÀϾ´Â Çö»ó

Laboratory evaluation

1. Thyroid hormone ÃøÁ¤

4¼¼´ë TSH IRMA(immunoradiometric assay)´Â TSH levelÀ» 0.004 mU/LÀÌÇϱîÁö ÃøÁ¤°¡´É

Çϳª ½ÇÁ¦ ÀÓ»ó¿¡¼­´Â 0.1 mU/LÀÌÇϱîÁö ÃøÁ¤°¡´ÉÇÑ ¹Î°¨µµ¸é ÃæºÐÇÏ´Ù.

serum total T4 & total T3¿¡ ´ëÇØ radioimmunoassay°¡ ³Î¸® »ç¿ëµÇ´Âµ¥ total T3 & T4´Â

¸¹Àº ÀÎÀÚ(illness, medications, genetic factors)ÀÇ ¿µÇâÀ» ¹Þ´Â´Ù. ±×·¯¹Ç·Î

free(=unbound) hormone levelÀ» ÃøÁ¤ÇÏ´Â °ÍÀÌ ´õ À¯¿ëÇÏ´Ù. Free thyroid hormone level

À» °£Á¢ÀûÀ¸·Î ÃøÁ¤ÇÏ´Â ¹æ¹ýÀ¸·Î total T4 or T3 ³óµµ ¹× THBR(thyroid hormone binding

ratio)·Î free T3 or free T4 index¸¦ °è»êÇÏ´Â ¹æ¹ýÀÌ Àִµ¥ THBRÀº T3-resin uptake test¸¦

ÅëÇØ ±¸ÇÑ´Ù.

total thyroid hormone levelÀº TBG°¡ Áõ°¡ÇÒ¶§ Áõ°¡Çϰí, TBG°¡ °¨¼ÒÇÒ ¶§ °¨¼ÒÇÑ´Ù.

TBG¡è: pregnancy, oral contraceptives, hormone replacement, tamoxifen

TBG¡é: androgen, nephrotic syndrome

´ëºÎºÐ thyrotoxicosis¸¦ È®ÁøÇϴµ¥ free T4 levelÇϳª·Î ÃæºÐÇÏ´Ù. T3 levelÀÌ Áõ°¡µÈ °æ¿ì

´Â 2-5%¿¡ ºÒ°úÇÏ´Ù(T3 thyrotoxicosis). ±×·¯¹Ç·Î free T3 levelÀº TSH°¡ ¾ïÁ¦µÈ ȯÀÚ¿¡¼­

ÃøÁ¤ÇØ¾ß ÇÏÁö¸¸ normal free T4 levelÀ» º¸À϶§´Â ÃøÁ¤ÇÒ Çʿ䰡 ¾ø´Ù. free T3 levelÀº

hypothyroidismȯÀÚÀÇ 25%¿¡¼­ Á¤»óÀ̹ǷΠÀÌ·± °æ¿ì¿¡ À¯¿ëÇÑ Á¤º¸¸¦ Á¦°øÇÏÁö ¸øÇÑ´Ù.

hypothalamic-pituitary disease·Î ÀÎÇÑ secondary hypothyroidismÀº ´Ù¾çÇÑ TSH levelÀ»

º¸À̱⠶§¹®¿¡ pituitary disease°¡ Àְųª ÀǽɵǴ °æ¿ì¿¡ thyroid functionÀ» Æò°¡ÇÔ¿¡

ÀÖ¾î TSH¸¦ »ç¿ëÇØ¼­´Â ¾ÈµÈ´Ù.

<Âü°í>

* total T3 : 70-190 ng/dL, total T4: 5-12 ug/dL, TSH 0.4-5 uU/ml

* T3 resin uptake(T3RU) Á¤»ó 25-30%

TBG°¡ ÀÏÁ¤ÇÏ´Ù°í °¡Á¤Çϸé hyperthyroidism½Ã thyroid homoneºÐºñ°¡ Áõ°¡ÇϹǷÎ

T3RU°¡ Áõ°¡ÇÏ°í ¹Ý´ë·Î hypothyroidism¶§´Â °¨¼ÒÇÏ°Ô µÈ´Ù.

ÃøÁ¤¹ýÀÌ °£´ÜÇÏ°í °©»ó¼± ±â´É»óŸ¦ ºñ±³Àû Àß ¹Ý¿µÇÑ´Ù´Â ÀåÁ¡ÀÌ ÀÖÀ¸³ª

TBGÀÇ ¾ç¿¡ µû¶ó Àý´ëÀû ¿µÇâÀ» ¹Þ°í, T3, T4ÀÇ Á÷Á¢ ÃøÁ¤ÀÌ ¾Æ´Ï¹Ç·Î °£Á¢ÀûÀÎ °©»ó¼±

±â´É»óÅ Æò°¡¹æ¹ýÀÌ´Ù. ±×·¡¼­ º¸´Ù Á¤È®È÷ °©»ó¼± ±â´É»óŸ¦ Æò°¡ÇϰíÀÚ FT4I(free T4

index)¸¦ ±¸ÇÏ°Ô µÈ´Ù.

* FT4I(Free T4 index)

TBGÁõ°¡(ÀÓ½Å, extrogenÅõ¿© µî)½Ã total T4´Â Áõ°¡Çϰí, T3RU´Â °¨¼ÒÇÏ°Ô µÈ´Ù.

ÀÌ µÎ°¡Áö °á°ú·ÎºÎÅÍ °£Á¢ÀûÀ¸·Î free T4¾çÀ» ¾Ë°íÀÚ FT4I¸¦ ±¸ÇÑ´Ù.

* FT4I = total T4 ¡¿ T3RU Á¤»óÄ¡ 5¡­12

2. Thyroid dysfunction ¿øÀÎÀ» ±Ô¸íÇϱâ À§ÇÑ °Ë»ç

euthyroid womenÀÇ 5-15%, euthyroid menÀÇ 2%°¡ thyroid antibody¸¦ °¡Áö°í ÀÖÀ¸¸ç

À̵éÀº thyroid dysfunctionÀÌ »ý±æ À§ÇèÀÌ ³ô´Ù.

1) TPO antibody

autoimmune hypothyroismÀÇ ´ëºÎºÐ, Graves' diseaseÀÇ 80%¿¡¼­ high level·Î Á¸Àç

2) TSI

Graves' disease¿¡¼­ TSH-R¸¦ ÀÚ±ØÇÏ´Â Ç×ü

ÀÓ½ÅÁß 1st trimester¶§ maternal TSI levelÀÌ ³ôÀ» ¶§ neonatal thyrotoxicosis¸¦ ¿¹ÃøÇÏ´Â

µ¥ ÁÖ·Î »ç¿ëµÈ´Ù.

3) serum Tg level

thyrotoxicosis factitia¸¦ Á¦¿ÜÇÑ ¸ðµç ÇüÅÂÀÇ thyrotoxicosis¶§ Áõ°¡ÇÑ´Ù.

TgÃøÁ¤ÀÇ ÁÖ ¿ªÇÒÀº thyroid cancer f/u¿¡ ÀÖ´Ù.

total thyroidectomyÈÄ¿¡´Â TgÀÌ °ËÃâµÇ¾î¼± ¾ÈµÇ´Âµ¥ 1-2 ng/mLÀÌ»ó °ËÃâÀº incomplete

ablation or recurrent cancer¸¦ ÀǹÌÇÑ´Ù.

4) Radioiodine uptake and thyroid scanning

(1) RAIU

131IÀ» ¸ÔÀ̰í 24½Ã°£ÈÄ uptakeÁ¤µµ¸¦ ÃøÁ¤ (Á¤»ó 5-30%)

* hyperthyroidismÀÌÁö¸¸ RAIU°¡ °¨¼ÒµÈ °æ¿ì

i) painless chronic or subacute thyroiditis

(=spontaneous resolving hyperthyroidism)

ii) iodine-induced hyperthyroidism

iii) thyrotoxicosis factitia

iv) struma ovarii

(2) perchlorate discharge test: perchlorate¸¦ ¸ÔÀ̰í uptakeÁ¤µµ¸¦ º»´Ù.

organification defect¸¦ ã¾Æ³»´Â °Í

15%ÀÌÇÏ·Î ¶³¾îÁú ¶§ positive

: pendred disease, Hashimoto's thyroiditis, hyperthyroidismȯÀÚ PTUÄ¡·áÁßÀ϶§

5) thyroid ultrasound

10 MHz¸¦ »ç¿ëÇϸé spatial resolution & image quality°¡ ¿ì¼öÇÏ¿© 3mmÀÌ»óÀÇ nodule°ú

cyst¸¦ ¹ß°ßÇÒ¼ö ÀÖ´Ù. noduleÀ» ¹ß°ßÇÏ´Â °Í¿Ü¿¡ nodule size¸¦ monitorÇÒ¼ö ÀÖ°í FNA

biopsy ¹× cystic lesion aspiration¶§ guidingÇÒ¼ö ÀÖ´Ù.

Autoimmune basis of thyroid disease

1. ºóµµ

thyroid autoimmunity : several forms of thyroiditis, hypothyroidism, Graves' diseaseÀ¯¹ß.

ºÎ°Ë½Ã 20-40%¿¡¼­ focal thyroiditis°¡ °üÂûµÇ´Âµ¥ TPO antibodyÀÇ Á¸Àç¿Í °°Àº

autoimmunityÀÇ serologic marker°¡ µ¿¹ÝµÈ´Ù. ÀÌ·¯ÇÑ Ç×ü´Â ³²ÀÚº¸´Ù´Â ¿©ÀÚ¿¡¼­ 4-10¹è

´õ ÈçÇÏ´Ù.

¿©¼ºÀÇ 5%°¡ ºÐ¸¸ÈÄ self-limited postpartum(silent) thyroiditis¸¦ °æÇèÇϴµ¥ À̶§

ante-partum TPO antibody°¡ Á¸ÀçÇϸç postpartum thyroiditis¸¦ °æÇèÇÑ ¿©¼ºÀÇ 20%°¡±îÀÌ

ºÐ¸¸ÈÄ 5-10³âÈÄ¿¡ permanent hypothyroidismÀ¸·Î ¹ßÀüÇÑ´Ù.

2. susceptibility factors

´ëºÎºÐÀÇ autoimmune disorderó·³ genetic & environmental factor¿¡ ÀÇÇØ °áÁ¤µÈ´Ù.

¨ç genetic factors

monozygotic twins¿¡¼­ Graves' disease concordance´Â 20-30%ÀÌ´Ù.

autoimmune polyglandular syndrome 2 = autoimmune thyroid dysfunction + other

autoimmune diseases(type 1 DM, addison's ds, pernicious anemia, vitiligo)

ÀÌ·¯ÇÑ autoimmune disorder group¿¡¼­´Â ¸î°¡Áö genetic factor¸¦ °øÀ¯ÇÑ´Ù.

Graves' disease & ¹éÀο¡¼­ÀÇ autoimmune hypothyroidismÀÇ °¡Àå Àß ¹àÇôÁø genetic risk

factor´Â HLA DR3ÀÌ´Ù. T-cell regulatory gene TCLA-4ÀÇ polymorphismÀÌ ¸î¸î Á¾Á·¿¡¼­

¹ß°ßµÇ¾úÀ¸³ª °ü·Ã¼ºÀº ¾àÇÏ´Ù.

¨è environmental factors

i) sex hormone

thyroid autoimmunity°¡ ¿©¼º¿¡¼­ ¿ì¼¼ÇÑ °ÍÀº sex steroidsÀÇ ¿µÇâ ¶§¹®ÀÏ °ÍÀ¸·Î »ý°¢

µÈ´Ù.

ii) smoking

Èí¿¬Àº Graves' disease¹ß»ý¿¡ À־´Â minor riskÀÌÁö¸¸ ophthalmopathyÀÇ ¹ß»ý¿¡

À־´Â major risk factorÀÌ´Ù.

iii) infection

congenital rubella syndromeÀ» Á¦¿ÜÇϰí´Â °¨¿°ÀÇ ¿ªÇÒ¿¡ ´ëÇØ È®¸³µÈ Áõ°Å°¡ ¾ø´Ù.

congenital rubella infectionÀº autoimmune hypothyroidism¹ß»ýÀ§ÇèÀ» Áõ°¡½ÃŰÁö¸¸

viral thyroiditis°¡ autoimmune thyroiditisÀ» À¯¹ßÇÏÁö´Â ¾Ê´Â´Ù.

3. Humoral factors

Graves' disease´Â TSH-R stimulating immunoglobulin(TSI)¿¡ ÀÇÇØ ¹ß»ýÇÑ´Ù.

TSI´Â ŹÝÅë°ú°¡ °¡´ÉÇÏ¿© transient neonatal thyrotoxicosis¸¦ ÀÏÀ¸Å°¸ç Graves' disease

¿©¼ºÀÇ 1-2%¿¡¼­ ÇÕº´µÈ´Ù.

TSH functionÀ» blockÇÏ´Â Ç×ü´Â hypothyroidismÀ» ÀÏÀ¸Å°´Âµ¥ TSH-R blocking antibody

´Â autoimmune hypothyroidismÀ» °¡Áø ¾Æ½Ã¾Æ ȯÀÚÀÇ 20%¿¡¼­ ¹ß°ßµÈ´Ù.

* Antibody¸¦ ÃøÁ¤ÇÏ´Â ¹æ¹ý

i) TBII(TSH-binding inhibiting immunoglobulin)

functional effect¿¡ ´ëÇÑ Á¤º¸¸¦ Á¦°øÇÏÁö ¸øÇϸç, ºñÀüÇüÀûÀΠȯÀÚ¿¡¼­ TSH-R AbÀÇ Á¸Àç

¸¦ Áõ¸íÇϱâ À§ÇØ ÀÏÂ÷ÀûÀ¸·Î »ç¿ëÇÑ´Ù.

ii) Ab to Tg & TPO

thyroid autoimmunity marker·Î ÀÓ»óÀûÀ¸·Î À¯¿ëÇÏ´Ù.

4. Cell-mediated factors

autoimmune thyroid disease¿¡¼­ activated circulating T cellÀÌ Áõ°¡µÇ¾î ÀÖÀ¸¸ç thyroid

gland´Â CD4+ and CD8+ T cellsÀÌ infiltrationµÇ¾î ÀÖ´Ù.

¶Ç, thyroid gland´Â cytokine-mediated upregulation of Fas(and possibly Fas ligand)¸¦

ÅëÇÏ¿© apoptosisµÈ´Ù.

infiltrating immune cells¿¡ ÀÇÇØ »ý¼ºµÈ cytokineÀº thyroid cell-surface moleculesÀ» ¹ßÇö

ÇÏ¿© ´ÙÀ½°ú °°Àº °á°ú¸¦ ÃÊ·¡ÇÑ´Ù.

i) engagement by immune cells(¿¹, adhesion molecules, HLA class I & II molecules)

ii) thyroid cellÀÚü¿¡ ÀÇÇÑ cytokine secretionÀ¯µµ

iii) NO production

iv) TSH-R inhibition, TPO, and Tg synthesis¸¦ ÅëÇÏ¿© thyroid hormone»ý»ê °¨¼Ò

cytokineÀº ¶ÇÇÑ thyroid-associated ophthalmopathy¿¡ Áß¿äÇÑ ¿ªÇÒÀ» ÇÑ´Ù.

extraocular muscle¿¡ activated T cellÀÌ Ä§ÂøÇÏ¿© cytokineÀ» ºÐºñÇÏ¿© fibroblast¸¦

activation½Ã۰í glycosaminoglycanÇÕ¼ºÀ» Áõ°¡½ÃÄÑ °á±¹ muscle swellingÀ» ÃÊ·¡ÇÑ´Ù.

º´ÀÇ Èı⿡´Â fibrosisµÈ´Ù.

Hypothyroidism

1. ¿øÀÎ Tab 330-4

iodine deficiency : mc cause

iodine sufficiency area¿¡¼­´Â autoimmune ds(Hashimoto's thyroiditis), iatrogenic

cause(hyperthyroidism tx)°¡ mc cause

2. Congenital hypothyroidism

1/3000-4000 newborns

¾ö¸¶°¡ TSH-R blocking ab°¡ Àְųª antithyroid drugÀ» º¹¿ëÁßÀÏ ¶§ ÀϽÃÀûÀ¸·Î ¹ß»ý

*neonatal hypothyroidism

thyroid gland dysfunction(85%)

inborn errors of thyroid hormone synthesis(10-15%)

TSH-R Ab-mediated

F>M

1) ÀÓ»ó¹ßÇö(Tab 330-5: adult hypothyroidismÀÇ ÀüÇüÀû Ư¡)

Ãâ»ý½Ã ´ëºÎºÐ Á¤»óÀ̸ç 10% ¹Ì¸¸¿¡¼­ ÀÓ»óÀû Ư¡À» º¸ÀδÙ.

: prolonged jaundice, feeding problems, hypotonia, enlarged tongue,

delayed bone maturation, umbilical hernia

Ä¡·á°¡ Áö¿¬µÇ¸é permanent neurologic damage°¡ ÃÊ·¡µÈ´Ù.

2) Áø´Ü ¹× Ä¡·á

TSH or T4 screening

Áø´ÜµÇ¸é T4¸¦ Åõ¿©(10-15 ug/kg/d)Çϰí TSH¸¦ monitoringÇϸ鼭 ¿ë·®À» Á¶ÀýÇÑ´Ù.

T4·Î Á¶±âÄ¡·á½Ã normal IQ levelÀ» À¯ÁöÇÒ¼ö ÀÖÀ¸³ª ´ëºÎºÐÀÇ severe hypothyroidism

ȤÀº Ä¡·á°¡ ¹ÌÈíÇÒ ¶§ subtle neurodevelopmental abnormality°¡ ¹ß°ßµÈ´Ù.

3. Autoimmune hypothyroidism

1) ºÐ·ù

i) goiter(Hashimoto's or goitrous thyroiditis) or at the later stages of the disease

ii) minimal residual thyroid tissue(atrophic thyroiditis)

¼­¼­È÷ °©»ó¼± ±â´ÉÀÌ ÀúÇϵǸ鼭 º¸»ó±âÀüÀ¸·Î TSH°¡ Áõ°¡ÇÏ°Ô µÈ´Ù.

ÀϺΠȯÀÚµéÀº minor symptomÀ» °¡Áö´Âµ¥ ÀÌ·± »óŸ¦ "subclinical hypothyroidism"À̶ó

ÇÑ´Ù.

Èı⿡ free T4 levelÀº °¨¼ÒÇϰí, TSH levelÀº Á¡Â÷ Áõ°¡Çϸ鼭 Áõ»óÀº ´õ¿í ¶Ñ·ÇÇØÁø´Ù.

(º¸Åë TSH>10 mU/L)

À̶§¸¦ "clinical hypothyroidism(=overt hypothyroidism)"À̶ó ÇÑ´Ù.

2) À¯º´·ü

annual incidence: F= 4/1000, M= 1/1000

subclinical hypothyroidismÀ̸鼭 TPO antibody(+)ÀÏ ¶§ clinical hypothyroidism

À¸·Î ÁøÇàÇÒ À§ÇèÀº ¸Å³â 4%ÀÌ´Ù.

3) pathogenesis

Hashimoto : marked lymphocyte infiltration, thyroid follicle atrophy

Atrophic thyroiditis: fibrosis°¡ more extensive, lymphocyte infiltrationÀº ´úÇÏ´Ù.

µÑ´Ù TSH-R blocking Ab(+) -> T cell mediated thyroid follicular destructionÃÊ·¡

4) ÀÓ»ó¹ßÇö

Hashimoto's thyroiditisÀÇ °æ¿ì hypothyroidism sxº¸´Ù goiter°¡ ¸ÕÀú ³ªÅ¸³­´Ù.

Å©Áø ¾ÊÁö¸¸ irrgular & firmÇÏ´Ù.

atrophic thyroiditis³ª Hashimoto's thyroiditisÀÇ late stage´Â hypothyroidismÀÇ sx & sign

À¸·Î ¹ßÇöµÈ´Ù.

ÀüÇüÀû Ư¡Àº puffy face with edematous eyelids & nonpitting pretibial edemaÀÌ´Ù.

myocardial contractility & PR°¨¼Ò·Î SVÀÌ °¨¼ÒÇϰí, bradycardia°¡ »ý±ä´Ù.

peripheral resistace°¡ Áõ°¡ÇÏ¿© hypertension(ƯÈ÷ diastolic)ÀÌ »ý±ä´Ù.

pericardial effusion(30%)ÀÌ »ý±æ¼ö ÀÖÀ¸³ª cardiac function¿¡´Â Àå¾Ö¸¦ ÁÖÁö ¾Ê´Â´Ù.

carpal tunnel syndrome & other entrapment syndrome, slow tendon reflex relaxation,

pseudomyotonia

´Ù¸¥ autoimmune disease°¡ µ¿¹ÝµÇ±âµµ ÇÑ´Ù.

: ƯÈ÷ vitiligo, pernicious anemia, Addison's disease, alopecia areata, type 1 DM

thyroid-associated ophthalmopathy´Â Graves' disease¿¡¼­ ÈçÇϸç autoimmune

hypothyroidism¿¡¼± 5%Á¤µµ¿¡¼­ º¼¼ö ÀÖ´Ù.

5) Lab

* Fig 330-5 Hypothyroidism evaluation

TSH°¡ Áõ°¡ÇØ ÀÖÀ¸¸é free T4¸¦ ÃøÁ¤ÇÑ´Ù.

(°¨¼Ò½Ã clinical hypothyroidism, Á¤»ó½Ã subclinical hypothyroidism)

ÀÏ´Ü clinical or subclinical hypothyroidismÀ¸·Î Áø´ÜÀÌ µÇ¸é TPO Ab¸¦ ÃøÁ¤ÇÑ´Ù.

autoimmune hypothyroidismÀÇ 90-95%¿¡¼­ ¾ç¼º

TBII : 10-20%

goiterÀÇ ¿øÀÎÀÌ Àǽɽº·´´Ù¸é È®ÁøÀ» À§ÇØ FNA¸¦ ½ÃÇàÇÒ¼öµµ ÀÖ´Ù.

other abnormal lab: CPK, cholesterol, TG¡è, anemia

6) °¨º°Áø´Ü

asymmetric goiter in Hashimoto's thyroiditis

: multinodular goiter or thyroid carcinoma¿Í È¥µ¿

-> USG½ÃÇàÇϸé solitary lesionÀÎÁö multinodular goiterÀÎÁö¸¦ º¼¼ö ÀÖ´Ù.

focal noduleÀ» Á¶»çÇÒ ¶§ FNA biopsy¸¦ ½ÃÇàÇÒ¼ö ÀÖ´Ù.

7) hypothyroidismÀÇ ´Ù¸¥ ¿øÀÎ

¨ç iatrogenic hypothyroidism

radioiodine tx 3-4°³¿ùÈÄ¿¡ transient hypothyroidismÀÌ »ý±æ¼ö ÀÖÀ¸¸ç À̶§´Â

cellular destruction¿¡ ÀÇÇÑ °ÍÀÌ ¾Æ´Ï¶ó radiation damage¿¡ ÀÇÇÑ °ÍÀ̹ǷΠ°¡¿ªÀûÀÌ´Ù.

subtotal thyroidectomyÈÄ mild hypothyroidismÀÌ »ý±æ¼ö Àִµ¥ ÀÌ ¶ÇÇÑ ¼ö°³¿ùÈÄ

ȸº¹µÈ´Ù.

¨è iodine deficiency

endemic goiterÀ¯¹ß

¸ð¼øµÇ°Ôµµ iodine excessÀ϶§µµ goiter & hypothyroismÀ» ÀÏÀ¸Å³¼ö ÀÖ´Ù(±âÀüÀº

Àß ¸ð¸§).

¿¹> amiodarone Ä¡·áȯÀÚÀÇ 13%, lithium

¨é secondary hypothyroidism

ant. pituitary hormonal deficiency

8) Ä¡·á

¨ç clinical hypothyroidism

residual thyroid functionÀÌ ¾øÀ»¶§ levothyroxine 1.5 ug/kg(100-150ug)

residual thyroid functionÀÌ ÀÖÀ¸¸é lower dose

60¼¼ ¹Ì¸¸, heart disease°¡ ¾øÀ» ¶§ : 50-100 ug(TSH level¿¡ µû¶ó Á¶Àý)

normal TSH levelÀ» ȸº¹ÇÑÈÄ 3-6°³¿ùÀÌ Áö³ª¾ß ¿ÏÀüÇÑ Áõ»óÀÇ È¸º¹À» °æÇèÇÑ´Ù.

TSH°¡ ³ô´Ù¸é 12.5-25 ugÁõ·®ÇÏ°í ³·´Ù¸é ¹Ý´ë·Î °¨·®ÇÑ´Ù.

TSH levelÀÌ stableÇÏ´Ù¸é ¸Å 2-3³â¸¶´Ù ÃøÁ¤°£°ÝÀ» ´Ã¸°´Ù. À̶§ compliance¸¦ À¯ÁöÇÏ´Â

°ÍÀÌ Áß¿äÇÏ´Ù.

* ¿ë·®À» ¿Ã·Á¾ß ÇÏ´Â °æ¿ì

: malabsorption(celiac disease or small-bowel surgery)

T4 Èí¼ö¸¦ ¹æÇØÇÏ´Â ¾à or clearance¸¦ Áõ°¡½ÃŰ´Â ¾à

(cholestyramine, ferrous sulfate, calcium supplement, lovastatin, aluminum hydroxide,

rifampin, amiodarone, carbamazepine, phenytoin)

¨è subclinical hypothyroidism

TPO Ab°¡ ¾ç¼ºÀ̸é overt hypothyroidismÀ¸·Î ÁøÇàÇÒ À§ÇèÀÌ ÀÖ´Ù.

TSH¸¦ Á¤»óÈ­½ÃŰ´Â °ÍÀ» ¸ñÇ¥·Î levothyroxine low dose(25-50ug/d)·Î Ä¡·á¸¦

½ÃÀÛÇÑ´Ù.

¨é special considerations

i) pseudotumor cerebri in children : rare

Ä¡·á ¼ö°³¿ùÈÄ °©Àڱ⠹߻ý

ii) hypothyroidism history³ª °¡´É¼º ³ôÀº ¿©¼º

ÀÓ½ÅÃʱ⿡ hypothyroidismÀº fetal neuronal development¿¡ ¾Ç¿µÇâÀ» ³¢Ä¡¹Ç·Î ÀÓ½ÅÀü

euthyroid state¸¦ À¯ÁöÇØ¾ß ÇÑ´Ù. ¿ë·®Àº 50%ÀÌ»ó Áõ·®ÇÏ¿´´Ù°¡ ºÐ¸¸ÈÄ¿£ ÀÌÀü level·Î

ÇÑ´Ù.

iii) ³ëÀÎ, ƯÈ÷ coronary artery disease°¡ ÀÖÀ» ¶§

12.5-25 ug/d·Î ½ÃÀÛÇÏ¿© TSH°¡ Á¤»óÈ­µÉ¶§±îÁö 2-3°³¿ù¸¶´Ù Áõ·®

iv) emergency surgery

untreated hypothyroidism¿¡¼­ ÀϹÝÀûÀ¸·Î ¾ÈÀüÇÏ´Ù.

v) myxedema coma : high mortality rate

³ëÀο¡¼­ ÈçÈ÷ »ý±â°í º¸ÅëÀº respiratory impairment¿¡ ÀÇÇØ Ã˹ߵȴÙ.

drug(sedatives, anesthetics, antidepressant), pneumonia, CHF, MI,

GI bleeding or CVA, sepsis, cold exposure

hypoventilation(-> hypoxia, hypercapnia)ÀÌ pathogenesis¿¡ Áß½ÉÀû ¿ªÇÒÀ» ÇÑ´Ù.

hypoglycemia, dilutional hyponatremia¶ÇÇÑ myxedema ¹ß»ý¿¡ ±â¿©ÇÑ´Ù.

*Ä¡·á

a. levothyroxine 500 ug IV(loading) or via NG tube -> 50-100 ug/d

alternative, T3 IV or via NG tube 10-25 ug q 8-12 hr(ºÎÁ¤¸Æ À¯¹ß°¡´É)

T4(200ug) + T3(25ug) -> T4(50-100ug) + T3(10ug q 8hr)

b. supportive tx : metabolic disturbance±³Á¤(external warmingµî)

c. hydrocortisone(50mg q 6hr) IV

d. precipitating factorÄ¡·á

broad-spectrum antibioticsÁ¶±â»ç¿ë

ventilatory support

hypertonic saline or IV glucose : hyponatremia or hypoglycemiaÀÖÀ» ¶§

hypotonic fluid´Â »ç¿ëÇÏÁö ¸» °Í: reduced renal perfusion & inappropriate

vasopressin secretionÀ¸·Î water retentionÀ» ¾ÇÈ­½Ãų¼ö ÀÖÀ¸¹Ç·Î

Thyrotoxicosis

thyrotoxicosis : the state of thyroid hormone excess

hyperthyroidism: excessive thyroid function

Tab 330-6 ¿øÀÎ

Graves' disease

1) ¿ªÇÐ thyrotoxicosisÀÇ 60-80%, ÁÖ·Î iodine intake¿Í °ü·ÃÀÖ´Ù.

(high iodine intake = increased prevalence of Graves' disease)

20-50¼¼¿¡ ÈçÇÏ´Ù. ¿©¼º>³²¼º(10¹è)

2) º´ÀÎ

TSI¿¡ ÀÇÇØ ¹ß»ýÇÑ´Ù.

extrathyroidal manifestation(ophthalmopathy & dermopathy)˼ extraocular muscle & skin

¿¡ immunologically mediated fibroblast activation, glycosaminoglycans accumulation->

water trapping & edema·Î ÀÎÇÏ¿© »ý±ä´Ù. ³ªÁß¿¡´Â fibrosis°¡ µÎµå·¯Áø´Ù.

locally infiltrating T cell & macrophage¿¡¼­ ³ª¿À´Â cytokine(IFN-¥ã, TNF, IL-1)¿¡ fibroblast

activationµÈ´Ù.

3) ÀÓ»ó¹ßÇö Tab 330-7 Thyrotoxicosis sx & sign

³ëÀο¡¼­ thyrotoxicosisƯ¡ÀÌ maskµÇ°í ÁÖ·Î fatigue & weight loss°¡ ÁÖ·Î ³ªÅ¸³¯ ¼ö

ÀÖ´Ù.(="apathetic hyperthyroidism")

mc cardiovascular manifestation: sinus tachycardia

ÀÚÁÖ palpitation, ¶§·Î SVT°¡ µ¿¹ÝµÈ´Ù.

high COÀ¸·Î ÀÎÇÏ¿© bounding pulse, widened pulse pressure, aortic systolic murmur¸¦

ÀÏÀ¸Å°°í preexisting heart disease, ³ëÀο¡¼­ angina or heart failure¸¦ ¾ÇÈ­½Ãų¼ö ÀÖ´Ù.

50¼¼ À̻󿡼­ AF°¡ ÈçÇÏ´Ù.

thyrotoxicosis¸¸ Ä¡·áÇÏ¿´À» ¶§ NSRÀ¸·Î ÀüȯµÇ´Â °ÍÀº ¹Ý¼ö ¹Ì¸¸Àε¥ ÀÌ´Â ³ª¸ÓÁö¿¡¼­

underlying cardiac problemÀÌ ÀÖÀ½À» ÀǹÌÇÑ´Ù.

skin : warm & moist, sweating, heat intolerance

Graves' ophthalmopathy: 75%¿¡¼­ Áø´ÜÀüÈÄ 1³â³»¿¡ ÁÖ·Î »ý±â±â¸¸ ¶§·Î´Â thyrotoxicosis

°¡ »ý±â±â Àü¿¡ »ý±â±âµµ Çϰí, ¼ö³âÈÄ¿¡ »ý±â±âµµ ÇÑ´Ù.

thyroid dermopathy(<5%) : pretibial myxedema

thyroid acropathy(<1%)

4) Lab Fig 330-7

2-5%´Â T3¸¸ Áõ°¡ÇÑ´Ù(T3 thyrotoxicosis)

5) °æ°ú

Ä¡·áÇÏÁö ¾ÊÀ¸¸é ¾ÇÈ­µÇ¸ç 10-30% mortality¸¦ º¸ÀδÙ.

Ä¡·áÈÄ remissionµÈ ȯÀÚÀÇ 10-15³âÈÄ hypothyroidismÀ¸·Î µÈ´Ù.

ophthalmopathy´Â thyroid disease°æ°ú¸¦ µû¸£Áö ¾Ê´Â´Ù.

: ù 3-6°³¿ù°£ ¾ÇÈ­µÇ´Ù°¡ ±×ÈÄ 12-18°³¿ù°£ plateau phase, ±×ÈÄ spontaneous

improvement

5%¿¡¼­´Â fulminant·Î ÁøÇàÇÏ¿© interventionÀÌ ÇÊ¿äÇÏ´Ù(optin n. compression or corneal

ulceration)

extraocular m. fibrosis·Î ÀÎÇØ Èı⿡ diplopia¹ß»ý

RI Ä¡·áÈÄ eye disease°¡ ¾ÇÈ­µÇ¾ú´Ù´Â ¿¬±¸°¡ ÀÖ´Ù(ƯÈ÷ smoker¿¡¼­).

antithyroid drug or surgery´Â ophthalmopathy°æ°ú¿¡ ¾Ç¿µÇâÀ» ³¢Ä¡Áö ¾Ê´Â´Ù.

6) Ä¡·á

¨ç antithyroid drug(PTU, carbimazole, methimazole)

TPO inhibition½ÃÄÑ oxidation, organificationÀ» ÀúÇØÇÔ

Àß ¸ð¸£´Â ¾î¶² ±âÀü¿¡ ÀÇÇØ thyroid Ab levelµµ °¨¼Ò½ÃÅ´

i) PTU(1T=50mg) T4->T3 deiodination inhibition(minor benefit)

¹Ý°¨±â(90ºÐ) cf. methimazole(6hr)

100-200 mg q 6-8hr(300-600mg)

ii) carbimazole or methimazole(1T=5mg) 10-20mg q 8-12hr(20-60mg)

euthyroidismµµ´ÞÈÄ¿£ ÇÏ·ç Çѹø °¡´É

"block-replace regimen"

drug-induced hypothyroidismÀ» ÇÇÇϱâ À§ÇØ high dose antithyroid drug°ú

levothyroxineÀ» ÇÔ²² Åõ¿©ÇÏ´Â °ÍÀ» ¸»Çϴµ¥ Ãʱ⿣ remission rate°¡ ³ô´Ù°í

ÇÏ¿´À¸³ª ´Ù¸¥ ¿¬±¸¿¡¼­´Â ¾Æ´Ï¾ú´Ù.

´ëºÎºÐ Ä¡·á½ÃÀÛÈÄ 6-8ÁÖÈÄ¿¡³ª euthyroidism¿¡ µµ´ÞÇϸç TSH´Â ¼ö°³¿ùµ¿¾È ¾ïÁ¦µÈ

»óÅ·ΠÀÖ´Ù. ±×·¯¹Ç·Î TSH°¡ Ä¡·á¹ÝÀÀÀÇ ¹Î°¨ÇÑ ÁöÇ¥·Î »ç¿ëµÉ¼ø ¾ø´Ù.

* À¯Áö¿ë·®

carbimazole or methimazole: 2.5-10mg, PTU: 50-100mg

* maximum remission rate: 30-50%(18-24°³¿ùÈÄ)

* severe hyperthyroidism & large goiter

Ä¡·áÁß´ÜÈÄ Àç¹ßÇϱ⠽¬¿ì³ª °á°ú¸¦ ¿¹ÃøÇϱâ´Â ¾î·Æ´Ù.

* common S/E : rash, urticaria, fever, arthralgia(1-5%)

ÀúÀý·Î ¾ø¾îÁö°Å³ª ´Ù¸¥ ¾àÀ¸·Î ¹Ù²Ù¸é ¾ø¾îÁø´Ù.

rare but major S/E: hepatitis, SLE-like syndrome, agranulocytosis(most important,

<1%)

¾àÁ¦¸¦ Áï½Ã Áß´ÜÇØ¾ß ÇÏ¸ç ´Ù½Ã »ç¿ëÇØ¼­´Â ¾ÈµÈ´Ù.

¨è propranolol(20-40mg q 6hr) or atenolol

adrenergic system control, ƯÈ÷ antithyroid drugÀÌ effect¸¦ ³ªÅ¸³»±âÀü Ãʱ⿡ »ç¿ë

¨é anticoagulation with warfarin

AF°¡ µ¿¹ÝµÈ ¸ðµç ȯÀÚ¿¡¼­ »ç¿ë

¨ê radioiodine

thyroid crisis risk°¡ ´Ù¼Ò ÀÖ´Ù. µû¶ó¼­ antithyroid drugÀ» ÃÖ¼Ò 1°³¿ùÀÌ»ó Ä¡·áÇÔÀ¸·Î½á

ÇÇÇÒ¼ö ÀÖ´Ù. ¸ðµç ³ëÀÎ & cardiac problemÀִ ȯÀÚ¿¡¼­ antithyroid drugÀ» °í·ÁÇÏ¿©¾ß

ÇÑ´Ù.

RIÅõ¿©Àü 3-5Àϰ£ antithyroid drugÀ» Áß´ÜÇÏ¿©¾ß Çϴµ¥ optimum iodine intake¸¦ ¾ò±â

À§Çؼ­ÀÌ´Ù.

*¿ë·® : È®¸³µÈ °ÍÀº ¾øÀ¸³ª ´ë·« 5 mCi-15mCi

RI°¡ full effect¸¦ ³ªÅ¸³»±â±îÁö 2-3°³¿ù°£Àº hyperthyroidismÀÌ Áö¼ÓÇϹǷΠÀÌ ±â°£¿¡´Â

Áõ»óÀ» Á¶ÀýÇϱâ À§ÇØ ¥â-blocker or antithyroid drugÀ» »ç¿ëÇÒ¼ö ÀÖ´Ù.

persistent hyperthyroidism¶§´Â 2nd dose·Î Ä¡·áÇϴµ¥ À̶§´Â first doseÈÄ 6°³¿ùÈÄ¿¡

½ÃÇàÇÑ´Ù.

Ä¡·áÈÄ hypothyroidismÀÇ ¹ß»ýÀº ¿ë·®°ú »ó°üÀÌ ÀÖÀ¸³ª ´ë·« ù 1³â¿¡ 10-20%, ±×ÈÄ¿£

¸Å³â 5%Á¤µµ µÈ´Ù. µû¶ó¼­ ù 1³â°£Àº close F/UÀÌ ÇÊ¿äÇÏ°í ±× ÈÄ¿£ ¸Å³â TFT¸¦ ½ÃÇà

ÇÑ´Ù.

* pregnancy & breast feeding

radioiodine txÀº Àý´ëÀû ±Ý±â

Ä¡·á 6-12°³¿ùÈÄ¿¡ ÀӽŠȤÀº ¼öÀ¯´Â ¾ÈÀü

* severe ophthalmopathyȯÀÚ´Â ÁÖÀÇÇØ¾ß Çϴµ¥ ÀϺΠÀúÀÚµéÀº RIÄ¡·á½Ã Pd 40mg/d»ç¿ë

ÇÒ °ÍÀ» ±ÇÇÑ´Ù. ±×ÈÄ 2-3°³¿ù°£ tapering

¨ë subtotal thyroidectomy

¼ö¼úÀü antithyroid drugÀ¸·Î thyrotoxicosisÀÇ careful controlÇÊ¿ä

±×ÈÄ potassium iodide(3 drops SSKI orally tid) ÇÊ¿ä(¡ñvascularity¸¦ °¨¼Ò½Ã۱â À§ÇØ)

*major cx : bleeding, laryngeal edema, hypoparathyroidism, recurrent layngeal n.

damage

Àç¹ßÀ² < 2%

¨ì Graves' disease in pregnancy

transplancental transfer°¡ ÀûÀº PTU¸¦ ÀϹÝÀûÀ¸·Î »ç¿ë

ÀӽŽà TSH-R Ab°¡ °¨¼ÒÇϹǷΠlowest effective dose¸¦ »ç¿ëÇØ¾ß Çϸç last trimester

¿£ Ä¡·á Áߴܵµ °¡´ÉÇÏ´Ù. ±×·³¿¡µµ ºÒ±¸Çϰí TSH-R AbÀÇ tranplacental transfer°¡

µå¹°°Ô fetal thyrotoxicosis or neonatal thyrotoxicosis¸¦ ÀÏÀ¸Å³¼öµµ ÀÖ´Ù.

poor intrauterine growth, fetal HR > 60bpm, high levels of maternal TSH-RÀÏ ¶§

fetal thyrotoxicosisÀǽÉ

postpartum period´Â Graves' ds relapseÀÇ major risk time

low doses of antithyroid drugÀº breast feeding½Ã ¾ÈÀüÇÏ´Ù.

¨í thyrotoxic crisis, or thyroid storm

rare, life-threatening exacerbation of hyperthyroidism

fever, delirium, seizure, coma, vomiting, diarrhea, jaundice

* mortality rate ¡­30%

ÁÖ»ç¸Á¿øÀÎ: cardiac failure, arrhythmia, or hyperthermia

* À¯¹ßÀÎÀÚ

acute illness(stroke, infection, trauma, DKA), surgery(ƯÈ÷ thyroid), or

untreated hyperthyroidism¿¡¼­ RI tx

* Ä¡·á : supportive care

large dose PTU(600mg loading -> 200-300 mg q 6hr)

PTUÅõ¿© Çѽð£ÈÄ stable iodideÅõ¿©(Wolff-Chaikoff effect)

saturated solution of potassium iodide(SSKI 5 drops q 6hr)

or ipodate or iopanoic acid(0.5mg q 12hr)

propranolol 40-60mg q 4hr PO or 2mg IV q 4hr

* ophthalmopathy: mild or moderate¶§´Â Àû±ØÀû Ä¡·á°¡ ÇÊ¿ä¾ø´Ù.(¡ñÈçÈ÷

spontaneous improveµÇ¹Ç·Î)

periorbital edema: more upright sleeping position

severe ophthalmopathy(optic n. involvement or chemosis·Î ÀÎÇÑ corneal damage)

¶§´Â ÀÀ±Þ»óȲÀ¸·Î ¾È°úÀÇ»ç¿Í ÇùÁø: high-dose glucocorticoid(Pd 40-80mg/d)·Î 2/3

¿¡¼­ short-term benefit, ¶§·Ð cyclosporine°ú combine

¸Å 1-2ÁÖ¸¶´Ù 5mg¾¿ tapering

ext. beam radiotherapy°¡ »ç¿ëµÇ¾î ¿ÔÀ¸³ª equivocal

* thyroid dermopathy: Ä¡·á°¡ ÇÊ¿ä¾ø´Ù.

Other causes of thyrotoxicosis

¨ç subacute or silent thyroiditis: circulating Tg, IL-6¡è

¨è thyrotoxicosis factitia : Tg¡é

¨é ectopic thyroid tissue(ƯÈ÷ ovarian teratoma = struma ovarii)

¨ê functional metastatic follicular carcinoma

¨ë amiodarone treatment(10%) ƯÈ÷ low iodine intake area¿¡

¨ì TSH-secreting pituitary adenoma

: TSHÀÇ ¥á subunit¡è

¨í toxic multinodular goiter

¨î hyperfunctioning solitary nodules

Thyroiditis

1. Acute thyroiditis : rare, supprative infection¶§¹®

1) mc cause: children & young adults - pyriform sinus

elderly - long-standing goiter & thyroid malignancy degeneration

2) DDx(thyroid pain)

subacute thyroiditis, rarely, chronic thyroiditis, hemorrhage into a cyst, malignancy

including lymphoma, rarely, amiodarone-induced thyroiditis or amyloidosis

3) Lab ESR¡è, WBC¡è, normal thyroid function, FNA: PMNL¡è, culture: organism(+)

4) Áï°¢ antibiotic tx

2. Subacute thyroiditis

= de Quervain's thyroiditis, granulomatous thyroiditis, or viral thyroiditis

: mumps, coxsackievirus, influenza, adenovirus, echovirus

30-50¼¼, F>M(3¹è)

1) º´Å»ý¸®

pathy inflammatory infiltrate with disruption of thyroid follicles and multinucleated giant

cells within some follicles

granuloma + fibrosis, Á¤»óÀ¸·Î ȸº¹Çϴµ¥ ¼ö°³¿ù ¼Ò¿ä

¨ç initial phase(thyrotoxic phase) Tg & thyroid hormone release

-> circulating free T4 & T3¡è, TSH suppression, RAIU¡é

¨è ¼öÁÖÈÄ hypothyroid phase: hypothyroism¹ß»ý, free T4¡é, TSH¡è, RAIU : Á¤»ó ȤÀº ¾à°£ ¡è

¨é recovery phase: thyroid hormone, TSH Á¤»óÈ­

2) ÀÓ»ó¹ßÇö painful & enlarged thyroid, ¶§·Ð fever

º´±â¿¡ µû¶ó thyrotoxicosis or hypothyroidism

´ëºÎºÐ ¿ÏÀüÈ÷ ȸº¹µÇ³ª ÀϺο¡¼­´Â permanent hypothyroidismÀÌ ¹ß»ýÇÒ¼öµµ Àִµ¥

ÀÌ·± °æ¿ì´Â ƯÈ÷ thyroid autoimmunity°¡ µ¿¹ÝµÈ °æ¿ìÀÌ´Ù.

3) Lab *3 distinctive phases(6°³¿ù °£°Ý)

thyrotoxic phase --> hypothyroid phase -> recovery phase

(IL-6¡è)

4) Ä¡·á

¨ç large dose aspirin(600mg q 4-6hr) or NSAID

¨è glucocorticoid : aspirin or NSAID·Î ºÒÃæºÐÇϰųª Áõ»óÀÌ Áö¼ÓµÇ¸é Pd 40-60mg/d

-> 6-8ÁÖ¿¡ °ÉÃÄ tapering

RAIU°¡ Á¤»óÈ­µÇ¸é Ä¡·á¸¦ Áß´ÜÇÑ´Ù(Áõ»óÀ¸·Î Ä¡·áÁß´Ü¿©ºÎ °áÁ¤ÇÏ´Â °Í ¾Æ´Ô)

¨é ¥â-blocker: thyrotoxic sx control

thyrotoxic phase¶§ antithyroid drugÀº »ç¿ëÇÏÁö ¾ÊÀ¸¸ç

hypothyroid phase¶§ low dose(50-100ug/d) levothyroxineÀ» »ç¿ëÇÒ¼ö ÀÖ´Ù.

3. Silent thyroiditis(=painless thyroiditis)

ÀÓ½ÅÈÄ 3-6°³¿ùÈÄ¿¡ °¡Àå ÈçÈ÷ ¹ß»ýÇϹǷΠpostpartum thyroiditis¶ó ÇÑ´Ù.

thyrotoxocosis phase(2-4ÁÖ) -> hypothyroidism(4-12ÁÖ) -> resolution

* subacute thyroiditis¿ÍÀÇ °¨º°Á¡: painless goiter, normal ESR, TPO Ab(+)

glucocorticoid´Â not indicated

severe thyrotoxic sxÀÌ ÀÖÀ» ¶§ propranolol 20-40mg tid or qid

hypothyroid phase¶§ thyroxine replacement(6-9°³¿ùÈÄ Áß´Ü), ±×ÈÄ annual F/U

4. Drug-induced thyroiditis

: IFN-¥á, IL-2, or amiodarone => painless thyroiditisÀ¯¹ß

¨ç IFN-¥á : chronic hepatitis B, CÀÇ Ä¡·áÁ¦·Î »ç¿ëµÇ¸ç 5%¿¡¼­ thyroid dysfunctionÀ»

ÀÏÀ¸Å²´Ù.

painless thyroiditis, hypothyroidism, Graves' disease

¨è IL-2 : malignancyÄ¡·á¿¡ ÀÌ¿ëµÇ¸ç, thyroiditis, hypothyroidismÀÏÀ¸Å´

¨é amiodarone : amiodaroneÆí ÂüÁ¶

5. chronic thyroiditis

mc = Hashimoto's thyroiditis

Riedel's thyroiditis : rare disorder, Á߳⿩¼º¿¡¼­ ¼­¼­È÷ ¹ß»ýÇÏ´Â painless goiter with

local sx(compression sx)

open biopsy·Î Áø´Ü, ¼ö¼úÀû Ä¡·á

Sick euthyroid syndrome

1. Á¤ÀÇ

acute, severe illness°¡ ÀÖÀ» ¶§ underlying thyroid disease°¡ ¾ø´Â »óÅ¿¡¼­ circulating

TSH or thyroid hormone level¿¡ ÀÌ»óÀ» ÃÊ·¡ÇÏ´Â °ÍÀ» ¸»ÇÑ´Ù.

ÀÌ·¯ÇÑ hormonal change¸¦ ÀÏÀ¸Å°´Â ´ëÇ¥Àû ¿øÀÎÀº "cytokine release"ÀÌ´Ù.

acutely ill patient¿¡¼­ thyroid disorder°¡ °­·ÂÈ÷ ÀǽɵÇÁö ¾Ê´Â´Ù¸é routine TFT´Â ÇÏÁö

¸»¾Æ¾ß ÇÑ´Ù.

2. ÇüÅÂ

1) low T3 syndrome(total & free T3 °¨¼Ò) with normal T4 & TSH level : most common

T3°¨¼ÒÁ¤µµ´Â illness severity¿Í ºñ·Ê

T4->T3·ÎÀÇ Àüȯ½ÇÆÐ·Î rT3Áõ°¡

TRH stimulation¿¡ ´ëÇÑ TSHÀÇ ¹ÝÀÀÀº Á¤»ó

2) low T4 syndrome

very sick patient¿¡¼­ total T4 & T3 level¸ðµÎ °¨¼ÒµÇ¸ç poor prognosis

TBG°¡ °¨¼ÒÇϱ⠶§¹®À̸ç, free T4´Â Á¤»ó level

TSH levelÀº <0.1 ¡­ >20 mU/L±îÁö ´Ù¾ç

TRH¿¡ ´ëÇÑ TSHÀÇ ¹ÝÀÀÀº blunting

3. ¿¹

1) acute liver disease: TBG releaseÁõ°¡·Î óÀ½¿¡´Â total T3, T4 levelÀÌ Áõ°¡µÇ´Ù°¡

liver failure°¡ ÁøÇàµÇ¸é¼­ Á¡Â÷ subnormal

2) acutely ill psychiatric patientÀÇ 5-30%¿¡¼­ ÀϽÃÀûÀ¸·Î total & free T4Áõ°¡, normal T3,

TSH °¨¼Ò, Á¤»ó, ȤÀº Áõ°¡

3) HIV infection

Ãʱ⿣ T3, T4Áõ°¡, ÁøÇàÇϸ鼭 T3°¨¼Ò, TSH´Â º¸Åë Á¤»ó

4) renal disease

T3¡é, rT3 normal ¡ñÀß ¸ð¸£´Â ¾î¶² ±âÀüÀ¸·Î liver·ÎÀÇ uptake°¡ Áõ°¡ÇϹǷÎ

4. Áø´Ü

thyroid diseaseÀÇ °ú°Å·ÂÀÌ ÀÖ´ÂÁö È®ÀÎ.

acutely illness severityÆò°¡

5. Ä¡·á

thyroid hormoneÄ¡·á¿¡ ´ëÇØ¼­´Â controversial. ´ëºÎºÐÀÇ ÀúÀÚµéÀº È£¸£¸óÀ» Åõ¿©ÇÏÁö

¸»°í thyroid functionÀ» monitoringÇÒ °ÍÀ» ÃßõÇÑ´Ù.

Amiodarone effects on thyroid function

1) °³¿ä

amiodaroneÀº type III antiarrhythmic agent·Î ±¸Á¶ÀûÀ¸·Î thyroid hormone°ú °ü·ÃÀÖÀ¸¸ç,

iodineÀÌ 39%³ª ÇÔÀ¯µÇ¾î ÀÖ´Ù. µû¶ó¼­ ÀϹÝÀûÀÎ amiodarone¿ë·® 200mg/d¿¡´Â »ó´ç·®ÀÇ

iodineÀÌ ÇÔÀ¯µÇ¾î plasma & urinary iodine levelÀÌ 40¹èÀÌ»ó Áõ°¡ÇÑ´Ù. adipose tissue¿¡

ÀúÀåµÇ¹Ç·Î ¾àÀ» Áß´ÜÈÄ¿¡µµ 6°³¿ù ÀÌ»ó high iodine levelÀÌ Áö¼ÓµÈ´Ù. amiodaroneÀº

deiodinase activity¸¦ ¾ïÁ¦Çϰí, thyroid hormone antagonist·Î¼­ ÀÛ¿ëÀ» ÇÑ´Ù.

2) multiple effects

¨ç acute, transient changes in thyroid function

¨è hypothyroidism : °¨¼ö¼º Àִ ȯÀÚ¿¡¼­

¨é thyrotoxicosis i) Jod-Basedow effect

ii) thyroiditis-like condition

iii) autoimmune Graves' disease induction

óÀ½¿£ ÀϽÃÀûÀ¸·Î T4°¡ °¨¼ÒÇÏ´Ù°¡ ±×ÈÄ iodine-dependent suppression of the

thyroid(Wolff-Chaikoff effect), deiodinase activity, thyroid hormone receptor actionÀÇ

inhibitory effects°¡ µÎµå·¯Áø´Ù. ±× °á°ú TFT¸¦ ½ÃÇàÇϸé T4¡è, T3¡é, rT3¡è, TSH ÀϽÃÀûÀ¸·Î

Áõ°¡(20mU/L±îÁö)

TSH´Â 1-3°³¿ùÈıîÁö Á¤»óÈ­ ȤÀº ¾à°£ °¨¼Ò

3) amiodarone-induced thyrotoxicosis(AIT)

low-iodine intake Áö¿ª¿¡¼± 10%, high-iodine intake Áö¿ª¿¡¼± 2%

°©»ó¼± È£¸£¸óÀÌ Áõ°¡ÇÔÀ¸·Î½á underlying arrhythmia & coronary a. disease¸¦ ¾ÇÈ­½ÃŲ´Ù.

¨ç type 1 AIT : underlying thyroid abnormality(+)(preclinical Graves' ds or nodular goiter)

Jod-Basedow phenomenon¿¡ ÀÇÇØ thyroid hormone synthesis¡è

¨è type 2 AIT : no intrinsic thyroid abnormality

drug-induced lysosomal activation -> destructive thyroiditisÀ¯¹ß

ÀúÀý·Î ȸº¹Çϰųª hypothyroidismÀ» À¯¹ßÇÒ¼ö ÀÖ´Ù.

IL-6 level¡è¡è(type 1 AIT¿¡¼­´Â ¾à°£ Áõ°¡)

AIT¿¡¼± amiodaroneÀ» Áß´ÜÇØ¾ß ÇÑ´Ù. ±×·¸Áö¸¸ ¹Ý°¨±â°¡ ±æ±â ¶§¹®¿¡ Áï½Ã Áß´ÜÈ¿°ú°¡

³ªÅ¸³ªÁø ¾Ê´Â´Ù. type 1 AIT¿¡¼­ high dose antithyroid drugÀ» »ç¿ëÇÒ¼ö ÀÖÁö¸¸ º¸Åë

È¿°ú´Â ¾ø´Ù.

* Ä¡·á

i) potassium perchlorate 200mg q 6hr : thyoid iodide content¸¦ °¨¼Ò½Ã۱â À§ÇØ

»ç¿ëµÇ³ª agranulocytosis¸¦ ÀÏÀ¸Å³¼ö ÀÖ´Ù.

ii) glucocorticoid: subacute thyroiditis¿¡¼­Ã³·³ Åõ¿©ÇÑ´Ù.

iii) lithium: thyroid hormone release block

iv) near-total thyroidectomy : thyoid hormone levelÀ» ±Þ°ÝÈ÷ °¨¼Ò½Ã۸ç most effective

long-term solution

Thyroid function in pregnancy

* factors

¨ç transient hCG increase(1st trimester)

TSH-RÀÚ±Ø -> TSH¡é(ÀÓ½ÅÁ߹ݱîÁö)

transient gestational hyperthyroidism and/or hperemesis gravidarumÀ» ÀÏÀ¸Å°±âµµ ÇÑ´Ù.

¨è estrogen¿µÇâÀ¸·Î TBGÁõ°¡

1st trimester¶§ Áõ°¡µÇ¾î Àӽų»³» Áö¼Ó

¨é urinary iodine excretionÁõ°¡

marginal iodine sufficiency area¿¡¼­ thyroid hormone productionÀå¾ÖÃÊ·¡

ÀÓ½ÅÁß iodine intake(<50ug)°¡ ºÎÁ·ÇÑ ¿©¼ºÀº goiter¹ß»ýÀ§ÇèÀÌ ³ôÀ¸¸ç, maternal and fetal

hypothyroidism, neonatal goiter¸¦ ¿¹¹æÇϱâ À§ÇØ iodine º¸ÃæÀÌ ÇÊ¿äÇÏ´Ù.

Àӽſ©¼ºÀÇ 2-3%¿¡¼­ maternal hypothyroidismÀÌ ¹ß»ýÇϸç ÀÚ³à ¹ß´Þ Áö¿¬À» ÃÊ·¡ÇÒ

À§ÇèÀÌ ³ô´Ù.

ÀÓ½ÅÁÖ thyroid hormone ¿ä±¸·®Àº 25-50 ug/d Áõ°¡ÇÑ´Ù.

cf. TSH, thyroid H: ŹÝÅë°ú¡¿

Goiter and nodular thyroid disease

goiter: thyroid gland enlargement

biosynthetic defect, iodine deficiency, autoimmune disease(Graves' disease,

Hashimoto's thyroiditis), nodular diseaseÀÏ ¶§ goiter¸¦ ÀÏÀ¸Å³¼ö ÀÖ´Ù.

nodular thyroid disease´Â ÈçÇÏ´Ù: ¼ºÀο¡¼­ P/E·Î 3-7%, USG·Î´Â 25%¿¡¼­ ¹ß°ß

1. Diffuse nontoxic(simple) goiter

1) ¿øÀÎ ¹× º´ÀÎ

iodine deficiency¿¡ ÀÇÇØ °¡Àå ÈçÈ÷ ¹ß»ýÇϸç Àα¸ÀÇ 5%ÀÌ»óÀÌ »ý±æ ¶§ endemic goiter¶ó

ÇÑ´Ù.

2) ÀÓ»ó Áõ»ó ¹× Áø´Ü

´ëºÎºÐ ¹«Áõ»óÀ̸ç Å©±â°¡ ³Ê¹« Å©¸é compression sxÀ» ÀÏÀ¸Å³¼ö ÀÖ´Ù.

substernal goiter´Â thoracic inlet obstructionÀ» ÀÏÀ¸Å³¼ö ÀÖ´Ù.

TFT : iodine deficiency¿¡¼­ total T4¡é, normal T3

³ëÀο¡¼­ low TSH levelÀÏ ¶§ undiagnosed Graves' disease or thyroid autonomy

°¡´É¼ºÀ» »ý°¢Çغ¸¾Æ¾ß ÇÑ´Ù(subclinical thyrotoxicosis)

low uninary iodine levels(<100 ug/L) : iodine deficiencyÁø´Ü

thyroid scan: ÀϹÝÀûÀ¸·Î ÇÊ¿äÄ¡ ¾ÊÀ¸¸ç uptake°¡ Áõ°¡µÈ´Ù.

USG: P/E¿¡¼­ noduleÀÌ ¸¸Á®ÁöÁö ¾Ê´Â´Ù¸é diffuse goiter Áø´Ü¸ñÀûÀ¸·Î´Â ÇÊ¿äÄ¡ ¾Ê´Ù.

3) Ä¡·á

iodine deficiency: iodine or thyroid hormone replacement

other cause: levothyroxine young-100(ug/d), elderly(50ug/d)

3-6°³¿ù ³»¿¡ ÈçÈ÷ significant regressionµÇ¸ç ±×ÈÄ¿¡´Â Àß ÀϾÁö ¾Ê´Â´Ù.

2. Nontoxic multinodular goiter

1) ¿øÀÎ ¹× º´ÀÎ

Àα¸ÀÇ 1-12%, ¿©¼º¿¡¼­ ´õ ÈçÇÏ°í ³ªÀ̰¡ µé¸é¼­ Áõ°¡ÇÑ´Ù.

iodine-deficient region¿¡¼­ ´õ ÈçÇÏÁö¸¸ iodine-sufficient region¿¡¼­µµ ¹ß»ýÇÑ´Ù.

=> multiple genetic, autoimmune, environmental influence°¡ °ü¿©ÇÔÀ» ÀǹÌ

2) ÀÓ»ó¹ßÇö

´ëºÎºÐ ¹«Áõ»óÀ̸ç, ¼ö³âÀÌ»ó¿¡ °ÉÃÄ »ý±â°í ÁøÂûÀ̳ª, ¸ñÀÌ Ä¿Á® ¹ß°ßµÈ´Ù.

³Ê¹« Å©¸é compressive sxÀ» ÀÏÀ¸Å²´Ù.

sudden pain¹ß»ý½Ã nodule³»·ÎÀÇ hemorrhage °¡´É¼ºÀÌ ¸¹À¸³ª, ¹Ýµå½Ã invasive

malignancy°¡´É¼ºµµ »ý°¢ÇØ¾ß ÇÑ´Ù. hoarseness(=laryngeal nerve paralysis)¶§µµ

malignancy¸¦ ÀǽÉÄÉ ÇÑ´Ù.

3) Áø´Ü

MNG´Â thyroid cancer or more aggressive caÀÇ ¼±ÇàÀÎÀÚ°¡ ¾Æ´Ï´Ù.

nodular lesion¿¡ ´ëÇØ ¸ðµÎ biopsy¸¦ ÇÒ ¼ö´Â ¾øÀ¸¸ç dominant or enlarging noduleÀÌ

malignancy°¡ ÀÇ½ÉµÉ ¶§ biopsy¸¦ ½ÃÇàÇÑ´Ù.

4) Ä¡·á

¨ç ´ëºÎºÐ º¸Á¸Àû Ä¡·á¸¦ Çϸç T4 suppressionÀº goiter size¸¦ ÁÙÀ̴µ¥ °ÅÀÇ È¿°ú°¡ ¾ø´Ù.

¸¸¾à levothyroxineÀ» »ç¿ëÇÑ´Ù¸é low dose(50ug)À¸·Î ½ÃÀÛÇϰí excessive suppression

µÇÁö ¾Êµµ·Ï ÇÑ´Ù. contrast agent³ª ´Ù¸¥ iodine-containing substance´Â ÇÇÇϵµ·Ï ÇÑ´Ù.

(¡ñJod-Basedow effect¸¦ ÀÏÀ¸Å³ À§Ç輺ÀÌ Áõ°¡ÇϹǷÎ)

¨è RI

»ç¿ëºóµµ°¡ Áõ°¡µÇ°í Àִµ¥ goiter size¸¦ ÁÙ¿©ÁÖ°í autonomy regionÀ» ¼±ÅÃÀûÀ¸·Î

ablation½Ã۱⠶§¹®ÀÌ´Ù.

´ë·« 0.1 mCi/tissue 1g(10-29 mCi), ÇÊ¿ä½Ã repeat tx, ´ëºÎºÐÀÇ È¯ÀÚ¿¡¼­ 40-50%

reduction

radiation-induced thyroid swelling & tracheal compressionÀº µå¹°Áö¸¸ »ý±æ¼ö Àִµ¥

ÀÌ·± acute compression¹ß»ý½Ã glucocorticoid or surgery°¡ ÇÊ¿äÇÒ¼öµµ ÀÖ´Ù.

radiation-induced hypothyroidismÀº µå¹°°í posttreatment autoimmune thyrotoxicosis

°¡ 5%¿¡¼­ »ý±æ¼ö ÀÖ´Ù.

¨é ¼ö¼ú : highly effectiveÇÏÁö¸¸ ´Ù¼ÒÀÇ À§Ç輺ÀÌ ÀÖ´Ù.

3. Toxic multinodular goiter

pathogenesis´Â nontoxic MNG¿Í µ¿ÀÏÇϳª °¡Àå Å« Â÷ÀÌ´Â toxic MNG¿¡´Â functional

autonomy°¡ ÀÖ´Ù´Â °ÍÀÌ´Ù.

goiter¿ÜÀÇ ÀÓ»ó¹ßÇöÀº subclinical hyperthyroidism or mild thyrotoxicosis

³ëÀο¡¼­ ÈçÇϰí, AF or palpitations, tachycardia, nervousness, tremor, or weight loss°¡

»ý±æ ¼ö ÀÖ´Ù.

iodine, contrast dye exposure°¡ thyrotoxicosis¸¦ ¾ÇÈ­½Ãų¼ö ÀÖ´Ù.

TSH¡é, T4 Á¤»ó ȤÀº ¾à°£ Áõ°¡, T3Áõ°¡Á¤µµ°¡ T4Áõ°¡Á¤µµº¸´Ù Å©´Ù.

thyroid scan: heterogenous uptake with multiple regions(increase or decrease)

24hr RI uptake : Áõ°¡¡¿

* Ä¡·á

i) antithyroid drug + ¥â-blocker

=> goiter¸¦ ´õ Å©°Ô ÇÒ¼ö ÀÖÀ¸¸ç spontaneous remissionÀº ÀϾÁö ¾Ê´Â´Ù.

ii) RI

iii) op : definite treatment, ¼ö¼úÀü antithyroid drugÀ¸·Î euthyroid state¸¦ ¸¸µé¾î¾ß ÇÑ´Ù.

4. Hyperfunctioning solitary nodule(=toxic adenoma)

pathogenesis : TSH-R signaling pathway¸¦ ÀÚ±ØÇÏ´Â mutation

ÀÏÂ÷ÀûÀ¸·Î receptor transmembrane domain¿¡¼­ Gs¥á¿¡ constitutive receptor coupling

-> cAMP level¡è -> thyroid follicular cell proliferation & function¡è

90%À̻󿡼­ TSH-R or Gs¥á subunit geneÀÇ activating mutation(+)

thyrotoxicosis : mild

thyroid scan: definitive diagnostic test

* Ä¡·á

i) RI ablationÀÌ treatment of choice

10-29 mCi, 75%¿¡¼­ 3°³¿ù³» thyrotoxicosis±³Á¤

hypothyroidism <10%(5³â³»)

ii) surgical resection(enucleation or lobectomy) : effective

iii) medical tx: antithyroid drug +¥â-blocker

thyroid functionÀ» Á¤»óÈ­½Ãų¼ö ÀÖÀ¸³ª long-term tx·Î´Â ÀûÇÕÇÏÁö ¾Ê´Ù.

iv) ethanol injection : ÀϺμ¾ÅÍ¿¡¼­ ¼º°øÀûÀ¸·Î ½ÃÇà

5ȸ ÀÌ»ó repeat injectionÀÌ ÇÊ¿äÇÏÁö¸¸ nodule size¸¦ °¨¼Ò½Ã۰í, normal thyroid

functionÀ» ȹµæÇÏ¿´´Ù.

Thyroid cancer

Tab 330-9 ºÐ·ù

Tab 330-10 thyroid noduleȯÀÚ¿¡¼­ cancer risk factor

* ÀϹÝÀûÀÎ poor prognosis

<20¼¼ or >65¼¼, male

1. Pathogensis & genetic basis

¨ç radiation

¨è TSH & growth factor

¸¹Àº ȯÀÚ¿¡¼­ thyroid cancer°¡ TSH receptor¸¦ ¹ßÇöÇϹǷΠTSH¿¡ ¹ÝÀÀÇÑ´Ù.

µû¶ó¼­ thyroid cancer¿¡¼­ T4 suppressionÇÏ´Â rationale°¡ ¿©±â¿¡ ÀÖ´Ù.

TSH receptorÀÇ residual expressionÀº 131I therapy½Ã¿¡ uptake¸¦ Áõ°¡½ÃŲ´Ù.

¨é oncogene & tumor suppressor genes

RET gene on chromosome 10

MEN type 2¿¡¼­ÀÇ MTC : point mutation

papillary cancer: rearrangement

2. Well-differentiated thyroid cancer

1) papillary cancer(mc)

* Ư¡Á÷ÀÎ cytologic features: psammoma bodies, papillary structure formation

multifocal, local invasion, bone, lung metastasis, slow growth, ÈçÈ÷ early stage(I, II)¿¡

Áø´ÜµÇ°í excellent prognosis

2) follicular cancer

iodine-deficient regions¿¡¼­ ´õ ÈçÇÏ´Ù.

vessel, nerve, adjacent structure¿¡ÀÇ invasionÀ¸·Î benign°ú malignancy°¡ °áÁ¤µÇ¹Ç·Î

FNA·Î Áø´ÜÇϱâ´Â ¾î·Æ´Ù.

hematogenous spreadÇϹǷΠ¸¹Àº ȯÀÚ¿¡¼­ stage IV¿¡¼­ Áø´ÜµÇ¹Ç·Î PTCº¸´Ù ¿¹Èİ¡

³ª»Ú´Ù.

* poor prognostic features

: distant metastasis, >50¼¼, >4cm, Hurthle cell histology, marked vascular invasion

3) Ä¡·á

¨ç surgery

stage IÀÏ ¶§ lobectomy ȤÀº near-total thyroidectomy»çÀÌ¿¡ »ýÁ¸·üÀº À¯»çÇÏ´Ù.

lobectomy´Â hypoparathyroidism, recurrent laryngeal nerve injuryÀÇ À§ÇèÀº ³·Áö¸¸,

residual lobe ¶§¹®¿¡ Tg levelÀ» monitorÇÒ¼ö ¾ø°í, 131I WBSÀ» ½ÃÇàÇÒ¼ö ¾ø´Ù.

±×¿Ü¿¡µµ RI scan or tx°¡ ÇÊ¿äÇÏ´Ù¸é ³²Àº thyroid tissueÁ¦°Å¸¦ À§ÇÑ Àç¼ö¼úÀÌ ÇÊ¿äÇÏ´Ù.

µû¶ó¼­ ÀúÀÚµéÀº Àç¹ßÀ» Æò°¡Çϱâ À§ÇØ RI scan°ú TgÀ» ÃøÁ¤ÇÒ¼ö ÀÖ´Â near-total

thyroidectomy¸¦ ´õ ¼±È£ÇÑ´Ù.

¨è TSH suppressive tx

´ëºÎºÐÀÇ tumor°¡ TSH-responsvieÇϹǷΠTSH¿¡ ´ëÇÑ levothyroxine suppressionÀÌ

thyroid cancerÄ¡·áÀÇ ±âº»ÀÌ´Ù.

Ä¡·á¸ñÇ¥´Â excess thyoid hormoneÀ¸·Î ÀÎÇÑ ºÎÀÛ¿ë(AF, osteopenia, anxiety, other

thyrotoxicosis Áõ»ó)ÀÌ ¾ø´Â »óÅ¿¡¼­ °¡´ÉÇÑ TSH¸¦ ¾ïÁ¦ÇÏ´Â °ÍÀÌ´Ù.

Àç¹ßÀ§ÇèÀÌ ³·À» ¶§, TSH 0.1-0.5 IU/L

Àç¹ßÀ§ÇèÀÌ ³ôÀ» ¶§, complete TSH suppresion

¨é radioiodine tx

RI uptake´Â ÀÏÂ÷ÀûÀ¸·Î sodium iodide symporter¿Í TSH stimulation¿¡ ÀÇÇØ °áÁ¤µÈ´Ù.

near-total thyroidectomyÈÄ thyroid tissue°¡ ³²¾ÆÀÖÀ»¼ö Àִµ¥, thyroid bed¿Í

parathyroid glandÁÖº¯ÀÌ Æ¯È÷ ±×·¸´Ù. °á°úÀûÀ¸·Î normal thyroid tissue¸¦ Á¦°ÅÇϰí,

residual tumor cellÀ» Ä¡·áÇϱâ À§ÇØ 131I ablationÀÌ ÇÊ¿äÇÏ´Ù.

* indications

i) larger papillary tumor¿¡¼­ ÁÖÀ§ LN·ÎÀÇ spread

ii) follicular tumor

iii) metastasis evidence(+)¿¡¼­ thyroid ablation & RI tx½ÃÇà

* 131I thyroid ablation & treatment

¼ö¼úÈÄ ¼öÁÖ°£ liothyronine(25ug bid or tid)·Î Ä¡·áÇÑ´Ù.

±×´ÙÀ½ thyroid hormoneÀ» ²÷´Â´Ù.

ÀÌ»óÀûÀ¸·Î´Â TSH>50 IU/L(3-4ÁÖÀÌ»ó)ÀÌ µÈ »óÅ¿¡¼­ Ä¡·áÇÏ´Â °ÍÀÌ ÁÁ´Ù.

ÃÖ´ë outpatient dose: 29.9 mCi

known reisidual cancerȯÀÚ¿¡¼­´Â ´õ ¸¹Àº ¾çµµ »ç¿ë

* 131I whole body scan(4-5 mCi)

residual tissue¸¦ È®ÀÎÇϰí ablationÀ» ÇÒ°ÍÀÎÁö guidance¸¦ Á¦°øÇÑ´Ù.

* F/U whole body scanning & Tg determination(Tab 330-12)

initial F/U: ¼ö¼ú ¹× thyroid ablationÈÄ 6°³¿ùÈÄ

initial scanÀÌ negative À̰í TgÀÌ ³·À¸¸é 1³âÈÄ¿¡ repeat

1³âÈÄ¿¡µµ ¿©ÀüÈ÷ negativeÀ̸é suppressive tx¸¦ ½ÃÇàÇϰí

¸Å 6-12°³¿ù¸¶´Ù Tg¸¦ checkÇÑ´Ù.

2nd F/U scanÀÌ negativeÀ̸é labÀÌ Á¤»óÀÎÇÑÀº further scanÀº ´õ ÇÊ¿äÄ¡ ¾Ê´Ù.

Tg >5-10 ng/mLÀ̰í scan negativeÀÏ ¶§ large dose 131I Ä¡·á¸¦ ÃßõÇÑ´Ù.

3. Anaplastic & other forms of thyroid cancer

1) anaplastic thyroid cancer

poorly differentiated & aggressive cancer, poor prognosis, 6°³¿ù³» »ç¸Á

RI uptake´Â ¹Ì¹ÌÇÏÁö¸¸ Ä¡·áÀûÀ¸·Î ÀÌ¿ëÇØº¼¼ö´Â ÀÖ´Ù.

CTx(antracycline & paclitaxel)¸¦ ½ÃÇàÇϱ⵵ ÇÏÁö¸¸ ÈçÈ÷ È¿°ú ¾ø´Ù.

external radiationÀ» ½ÃµµÇغ¼¼öµµ ÀÖ´Ù.

2) thyroid lymphoma

ÈçÈ÷ Hashimoto's thyroiditis¿¡¼­ ¹ß»ýÇϰí rapid expanding thyroid massÀÏ ¶§ ÀǽÉÇÑ´Ù.

diffuse large cell lymphoma°¡ °¡Àå ÈçÇÑ typeÀ̰í

biopsy¸¦ Çϸé small cell lung cancer³ª ATC¿Í ±¸º°ÀÌ ¾î·Æ´Ù.

ext. radiation¿¡ highly sensitiveÇϰí spread dsÀ̹ǷΠinitial tx·Î surgical resectionÀ»

ÇÏ¿©¼­´Â ¾ÈµÈ´Ù.

´Ù¸¥ ÇüÅÂÀÇ lymphoma Ä¡·á¿¡ µû¸¥´Ù.

3) medullary thyroid cancer(5-10%)

sporadic or familial

* familial: MEN-2A, 2B, MTC without MEN

* more aggressive

MEN-2B > 2A

familial > sporadic

* s-calcitonin¡è: residual or recurrent disease marker

* ¸ðµç ȯÀÚ¿¡¼­ MET mutation testÇÏ´Â °ÍÀÌ ÁÁ°í, mutationÀ» °¡Áö´Â family member¿¡

´ëÇØ¼­´Â genetic counselingÇÑ´Ù.

* Ä¡·á : surgical

RI uptake°¡ µÇÁö ¾ÊÀ¸¹Ç·Î RIÄ¡·á´Â ÇÏÁö ¾ÊÀ¸¸ç

ext. RT & CTx¸¦ palliation¸ñÀûÀ¸·Î ½ÃÇàÇÒ¼ö ÀÖ´Ù.