Part 26-1. The Endocrine System
PART 26. The Endocrine System
Section 1. Disorder of the Hypothalamus and Pituitary Gland
#
Ant. pituitary gland
1.
origin
; Rathke pouch as
invagination of the oral endoderm
2.
5 cell types
; produce six peptide
hormones
¨ç somatotropes --
produce GH
¨è lactotrops -- produce
prolactin
¨é thyrotrops -- make
thyrotropin or TSH
¢¾ Pit-1
; a single transcriptional activation
protein
; contribute to embryologic development
& differentiated function of above 3 cell types
¨ê
gonadtropins -- make lutropin or LH and follitropin or FSH
¨ë
orticotropin -- produce corticotropin (ACTH)
Ant. Lobe Hormones
;
act on other endocrine gland, certain body cell
;
controlled by neuropeptide releasing and release-inhibiting hormones by
hypothalamic neuron
--> capillaries of median
eminance
--> ant. pituitary through
portal vein
Human GH
;
protein with 191 amino acid
;
genes (GH1)
- *long arm of chromosome 17 (q22-24)
- expressed in pituitary
somatotropes
;
¡ÚOther 4 Genes Identiying More Than 90%
- CS1 & CS2 genes
/
¡Ø93°´ encode human chorionic
somatomammotropin (hCS)
- GH2(placental GH gene)
- CSP(partly disabled
pseudogene)
;
pulstile secretion
- *highest level during sleep
;
measured by standard radioimmunoassay(RIA) or ultrasensitive immunoradiometric
assay(IRMA)
;
regulation
- GHRH & somatostatin
;
action mechanism
- binding to receptor
molecules on the surface of target cells
-->
induces receptor dimerization and activation of recptor-associated *Janus kinase(Jak2)
-->
nuclear gene transcription
-->
IGF-I, IGF-II
#
somatostatin
; not limited 14- and 28-
amino acid formÀ¸·Î Á¸Àç
-
ÃéÀåÀÇ D cell¿¡¼ ºÐºñµÇ¸ç
- insulin, glucagon,
secretin, gastrin, VIP, GH, thyrotropinÀÇ ºÐºñ¸¦ ¾ïÁ¦ÇÔ.
#
octreotide
- potent, long acting
somatostatin analog
-
insulin º¸´Ùµµ ¿ì¼±ÀûÀ¸·Î GH ºÐºñ¸¦ ¾ïÁ¦,
µû¶ó¼ GH-secreting tumor ȯÀÚ¿¡ »ç¿ëµÇ¸ç
- ±× À̿ܿ¡
gastrinoma, insulinoma, glucagonoma, VIPnoma, carcinoid µîÀÇ Ä¡·á¿¡ »ç¿ëµÊ.
- 123I-labeled octreotide´Â somatostatin
receptor-positive tumor¿Í metastasisÀÇ
localization¿¡ À¯¿ë.
;
*mitogenic actionÀº increase synthesis of IGF-I¿¡ÀÇÇØ¼ ÀϾÙ.
- IGF-I (insulin-like growth
factor-I, formly somatomedin C)
/
70°³ÀÇ amino acid
/ chromosom 12ÀÇ long arm¿¡ Á¸Àç
/ insulin°ú »ó´çÇÑ ±¸Á¶Àû »óµ¿°ü°è¸¦ °¡Áü
/ »ý¼ºÀº ÀÏÂ÷ÀûÀ¸·Î liver¿¡¼ ÀϾ¸ç ±¹¼ÒÀûÀ¸·Î
mesoderm°ú ectodermal cells¿¡¼ ÀϾ
(ƯÈ÷ ¼Ò¾ÆÀÇ growth plate)
/
circulating levelÀº GHÀÇ Ç÷Áß ³óµµ¿¡ Å©°Ô °ü·ÃµÊ. (žƱâ¿Í ½Å»ý¾Æ±â´Â
¿¹¿Ü)
#
IGF-II
- 67 amino acids·Î µÈ single chain protein
- À¯ÀüÀÎÀÚ´Â chromosom 11ÀÇ
short arm¿¡ À§Ä¡
- homology to IGF-I
- bone cells¿¡¼ Áß¿äÇÑ mitogenÀÌÁö¸¸
physiologic rolesÀº À߾˷ÁÁ® ÀÖÁö ¾ÊÀ½
# ¡Úseveral disorder of growth
;
caused by abnormalites of the gene encoding GHRH receptor, Pit-1, GH1, GH receptor
; *no growth disorders in genes encoding GHRH, IGF-I, IGF-I
receptor or IGF-II
Prolactin
;
199 amino acids·Î ±¸¼º
;
geneÀº chromosome 6¿¡ À§Ä¡
;
dopamine
- major prolactin inhibiting factor
- hypothalamic dopaminergic pathway¸¦
disruptionÇÏ¿© prolactinÀÇ
Ç÷Á߳󵵸¦
»ó½Â½ÃÅ´
;
Ç÷Áß prolactin ÀÌ »ó½ÂÇÏ´Â °æ¿ì
- administration of TRH
- primary hypothyroidism
- disruption of pituitary stalk ( <--
craniopharyngioma )
;
main established role
- *initiation and maintenance of lactation
;
mean serum level
- child and fasting adult ; 5 - 20 ug/L
- fetus and neonate during 1st wk ; >
200 ug/L
TSH
;
two glycoprotein chains linked by hydrogen bonding
¥á-chain
; identical to FSH, LH, hCG
¥â-chain
; unique & specific
;
mapped on chromosome 6
; ¢¾ Functions : Increase of
- iodine uptake
- iodide clearance from the
plasma
- iodotyrosine &
iodothyronine formation
- thyroglobulin proteolysis
- release of thyroxine (T4)
and triiodothyronine (T3) from the thyroid
;
action mechanism mediated by cyclic adenosine monophosphate
;
deficiency of TSH ; atrophy of thyroid
;
excess of TSH --> hypertrphy, hyperplasia of thyroid
#
TRH
- 1st isolated tripeptide
- T4, T3 ; pituitary cell¿¡ ´ëÇÑ TRHÀÇ ÀÛ¿ëÀ» Â÷´ÜÇÏ¿©
TSHÀÇ ºÐºñ¸¦ ¾ïÁ¦
- prolactin ºÐºñ¸¦ ÀÚ±Ø
- synthetic TRH ; TSH¿Í prolactinÀÇ
pituitary reserve¸¦ °Ë»çÇϴµ¥ À¯¿ë
ACTH
; production
- pituitary glandÀÇ large precusor glycoprotein product (POMC)·ÎºÎÅÍ proteolytic cleavage¿¡ÀÇÇØ »ý¼º
POMC --cleavage--> ACTH + ¥â-lipotropin (¥â-LPH)
ACTH --cleavage--> ¥á-melanocyte-stimulating hormone
; first 13 amino acids of ACTH
no corticotropic activity
¥â-LPH +-cleavage--> neurotropic peptides
| ; morphinomimetic activity
| fragment 61-91, ¥â-endorphin
+------------> ¥â-melanocyte-stimulating hormone
; 17-amino acid fragment of ¥â-LPH
;
¡ÚSecretion
- diurnal rhythm
-
*lowest level between 10 PM and 2
AM
- *peak levels at 8 AM
- regulation by CRH
; *ACTH »ó½Â½Ã
¥â-LPH¿Í
¥â-endorphin ÀÌ
»ó½ÂÇÔ
; *principal
pigmentary hormone in humam rather than FSH
POMC peptides
CRH
- ACTH, ¥â-endorphin, other POMC related peptidesÀÇ ºÐºñ¸¦ Á¶Àý
- median eminence¿¡¼ predominanatÇÏ°Ô ¹ß°ßµÇ¸ç brain, placenta µî¿¡¼µµ »ý¼ºµÊ
- synthetic ovine (oCRH)°ú human CRH (hCRH)°¡ ÀÓ»óÀûÀ¸·Î »ç¿ëµÊ
/ oCRH°¡ hCRHº¸´Ù ÀÛ¿ëÀÌ Å©°í ¿À·¡°¡±â ¶§¹®¿¡ choice°¡ µÇ¸çcushing syndromeÀÇ DDx¿¡ À¯¿ëÇÔ
Gonadotropin (LH, FSH)
; ¥á & ¥â subunit·Î ±¸¼ºµÇ¸ç, ¥á-subunit´Â TSH¿Í µ¿ÀÏÇÔ.
-
*¥â-subunit°¡ specific hormonal
action
; FSH
- mediated by receptors on ovarian granulosa cell & testicular sertoli cells
- follicualr develpment & gametogenesis
- *suppressed by inhibin
- ¢À¡Ú
Activin(¥â-¥â dimer)
/ stimulate FSH stimulation
/ paracrine effect in the testis
; LH
- mediated by receptors on ovarian theca cells & testicular Leydig cell
- luteinization & Leydig cell function
- *suppressed by androgen, estrogen
Post lobe hormones
Post Lobe Of Pituitary
; *functional
unit(=neurohypophysis)ÀÇ ÀϺκп¡
ºÒ°úÇÏ´Ù.
¨ç neuron of supraoptic and paraventricular nuclei of hypothalamus
¨è neuronal axons
¨é neuronal terminals in the median eninence or in the post. pituitary
Hormones (AVP, Oxytocin)
; octapeptide·Î hypothalamusÀÇ supraoptic & paraventricular nuclei¿¡¼ neurosecretionÀ¸·Î »ý¼º, ºÐºñµÊ
AVP
; *affect
blood pressure, intestinal contractility, hepatic glycogenolysis, platelet
aggragation, release of coagulation factor VIII
; *permeability
of the renal tubular cell membrane through cAMP
; stimuli for AVP release
- increased plasma osmolality perceived by osmoreceptor in hypothalamus
- decreased blood volume perceived by baroreceptor in carotid sinus of aotic arch
; *umbilical
cord plasmaÀÇ AVP³óµµ´Â fetal stressÀÇ
sensitive indicator
; Desmopresin
- synthetic analog, high potency, selectivity for ADH receptors
- DI Ä¡·á½Ã¿¡ intranasal small amount°¡ È¿°úÀû
Ocytocin
; ÀڱüöÃàÀ» À¯µµÇϰí À¯ÁóºÐºñ¿¡ °ü¿©ÇÔ
Chapter 512. Hypopituitarism
¡ÊEtiology (Table 512-1)
Congenital defect
Pituitary Hypoplasia
;
isolated phenomenon or association with more extensive developmental
abnormalies
¨ç
anencephaly
¨è
holoprosencephaly ; cyclopia, cebocephaly, orbial hypotelorism
¨é
septo-optic dysplasia (de Morsier syndrome)
;
hypoplastic optic discs with typical double rims and sparse retinal vessels,
absence of septum pallucidum
¡ÚHall
Pallister Syndrome
;
absence of pituitary gland associated with
- *hypothalamic hamartoblastoma, postaxial polydactyly, nail
dysplasia, bifid epiglottis, imperporated anus, anomalies of heart, lungs,
kidneys
;
*neonate¿¡¼ hypopituitarism°ú
postaxial polydactyly & bifid epiglottis°¡ ÀÖÀ»
°æ¿ì ÀÌ
ÁõÈıºÀ» ÀǽÉ
Cleft Lip And Palate
;
4%¿¡¼ GH deficiency ¹ß»ý, short stature°¡ ÀÖÀ¸¸é
32%¿¡¼ ³ªÅ¸³²
Midfacial Anomalies Or Solitary Maxillary
Central Incisor
;
high likelihood of GH deficiency
Unilateral Or Bilateral Optic Nerve Hypoplasia
;
endocrine abnormalities
- extremely variable from
only GH to multiple pituitary deficiencies
;
delay in linear growth
- ºü¸£°Ô´Â
3moºÎÅÍ ½ÃÀÛµÇÁö¸¸ ´ë°³ 3-4¼¼ Àü¿¡´Â ¹ß°ßÀÌ À߾ȵÊ
;
¡Úaffected newborn
- *apnea, hypotonia, seizures, prolonged jaundice, hypoglycemia
without hyperinsulinism, microphallus (in males)
Aplasia Of Pituitary Without Brain Or Skull Abnomalies
;
affected infant
-
early hypoglycemia & microphallus in males
;
some infants
-
evidence of neonatal hepatitis syndrome
;
suggested autosomal recessive inheritance
Empty-Sella Syndrome (Enlarged Sella & Hypopituitarism)
;
deficient sella diaphragmÀ¸·Î ÀÎÇØ suprasella
subarachnoid space°¡ sella turcica·ÎherniationµÇ¾î
sella°¡ remodelingµÇ°í
pituitary gland°¡ flattenedµÊ
;
¼ö¼úÀ̳ª ¹æ»ç¼±Ä¡·á ÈÄ¿¡ ¹ß»ýÇϸç idiopathicÇϰԵµ »ý±è
Other Syndromes with Prominant Short Stature
;
*Turner, Fanconi, Russell-Silver,
Rieger, Williams, CHARGE syndromes
Destructive Lesions
;
usually multiple hormonal deficiencies
Craniopharyngioma
;
*¡ãcommon
lesion
CNS Gerninoma, Eosinophilic Granuloma,
Tuberculosis, Sarcoidosis, Toxoplasmosis, And Aneurism
¨ç
may cause hypothalamic-hypophyseal destruction
¨è Á¾Á¾
skull¿¡¼ ¹æ»ç¼±Àû º¯È¸¦ ÀÏÀ¸Å´
¡Ø indications of tumor
of roentgenogram
- enlargement of sella
- deformation or destruction of
clinoid process
- intrasella or suprasella
calcification (craniopharyngioma)
Histiocytosis
ƯÈ÷, cranial irradiationÀ» ¹ÞÀº °æ¿ì
Truma Including Child Abuse, Traction At Delivery, Anoxia, And Hemorrhagic Infarction
;
may damage pituitary, stalk, or hypothalamus
Radiotherapy for malignancy of CNS or other cranial structure and ALL with prophylactic cranial irradiation
; slow growth during
radiation therapy or chemotherapy
-->
improved growth for a yr or two
-->
and then declined growth & develop hypopituitarism
; *dose & fractional scheduleÀÌ
incidence¿¡ Áß¿ä
; total dose of *35-45GY
-
*mostly GH deficiency 5yr after
treatment
; *20GY doses
-
*subtler defects
Spinal Irradiation
; disproportionally poor
growth of the trunk
Idiopathic Hypopituitarism
;
no demonstrable lesion of pituitary or hypothalamus
;
¡ãcommon
;
¡Úin most, functional defect of hypothalamus
;
GH only or multiple hormones deficiency
;
most often sporadic
;
asso. /c breech birth, forceps delivery, intrapartum & maternal bleeding
--> *pathologic factor is birth traum & anoxia
Genetic Forms Of Hypopituitarism (5%)
;
GH deficiency only or several other ant. hornone deficiency
;
¢ÀMcKusik Classification Of Isolated GH Deficiency (IGHD)
¨ç
type I ; autosomal recessive
- type IA ;
complete deletion of GH1 gene
- type 1B ;
heterogenous with respect to severity and sites of mutations
¨è
type II ; autosomal dominant
¨é
type III ; X-linked
;
multiple pituitary hormones deficiency
- same classification
#
Type IA
- *GH Ä¡·á½Ã AbÇü¼ºÀ»
ÀßÇÏ¿© poor response
/
PCR, southern blottingÀ» ½ÃÇàÇÏ¿© less antigenic
biosynthetic GHÀ» ¸¸µé¾î Åõ¿©
- differnt size deletion
/
*¡ãcommon
& smallest deletions : 6.7kb long
/
other deletion : 7.0, 7.6, greater than 45kb
- extreme postnatal growth
failure, failure to release GH after stimulation with GHRH
#
Type IB
- genetic defect Á¾·ù
/
1- or 2-bp deletions in GH1 gene
/
mutations within 4th and last intron of GH1 gene
:
comprimise normal pre-mRNA splicing at the usual exon 3 to 4 splice boundary
/
mutations in GHRH receptor gene
#
Type II
- singe-base substitutions in
intron 3
-->
omission of exon 3 from spliced mRNA
-->
proteins lacking amino acids 32 to 71 & lacking one of cysteine residues
#
Type III
- not identified
- transmitted along with
immunoglobulin deficiency
#
¡Úmultiple pituitary hormone deficiency in Type I & Type III
- underproduction of GH, TSH,
ACTH, LH, FSH
- prolactin tend to normal or
high
- hypothalamus defectÀÇ °¡´É¼ºÀÌ ´õ ³ôÀº °ÍÀ¸·Î »ý°¢µÇ°í ÀÖ´Ù.
- gene defects
/
*defect in gene for Pit-1
:
gene deletion
:
nonsense and missense muation
:
substitutioning tryphtophan for rginine at position 271
Growth Hormone Receptor Defects
¡Ø87 Laron syndrome
¨ç
hypopituitarismÀÇ all clinical finding
;
but *increased circulating leve of GH
¨è *very low level of
IGF-I
¨é not respond to
exogenous hGH
¨ê absence of GH-binding
activity
;
confirm
;
point to abnormality of GH receptor
¨ë gene mutation
-->
*loss of GH-binding activity in
membrane receptor
¨ì
parent of patients¡¯ stature is normal range
Clinical Manifestation
Patients Without Demonstable Lesions Of The
Pituitary
;
¡Ø93Ãâ»ý½Ã
Á¤»ó üÁß ¹×
½ÅÀå
;
delayed epiphyseal clusure
- growth beyond age
- without treatment, 4-12SD
below the mean
; ¡Úinfant
with congenital defects of the pituitary or hypothalamus
- neonatal emergency
/
apnea, cyanosis, severe hypoglycemia
- *microphallus - additional diagnostic clue
- accom. with hypoadrenalism,
hypothyroidism
- prolonged neonatal jaundice
;
¡Úround head, short & broad face, promiment frontal bone,
depressed nasal bridge & saddle shaped small nose with well developed
nasolabial folds, late eruption of teeth, short neck
;
small larynx, high pitched voice
& remains after puberty
;
well proportioned extremities with
small hands & feet
;
underdeveloped genitalia for the
child's age, delayed or absent sexual maturation, usually lack of facial,
axillary & pubic hair, fine scalf hair
;
symptomatic hypoglycemia usually
after fasting
;
usually normal intelligence
Patient With Demostrable Lesions Of The Pituitary
;
initially normal, simialr to idophathic pituitary growth failure or growth
ceases
;
*atrophy of the adrenal cortex,
thyroid, and gonads
- loss of weight, asthenia,
senstive to cold, mental torpor, and absence of sweating
;
failure of sexual maturation
-
atrophy of gonads and genital tract, amenorrhea and loss of pubic hair and axillary
hair
;
tendency to hypoglycemia and coma
;
Ãʱ⿡ DI ¹ß»ý
- *ant. pituitary°¡ Á¡Â÷
ÆÄ±«µÇ¸é¼ spotaneously improved
;
*expading tumor¿¡ÀÇÇÑ lesionÀÏ °æ¿ì
- headache, vomiting, visual
disturbance, pathologic sleep, decreased school performance, seizures, polyuria,
and growth failure µîÀÌ ³ªÅ¸³²
- craniopharyngioma
/
visual field defects, optic atrophy, papilledema, and cranial nerve palsy µîÀÌ ÈçÇÔ
¡Ø95 Laboratory Data
;
profound postnatal growth failure ( < 3SD mean for age and gender)
- suspection of classic GH
dediciency
;
low serum levels of IGF-I & GH dependent IGF-BP3
;
low or absent response of GH for stimulation
--> *definitive diagnosis
; ¡Ø88,
95 Provocative Tests
- 20 min period of strenous
exercise or administration of L-dopa, insulin, arginine, clonidine, glucagon
- *Ç¥22-4, 22-5(p940-941)
¨ç
GH deficiency
; *peak level of GH < 7 ug/L
¨è
false negative response in any single test
; 20%
¨é
false negative response in both test
;
4%
¨ê
majority of prepubertal children
;
fail to achieve GH value above 7ug/L with two test
-->
*3days of estrogen priming recommand
;
¡Ø95 measuring the spontaneous
secretion of GH level
-
every 20 min during a 24- or 12-hr (8P.M. -- 8 A.M.) period
;
¡Ø96 GH
neurosecretory dysfunction
- normal porvocation tests
- little spontaneous GH
secretions
- *GH replacement Ä¡·á½Ã °¡Àå
ÁÁÀº È¿°ú
;
exam other pituitary functions
- levels of TSH, T4, ACTH,
cortisol, dehydroepiandrosterone sulfate, gonadotropins, gonadal steroids
;
hypothalamic lesion
- hypothalamic-releasing
hormones stimulations
- *TRH administration
-->
normal rise in TSH, PRL
-->
hypothalamic defect
- *elevated PRL level
-->
strong evidence of hypothalamus lesion
Rentgenographic Examination
1)
skull x-ray
¨ç
destructive or space-occupying lesion causing hypopituitarism (most helpful)
¨è evedence of IICP
¨é enlargement of
sella
;
ƯÈ÷ ballooning with erosion and
calcifications within or above sella
2)
MRI
¨ç *hypopopituitarismÀ»
°¡Áø ¸ðµç
ȯÀÚ¿¡°Ôs indicated
¨è
space occupying lesionÀ» »ó¼¼È÷ ¾Ë¼öÀÖÀ½
¨é
ant. & post. pituitary lobe¿Í pituitary stalkÀÇ
size¸¦ ¸íÈ®ÇÏ°Ô ¾Ë¼öÀÖ½¿
¨ê
empty sella turcica·ÎºÎÅÍ differentiatingÇϴµ¥
C-Tº¸´Ù ¿ì¼öÇÔ
¨ë
post. pituitary°¡ bright spotÀ¸·Î ½±°Ô ±¸º°µÊ
¨ì
hypoglycemia and micropenis¸¦ °¡Áø newborn
;
suspected hypopituitarim¿¡´ëÇÑ conformative
diagnostic technique
3)
Skeletal matration
¨ç
markedly delayed in longstanding GH deficiency
¨è
bone age ; approximately 75% of chromological age, TSH & GH deficiency½Ã¿¡ ´õÇöÀúÇÏ°Ô delay
¨é
fontanell ; 2¼¼ ÀÌÈıîÁö open
¨ê
found intersutural warmian born
¨ë
long born ; slender & osteopanic
4)
Dual photon x-ray absorptiometry
¨ç
newer method of assessing body composition
¨è deficient bone
mineralization
¨é deficincy in lean body
mass and corresponding increased in adiposity
Differential Diagnosis
Legion : systemic conditions
; Inflammatory Bowel Disease,
Occult Renal Disease, Turner Syndrome, Theoretical Defects of Molecular
Structure
¢ÞConstitutional Growth Delay
;
one of variants of normal growth
;
¿øÀÎ - »ó´ëÀûÀÎ hypogonadotropic stateÀÇ Áö¼Ó
;
normal length & weight at birth
;
*normal growth for first 4-12mo
--> *and then decelerated growth below the 3percentile
--> *growth rate of 5cm/yr or more by 2-3yr
;
GH secretion or other study
- within normal limit
;
bone age
- ¡Úcloser
to height age than to chronological age
;
other family members
- history of short stature in
childhood, delayed puberty, and eventual normal stature
;
prognosis
- *good °á±¹ Á¤»ó¼ºÀÎÀÇ
Ű¿¡ µµ´ÞÇÔ
;
*³²¾Æ¿¡¼
unusal degree of delayed pubertyÀÎ °æ¿ì
- short course testosterone
therapy¸¦ Çϸé puberty¸¦ ¾Õ´ç±æ¼ö ÀÖ½¿
;
DDx
- *genetic short stature ˼
skeletal maturation ÀÌ chronological age¿Í
ÀÏÄ¡ÇÔ
Genetic Short Stature
;
found in other family members
;
growth¿¡ °ü·ÃµÈ hormon study - Á¤»ó
Primary Hypothyroidism
;
easily diagnosed on clinical grounds
;
GH provocative test - subnormal
;
enlargement of sella°¡ ³ªÅ¸³¯¼ö ÀÖ½¿
;
low T4, elevated TSH levels
- estabilsh the diagnosis
;
thyroid hormoneÀ¸·Î Ä¡·áÇÏ´Â µ¿¾È¿¡ pituitary hyperplasia°¡ È£ÀüµÊ
Emotional Deprivation
(=psychologic
dwalfism, deprivation dwarfism, or reversible hyposomatotropism)
;
growth retardationÀÇ important cause·Î
hypothyroidism°ú À¯»çÇÔ
;
mechanism
- not fully understood,
sensory and emotional deprivation ÀÌ ¼ºÀåÀ» ¹æÇØ
;
funtional hypopituitarism
- *low levels of IGF-I, inadequate response of GH to provocative
stimuli, delayed puberty
;
clue the diagnosis
- history of disturbed
mother-child or family relations
- ºÎ¸ð°¡ »óȲÀ» °¨Ã߰ųª ¾ÆÀ̵µ µå·¯³»Áö ¾Ê¾Æ Áø´ÜÀÌ Èûµé´Ù.
;
¡Ø89
Clinical Manifestation
- perverted or voracious
appetites, enuresis, encoporesis, insomnia, crying spasmus, sudden tantrums
- excessively passive or
aggressive
-
boderline or dull-normal intelligence
;
child-rearing practices°¡ ¹Ù²ï´Ù´øÁö, abuse°¡ Á¦°ÅµÇ¸é ¼ºÀåÀÌ ÇöÀúÇÏ°Ô È£ÀüµÊ
;
period of catch up growth
- *seperation of cranial stuture, other evidence of pseudotumor
cerebri µîÀÌ ÀϾ sign of mass lesion À¸·Î ¿ÀÀÎÇÒ¼ö
ÀÖ½¿
Silver-Russell Syndrome
;
*short stature, frontal bossing,
small triangular facies, sparse subcutaneous tissue, shortened and incurved 5th
fingers, asymmetry(hemihypertrophy)
;
low birth weightÀÇ ºÐ¸¸·ÂÀÌ ÀÖ½¿
;
short term treatment with GH
- often increased rate of
growth but, long term benefits´Â unknown
¢ÀTreatment
#
classic GH deficiency
¨ç Ä¡·á´Â °¡´ÉÇÑ Á¶±â¿¡ ½ÃÇàÇϸç, Ä¡·á½Ã±â°¡
ºü¸¦¼ö·Ï long term expectationÀº ÁÁÀ½
¨è recommended dose of
hGH
; *0.18-0.3mg/kg/wk, SC in six or seven divided doses
¨é *Ä¡·á´Â ´õÀÌ»ó
¹ÝÀÀÀÌ ¾øÀ»
¶§±îÁö ȤÀº epiphyseal closure µÉ¶§±îÁö °è¼Ó
¨ê Ä¡·áµµÁß È¿°ú°¡ ¶³¾îÁú °æ¿ì ¿ë·®À» ¿Ã¸®±â Àü¿¡ complianceºÎÅÍ Æò°¡
¨ë Ä¡·á¹ÝÀÀ
; *max. response´Â Ä¡·á
ù 1³â
µ¿¾È ÀϾ¸ç, °è¼Ó »ç¿ëÇϸé¼
¹ÝÀÀµµ°¡ ¶³¾îÁü
#
¢¾Side Effect Of GH
; leukemia
-
double risk than general population
;
pseudotumor cerebri
;
slipped capital femoral epiphysis
;
worsening of scoliosis
; *increased total body water during first 2wks
; Creutzfeldt-Jakob disease
; *development of reversible hypothyroidism
-
due to enhanced converseion T4 to T3 & decreased TSH level
; change in fasting and
postprandial insulin level
-
before treatment : characteristically low
-
during GH treatment : normalize
-
DM °¡´É¼º ÀÖÁö¸¸ ½ÇÁ¦·Î´Â µå¹°´Ù
#
¡ÚRecombinant IGF-I°¡ À¯¿ëÇÑ
°æ¿ì
¨ç
Laron syndrome
¨è
GH1 gene deletion with high titer of antibodies
#
GH ÀÌ »ç¿ëµÇ¾îÁú¼ö ÀÖ´Â ´Ù¸¥ °æ¿ì
¨ç
children with IUGR
¨è
chronic renal failure
¨é
Noonan syndrome
¨ê
Turner syndrome ; untreated¿Í ºñ±³ÇÒ¶§ final height°¡ ¼öcm
´õÄ¿Áü
#
other hormonal deficiencies should be replaced
¨ç TSH deficient subjects
;
thyroid hormoneÀ» full replacement dose·Î Åõ¿©
¨è ACTH-dependent patient
; optimal dose of hydrocortison Åõ¿© (should not exceed
10mg/m2/24hr)
; ¼ö¼ú µîÀÇ stress »óȲ½Ã¿¡´Â
Áõ·®
;
¸¸¾à partial deficiency°¡ ÀÖ´Â °æ¿ì¿¡´Â ¼ºÀåÀÌ ¿ÏÀüÈ÷ ³¡³¯¶§±îÁö
Ä¡·á¸¦ ¹Ì·ê¼öµµ ÀÖ½¿
¨é gonadotropins
deficiencies
;
gonadal steroid´Â puberty°¡ ÀϾ ¶§±îÁö ȤÀº °ñ¿¬·É¿¡ µµ´ÞÇÒ¶§±îÁö
Åõ¿©
¨ê microphallus¸¦ °¡Áø
infant
;
one or two 3-mo courses of monthly injection of 25mg of testosterone enanthate
- osseous
maturation¿¡´ëÇÑ Áö³ªÄ£ ¿µÇâ¾øÀÌ penis¸¦
normal size·Î ¼ºÀå½ÃÄÑÁÜ
Chapt. 513. Diabetes Insipidus (Arginine Vasopressin deficiency)
; lack of the antidiuretic hormone,
arginine vasopressin (AVP)À¸·Î ÀÎÇØ polyuria, polydipsiaÀ» º¸ÀÌ´Â °æ¿ì
#
Permanent DI
; due to destruction of
supraoptic and paraventricular neuclei, division of supraoptic-hypophyseal
tract above median eminence
#
Transitory Polyuria
; due to transection of tract
below median eminence, removal of just post. lobe
; median eminence·Î À¯¸®µÇ´Â
AVP ¶§¹®¿¡ DI´Â ¹ß»ýÇÏÁö ¾ÊÀ½
#
AVP
; V2
recepor¿¡ °áÇÕÇÔÀ¸·Î½á kidneyÀÇ
distal tubules°ú collecting duct¿¡ Á÷Á¢ ÀÛ¿ë
; ¡ÚV2 receptor is responsible for
¨ç
vasodilator effect of the hormone
¨è
increasing for VIII activity
¨é
increasing the concentration of von Willebrand factor
Etiology
1)
tumor of the suprasellar and chiasmatic regions
; craniopharyngioma, optic
glioma, germinoma°¡ common causes
2)
Langerhans cell histiocytosis
; *25%¿¡¼
hypothalamus¿Í pituitary histiocytic
infiltrationÀÇ °á°ú·Î DI ¹ß»ý
; *4-5³âÀ̳»¿¡ °ÅÀÇ
¹ß»ý
; cytoplasmic Ab to
AVP-producing cells
3)
*encephlitis, sarcoidosis,
tuberculosis, actinomycosis, leukemia
4)
injuries to the head
; esp. skull base fractures
-
*Áï½Ã ȤÀº
¼ö°³¿ù ÈÄ¿¡µµ
¹ß»ý
5)
operative procedures near pituitary or hypothalamus
; transitory or permanent DI
6)
hereditary
; autosomal dominant form
-
Ãâ»ý½ÃºÎÅÍ ¼ö³â »çÀÌ¿¡ ¹ß»ý
- *Áõ»óÀº 3rd-5th decades¿¡ °¨¼Ò
-
AVP level ; absent (< 0.5 pg/ml) ȤÀº variable
-
AVP & neurophysin II(NP II) gene in chromosome 20
-->
*º» ÁúȯÀº neruophysin II mutation
-->
mutant AVP-NPII complex
; ¡ÚWolfram
syndrome (acronym DIDMOD)
- consist of DI, DM, optic atrophy, deafness
- autosomal recessive inheritance pattern
- gene on chromosome 4p
- pathology
/ *¥â-cells, supraoptic and
paraventriculare nuclei, optic nerve, cranial nerve VIII ¿¡ degenerative process
7)
septo-optic dysplasia
8)
idiopathic
; Ãʱ⿡ Áø´ÜÀÌ ¿øÀÎÀÌ ¸ð¸£´Â °æ¿ì·Î¼ ¾à
20% ¸¦ Â÷Áö
; *±×·¯³ª ÀÌ·¯ÇÑ
ȯÀÚµéÀÇ ¹ÝÀÌ»óÀÌ intracranial tumor
-
DI ³ªÅ¸³ ÈÄ 1³â±îÁö no clinical,
neuroradiologic sign
-
25%´Â 4¼¼±îÁö no clinical,
neurologic sign
-->
¡Ú±×·¯¹Ç·Î idiopathic DI´Â Àû¾îµµ 4³â µ¿¾ÈÀÇ periodic reevaluation ÀÌ ÇÊ¿äÇÔ
; ¨÷¿¡¼ AVP-producing cell¿¡ ´ëÇÑ
antibody¸¦ °¡Áü
9)
autoimmune
10)
¡Ø82
newborn¿¡¼ DI¸¦ ÀÏÀ¸Å°´Â
°æ¿ì
¨ç
asphyxia
¨è
intraventricular hemorrhage
¨é
intravascular coagulopathy
¨ê
Listeria monocytogenes
¨ë
group B ¥â-hemolytic streptococcal
meningitis
Clinical Manifestations
;
polyuria & polydypsia - outstanding features
#
Infancy
; *¸Å¿ì º¸Ã¤¸ç
¿ìÀ¯¸¦ ¸ÔÀ̸é
¸¸Á·ÇÏÁö ¾Ê°í
¹°À» ÁÖ¸é
Á¶¿ëÇØÁü
; *hyperthermia, rapid loss of weight,
collapse are common
;
dehydrationÀ¸·Î brain damage ¹Þ¾Æ¼ *mental impairment ¿Ã¼ö
ÀÖ½¿
; *vomiting, constipation, & growth failure
#
Children
;
wide variationin of the manifestations
-
³ªÀÌ¿Í ÇÔ²² severity°¡ Áõ°¡ÇÏ´Â ¼öµµ ÀÖ°í,
¾î¶² °æ¿ì´Â »çÃá±â±îÁö ¹«Áõ»óÀ¸·Î Áö³¾¼öµµ ÀÖ½¿
; *acquired bladder controlÀ» °¡Áø children¿¡¼ enuresis°¡
ù Áõ»óÀϼö
ÀÖ´Ù.
; ½ÉÇÑ °¥Áõ ¶§¹®¿¡
play, learning, sleep µîÀ» ¹æÇØ ¹Þ±âµµÇÔ
; ¶¡ÀÌ ³ªÁö ¾Ê°í ÇǺδ Â÷°í °ÇÁ¶Çϰí â¹éÇÔ
;
anorexia°¡ ÈçÇÏ°Ô ³ªÅ¸³²
#
primary lesion¿¡ µû¸¥ sx and sg
; hypothalamus tumor
-
growth disturbance, progressive cachexia or obesity, hyperpyrexia, sleep
disturbance, sexual precoccity, emotional disorder
; *initial·Î DI¸¦ ÀÏÀ¸Å² lesion ÀÌ ant. pituitary¸¦
ÆÄ±«ÇÏ´Â °æ¿ì
-
*DI ÀÚü´Â milder ÇØÁö°Å³ª ȤÀº
¿ÏÀüÈ÷ »ç¶óÁú¼öµµ
ÀÖ½¿
Loboratory data
;
¡Êdaily
urine volume - 4-10 L or more, urine color - ¿¯°Å³ª ¹«»ö, S.G - 1.001~1.005, urine osmolality - 50~200 mOsm/kg water
;
severe dehydration ½Ã¿¡´Â S.G°¡
1.010±îÁö »ó½Â ÇÒ ¼ö ÀÖÀ¸¸ç, urine osmolality´Â
300±îÁö »ó½Â ÇÒ¼ö ÀÖ½¿
;
serum osmolality´Â ÀûÀýÇÑ ¼öºÐ¼·Ãë ½Ã¿¡´Â *Á¤»óÀ» À¯ÁöÇÔ
;
water deprition tests
- 3hr-period of dehydration
(water deprivation test) ½Ã¿¡ plasma osmolality »ó½Â,
¹Ý¸é¿¡ urine osmolality´Â
plasma level ÀÌÇÏ·Î À¯ÁöµÊ.
- ÀÌ °æ¿ì
ADH¸¦ Åõ¿©Çϸé urine osmolality°¡ »ó½ÂÇÔ
;
radioimmunoassy of vasopressin
- severe neurognic DI
/
plasma levelsÀº Áö¼ÓÀûÀ¸·Î 0.5 pg/mL ÀÌÇÏÀÓ
- partial neurogenic DI
/
hyperosmolality & subnormal AVP levels
- *partial DI¿Í primary polydypsiaÀÇ
°¨º°¿¡ À¯¿ë
;
skull x-ray
-
reveal evidence of intracranial tumor
/
calcification, enlargement of sella turcica, erosion of clinoid process,
increased width of suture lines
;
MRI
- indicated for all patients
suspected DI
-
T1-weighted image
/
hyperintense signal (=bright signal or bright spot)
:
post. pituitary¿¡¼ ³ªÅ¸³ª¹Ç·Î ant. ¿Í ±¸ºÐ
/
*autosomal dominant DI½Ã¿¡ mutant AVP-NP II complexÀÇ ÃàÀûÀ¸·Î bright spotÀÌ hypothalamic-neurohypophyseal
tract lesion¿¡ ³ªÅ¸³ªÁö
¾Ê´Â´Ù.
/
thickening of pituitary stalk
: DI and *Langerhans cell histiocytosis or
lymphocytic infiltration
Differential Diagnosis
1)
Hypercalcemia or Potassim Deficiency
2)
Nephrogenic DI
; male infant¿¡¼ °¨º°¿ä
3)
Familial Nephronophthisis
¨ç mimic DI
¨è elevated plasma urea
and creatinine
¨é anemia
¨ê isotonic rather than
hypotonic urine
4)
Compulsive Water Drinking (Psychogenic Polydypsia, Primary Polydypsia)
¨ç
rare but, easily confused with DI
¨è ¼öºÐÀÇ ¼·Ã븦 Á¦ÇÑÇÏ¸é ¼Òº¯ÀÇ ³óÃàÀÌ ÀϾ
¨é Áö¼ÓÀûÀÎ
polydipsia°¡ ÀÖÀ» ¶§´Â maximal urine
concentrationÀÌ ÀúÇϵÇÁö¸¸, hypertonic saline
solutionÀ» Åõ¿© ȤÀº dehydrationÈÄ¿¡´Â ³óÃàÀÌ ÀϾ
¨ê
urine osmolality°¡ AVP Åõ¿©½Ãº¸´Ù
dehydration ÈÄ¿¡ ´õ¿í »ó½Â
5)
Adipsia or Hypodipsia
¨ç
isolated defect of the thirst center, extremely rare
¨è
AVP¿Í thirst¿¡ ´ëÇÑ
osmoreceptor°¡ ant. hypothalamus¿¡¼ ÀÎÁ¢Çϱ⠶§¹®¿¡
hypodipsic hypernatremia°¡ antidiuretic function defect¿¡ °ü°èµÊ
¨é
hypothalamic tumor ¶§¿¡ ÈçÇϸç, ƯÈ÷
gerninoma, gliomas, histiocytosis, congenital malfomation, microcephaly ¶§ Àß¿È
¡Ê¿äºØÁõÀÇ ¼¼°¡Áö Çü
¹× °¨º°Áø´ÜÀ» À§ÇÑ
¹æ¹ý°ú Â÷ÀÌÁ¡.
# Water deprivation test
;
Prognosis
¨ç DI ÀÚü´Â rarely threatens lifeÀ̸ç,
serious underlying condition ÀÌ Áß¿äÇÔ
¨è hypothalamus or pituitary lesionÀÇ
trauma³ª surgical interventionÈÄ¿¡ ÃÊ·¡µÈ
DI´Â ´ë°³ ÀϽÃÀûÀÓ
¨é Langerhans cell reticuloendothelioses¸¦ °¡Áø ÀϺΠȯÀÚ¿¡¼´Â
spontaneous remission
ÀÌ ÀϾ ±×·¯³ª ³ª¸ÓÁö´Â pri conditionÀÇ
remissionÈÄ¿¡µµ only long residuumÀ¸·Î
³²À» ¼öµµ ÀÖ½¿
¨ê clinical DIÀÇ °³¼±ÀÌ
ant. pituitary insufficiencyÀÇ ¹ß»ý¿¡ ¼±ÇàÇÒ¼öµµ ÀÖ½¿
¨ë brain tumor ; lesion site¿Í
neoplastic cell type¿¡ µû¶ó ¿¹Èİ¡ °áÁ¤µÊ
¡Ø84 Treatment
1)
causative factorsÀ» ¸ÕÀú °í·Á
2)
desmopressin (1-desamino-8-D-arginine vasopressin ; DDAVP)
;
drug of choice
;
highly effective analog of AVP
;
more resistant to degradation by peptidase than native AVP
;
antidiuretic activity of DDAVP
-
*2000-3000 times greater than its
pressor activity
;
1ug ; antidiuretic avtivity°¡ 8-10 hr µ¿¾È Áö¼Ó
(native AVP ; 2-3 hr )
;
nasal tube delivery systemÀ¸·Î Åõ¿© (nasal spray)
-
5-15 ug, single dose or divided into two doses
- *2¼¼
ÀÌÇÏ¿¡¼´Â small doses·Î
Åõ¿© (0.15-0.5 ug/kg/24hr)
;
parenteral preparation
-
*0.03-0.15 ug/kg
-
useful postoperatively
/ ƯÈ÷
transsphenoidal surgeryÈÄ¿¡ nasal packingÀ» Çϰí ÀÖ´Â °æ¿ì
;
polyuria°¡ ´Ù½Ã ³ªÅ¸³ª°Å³ª effect°¡ »ç¶óÁø °æ¿ì¿¡´Â
effective dose¸¦ repeat
; ¡ÚDI À̿ܿ¡
Åõ¿©ÇÏ´Â °æ¿ì
-
hemophilia A or von Willebrand disease
/
15 times
-
Enuresis
/
slightly higher dose (20-40ug)
513.1 Nephrogenic Diabetes Insipidus(Vasopressin Receptor Defect)
Chapter 514. Inappropriate Secretion Of Antidiuretic Hormone (=Hypersecretion Of Vasopressin)
#
¡ÊƯ¡
- one of most common
aberrations of AVP secretion
- inapproate high plasma AVP
level
- not suppresed by further
dilation of body fluids
Etiology
#
conditions involved CNS
;
meningitis, encephalitis, brain tumor and abscess, *subarchnoid hemorrhage, Guillain-Barre syndrome, head
trauma, after transsphenoidal surgery for pituitary tumors
#
pneumonia, tuberculosis, *acute
intermittened porphyria, cystic fibrosis, infant botulism, perinatal
asphyxia, use of positive-pressure respirators, *drugs(vincristin, vinblastine)
#
*Ewing sarcoma, malignant tumor of
pancreas, duodenum, thymus, oat cell carcinoma of the lung
#
chloropropamide theray for DM
#
antidiuretic preparationÀ¸·Î Ä¡·á ¹Þ´Â DIȯÀÚ¿¡¼
IV fluid therapy ȤÀº excessive ingestion of fluids
Clinical Manifestations
;
*most often latent and asymptomatic
;
hypotonicity & water intoxicationÀ¸·Î ÀÎÇÑ Áõ»ó
- s-Na > 120 meq/L maybe
normal
/
*loss of appetite, nausea, vomiting :
early
/
irritability, personality change(hostility, confusion)
- s-Na < 110 meq/L
/
*neurologic abormalities : stupor,
convulsive seizure
;
*normal skin turgor & BP, no
dehydration
Laboratory Data
;
low serum sodium & chloride
- normal serum bicarbonate
level
;
*continued renal sodium excretion
;
hypo-osmolar serum, urine is less than maximally dilute
;
urine osmolality is greater than appropriate for serum osmolality
;
hypouricermia
- common
- volume expansion¿¡´ëÇÑ
2Â÷ÀûÀÎ ¹ÝÀÀÀ¸·Î urate clearance°¡ Áõ°¡Çϱ⠶§¹®
- ¡Úhyponatremia¸¦ µ¿¹ÝÇÑ hypouricemia°¡ SIADHÀÇ
Áø´ÜÀû ´Ü¼°¡
µÊ
;
renal & adrenal functionÀº Á¤»ó
¡Ø92 Treatment
1)
underlying disorderÀÇ Ä¡·á (eg. meningitis,
pneumonia)
; ¿øÀÎÄ¡·á¸¦
ÇÏ¸é ¾ø¾îÁü
2)
*fluids restriction
;
sodiumÀº ¼Ò½ÇÇÑ ¾ç¸¸Å º¸Ãæ
3)
hypertonic saline solution
; little benefit
;
severe water intoxicationÀ¸·Î convulsion, coma µîÀÌ ÀÖÀ» ¶§´Â
osmolality¸¦ Áõ°¡½ÃÄѼ CNS Áõ»óÀ» ¿ÏÈ
; *furosemide with 300 ml/m2 of 1.5% sodium chlorideÀÇ
Åõ¿©·Î sodium levelÀ»
¿Ã¸®°í diuresis¸¦
À¯µµÇÔ
4)
demeclocycline
; AVPÀÇ
renal tubule¿¡ ´ëÇÑ ÀÛ¿ëÀ» interfere
; *¼ºÀÎÀÇ SIADH
Ä¡·á¿¡ À¯¿ëÇϸç, ¼Ò¾Æ¿¡¼ÀÇ ¿ªÇÒÀº
È®¸³µÇ¾î ÀÖÁö
¾ÊÀ½
5)
Chronic SIADH
; single daily dose of
furosemide
514.1 Cerebral Salt Wasting
1) acute or chronic CNS damage
¨ç
develop a distintive syndrome of salt wasting
¨è
associated with head trauma, CNS surgery, tumor or meningitis
2) SIADH¿ÍÀÇ Â÷ÀÌÁ¡
¨ç hypovolemia
¨è
maintenance fluids¸¦ Åõ¿© ¹Þ´Âµ¥µµ excessive urine flow
rate
¨é
large net loss of sodium
¨ê Ç÷Àå
ADHÀÇ ³óµµ °¨¼Ò
3) increased ADH & decreased plasma
renin and aldosteron level
; ¿øÀÎÀÌ
ANHÀÇ inappropriate secretionÀÓÀ» ¾Ï½Ã
4) therapy
; volume-for-volume
replacement of urine loss with 0.9% or 3% sodium chloride
Chapter 515. Hyperpituitarism
;
primary hypersecretion of pituitary hormones ; adenoma¿¡ÀÇÇÑ °æ¿ì´Â ¼Ò¾Æ¿¡¼´Â
rare
;
°¡Àå ÈçÈ÷ ¹ß»ýÇÏ´Â pituitary tumor´Â
corticotropin, prolactin or growth hormone µîÀ» ºÐºñÇÏ´Â °æ¿ìµéÀÓ
;
hypothalamic harmartomas
- secrete
gonadotropin-releasing hormone
-
cause precoccious puberty
Pituitary Gigantism And Acromegaly
;
open epiphyses, overproduction of GH --> gigantism
;
closed epiphyses, overproduction of GH --> acromegaly
Etiology
(¼Ò¾Æ¿¡¼´Â
rare)
¨ç
pituitary adenoma
¨è
hypothalamic tumor ; GHRH secretion
¨é
other tumors particulary in the pancreas
; somatotrophÀÇ hypersecretion & large amountÀÇ
GHRH¸¦ ºÐºñÇÏ´Â °æ¿ì
- pancreatic tumor
- McCune-Albright syndrome ; GH secreting adenoma¿Í ¿¬°üÀÌ ÀÖ´Â °æ¿ì
Clinical manifestations
¨ç rapid linear growth
¨è coarse facial
features, enlarging hands and feets, young children¿¡¼´Â
linear growth¿¡ ¼±ÇàÇÏ¿© headÀÇ
rapid growth°¡ ³ªÅ¸³²
¨é ÀϺΠȯÀÚ¿¡¼´Â behavioral or visual
problemsÀ» ÀÏÀ¸Å´
¨ê ´ëºÎºÐÀÇ È¯ÀÚ¿¡¼ abnormal growth´Â »çÃá±â¿¡ ÇöÀúÇØÁü
¨ë bodyÀÇ
distal partÀÇ ºñ´ë°¡ ÁÖ·Î ³ªÅ¸³²
; µÎ°³°ñÀÇ µÑ·¹°¡ Áõ°¡,
ÄÚ°¡ ³Ð¾îÁö°í Çô°¡ Ä¿Áö¸é¼ ¾ó±¼ÀÇ ÇüŰ¡ °ÅÄ¥¾îÁü
ÅÎÀÌ °úµµÇÏ°Ô Ä¿Áö°í Ä¡¾Æ°¡ ¼·Î ¹ú¾îÁö¸ç ¼Õ°¡¶ô°ú ¹ß°¡¶ôÀÌ µÎ²¨¿öÁü
¨ì dosal kyposis ;
fatigue & lassitude°¡ early sxÀ¸·Î ³ªÅ¸³²
¨í delayed sexual
maturation ȤÀº hypogonadism ÀÌ ³ªÅ¸³¯¼ö ÀÖ½¿
¨î ³ªÁß¿¡ IICP signs ÀÌ ³ªÅ¸³²
Laboratory Data
¨ç
elevated growth hormone (400 ng/ml)
¨è
glucose tolerance test½ÃÀÇ hyperglycemia¿¡ ÀÇÇØ¼µµ
GH level ÀÌ °¨¼ÒµÇÁö ¾ÊÀ½
¨é
L-dopa¿¡ÀÇÇØ GH level ÀÌ
paradoxicÇÏ°Ô °¨¼ÒµÉ¼ö ÀÖ½¿
¨ê ÀϺÎÀÇ È¯ÀÚ¿¡¼´Â
thyrotropin-releasing hormone Åõ¿©½Ã GH levelÀÇ »ó½ÂÀÌ ³ªÅ¸³²
¨ë
insulin-like growth factor-I (IGF-1) levelÀº Áö¼ÓÀûÀ¸·Î »ó½ÂµÇ¾î ÀÖ½¿
; ´ë°³ 2.6-21.7 u/ml, normal 0.3-1.4 ul/ml
¨ì
plurihormonal adenomas (secrete GH & prolactin)
; marked hyperprolactinemiaº¸ÀÓ
¨í
impaired secretion of gonadotropin, thyrotropin or corticotropin
¨î
radiologic finding
(skull x-ray)
enlargement of sella turcica and paranasal sinuses
(CT
or MRI)
delineates the tumor
¨ï
tufting the pharanges, increased heel pad thickness
¨ð
normal osseous maturation
Differential Diagnosis
¨ç
hereditary tall stature
; ´ë°³ °¡Á·À̳ª ģô Áß¿¡ abnormal height°¡ ÀÖ½¿
tall person˼ well proportioned, free of IICP
¨è
excessive growth during preadolescence in obese children
; temporary state·Î ۰¡ giant¿¡ µµ´ÞÇÏÁö´Â
¾ÊÀ½
¨é
precocious puberty
; ´ë°³ tall stature¸¦ º¸ÀÓ
epiphysis°¡ Á¶±â¿¡ closureµÇ°í
¼ºÀåÀÌ Á¶±â¿¡ ³¡³ª±â ¶§¹®¿¡ giant¿¡ µµ´ÞÇÏÁö´Â
¾ÊÀ½
¨ê
hypogonadism or Marfan syndrome
; ÀÓ»óÀûÀ¸·Î½±°Ô ±¸ºÐµÇ¸ç Á¤»ó GH levelÀ» °¡Áü
¨ë
lipodystrophy
; ÀϺο¡¼ GH level »ó½Â°ú
gigantismº¸ÀÓ
±×·¯³ª subcutaneous fat´Â ¹ß´ÞÇÏÁö ¾ÊÀ½
hypothalamic function disorder¸¦ º¸ÀÓ
¨ì
sotos syndrome
; pituitary gigantismº¸´Ù more common
Treatment
¨ç
surgery
¨è
irradiation
¨é
medical therapy
octreotide
; long acting analog of somatostatin
native peptideº¸´Ù GH ¾ï¾ÐÈ¿°ú°¡ ¾à 45¹è Á¤µµµÊ
acromegaly¸¦ °¡Áø ¼ºÀο¡¼ Áö¼ÓÀûÀ¸·Î
GH°ú IGF-IÀÇ ³óµµ¸¦
³·Ã߸ç tumor sizeµµ °¨¼Ò½ÃÅ´
Sotos Syndome (Cerebral Gigantism)
;
characterized by rapid growth, but *not
endocrine disorder
Cause
;
unknown
; hypothalamic defect°¡
suggested
; ´ëºÎºÐ
sporadicÇÏ°Ô ¹ß»ý
Clinical Manifestation
¨ç
birth weight and length ; above 90 percentile, macrocrania
¨è
rapid growth
;
*1¼¼°æ
affected infantÀÇ height°¡ 97 percentile ÀÌ»óÀÓ
¨é *4-5 ¼¼±îÁö´Â accelerated growth, ±× ÀÌÈÄ normal rate·Î µ¹¾Æ¿È
¨ê
usually normal but may slightly early puberty
¨ë
large hand & feet, thickened subcutaneous tissue
¨ì
large & dolichocephalic head and prominent jaw, hypertelorism,
antimongoloid slant eyes
¨í
clumsiness and awkward gait , great difficulty in sports, riding bicycle, other
tasks requiring coordination
¨î
some degree of mental retardation, and predominately perceptual defficiency
Laboratory finding
¨ç
lagre skull, high orbital roof, normal sized sella but slightly post.
inclination,
and increased interorbital distance
¨è
oseous maturation ; compatable with height
¨é
normal level of GH and other endocrine hormones
¨ê *abnormal EEG°¡
ÈçÇÔ
¨ë *dilated ventricular
system ÀÌ Á¾Á¾
³ªÅ¸³²
5)
increased risk of neoplasia
;
hepatic carcinoma and wilms, ovarian and parotid tumor
Prolactinoma
1)
*¡ãcommon
pituitary tumor in adolescents
; esp. microadenoma (<1cm)
2)
Clinical Manifestation
¨ç *headache, amenorrhea, galactorrhea
;
*¡ãcommon
¨è ¿©¾Æ¿¡¼ 2¹è ³ôÀº ¹ß»ýºóµµ
¨é type I multiple
endocrine neoplasm¿¡¼ prolactinoma°¡
adolescence½Ã¿¡ ³ªÅ¸³²
¨ê prolactin level
;
moderately (40-50 ng/ml) or *markedly
(10000-15000 mg/ml) elevation
¨ë chileren
;
macroadenomas
;
may be visual defect
;
*¨÷¿¡¼
hypopituitarism, GH deficiency
3)
DDx
¨ç primary hypothyroidism
;
hyperprolactinemia due to pituitary hyperplasia
¨è variety of medications
¨é pituitary stalk
dysfunction (eg, craniopharyngioma)
¨ê other benign
conditions
4)
Treatment
¨ç surgical resection by
transfrontal or transsphenoidal approach
¨è bromocryptine ;
standard drug for treating hyperprolactinemia
Chapter 516. Physiology of Puberty
1.
pubertyÀÇ ¹ßÇö´Ü°è
1) prepubetal stage
(1) early childhood¿¡¼
8-9¼¼ »çÀÌ
(2) hypothalamic-pituitary-gonadal axis´Â
dormant state
; LH¿Í
sex hormone (estradiol in girls, testosterone in bosy)ÀÇ Ç÷Áß³óµµ´Â
variable
(3) hypothalamus¿Í
pituitary actiavity´Â ¾ï¾ÐµÇ¾î ÀÖ½¿
by ¨ç
neuronal restraint pathways
¨è
negative feedback
¨é
minute amounts of circulating gonadal steroids
2) pubety onset 1-3³âÀü
¨ç
sleepµ¿¾È¿¡ low serum LH level secretionÀÇ º¯È°¡ ¿Í¼
sleep-entrained LH
secretion ÀÌ
pulsatile fashionÀ¸·Î º¯Çϸç À̰ÍÀº hypothalamic GnRHÀÇ
endogenous
episodic discharge·ê ¹Ý¿µÇÔ
¨è
gonadotrpinÀÇ pulsatile secretionÀ¸·Î
gonadsÀÇ ¼º¼÷°ú sex hormineºÐºñ°¡ ÀϾ
3) early puberty
2Â÷ ¼ºÂ¡ÀÌ ³ªÅ¸³²
hypothalamus, pituitary and
gonads »çÀÌ¿¡ Áö¼ÓÀûÀ̰í Ȱ¹ßÇÑ »óÈ£ ÀÛ¿ëÀÌ ±Ø´ëȵÊ
4) midpuberty
LH pulse°¡
daytime µ¿¾È¿¡µµ ³ªÅ¸³² (90-120 min °£°ÝÀ¸·Î ÀϾ)
5) middle or late adolescence
¨ç
cyclicity and ovulation ¹ß»ý
¨è
positive feedback mechanism ¹ß»ý ; midcycle µ¿¾È »ó½ÂµÈ
estrogen levels ÀÌ LHÀÇ
ÇöÀúÇÑ »ó½ÂÀ» ÀÏÀ¸Å´
2.
GnRH
pubetyÀÇ
onset°ú progression¿¡ °ü¿©ÇÏ´Â
major factorÀÓ
(°£Á¢Áõ°Å) sexually immature
animal¿¡ GnRHÀÇ
pulsed administration½Ã¿¡
pubertal development ³ªÅ¸³²
#
age of onset of puberty
; variable & more closely
correlated with osseous maturation
;
in girls
-
*breast bud : usually 1st sign (10-11
yr)
-
*breast bud 6-12 moÈÄ pubic hair°¡ ³ªÅ¸³´Ù.
-
*2-2.5³âÈÄ menarche°¡ ³ªÅ¸³ª¸ç, 6³â Á¤µµ±îÁö
´Ê¾îÁú¼ö ÀÖ´Ù.
/
mean age of menarche ; 12.75 yr (¹Ì±¹)
-
¹Ì±¹ÀÇ °æ¿ì ; 12¼¼±îÁö
95%, 13¼¼±îÁö 99%¿¡¼ puberty sign ÀÌ ³ªÅ¸³´Ù.
-
¡Úpeak height velocity
/
always precedes menarche
/
*at breat stage II-III, 11-12yr
; in boys
-
*growth of testes (>3ml in volume
or 2-5 cm in longest diameter) and thinning of penis
/
*1st sign
-
followded by pigmentation of the scrotum and growth of penis
-
and then pubic hair
-
¡Úpeak height velocity
/ *at
maximal genital stage IV-V, 13-14yr
-
growth spurt°¡ ¿©¾Æº¸´Ù ¾à 2³â Á¤µµ ´ÊÀ¸¸ç
18¼¼ ÀÌÈıîÁöµµ °è¼Ó ¼ºÀåÇÒ¼ö ÀÖ½¿
#
»çÃá±â ¹ßÇö¿¡ ¿µÇâÀ» ¹ÌÄ¡´Â ¿ä¼Ò
¨ç genetic and
environmental factors
; menarcheÀÇ
age°¡ ³·¾ÆÁö°í ÀÖÀ¸¸ç,
À̰ÍÀº
better nutrition°ú °³¼±µÈ genital health¸¦ ¹Ý¿µÇÔ
¨è ¹Ì±¹ÈæÀÎÀÌ ¹éÀκ¸´Ù ºü¸§
¨é ballet dancers,
gymnasts, runners, and other girl athletes
; early
childhoodºÎÅÍÀÇ leanness and strenous physical
activity°¡ puberty
ȤÀº
menarche¸¦ ÇöÀúÈ÷ °¨¼Ò½Ã۸ç, ¼ºÀÎÀÌ µÇ¾î¼µµ
oligomenorrhea ȤÀº
amenorrhea¸¦ º¸Àϼö ÀÖ½¿
¨ê adrenal cortical
androgens
; LH ȤÀº
sex hormoneÀÇ »ó½Â
±×¸®°í
pubertyÀÇ Ãʱ⺯Ȱ¡ ÀÖ±âÀü ¾à 6-8¼¼ °æ¿¡ »ó½ÂÇÏ´Â °æ¿ì
(adrenarche)
Chapter 517. Disorder of Pubertal Development
#
Precocious Puberty
;
puberty°¡ ½ÃÀÛÇÏ´Â ½Ã±â°¡ variation ÀÌ ½ÉÇϱ⠶§¹®¿¡ Á¤ÀÇÇϱⰡ
¾î·Æ´Ù.
; ´ë°³ ¼ºÂ¡ÀÇ ÃâÇöÀÌ ¿©¾Æ¿¡¼´Â
8¼¼ ÀÌÀü, ³²¾Æ´Â 9¼¼ ÀÌÀü¿¡ ³ªÅ¸³ª´Â °æ¿ìÀÓ
#
Classifications
1) true or central precocious
puberty
;
gonadotropin dependent
2)
peripheral precocious puberty or precocious pseudopuberty
;
gonadotropin independent
¡ÚTable
517-1
#
True Precocious Puberty
;
always isosexual
;
involved hypothalamic-pituitary-gonadal activation
;
2ndary sexual characteristics & gonadotropin-mediated increase in size
& activity of gonads
#
Precocious Pseudopuberty
;
some of 2ndary sexual characteristics
; no activation of normal
hypothalamic pituitary gonadal interplay
; isosexual or heterosexual
#
Mixed Type Of Precocious Puberty
; precocious pseudopuberty°¡
maturation of hypothalamic-pituitary-gonadal axis & trigger onset of true
precocious puberty
; ¢¾ÈçÈ÷ ÀϾ´Â
°æ¿ì
-
congenital adrenal hyperplasia
-
McCune-Albright syndrome
-
familial male precocious puberty
517.1 Gonadotropin-Dependent Precocious Puberty
;
°ú°Å¿¡´Â ºóµµ°¡ ³ô¾ÒÀ¸³ª CT scan°ú
MRIÀÇ ¹ß´Þ·Î ÇöÀç´Â idiopathic sexual
precocityºóµµ°¡ °¨¼Ò
;
*¿©¾Æ¿¡¼ 10¹è
ÀÌ»óÀÇ ¹ß»ýºóµµ
;
´ë°³´Â sporadicÇÏ°Ô »ý±â³ª ÀϺο¡¼´Â
familialÇÏ°Ô ¹ß»ý
Clinical Manifestations
#
advanced height, weight and osseous maturation
-->
early epiphyseal closure
--> ultimate short stature
in adults
:
less than 5 percentile in 1/3 girl, most boys
#
compatible mental development
#
*emotional behavior, mood swings
; but no serious psychologic
problems
#
¡ÚThree Main Patterns Of Progression
; rapidly progressive sexual
precocity
-
*6¼¼ ÀÌÀü¿¡
onset
-
rapid physical and osseous maturation
-
*height potentialÀÇ loss
; slowly progressive variant
-
6¼¼ ÀÌÈÄ¿¡ onset
-
*osseous maturation°ú linear growth°¡ º´ÇàÇÏ¿© height potentialÀº À¯ÁöµÊ
; unsustained central
precocious puberty
-
spontaneously regression
Laboratory Data
1) immunoradiometric, immunofluorimetric
and chemiluminescent assy for LH
; great diagnostic
sensitivity using random blood samples
LH°¡
prepubertal children¿¡¼´Â undetectable,
±×·¯³ª
central sexual precocity ¶§´Â 50-70%¿¡¼
detectable
2) ¼ö¸é½ÃÀÇ serial blood sample¿¡¼
LH ÃøÁ¤
; great diagnostic power
-- LHÀÇ
well-defined pulsatile secretionÀÌ ³ªÅ¸³²
3) GnRH stimulation test
; helpful diagnostic
tool particulary for boys
¿©¾Æ¿¡¼´Â
sexual developmentÀÇ early phase½Ã¿¡´Â
LHÀÇ ¹ÝÀÀÀÌ ³·À½
4) LH : FSH ratio
; midpubertal ±îÁö´Â
low
5) ¿©¾Æ¿¡¼ Ãʱ⿡´Â estrogen³óµµ°¡ ³·°Å³ª
undectable
³²¾Æ¿¡¼
s-testosterone levels°¡ detectable
6) both sex¿¡¼ sex hormone³óµµ´Â
puberty stage¿Í ÀÏÄ¡
7) osseous maturation ; variable advanced
8) pelvic ultrasonography
; ¿©¾Æ¿¡¼
ovaries°¡ progressive enlargement
µÚµû¶ó
uterus°¡ pubertal size·Î Ä¿Áü
9) CT, MRI scan
; Á¤»ó
puberty¿¡¼Ã³·³ pituitary gland°¡
physiologicÇÏ°Ô enlargement
Differential Diagnosis
1) organic central nervous system causes
of central sexual precocity
2) gonadotropin-independent causes of
isosexual precocious puberty
¨ç
in girls ; ovarian tumor, anovulatory functioning ovarian cysts, ferminizing
adrenal
tumors, McCune-Albright syndrome, exogenous source of estrogen
¨è
in boys ; congenital adrenal hyperplasia, adrenal tumors, Ledig cell tumors,
chorionic-gonadotropin-producing hepatoma, familial male precocious
puberty
Treatment
#
GnRH analog
; stimulatory effect·Î
pituitaryÀÇ gonadotropic cellsÀ»
desensitization
; rapidly progressive
precocious puberty°¡ ´ë»óÀÌ µÊ
; *leuprolide acetate (Lupron Depot Ped)
- *0.25-0.3 mg/kg IM once every 4wk
; other long active
preparations
-
*D-Trp6-GnRH(Decapeptyl), goseretin
acetate (Zoladex)
; side effect
-
fewer than 5%
-
*recurrent sterile fluid collection
at sites of injection
/
*¡ãserious
-
*change to daily s.c. injection of
aqueous analog (e.g. histrelin acetate[Supprelin], 10ug/kg/24hr
Effect Of Treatment
(1) decrease of the growth rate,
and even greater decrease of the rate of
osseous
maturation
(2) advanced (pubertal) bone age °æ¿ì
;
marked deceleration of their growth rate
complete arrest in the rate of osseous maturation
(3) in girls
¨ç ´ëºÎºÐ
breast size´Â º¯È°¡ ¾øÀ¸¸ç stage III-V Á¤µµÀ̸ç,
Á¡Â÷ÀûÀÎ adipose tissueÀÇ
Ä§ÂøÀ¸·Î ¾à°£Ä¿Áú¼öµµ
ÀÖ´Ù
¨è
pubic hair´Â does not progress
¨é
pelvic ultrasonography ; decrease
of the ovarian and uterus size
(4) in boys
¨ç
decrease of testicular size
¨è
variable regression of pubic hair
¨é
decrease in the frequeny of erections
(5) serum sex hormone
concentrations
¨ç
testosterone < 20 ng/dl in boys
¨è
estradiol < 10 pg/ml in girls
¨é
LH concentration< 1 IU/L
¨ê GnRH stimulation¿¡ ´ëÇÑ
FSH¿Í LHÀÇ Áõ°¡°¡ 1-2 IU/L ÀÌÇÏ
517.2 Precocious Puberty Resulting From Organic Brain Lesions
Etiology
-- involve the hypothalamus by scarring,
invasion, or pressure
(1) postencephalitic scars
(2) tuberculous
meningoencephalitis
(3) hydrocephalus
(4) tuberous sclerosis
(5) severe head truma
(6) optic glyoma, astrocytoma,
ependymomas, neurofibromas
(7) irradiation of the brain (eg.
children with leukemia)
(8) hypothalamic hamartoma
¨ç
most common brain lesion causing precocious puberty
¨è
ectopically located neural tissue containing GnRH secretory neurons
¨é
functions as an accessory GnRH pulse generator
¨ê
MRI
; small pedunculated mass attached to the tuber cinerium or the floor of the third
ventricle, less often sessile mass
¡Ø
intracranial hCG secreting germinomas
; do not produce precocious puberty in girls
because of complete ovarian function can not occur without FSH priming
Clinical manifestations
(1) precocious puberty
; neuroendocrine
manifestationÀº tumor°¡ ¹æ»ç¼±ÀûÀ¸·Î detectionµÇ±â 1-2³âÀü¿¡ ³ªÅ¸³²
(2) hypothalamic signs or Sxs
; DI, adipsia,
hyperthermia, unnatural crying or laughing (gelastic seizure),
obesity and cachexia
(3) growth hormone deficiency
; hypothalamic
hamartoma¶§ ÀϾ¼ö ÀÖÀ½
Áõ°¡µÈ
sex hormone levelÀÇ growth-promoting effect ¶§¹®¿¡
masked
Treatment
(1) neurosurgical intervention
; hypothalamic
harmartoma¶§´Â indicationÀÌ µÇÁö ¾ÊÀ¸¸ç
µå¹°°Ô
intractable seizure¶§ Àû¿ë
(2) Ä¡·á´Â pathogenic processÀÇ ¼º»ó°ú À§Ä¡¿¡ µû¶ó¼ ½ÃÇà
(3) GnRH analog
¨ç
central precocious puberty¸¦ ÀÏÀ¸Å°´Â organic brain lesion¿¡ È¿°úÀû
( idiopathic sexual precocity¿Í È¿°ú ºñ½Á )
¨è
choice to halt premature sexual development
(4) combined growth hormone
therapy
; associated
growth hormone deficiency°¡ ÀÖ´Â °æ¿ì
517.3 Syndrome of Precocious Puberty and Hypothyroidism
#
untreated hypothyroidism¿¡¼ unphysiologic precocious pubery
& prepubertal bone ageÀ» º¸ÀδÙ.
#
cause of hypothyroidism
; lymphocytic thyroiditis,
thyroidectomy, over treatment with antithyroid drugs
Clinical Manifestation
; growth retardation, osseous
maturation
; sexual development
-
breast enlargement, menstrual bleeding
-
large, multicystic ovaries in pelvic sonography
-
unlike in true precocious puberty
/
*testicular enlargement without
substantial leydig cell stimulation & testosterone secretion
/
*ovarian estrogen production without
concomitant increase androgens
Laboratory Finding
;
skull X-ray or MRI
-
enlargement of the skull
; TSH level
-
markedly elevated, often over 1000 ¥ìU/ml
; *mildly elevated prolactin and FSH, LH
; ¡Úhigh
FSH : LH ratio due to low LH level
Pathogenesis
; *¡°specificty spillover¡± by greatly elevated TSH ( TSH &
gonadotropin share indentical ¥á-chain)
; *impaired degradation of FSH and LH
Treatment
; thyroid hormoneÅõ¿©½Ã
biochemical profileÀÌ ºü¸£°Ô Á¤»óÀ¸·Î µ¹¾Æ¿È
; macroorchidism ( testicular
vol > 30 ml )Àº ÀûÀýÇÑ L-thyroxineÅõ¿© ÈÄ¿¡µµ Áö¼ÓÀûÀ¸·Î
³²À»¼ö ÀÖ´Ù
517.4 Gonadotropin-Secreting Tumor
Hepatic Tumor
(1) hepatoblastomaÀÇ ¾à
30%¿¡¼ isosexual precocious puerty¹ß»ý
(2) male¿¡¼¸¸ ³ªÅ¸³ª¸ç,
¹ß»ý½Ã±â´Â 4mo-8yr±îÁö ´Ù¾ç
( Æò±Õ 2yr )
(3) enlarged liver or mass in
upper quadrent
; suggest
the diagnosis
(4) tumor cells
; HCG¸¦ »ý»êÇÏ¿©
testesÀÇ Leydig cell¿¡ ÀÖ´Â
LH receptor¸¦ ÀÚ±Ø
(5) testicular histolgy
;
interstial cell hyperplasia and absence of spermatogenesis
(6) plasma hCG & ¥á-fetoprotein
; usually
markedly elevated
useful marked for following the effect of therapy
(7) plasma testosterone
; elevated
(8) treatment
; same as
other carcinoma of the liver
survivalÀº ´ë°³ Áø´Ü½ÃºÎÅÍ 1³â ÀÌÇÏ
Other Tumor
(1) Á¾·ù
¨ç
chorionic gonadotropin-secreting choriocarcinomas
¨è teratocarcinoma
¨é
teratomas
(2) location
CNS, mediastinum, gonads
(3) ³²¾Æ¿¡¼ more common
(4) affected patients
; often
marked elevation of hCG & ¥á-fetoprotein
Precocious Pseudopuberty
discussed in chapter 532 ( adrenal cause )
chapter 536 & 539 ( gonadal cause )
517.5 Mccune - Albright Syndrome
(=precocious
puberty with polyostotic fibrous dysplasia and abnormal pigmentation)
#
¡ÚƯ¡
1) endocrine dysfunction ; autonomous
hyperfunction of multiple glands
2) patchy cutaneous pigmentation
3) fibrous dysplasia of the skelatal
system
Etiology
;
*missense mutation in the gene
encoding the ¥á-subunit of Gs
--> *activation of receptors (e.g. ACTH, TSH, FSH, LH)
Clinical Manifestation
#
Precocious puberty
; predominantly in girls
-
*onset about 3yr
- vaginal bleeding
/
as early as 4mo
-
secondary sex characteristics
/
as early as 6mo
-
suppressed LH, FSH
-
no response to GnRH stimulation
-
Estradiol
/ normal to markedly
elevated ( > 900pg/ml ), often cyclic
/ correlate with the
size of the cysts
; in boys
-
less common
-
testicular enlargement
/ fairly symmetric
/ fallowed by appearance of phallic
enlargement, pubic hair as in normal puberty
-
testicular histology
/ large seminiferous
tubules
/ no or minimal Leidig cell hyperplasia
; bone age°¡
usual pubertal age¿¡ µµ´ÞÇßÀ»¶§
-
gonadotropin serecretion
-->
pubertal response to GnRH
-->
*true precocious puberty°¡ combined µÇ¾î mixed typeÀ¸·Î
µÈ´Ù.
#
hyperthyroidism
; equal in male and female
; multinodular
; uncommon clinical symptoms
but goiters
; mildly elevated T3 level
but suppressed TSH level
#
¡ÚCushing Syndromes
; *bilatal nodular adrenocortical hyperplasia in early infancy
; preceding sexual precoicity
;
low ACTH level, not suppressed adrenal function by large dose dexamethasone
#
gigantism or acromegaly
; elevated GH due to
increased TRH
#
increased serum prolactin level
#
extraglandular manifastation
; *phosphaturia, leading to richets or
osteomalacia
; rare cardiovascular and
hepatic involvement
Treatment
1) functioning ovarian cyst
¨ç
often disappear spontaneiusly
¨è
aspiration or surgical excision of cyst ; rarely indicated
2) persistent estradiol secretion
; testolactone,
aromatase inhibitor (estrogen »ý¼ºÀÇ ¸¶Áö¸· ´Ü°è¸¦ Â÷´Ü)
--
estrogen productionÀ» normalize ½ÃŰÁö´Â ¸øÇÔ
3) long-acting agonist of GnRH
; puberty°¡
gonadotropin-independent¿¡¼ ¸í¹éÇϰÔ
gonadotropin-dependent mechnismÀ¸·Î ÀÌÇàÇϴ ȯÀÚ¿¡ ÀûÀÀ
4) cushing synd
; adrenalectomy
5) hypersomatotropism
; octreotide, a
long-acting somatostatin inhibitor
Prognosis
1) favorable for longevity
2) deformities, repeated fracture, pain
and
ocasional cranial n.
compressionÀÌ bony lesionÀ¸·Î ÀÎÇØ ¿Ã¼ö ÀÖÀ½
517.6 Familial Male Gonadotropin - Independent Precocious Puberty
1.
male-limited autosomal dominant sexual precoicity
¨ç
gonadotropin independent
¨è
transmitted through affected males,
unaffected female carriers of the gene
¨é
sign of puberty ; 2-3 yr of age
¨ê
testis ; slight enalrged
biopsy»ó¿¡¼ Leidig cell matuartion°ú ÀϺο¡¼´Â
marked hyperplasia ¼Ò°ßº¸À̸ç seminiferous tubuleµµ
matuartion
¨ë
testosterone levels
; marked elevated
¨ì
LHÀÇ baseline levels
; prepubertal state, pulstile secretionÀº ¾øÀ¸¸ç,
GnRH stimulation¿¡ no response
¨í
osseous maturation
; markedly advanced
¨î
sexual precoicity´Â gonadotropin independentÀÌÁö¸¸,
Á¡Â÷ gonadotropin dependent·Î µÊ
Treatment
1) ketoconazole (600mg/ 24hr in # 3)
inhibit
C-17, 20- lyase and testosterone synthesis
2) combination of spironolactone (block
androgen action) &
testosterone (competitive inhibitor of aromatase)
; serum testosteroneÀ» prepubertal ³óµµ·Î ³·ÃßÁö ¸øÇϰųª,
testosterone effect¸¦ ¿ÏÀü Â÷´ÜÇÏÁö´Â ¸øÇÔ
517.7 Incomplate (Partial) Precoicous Development
* pubertyÀÇ ´Ù¸¥ signsÀº ³ªÅ¸³ªÁö ¾Ê°í
precoicityÀÇ isolated manifestation¸¸ ÀÖÀ¸¸ç,
µå¹°Áö ¾Ê°Ô ¹ß»ýÇÔ
* two most common
(1) development of breast in
girls
(2) growth of sexual hair in
both sex
Premature Thelarche
(1) transient condition of
isolated breast development,
sporadicÇÏ°Ô ¹ß»ýÇÏ¸ç µå¹°°Ô familial
(2) ´ëºÎºÐ »ýÈÄ Ã¹ 2³â³»¿¡ ³ªÅ¸³ªÁö¸¸,
ÀϺο¡¼´Â Ãâ»ý½ÃºÎÅÍ ³ªÅ¸³¯¼ö ÀÖÀ½
(3) ´ë°³ ¾çÃø¼ºÀÌÁö¸¸ unilateral or
asymetric Àϼöµµ ÀÖÀ½
(4) growth & ossoeus
maturation
; normal or slight advanced
(5) genitalia
; no evidence of estrogen stimulation
(6) menarche
; occurs at expected age & reproductionµµ
normal
(7) LH¿Í
estriol
; below the limit of the assay
(8) basal FSH¿Í
GnRH stimulation¿¡ ´ëÇÑ LHÀÇ ¹ÝÀÀ
; normal controls°æ¿ì º¸´Ù greater
cf) true precocious puberty¶§´Â
LH°¡ ÇöÀúÇÏ°Ô »ó½Â
(9) ultrasound examination of ovaries
; normal size, ÀϺο¡¼´Â
small (< 9cm) cyst°¡ ÈçÇÔ
(10) ÀϺο¡¼´Â breast develpoment°¡ ¸í¹éÇϰÔ
systemic estrogen effect ¿Í
°ü·ÃÀÌ ÀÖÀ¸¸ç ÃÊÀ½ÆÄ»ó
ovaries or uterus°¡ enlarged
(exaggerated or atipical thelarche)
spontaneously
regressionÇÑ Á¡¿¡¼ central precocity¿Í ´Ù¸§
(11) premature thelarche´Â
benign conditionÀÌÁö¸¸ true or pseudoprecocious puberty ÀÇ
1st sgÀ̰ųª,
exogeneous estrogenÀÇ È¿°úÀÏ ¼ö ÀÖÀ¸¹Ç·Î »ó¼¼ÇÑ history¸¦ Çϰí
bone age¸¦ ÃøÁ¤ÇÑ´Ù.
serum LH, FSH,
estradiol ³óµµ°¡ ³·Áö¸¸ Áø´ÜÀû °¡Ä¡´Â ¾øÀ¸¸ç,
continued
observation ÀÌ Áß¿äÇÔ
¡Ø 3¼¼ ÀÌÈÄÀÇ
thelarche
; ´ëºÎºÐ¿¡¼
precocious thelracheº¸´Ù´Â ´Ù¸¥ ¿øÀÎÀ» »ý°¢
¡Ø regression &
recurrence thelarche
;
functioning of follicular cyst¸¦ ¾Ï½Ã
Premature Adrenarche
(1) sexual hair°¡ ¿©¾Æ¿¡¼
8¼¼,
³²¾Æ¿¡¼
9¼¼ ÀÌÀü¿¡ ³ª´Â °æ¿ì·Î ´Ù¸¥ ¼º¼÷ÀÇ Áõ°Å°¡ ¾ø´Ù
(2) ³²¾Æº¸´Ù ¿©¾Æ¿¡¼ ´õ ÈçÇÔ
(3) hair´Â
labia majora¿¡¼ ½ÃÀÛÇÏ¿© Á¡Â÷ pubic region°¡Áö ÁøÇàµÇ¸ç,
¸¶Áö¸·¿¡
axilla¿¡ ³ªÅ¸³ª¸é¼ ¼ºÀÎÇüÀÇ axillary oder°¡ ÈçÇÏ°Ô µ¿¹ÝµÊ
(4) height & osseous
maturation
; sl
advanced
(5) adrenal androgen productionÀÇ
early matuartion event·Î zona reticularÀÇ
Á¶±â ¼º¼÷°ú ÇÔ²²
3¥â-hydroxy steroid-dehydrogenase
activity°¡ °¨¼ÒµÇ°í
C-17, 20-lyase
activity°¡ Áõ°¡ÇÔ
°á°úÀûÀ¸·Î
basal and ACTH-stimulated ¡â5 _ steroid (17-hydroxypregnenolne and
DHEA)ÀÇ Ç÷Áß³óµµ°¡ »ó½Â
(6) benign conditionÀ¸·Î Ä¡·á´Â ÇÊ¿äÄ¡ ¾Ê´Ù
(cf) atypical premature adrenarche
- ¼Ò¼ö¿¡¼ marked growth acceleration, clitorial or
phallic enlargement,
cystic acne, advanced bone ageµîÀÇ systemic androgen
effectÀÇ Æ¯Â¡ÀÌ
1°¡Áö ȤÀº ±× ÀÌ»ó ³ªÅ¸³²
- ACTH stimulation test¸¦ ÇÏ¿©
17-hydroxyprogesteronÀ» ÃøÁ¤ÇÔÀ¸·Î½á
nonclassic congenital adrenal hyperplasia¸¦ rule out
(7) ¼ºÀÎÀÌ µÇ¾úÀ»¶§ hyperadrenalism°ú
polysystic ovarian syndromeÀÇ high riskÀÓ
Premature Menarche
(1) premature thelarche, or
adrenarcheº¸´Ù less frequent
(2) affected girlsÀÇ ´ëºÎºÐÀº
1-3 ¹ø bleeding episode°¡ ÀÖÀ½
(3) plasma gonadotropinÀº Á¤»óÀ̸ç,
estradiol levelÀº »ó½Â
(4) °¨º°Áø´ÜÀ¸·Î´Â vulvovaginitis, foreign body, urethral
prolapse,
sarcoma
botryoides µîÀÌ ÀÖÀ½
517.8 Medicatinal Precoicity
(1) sex hormone¿¡
exposeµÇ°Å³ª ingestionÇÑ
Hx °¡ ÀÖÀ½
¨ç
estrogen in cosmetics
¨è
hair cream
¨é
breast augmentation cream
(2) vitamin tablet°¡
sex hormoneÀ¸·Î contaminationµÈ °æ¿ì
(3) exogenous estrogen
; breastÀÇ areolar°¡
intense, dark, brown color
(4) precocious´Â
hormone exposure°¡ Áß´ÜµÇ¸é »ç¶óÁü
Section 2. Disorders of the Thyroid Gland
Thyroid Physiology
#
main function
; thyroxine(T4), 3, 5,
3'-triiodothyronine(T3) synthesis
#
iodine
1) recommended dietary allowance.
¨ç
40-50ug/24h for infants
¨è
70-120ug/24h for children
¨é
150ug/24h for adolescences & adults
2) *reaches
thyroid gland as iodide
#
ÇÕ¼º °úÁ¤
1)
oxidization of iodide by thyroidal peroxidase
2) iodination of tyrosine
->
monoiodotyrosine, diiodotyrosine
3) production
of T3, T4
;
diiodotyrosine + diiodotyrosine ---> T4
; diiodotyrosine +
monoiodotyrosine ---> T3
4)
storage as thyroglobulin in lumen of the follicle
5) liberation from
thyroglobulin
;
by activation of protease & peptidase
#
T3
1) T3°¡ T4º¸´Ù 3-4¹è Á¤µµ ´ë»ç¼º ¿ª°¡¸¦ °¡Áü
2) adult : T4 100 ug
T3 20 ug ¸ÅÀÏ »ý¼º
3) »ý¼º
¨ç
20% : thyroid ¿¡¼ »ý¼º
¨è ³ª¸ÓÁö
: T4ÀÇ deiodinationÀ¸·Î »ý¼º
in liver, kidney, other peripheral tissue by type I 5'-deiodinase.
in pituitary gl. & brain
-- ´ë·« 80%À» type ¥±
5`-deiodinase¿¡ÀÇÇØ
T4·Î ºÎÅÍ »ý¼º.
4) T3 °¡ »ý¸®ÇÐÀû ÀÛ¿ëÀÇ ´ëºÎºÐÀ» ÇÔ
#
T4
1) T4´Â ¾çÀº ¸¹À¸³ª nuclear receptor¿Í ¾àÇÏ°Ô °áÇյǾî ÀÖ°í
T3·Î ÀüȯÇÏ¿© »ý¹°ÇÐÀû
Ȱ¼ºÀ» ³ªÅ¸³¿
2) Ç÷¾× ³» T3 level Àº
T4ÀÇ 1/50 ÀÓ
#
ÀÛ¿ë
1)
increase oxygen consumption
2)
stimulate protein synthesis
3)
influence growth & differentiation
4)
affect carbohydrate, lipid, & vitamin metabolism
#
ÀÛ¿ë ±âÀü
1) intracellular T3´Â
nucleus ³»·Î µé¾î°¡ thyroid hormone
receptor¿Í °áÇÕÇϴµ¥,
ÀÌ
receptorµµ steroid hormone receptor (
glucocorticoid, estrogen, progesterone,
Vit
D, retinoids ) °è¿ÀÌ´Ù.
4°¡Áö
type ¥á1 & 2 , ¥â1
& 2
2) circulating T4ÀÇ
70%´Â thyroxine-binding globulin (TBG)¿Í °áÇÕÇØ ÀÖ°í,
³ª¸ÓÁö´Â
thyroxine-binding prealbumin°ú °áÇյǾî ÀÖ´Ù
´ÜÁö
0.03%¸¸ÀÌ free thyroxine (FT4)¸¦ ±¸¼ºÇÑ´Ù.
3) circulating T3ÀÇ
50% °¡ TBG¿Í °áÇÕÇϰí 50%´Â
albumin¿¡, 0.3%¸¸ÀÌ
unbound or
free T3·Î Á¸ÀçÇÔ.
#
Regulation
1) TSH (thyroid - stimulating hormone)
¨ç
glycoproteinÀ¸·Î ant. pituitary¿¡¼ »ý¼º ºÐºñµÊ
¨è
thyroid gland³» adenylate cyclase¸¦ Ȱ¼ºÈ ½ÃÅ´
¨é
2°³ÀÇ noncovalently bound
subunits(chain)·Î ±¸¼ºµÊ. ¥á ¥â(hTSH-¥â)
(i) ¥á-subunit
: LH, FSH, chorionic gonadotropin°ú °øÅë
(ii)
¥â-subunit : hormoneÀÇ Æ¯À̼ºÀ» ºÎ¿©
2) TRH (thyroid - releasing hormone )
¨ç
hypothalamus¿¡¼ ÇÕ¼ºµÇ¾î pituitary ·Î ºÐºñ
¨è
tripeptide
¨é
endocrine function + neurotransmitter.
3) excess TSH or TSH °úÀ×
-->
hypertrophy & hyperplasia of thyroid cells increased trapping iodine.
increased synthesis of tyroid hormone.
4) exogenous thyroid hormone or
increased thyroid hormone synthesis
--> inhibit
TSH & TRH production
5)
decreased extrathyroidal production of T3
( fasting,
malnutriton, acute illness, drug )
-->
inhibition of thyroxine 5'-deiodinase
--> T3 ¡é
T4 TSH normal
Chapter 518. Thyroid Hormone Studies
Serum Thyroid Hormone
;
T4, free T4, T3, free T4, diiodothyronine, reverse T3( 3,
5¡¯3¡¯-triiodothyronine)
#
Thyroglobulin (Tg)
; glycoprotein dimer
; thyrocyteÀÇ
apical surf.¸¦ ÅëÇØ colloid³»·Î ºÐºñµÊ
; ¡è
-
TSH stimulation
-
neonate
-
Graves¡¯ ds.
-
endemic goiter
- *Ca of thyroid(¡è¡è)
; ¡é
-
TSH suppression
-
athyreotic infant(¡é¡é)
#
TSH
; extremely sensitive
indicator of primary hypothyroidism
; assay
-
radioimmunoassay
-
immunometeric assay
- *chemiluminescent assay
/
at now standard method
; normal level < 6 uU/ml
¡Ø92
TRH stimulation test
; 7ug/kg IV
; normal
-
30ºÐ À̳» TSH baseline level Áõ°¡
; hyperthyroidism - no rise
in serum TSH level
; mild thyroid failure -
exaggerated TSH responce
; pituitary or hypothalamic
failure - low basal level of TSH
Fetal & Newborn Thyroid
1)
¸ðüÀÇ ¿µÇâ°ú´Â µ¶¸³ÀûÀ¸·Î hypothalamic-pituitary
system¹ß´Þ
ÀÓ½Å
10-12ÁÖ fetal thyroid : iodineÀ»
conc.--> iodothyronineÇÕ¼º ´É·ÂÀ» °¡Áü
fetal pituitary
: TRH ÇÔÀ¯
2)
fetus
(1) serum T4 : ÀӽŠÁß¹Ý ºÎÅÍ Á¡Â÷ Áõ°¡ÇÏ¿©
term¿¡ 11.5ug/dl.
(2) serum T3 : ÀÓ½Å
20ÁÖ ÀÌÀü¿¡´Â ³·´Ù°¡ term¿¡
60ug/dl
(3) reverse T3 : fetus½Ã ¸Å¿ì ³ô´Ù°¡
(250ng/dl at 30ÁÖ), term¿¡
150ng/dl±îÁö ¶³¾îÁü.
(4) serum TSH : Á¡Á¡ Áõ°¡ÇÏ¿©
term¿¡ 10uU/ml
3)
maternal T4 : 1/3Á¤µµ°¡ ŹÝÀ» Åë°úÇÏ¿© fetal thyroid H. ÇÕ¼º Àü±îÁö
fetal development
(ƯÈ÷ brain)¿¡ ¿ªÇÒÀ» ÇÔ.
(1) hypothyroid mother --> at
risk for neurologic damage.
(2) hypothyroid fetus --> ºÐ¸¸ Àü±îÁö
maternal T4¿¡ ÀÇÇÑ partial protection
4)
¢¾Change at birth
; acute release of TSH
-
*peak serum conc. 70uU/ml in 30min in
full term
-
*rapid decline in 24hr within the
next 2days to 10uU/ml
;
T4
-
dramatic rise (*16ug/dl)
-
*gradually fall during the first 2wks
to 12ug/dl
; T3
-
*300ng/dl in about 4hr
(largely peripheral conversion of T4)
-
*decline during the 1st wks to
200ng/dl
; reverse T3
-
2ÁÖ µ¿¾È 200ng/dl ·Î À¯ÁöµÇ´Ù°¡
4ÁÖ¶§ 50ng/dl Á¤µµ·Î °¨¼Ò
Serum Thyroxine-Binding Globulin
;
liver¿¡¼ »ý¼ºµÇ´Â glycoprotein.
;
T4ÀÇ 70%, T3ÀÇ
50%¿Í °áÇÕÇÔ
#
¢¾Áõ°¡ÇÏ´Â
°æ¿ì
; pregnancy
;
newborn period
;
estrogen (oral contraceptives)
; *perphenazine
;
heroin
#
¢¾°¨¼ÒÇÏ´Â
°æ¿ì
; androgen
;
anabolic steroid
;
glucocorticoid
; *L-asparaginase
; ¡Úphenytoin, phenobarbital
-
increased hepatic degradation of TBG
-
accelerated transport T4 to tissue
-
inhibition of T3, T4 binding to TBG
; *congenital NS
#
ÃøÁ¤¹æ¹ý
; RT3U (resin
triiodothyronine uptake test)
-
TBG level¿¡ µû¸¥ T4 level ÇØ¼®
; *T4-RT3U index (thyroxine-resin T3 index)
-
correlation with free T4
-
¡è : hyperthyroidism
-
¡é : hypothyroidism
- normal : euthyroid /c
mild abnormal
In Vivo Radionuclide Studies
1)
123I (half-life ;13hr)
cf. 131I ; known thyroid cancer ¿¡¸¸
»ç¿ë
2)
¡Ú99mTc (half-life ;6hr)
; *ƯÈ÷ ¼Ò¾Æ¿¡
¸¹ÀÌ »ç¿ë
;
trapping but *no organification
3)
Thyroid scan
; ¢¾Ix
-
ectopic thyroid tissue
- thyroid nodule
- assess the presense of thyroid tissue in thyroid agenesis
; 99mTc perechnetate »ç¿ë½Ã ÀÕÁ¡
¨ç
lower radiation exposure
¨è
high-quality scintigram
Chapter 519. Defects of Thyroxine-Binding Globulin
;
*clinical ds¿Í
°ü·ÃÀÌ ¾ø°í
Ä¡·áÇÒ Çʿ䰡
¾ø´Ù
TBG deficiecy
1) *X-linked
dorminant disorder
2) Á¾Á¾ neonatal
hypothyroidism screening½Ã ¹ß°ßµÊ
¡ÚLaboratory Finding
; *T4(¡é), RT3U(¡è), freeT4(¡æ), TSH(¡æ)
¡ÚDiagnosis
; TBG (-) or low level
Pathogenesis
; codon mutation(leucine to
proline), point mutation
Epidermiology
¨ç
male > female
¨è
1/2400 newborn males
¨é
36 % : TBG < 1mg/l
¨ê
mild TBG deficiency
1/42000 heterozygous females
¨ë
complete TBG deficiency ( < 5¥ìg/l ) : less frequently
3/8
: codon mutation ( leucine -> proline )
5/8
: reduced affinity of TBG for T4
Elevated TBG
1) *harmless
X-linked dominant
2) 1/2500
Laboratory Finding
;
T4 ¡è ( partly due to maternal estrogen
)
;
T3 ¡è
; *normal TSH, free T4
; *RT3U ¡é
Diagnosis
; TBG ¡è,
free T4 n'l
5) euthyroid
6) acquired ¡è
¨ç
pregnancy
¨è
estrogen Tx
¨é
hepatitis
Familial Dysalbuminemic Hyperthyroxinemia
1) autosomal dominant disorder
2) DDx : hyperthyroidism
3) Lab
¨ç
T4 ¡è : abnormal albumin variant¿Í °áÇÕÇÏ´Â
T4 ¡è
¨è
free T4, free T3, TSH n'l
¨é
T3 : normal or sl. ¡è
4) euthyroid
Chapter 520. Hypothyroidism
;
deficient production of thyroid hormone or defect in its receptor
¢¾Table
520-1
Congenital Hypothyroidism
Etiology
Thyroid dysgenesis
;
prevalence
- 1/4000 worldwide
- lower in black americans
;
*90% of infant hypothyroidism
- 1/3 : thyroid aplasia on
radionuclide scan
-
2/3 : rudimentsÀÇ ectopic location
-
base of tongue (lingual thyroid) to normal position of neck
;
*asymptomatic at birth even if
complete agenesis
- due to transplacental
passage of maternal thyroxine(T4)
; Diagnosis
- T4¡é,
TSH¡è
- screenÀ¸·Î
hypothyroid neonate °¨º° °¡´É
;
*M : F = 1 : 2
;
¡ÚPathogenesis
1) *thyroid growth-blocking & cytotoxic
antibody
2) *maternal TSH-binding Ab
;
Ectopic thyroid tissue ( lingual, sublingual, subhyoid )
¨ç ¼ö³â µ¿¾È ÃæºÐÇÑ ¾çÀÇ thyroid hormoneÀÌ °ø±ÞµÇ°Å³ª
À¯¾Æ Ãʱ⿡ ºÎÁ·ÇØÁü
¨è ÀÓ»óÀûÀ¸·Î tongue base ¶Ç´Â
neck midline ( hyoid ) ÀÇ growing mass·Î ÀÎÁöµÊ
¨é ¶§·Î thyroglossal duct cyst¿Í °ü·ÃµÇ±âµµ
µÊ
¨ê euthyroid ȯ¾Æ¿¡¼
ectopic thyroid tissueÀÇ surgical removal·Î
hypothyroidismÀ» ÃÊ·¡Çϱ⵵ ÇÔ
Thyrotropin Receptor-Blocking Antibody ( TRBAb )
;
formly called thyroid-binding inhibitor immuniglobulin ( TBII )
;
cause of transitory congenital hypothyroidism
;
frequency 1/50000-100000
#
¢¾suspicion condition
; maternal autoimmune thyroid
ds (Hashmoto thyroiditis)
; maternal Graves ds.
;
maternal hypothyroidism on replacement Tx
;
recurrent congenital hypothyroidism of a transient nature in subsequent
siblings
--> measure maternal TRBAb
level
;
often have thyrotropin receptor-stimulating antibody(TRS Ab),
antiperoxidase(=antimicrobial) Ab
;
Thyroid scan
- *thyroid tissue (-)
- but replacement Tx Áß´ÜÈÄ
normal thyroid gl.
;
half-life of Ab
- 7.5 days
;
remission in about 3 mo
Defective Synthesis of Thyroxine
#
¢¾Characteristic
; congenital hypothyroidism
; incomplete defect
; compensation
; *delayed onset
; *almost always goiter
; autosomal recessive
Defect Of Iodide Transport
¨ç
1/3 : consanguinity ( Japan )
¨è °ú°Å¿¡´Â
goiterµ¿¹Ý À¯¹«¿Í °ü°è¾øÀÌ clinical
hypothyroidismÀÌ »ýÈÄ ¸î´Þ
³»¿¡ »ý°åÁö¸¸, ÃÖ±Ù
neonatal screening program¿¡¼ detectµÊ
¨é ÀϺ»¿¡¼´Â
½Ä»ç¿¡ iodine content ÇÔ·®ÀÌ ¸Å¿ì ³ô´Ù
( 19 ng/24 hr )
--> 10³â ÈÄ goiter¿Í
hypothyroidismÀ¸·Î ¹ß»ý
¨ê
thyroid & salivary gl.¿¡¼ iodine concentration ´É·ÂÀÌ ºÎÁ·ÇÔ
¨ë
uptake of radioiodine & pertechnetate °¨¼Ò
¨ì
saliva ; serum ratio of 123I : Áø´Ü¿¡ µµ¿ò
¨í
Tx ; °ú·®ÀÇ potassium iodine Ä¡·á¿¡µµ ¹ÝÀÀÇÏÁö¸¸
thyroxineÀ¸·Î
Ä¡·áÇϴ°ÍÀÌ ´õ ¹Ù¶÷Á÷ÇÔ
Thyroid Peroxidase Defects Of Organifiaction & Coupling
¨ç
most common defect
¨è
iodide°¡ thyroid¿¡
trapµÇ°í oxidationµÇ¾î
reactive iodineÀ¸·Î µÈÈÄ
tyrosine units¿¡ Æ÷ÇÔµÊ
; ÀÌ °úÁ¤Àº H2O2, thyroid
peroxidase hematin»ý¼ºÀÌ ¿ä±¸µÊ
¨é
Dx
(i) radioiodine
test doseÅõ¿© 2½Ã°£ÈÄ perchlorate or
thiocyanate Åõ¿©½Ã
thyroid radioactivityÀÇ marked decrease
(ii) perchlorate discharge°¡ Á¤»ó¿¡¼´Â 10%ÀÌÇÏ¿¡ ºñÇØ ÀÌ·± ȯ¾Æ¿¡¼´Â
40-90% radioiodineÀ» ¹æÃâÇÔ
¨ê
Pendred syndrome
(i)
sensorineuronal defness & goityer
(ii) (+) perchlorate discharge
Defects Of Thyroglobulin Synthesis
¨ç
goiter
¨è
Lab
©Í TSH Áõ°¡
©Î T4 °¨¼Ò
©Ï thyrogloburin( Tg) ; (-) or low
Defects In Deiodination
; *deficiency of deiodinase
-->
inhibition of deiodination of monoiodotyrosine & diiodotyrosine in thyroid
& pph tissue
-->
*no recycling of iodine
-->
*urinary loss of nondeiodinated
tyrosine
-->
hormonal deficiency & goiter
Radioiodine
¨ç
thyroid ca. ¶Ç´Â hyperthyroidismÀÇ Ä¡·á¸¦ À§ÇØ ÀӽŽÃ
radioiodineÀ»
ºÎÀûÀýÇÏ°Ô Åõ¿©ÇÑ °æ¿ì hypothyroidismÀÌ À¯¹ßµÊ
¨è
fetal thyroid´Â 70-75ÀÏ Âë¿¡
iodine trappingÀ» ÇÒ¼ö ÀÖÀ½
¨é °¡Àӱ⠿©¼º¿¡
radioiodineÅõ¿©ÇÒ ¶§´Â Åõ¿©Àü pregnancy test¸¦ ¹Ýµå½Ã
½ÃÇàÇϸç, ¼öÀ¯ ¿©¼º¿¡°Ô radioactive iodineÅõ¿©´Â ±Ý±âÀÓ
Thyrotropin defeciency
#
developmental defect of pitiutary or hypothalamus
(2) TSH - deficient
hypothyroidism
¨ç
1/30000 - 1/50000
¨è
neonatal thyroid screening ¿¡¼ 30-40% detect
¨é ´ëºÎºÐ
multiple pituitary deficiency
¨ê Sx
+-hypoglycemia
| persistent jaundice
| micropenis ~c septooptic dysplasia
| midline cleft lip
| midface hypoplasia
+-other midline facial anomalies
#
¢ÀPit-1 gene Mutations
; deficiency of thyrotropin,
growth hormone & prolactin
; Pit-1
-
tissure transcription factor
- differentiation, maintenance & proliferation of somatrophs,
lactotrophs & thyrotrophs
; TRH stimulation test
-
*failure of prolactin response to TRH
--> exam
of Pit -1 gene
#
mutation in the TSH -receptor (TSHR) gene
¨ç Lab
; TSH Áõ°¡, T4 Á¤»ó
¨è
autosomal recessive
¨é
TSH¿¡ ´ëÇÑ resistance¸¦ º¸ÀÓ¿¡µµ ºÒ±¸Çϰí Ä¡·á¾øÀ̵µ
euthyroid·Î
³²´Â °æ¿ìµµ ÀÖ°í, severe hypothyroidismÀ¸·Î Ä¡·áÇÑ °æ¿ìµµ ÀÖÀ½
#
Isolated deficiency of TSH
¨ç
rare autosomal recessive
¨è
different point mutations in TSH ¥â- subunit gene
Thyrotropin hormone Unresponsiveness
(1) mild congenital
hypothyroidismÀ¸·Î detectµÈ
newborn infant°¡ ÈÄ¿¡ type Ia
pseudohypoparathyroidismÀ¸·Î Áõ¸íµÊ
(2) generalized impairment
of cAMP activation
by genetic deficiency of ¥á subunit of guanine nucleotide
regulating protein (G5¥á)
(3) Lab
¨ç
T4 °¨¼Ò
¨è
TSH Áõ°¡
¨é
no response to exogenous TSH administration
Thyroid hormone unresponsiveness
(1)´ëºÎºÐÀÇ È¯ÀÚ´Â
goiter¸¦ °¡Áö°í ÀÖ½¿
(2) Lab
T4,
T3 free T4 , free T3 Áõ°¡
( DDx; graves ds)
(3) Sx
¨ç
mild mental retadation
¨è
growth retadation
¨é
delayed skeletal maturation
¨ê attention - deficit
hyperactivity disorder ( ADHD )
(4) Dx
¨ç
TSH ; diagnostic
not- suppressed (as in graves ds)
mod. Áõ°¡ ȤÀº Á¤»ó
¨è
TSH response to TRH (+)
¨é
failure of TSH suppression
; resistance°¡
generalizedÇϰí, peripheral tissues »Ó¸¸¾Æ´Ï¶ó
pituitary±îÁö ¼Õ»ó.
(5) autosomal dorminant
(6) neonatal thyroid
screening½Ã T4 »ó½Â½Ã ÀǽÉÇÒ¼ö ÀÖ°í, growth & skeletal
retardationÀÌ
¾øÀ¸¸é Ä¡·á´Â ÇÊ¿äÇÏÁö ¾ÊÀ½.
(7) autosomal recessive form
of thyroid resistance
¨ç
hypothyroidism early in life
¨è
DNA study, major deletion of ¥â-thyroid receptor
(8) selectively resistance
to thyroid hormone
¨ç
pituitary gl.¿¡¸¸ ¿µÇâ
¨è
peripheral tissue´Â thyroid hormone¿¡
resistant ÇÏÁö ¾ÊÀ¸¹Ç·Î ȯ¾Æ´Â goiter &
hyperthyroidismÀÇ ¾ç»óÀ» º¸ÀδÙ
¨é
DDx : pituitary TSH-secreting tumor
Other Cauce of Hypothyroidism
(goiter µ¿¹Ý)
¨ç
fetal exposure to excessive or antithyroid drugs
; transient
¨è
topical iodine-containing antiseptics
; transient
ƯÈ÷ low birthweight infant
--> neonatal screening test»ó abnormal result ¾ß±â
¨é
asthma Tx drug
¨ê
amiodarone
; antiarrhythmic drug /c high iodine content
¡Ø°´ Clinical Manifestations
;
*M : F = 1 : 2
;
normal birthweight & length
- but increased head size due
to myxedema of brain
;
¡Ø°´prolongation of physiologic
icterus
- *earlist sign
- due to delayed maturation
of glucuronide
;
feeding difficulties, sluggishness, lack of interest, somnolence, choking
spells during nursing
- during 1mo
;
resp. difficulties
- due to large tongue)
;
apneic episode, noisy respiration, nasal obstruction
;
typical respiratory distress syndrome
;
weak crying, poor appetite
;
constipation
- not respond to Tx
;
large abdomen
;
umbilical hernia
;
*subnormal body temperature (<35¡É)
;
skin (esp. extremities) - cold, mottled
;
edema of genitalia & extremites
;
slow pulse
;
heart murmur, cardiomegaly, asymptomatic pericardial effusion
;
anemia - refractory to Tx with hematonics
=>
progress above Sx & Sg
=>
retardation of physical and mental development
=>
fully developed by 3-6mo of age
;
stunted growth, short extremities
;
open ant. & post. fontanel
- initial clue of congenital
hypothyroidism
;
face
¨ç eyes : far apart
¨è bridge of broad nose :
depressed
¨é narrow palpebral
fissure.
¨ê swollen eyelids.
;
short & thick neck
;
deposit of fats above clavicle, neck, shoulder
;
delayed dentition
;
hand - broad, short fingers
;
carotenemia
-
yellow discoloration of skin, white sclera
;
thickened scalp, coarse, brittle, scanty hair, far down hairline
;
Developmental retardation
¨ç
lethargic
¨è
late in learning to sit & stand
;
delayed sexual maturation
;
hypotonic
#
¡ÚKocher-Debré-SéMé-Laigne Syndrome
; generalized m. hypertrophy
;
athletic appearance due to pseudohypertrophy
-
esp. calf muscle
; Ä¡·áÈÄÀÇ
m. biopsy ¼Ò°ß ; Á¤»óÀ¸·Î µ¹¾Æ¿È.
;
boy > girl
;
longer duration & severity of hypothyroidism
Laboratory Data
#
¢¾Neonatal screening
1)
measure levels of T4, and then TSH when low T4
; identifies primary
hypothyroidism, low TBG, hypothalamic or pituirary hypothyroidism,
hyperthyroxinemia
; *miss ectopic thyroid, thyroid dysgenesis, compensated
hypothyroidism
2)
measure levels of TSH
; detect compensated hypothyroidism
; *miss hyperthyroxemia, low TBG, hypothalamic or pituitary
hypothyroidism
#
TFT
; T4¡é,
T3 normal - not helpful
; TSH¡è
(*> 100uU/ml) if defect
primarily in the thyroid
; *Tg¡éin thyroid dysgenesis,
defects of Tg synthesis or secretion
-
Tg (-) in thyroid aplasia
; *prolactin¡è
#
Retardation Of Osseous Development On X-Ray
; *60% at birth
; intrauterine life µ¿¾È
thyroid H deprivationÀǹÌ
; no femoral distal epiphysis
; untreated patients
-
discrepancy between chronological age & osseous development
-
multiple foci of ossifocation on epiphyses(=epiphyseal dysgenesis)
-
deformity (" breaking ") of the 12th thoracic or 1st or 2nd lumbar
vertebra
#
*skull
; large fontanel, wide
suture, intersutural(wormian) bone, sella turnica : enlarged & round
erosion & thinning
#
delay in formation & eruption of teeth
#
cardiac enlargement & pericardial effusion
#
Scintigraphy
; 125 I - sodium iodide °¡ 99mTc-sodium pertechnetateº¸´Ù ¿ì¼öÇÔ
;
thyroid tissue°¡ º¸ÀÌÁö ¾Ê´Â °æ¿ì
¨ç
thyroid aplasia
¨è
neonate /c TRBAb
¨é
infant /c the iodide - trapping defect
©é
normal site thyroid gl. /c normal or avid uptake of radionuclide.
¡æ defect on thyroid hormone
biosynthesis.
#
goitrous hypothyroidism
;
radioiodine study
;
perchrate dischange test
;
kinetic studies
;
chromatography
;
thyroid tissue study ( biochemical nature Àǽɽà )
#
EKG
¨ç
low voltage P & T
¨è
diminished amplitude of QRS complex
¡æ poor left ventricular function
& pericardial effusion
#
EEG
low voltage
#
2¼¼ À̻󿡼 serum cholesterol Áõ°¡.
Prognosis
;
neonatal screenig program º¸±ÞÈÄ congenital
hypothyroidismÀÇ ¿¹ÈÄ´Â ¸Å¿ì ÁÁ¾ÆÁü
- »ýÈÄ ¸îÁÖ³»ÀÇ Á¶±âÁø´Ü°ú
ÀûÀýÇÑ Ä¡·á·Î °ÅÀÇ Á¤»óÀûÀÎ linear growth &
intelligence¸¦ º¸ÀÓ
;
thyroid hormoneÀº »ýÈÄ ÃÊ±â ¸î ´Þ µ¿¾ÈÀÇ Á¤»óÀûÀÎ cerebral development¿¡ Áß¿äÇϹǷÎ
irreversible brin damage¸¦ ¹æÁöÇϱâ À§ÇØ ÀûÀýÇÑ Ä¡·á°¡ Áï½Ã ½ÃÀ۵Ǿî¾ß ÇÔ
;
2¼¼ ÀÌÈÄ hypothyroidismÀÌ
onsetÇÑ °æ¿ì ¿¹Èİ¡ ´õ¿í ÁÁÀº °ÍÀ¸·Î º¸¾Æ thyroid hormoneÀÇ
brain growth¿¡ ´ëÇÑ ¿ªÈ°ÀÌ Áß¿äÇÔÀ» ¾Ë ¼ö ÀÖÀ½
Treatment
# *sodium
L- thyroxine
; drug of choice
1) circulating T3ÀÇ
80%´Â T4ÀÇ monodeiodination¿¡ ÀÇÇØ Çü¼ºµÇ¹Ç·Î
Ä¡·áÇÑ °æ¿ì
T3, T4´Â Á¤»ó ¹üÀ§
; ¡ÚDosage
-
neonate 10-15 ug/kg/day
-
children 4 ug/kg/day
-
adult 2 ug/kg/24hrs
; Ä¡·áÈ¿°ú
: T4 & TSH°¡ Á¤»ó¹üÀ§ À¯ÁöÇØ¾ß ÇÔ
4) 3¼¼¶§ 3-4ÁÖ°£ Ä¡·áÁߴܽÃ
permanent hypothyroidism¿¡¼´Â TSH levelÀÌ
¸Å¿ì Áõ°¡ÇÔ
;
side effects : ´ëºÎºÐ ¿ë·®°ú °ü°è ÀÖÀ½
¨ç
pseudotumor cerebri : Ä¡·á 4°³¿ù ³»
8-13¼¼ÀÇ acquied hypothyroidismȯ¾Æ¿¡¼ º¼ ¼öÀÖÀ½
¨è
change in behavior & activity
Acquired Hypothyroidism
Etiology
1)
lymphocytic thyroiditis
; *¡ãcommon
2)
congenital thyroid dysgenesis or with incomplete genetic defects in thyroid
hormone synthesis
; ¼Ò¾Æ±â¿¡´Â
ÀÓ»óÁõ»óÀÌ ¾ø¾î acquired hypothyroidismÀ¸·Î º¸À̳ª ¿äÁò
newborn screening program¿¡¼ detectÇÔ.
3)
subtotal thyroidectomy for thyrotoxicosis or cancer
4)
removal of ectopic thyroid tissue.
¨ç lingual thyroid, subhyoid median
thyroid, thyroid tissue in a thyroglosal duct cyst.
¨è subhyoid gl. ´Â
thyroglossal duct cyst¿Í À¯»çÇØ º¸À̹ǷΠ¼ö¼úÀü radionuclide scan
¹Ýµå½Ã ½ÃÇà
5)
¡ÚNephropathic Cystinosis
; intralysomal storage of
cystine in body tissue
-->
impaired thyroid function
; more common compensated
form
6)
*histiocytic infiltration of thyroid
in children with Langerhans cell histiocytosis
7)
irradiation to thyroid
;
Hodgkin ds. ¶Ç´Â ±âŸ ¾Ç¼ºÁ¾¾ç Ä¡·á½Ã
bone marrow
transplantation Àü irradiation
¡æ
thyroid damage
; 1/3 : Ä¡·á
1³â À̳» TSH ¡è
15 - 20 % ; 5-7³â ³»
hypothyroidismÀ¸·Î ÁøÇà
8)
protracted ingestion of mediations containg iodides
; accompanied by a goiter
; ¡Úamiodarone
¨ç
cardiac arrhythmia¿¡ »ç¿ë
¨è
37% iodine ÇÔÀ¯
¨é *Ä¡·áȯ¾ÆÀÇ 20%¿¡¼ hypothyroidism
¨ê
high iodine content
¨ë
inhibition of 5¡Ç-deiodinase (T4¡æT3)
¨ì
T4, T3, TSHÀÇ serial measurement ÇÊ¿ä
Clinical Manifestation
1) Sx
¨ç
deceleration of growth ( 1st Sg )
¨è
myxedematons changes of skin.
¨é
constipation
¨ê
cold intolerance
¨ë
decreased energy
¨ì
increased need for sleep
¨í
school work & grades ; not suffer
¨î
delayed osseous maturation
: Ix of duration of hypothyroidism.
¨ï
headache, visual problem, precocious puberty, galactocemia
: hyperplastic enlargement of pituitary gl. /c suprasella extension
( DDx ; pituitary tumor )
2) T4 replacement ÀûÀýÈ÷ Ä¡·áÈÄ ÀÓ»ó Áõ»ó È£ÀüÀ» º¸À̳ª,
¿À·¡µÈ hypothyroidism
ȯ¾Æ¿¡¼´Â
catch-up growth ºÒ¿ÏÀüÇÔ ( predicted adult heightº¸´Ù
7cm Á¤µµ ÀûÀ½ )
Chapter. 521. Thyroiditis
Lymphocytic Thyroiditis (=Hashmoto thyroiditis ; Autoimmune
thyroiditis)
;
*children & adolescents¿¡¼
¡ãcommon thyroid ds.
;
*¡ãcommon
cause of acquired hypothyroidism
;
incidence - 1% among school children
Etiology
;
*typical organ-specific autoimmune
ds.
;
histologic finding
- lymphcytic infiltration of
thyroid.
-
early hyperplasia
-->
infiltration of lymphocytes & plasma cells between follicles
atrophy of follicles
- lymphoid follicle formation
/c germinal center
- Intrathyoidal lymphocytic
subset
/
*60% T cells : CD4+ (helper), CD8+ (cytotoxic)
/
30% B cells
;
HLA type
-
HLA - DR4, HLA - DR5
/
goiter, thyroiditis ¡è
- HLA - DR3
/
atrophic variant of thyroiditis
;
¡ÚThyroid Antigen Autoantibodies
1) thyroid antiperoxidase Ab
(TPOAb)
(=antimicrosomal
antibody)
-
90% in lymphocytic thyroiditis
- many patients /c Graves ds
-
*action : inhibit enzyme activity
& stimulate natural killer cell cytotoxicity
2) antithyroglobulin antibody
-
more common in adults
3) thyrotropin
receptor-blocking Ab(TRBAb)
-
*hypothyroidism & thyroid atrophy¿Í
°ü·ÃÀÌ ÀÖ´Ù°í
»ý°¢ÇÔ
Clinical Manifestations
;
M : F = 1 : 4-7
;
more common after 6yr
- peak incidence during
adolescencts
;
growth retardation, goiter
- *¡ãcommon symptoms
- goiters
/
insiduous, small or large
/
mostly diffusely enlarged, firm, nontender
;
*mostly euthyroid & asymptomatic
- some pressure symptoms in
the neck
- some clinically
hypothyroidism
- some clinically euthyroid
& laboratory hypothyroid
- some clinically
hyperthyroid & laboratory hypothyroid
#
Clinical course
; variable
;
goiter
-
smaller or disappear spontaneously
; nongoiterous (atrophic)
hypothyroidism
#
Familial tendency
(1) ȯ¾ÆÀÇ ÇüÁ¦³ª ºÎ¸ðÀÇ ¹ß»ý
: 25%
(2) thyroglobulin Ab. human
thyroid peroxidase(hTPO)
; autosomal dominant
(3) reduced penetrance in
males
(4) lymphocytic thyroiditis,
"idiopathic" hypothyroidism, Graves ds.
; ¼¼ Áúº´ÀÌ µ¿½Ã¿¡ ³ªÅ¸³²
(5) ´Ù¸¥
autoimmune disorder¿ÍÀÇ °ü°è
¨ç
type l polygrandular autoimmune syndrome
+- hypoparathyroidism
| Addison ds
+- mucocutaneous candidiasis
; 10%¿¡¼ autoimmune thyroiditis µ¿¹Ý
¨è
Schmitt syndrome or type II polyglandular autoimmune disease
Addison ds c IDDM or autoimmune thyroid ds or both
¨é
pernicious anemia, vitiligo, alopeciaµµ ¿¬°ü
¨ê
DM ȯ¾Æ¿¡¼ ¹éÀÎÀÇ 20%, ÈæÀÎÀÇ
4%¿¡¼ TPO Ab¹ß°ßµÊ
¨ë
congenital rubella ȯ¾Æ¿¡¼ ¹ß»ýÀ² Áõ°¡
¨ì
Turner synd & Down synd°úµµ ¿¬°üÀÌ ÀÖÀ½
Laboratory Data
1)
definitive Dx ; thyroid biopsy
2)
thyroid function
; slightly or moderately TSH
-
often normal
-->
*goiter°¡ lymphocytic infiltration¿¡ ÀÇÇÏ¿©
¹ß»ýÇÑ °ÍÀÌ
¾Æ´Ï°í, thyroid growth-
stimulating immunoglobulin¿¡ ÀÇÇÑ
¹ß»ýÇÔÀ» ½Ã»ç
;
progressive thyroid failure°¡ µÇ¸é
-
T4°¨¼Ò, T3°¨¼Ò, TSHÁõ°¡
3)
thyroid scan
¨ç 50% ; irregular &
patchy distribution of radio isotope
¨è > 60% ; perchlorateÅõ¿©½Ã
10% ÀÌ»óÀÇ dischrgeº¸ÀÓ
4)
thyroid ultrasonography
scattered hypoechogenecity.
5)
antibody titers to thyroid peroxidase(+)
antithyroglobulin test for thyroid
Ab(+) : < 50%
¡æ 95% Á¤µµ Áø´Ü
6)
antithyroid Ab
¨ç ȯ¾Æ ÇüÁ¦ÀÇ 1/2¿¡¼
(+)
¨è Down syndrome or
Turner syndromeÀ» °¡Áø ȯ¾ÆÀÇ ¾ö¸¶¿¡¼µµ ¶Ñ·ÇÇÑ thyroid ds.
¾øÀ̵µ
(+)
¨é DM ȯ¾ÆÀÇ
20%¿¡¼ (+)
¨ê congenital rubella syndrome
ȯ¾ÆÀÇ 23%¿¡¼(+)
Treatment
;
sodium -L -thyroxine( 50-150ug daily)
1) hypothyroidismÁõ»óÀÌ ÀÖÀ»¶§
2) goiter´Â size°¡ ÁÙ¾îµå³ª ¸î³â°£ Áö¼ÓµÊ
3) antibody levelÀº fluctuationÇÏ¸é¼ ¸î³â°£ Áö¼ÓµÊ
4) suppressive Tx¿¡µµ ºÒ±¸Çϰí
prominent noduleÀÌ Á¸Àç½Ã thyroid cancer¹ß»ý °¡´É¼ºÀÌ ÀÖÀ¸¹Ç·Î Á¶Á÷ÇÐÀû °Ë»ç¸¦ ½ÃÇàÇÔ
Other Causes Of Thyroiditis
: tuberculosis, sarcoidosis, mumps, cat-
scratch ds
1.
acute suppurative thyroiditis
1) uncommon
2) respiratory infection¼±Çà
3) left lower lobe°¡ ÈçÈ÷ ħ¹üµÊ
4) abscess formation
5) mc organism : anaerobic orgarnism
( Eikenella corrodens )
6) recurrent episodes or detection of
mixed bacterial flora
;
thyroglossal duct remnant or piriform sinus fistula ( more often ) ¿¡¼ »ý±è
7) Sx
¨ç
exquisite tenderness of gland
¨è
swelling
¨é
erythema
¨ê
dysphagia
¨ë
limitation of head motion
¨ì
leukocytosis
8) scintigram of thyroid
;
complex echogenic mass
9) thyroid function test : normal
thyrotoxicosis <-
aspergillus¿¡ ÀÇÇÑ suppurative thyroiditisÀÏ ¶§
10) Tx
¨ç
I & D
¨è
antibiotics Åõ¿©
¨é
infection»ç¶óÁø ÈÄ fistula tractã±âÀ§ÇØ barium esophagogramÇÏ¿© È®ÀÎÇϰí,
Á¸Àç½Ã
exterionization
2.
subacute nonsuppurative thyroiditis ( de Quervan ds )
1) rare in children
2) viral cause
3) spontaneous remission
4) Sx
¨ç
vague tenderness over the thyroid
¨è
low- grade fever
¶Ç´Â
severe pain in thyroid
¨é
high fever & chill
inflammationÀº ÀÌ¹Ì Çü¼ºµÈ thyroid hormoneÀÇ ¼øÈ¯³»·Î
leakage¶§¹®
5) Lab
T3, T4 »ó½Â
6) mild hyperthyroidism sx
7) radioiodine uptake ¡é
8) ESR »ó½Â
9) course
¨ç
variable
¨è
euthyroid -> hypothyroid
¨é ¼ö°³¿ù ÀÌÈÄ
remission
Chap. 522. Goiter
#
¡ÚEnlargement Of The Thyroid Gland
¨ç euthryroidism : normal
function of gland
¨è hypothyroidism :
thyroid deficiency
¨é hyperthyroidism :
overproduction of hormone
#
ºÐ·ù
¨ç
congenital or acquired
¨è
endemic or sporadic
#
¿øÀÎ
¨ç¡è pituitary secretion of
thyrotropic hormone in response to ¡é circulating thyroid
hormone
¨è infiltrative process <-
inflammatory or neoplastic
¨é with thyrotoxicosis <- TRS Ab
552.1 Congenital Goiter
;
usually sporadic
Etiology
Administration Of Antithyroid Drug Or Iodides
¨ç
during pregnancy for Tx of thyrotoxicosis
¨è
goitrogenic drugsÀ̳ª iodides´Â ŹÝÀ» Åë°úÇÏ¿© °í¿ë·®½Ã
thyroid hormone ÇÕ¼ºÀ» ¹æÇØÇÏ¿© žÆÀÇ goiter &
hypothyroidismÀ» À¯¹ßÇÔ
¨é
goitrogen°ú thyroid hormoneÀ» µ¿½Ã Åõ¿©½Ã¿¡µµ
ºÒÃæºÐÇÑ ¾çÀÇ T4°¡ ŹÝÀ»
Åë°úÇϹǷÎ
È¿°ú ¾øÀ½
Asthma Tx
Amiodarone
¨ç
37% iodine content
¨è
euthyroid
¨é
retardation of osseous maturation
¨ê
T4 »ó½Â, TSH »ó½Â
Mother With Antihyperthyroid Treatment
4) »ê¸ð°¡ propylthiouracil 100-200 mg/24hr º¹¿ë½Ã¿¡µµ
³ªÅ¸³ª¹Ç·Î Ãâ»ý½Ã thyroid study½ÃÇà
3.
ȯ¾Æ¿¡ thyroid hormone Åõ¿© ¸ñÀû
1) treat clincal hypothyroidism
2) hasten the disappearance of goiter
3) prevent brain damage
--> ÀÌ »óŰ¡ °è¼Ó Áö¼ÓµÇÁö´Â
¾ÊÀ¸¹Ç·Î thyroid hormoneÀº ¸î ´ÞÈÄ¿¡ Áߴܰ¡´É
4.
enlargement of thyroid at birth
1) respiratory distress --> nursing
difficulty & death
2) head extreme hyperextension
3) respiratory obstructionÀÌ ½ÉÇÑ °æ¿ì
tracheostomyº¸´Ù partial thyroidectomy°¡ ÀûÀÀÁõÀÌ µÊ
Congenital Hyperthyroidism
; almost goiter
-
not large goiter
; symptoms of hyperthyroidism
; often mother with Graves
dis
6. defect in synthesis of thyroid hormone
1) 1/30000 - 50000 in neonatal screening
program
2) hypothyroid infantÀÏ ¶§´Â
thyroid hormoneÀ¸·Î Áï°¢ Ä¡·áÇϰí Á¤¹Ð °Ë»ç´Â ¿¬±â½ÃÅ´
3) recessive geneÀ¸·Î À¯ÀüµÇ¹Ç·Î
genetic counselling Áß¿ä
´ÙÀ½ ÀӽŽÃ
ultrasound·Î fetal goiter detect
Iodine Deficiency
1) rare cause of congenital goiter
2)ÀӽŠÃʱ⠽ÉÇÑ iodine deficiency´Â
goiter°¡ ¾ø´õ¶óµµ neurologic damage¸¦ ¾ß±âÇÒ¼ö ÀÖ°í, maternal
& fetal hypothyroidismÀ» À¯¹ßÇÏ¿© maternal thyroid
hormoneÀÇ protective
transfer¸¦ ÀϺΠ¹æÁö
3) lobulated, asymmetric, firm large
goiter
; thyroid³» ¶Ç´Â ±ÙóÀÇ teratoma °í·Á
522.2 Endemic goiter & Cretinism
1.
moderate deficiency of iodine
: compensatory hypertrophy
& hyperplasia
+- thyroid
hormone ÇÕ¼ºÁõ°¡
+- hormoneÀÇ
return ¼Óµµ Áõ°¡
--> Á¶Á÷ÀÇ
thyroid hormone demand ÃæÁ·
2. sea water, fish, shellfish¿¡´Â
iodineÀÌ Ç³ºÎ
¹Ì±¹ÀÇ potassium iodide (100§¶/g)
Æ÷ÇÔÇÑ iodized salt´Â ÁÁÀº ¿¹¹æ È¿°ú¸¦ º¸ÀÓ
±ÇÀå·® infant 40-50 §¶/24hr
Clinical Manifestations
1) mild iodine deficiency
(1) adolescence &
pregnancy°°Àº rapid growth period¿Ü¿¡´Â
thyroid enlargement°¡
¶Ñ·ÇÇÏÁö ¾ÊÀ½
(2) girl > boy
(3) Lab
; T4¡é, TSH mod. ¡è
circulating T3 ¡è in normal T4
;
preferential secretion of T3 by the thyroid
2) Endemic cretinism
(1) iodine deficiency in
endemic goiter
(2) type
¨ç
neurologic type
¨è
myxedematous type
(3) neurologic syndrome
¨ç
mental retardation
¨è
deaf -- mutism
¨é
disturbances in standing & gait
¨ê
pyramidal sg
; clonus of foot, Babinski sg., patellar hyperreflexia
¨ë
goitrous, euthyroid
¨ì
normal purpertal development & adult stature
¨í
little or no impaired thyroid function
(4) myxedematous syndrome
¨ç
mental retardation
¨è
deaf
¨é
neurologic sx
¨ê
delayed sexual development & growth
¨ë
myxedema
¨ì
absence of goiter
-> T4¡é
TSH markedly ¡è
ultrasonography : thyroid atrophy
(5) Pathogenesis of
neurologic syndrome
¨ç
iodine deficiency & hypothyroxinemia during pregnancy
--> fetal & postnatal hypothyroidism
¨è
fetal thyroid ¹ß´ÞÀü fetal brain¿¡´Â
thyroid hormone¿¡ ´ëÇÑ receptorÁ¸Àç
¨é ŹÝÀ» Åë°úÇÑ ¸ðüÀÇ
thyroid hormoneÀÌ nervous system¹ß´Þ¿¡ µµ¿òÀ» ÁÜ
(6) Myxedematous syndrome
¨ç
thyroid autoimmunity : TGBI ( ? )
¨è
environmental factors
+- selenium deficiency
| goitrogenic foods
| thiocyanates
+- Yersinia
4.
Tx
1) 5³â°£ ÀӽŽà iodine deficiency¿¹¹æÀ» À§ÇØ
iodinated poppy seed oil single IM
ÀÌ Ä¡·á´Â
4¼¼ÀÌÀü myxedematous cretinismȯ¾Æ¿¡¼´Â
5°³¿ù ³» euthyroid state·Î µÊ
2) older children & adults
: T4Åõ¿©
522.3 Sporadic Goiter
;
lymphocytic thyroiditis
- *¡ãcommon cause
- ¡Úimportant
clue to diagnsis
/
disorder in siblings, onset in early life, possible association with
hypothyroidism
Iodide Goiter
1) cough medicines & asthma Tx¿¡
iodide ÇÔÀ¯
2) firm & diffuse enlarged
3) Wolff-Chaikoff effect
¨ç °ú·®ÀÇ
iodidineÀ» Åõ¿©½Ã iodine organification
& thyroid hormone synthesis¹æÇØ
¨è
short - lived
¨é
hypothyroidismÀ» À¯¹ß½ÃŰÁö´Â ¸øÇÔ
¨ê
iodideÅõ¿©°¡ °è¼Ó µÇ¸é autoregulatory
mechanism¿¡ ÀÇÇØ iodine trappingÁ¦Çѵǰí
thyroid³» iodine levelÀÌ °¨¼ÒÇϰí
organificationÀº Á¤»óÀûÀ¸·Î ÁøÇàµÊ
¨ë
iodide-induced goiter ȯ¾Æ¿¡¼´Â thyroid hormone
biosynthesis defect·Î ÀÎÇØ
escapeÀÌ ÀϾÁö ¸øÇÔ
+- lymphocytic thyroiditis
| subclinical inborn error
in thyroid hormone synthessi
+- partial thyroidectomy
4) Lithium carbonate
¨ç
psychotherapy drug
¨è
iodide¿Í °æÀïÀûÀ¸·Î ÀÛ¿ë
¨é
lithium°ú iodide´Â
synergistic effect°¡ ÀÖÀ¸¹Ç·Î È¥¿ëÀº ÇÇÇÔ
5) Amiodarone
¨ç
antiarrhythmic drug
¨è
potent inhibitor of 5`-deiodinase ( T4->T3 )
¨é
underlying autoimmune disease °¡Áø ȯ¾Æ¿¡¼´Â hypothyroidismÀ» ÀÏÀ¸Å°°í ±× ¿Ü´Â
hyperthyroidismÀ» ÀÏÀ¸Å´
Simple Goiter ( Colloid Goiter )
1)
euthyroid nontoxic goiter
2)
unknown etiology
;
not associated with hypothyroidism or hyperthyriodism
;
not caused by inflammation or neoplasia
3)
*girl predominantly
4)
*peak incidence before & during
the pubertal years
5)
Histologic examination
; normal
;
varialbe follicular size, dense collid, flattened epithelium
6)
goiter ; small or large
7)
scintiscan ; normal
8)
thyroid Ab (-)
9)
DDx ; lymphocytic thyroiditis, iodide goiter, mulinodular goiter
10)
Tx
; thyroid hormone
-
avoid progression to a large multinodular goiter
; Ä¡·áÇÏÁö ¾ÊÀº ȯ¾Æ´Â
periodic re-evaluation
Multinodular Goiter
1) firm goiter with a lobulated surface
single or multiple
palpable nodule
cystic change,
hemorrhage, fibrosis
2) ultrasound : multiple echo-free &
echogenic lesions
3) scintiscan»ó
nonfuction
4) thyroid study : normal
5) SH¡è
6) thyroid antibody (+)
7) McCune-Albright syndrome --------+ ¿¡¼ º¸°í
digital anomalies & cystic renal dis-+
8) Tx : T4
surgery
; T4 replacement Tx·Î noduleÀÌ ¾ø¾îÁöÁö ¾ÊÀ¸¸é
malignancy ¹èÁ¦À§ÇØ op
522.4 Intratrachel Goiter
1.
intraluminal thyroid beneath the tracheal mucosa.
continuous /c normal extratracheal
thyroid
airway obstruction½Ã
extra or endotracheal ±¸º°ÇÊ¿ä
2.
Tx ; sodium-L-thyroxine : mild
surgical removal of endotracheal goiter : severe
Chapter 523. Hyperthyroidism
* excessive secretion of thyroid hormone
diffuse toxic goiter(Graves ds.)
during childhood
* rare causes
¨ç
toxic uninodular goiter(Plummer ds)
¨è
hyperfunctioning thyroid Ca.
¨é
thyrotoxicosis factitia
¨ê
acute suppurative thyroiditis
¨ë
subacute thyroiditis
¨ì
McCune-Albright synd.( /c autonomous thyroid adenoma )
* ´ëºÎºÐ thyroid hormone¿¡ ´ëÇÑ
pituitary unresponsiveness
¨ç
TSH secreting pituitary tumors. only in adults
¨è
infants born to mothers with Graves ds.
¨é
transitory phenomenon
¨ê
classic Graves ds. during neonatal period
¨ë chorioca. hydatidiform
mole, stuma ovarii in adults
523.1 Graves Disease
Etiology
1) enlargement of thymus, splenomegaly,
lymphadenopathy
infiltration of
thyroid gl. & retroorbital tissues /c lymphocytes & plasma cells
peripheral lymphocytosis
2) thyroid gland
¨ç
T helper cell (CD4+) in dense lymphoid aggregates
cytotoxic T cells (CD8+) in lower dense area
¨è
failure of T suppressor cells
¡æ
expression of T helper cells
¡æ
sensitized to the TSH Ag
¡æ
interact with ¥â cell
( plsma cell¿¡ ºÐÈ.
thyrotropin receptor-stimulating Ab ( TRSAb ) »ý¼º
¡æ
TRSAb + receptor for TSH
¡æ
c AMP¡è
¨é
TRBAbµµ »ý¼ºµÇ¾î º¸Åë clinical course´Â
TRSAb & TRBAbÀÇ ºñ¿¡ °ü°èÀÖÀ½
3) ophthalmopathy
¨ç
thyroid & eye muscle¿¡ ÀÖ´Â antibody¸¦ °øÀ¯Çϱ⠶§¹®
¨è
extraocular muscles & orbital fibroblastÀÇ Ab°¡
orbital fibroblast¿¡ ÀÇÇÑ
glucosaminoglycanÀÇ ÇÕ¼ºÀ» ÀÚ±ØÇϰí m. cellÀÇ
cytotoxic effect¸¦ °¡Áö°Ô ÇÔ
4) HLA type°úÀÇ ¿¬°ü¼º
¨ç
HLA-B8
HLA-DR3(7 ¹è)
:
other HLA-D3-related disorders
( Addison disease, IDDM, myasthenia graves, celiac ds )
¨è
SLE, RA, vitiligo, ITP, pernicious anemia.
¨é °¡Á··Â¿¡¼´Â Graves ds.¿Í °¡Àå ¿¬°üÀÌ ÀÖ´Â °Íµµ lymphocytic
thyroiditis,
autoimmune hypothyroidism., neonatal hyperthyroidismÀÓ
Clinical Manifestations
1)
Incidence
; 15¼¼ ÀÌÇÏ
- 5%
; *peak incidence - during adolescence
; M : F = 1 : 5
2)
Clinical Course
; variable
; *not so fulminant, gradually
; *¹ß»ý°ú Áø´Ü»çÀÌ¿¡
Æò±Õ 6-12°³¿ùÀÇ interval
3)
Symptoms
; *emotinal disturbances with motor hyperactivity - earliest Sg
; irritable, excitble, cry
easily owing to emotional lability
;
school work suffers as a result of short attention span
; *tremor of the fingers on arm extension
; voracious appetite with loss
of or no increase in weight
; variable size of thyroid
-
goiter : almost
; eye
-
*exophthalmos in most but mild
-
lagging of the upper eyelid
-
impairment of convergence
-
*retraction of upper eyelid &
infrequent blinking
; skin
-
smooth & flushed, excessive sweating
; muscular weakness
-
uncommon
- severe -> spell
; tachycardia, palpitation,
dyspnea, cardiac enlargement & insufficiency
; atrial fibrillation ; rare
; mitral regurgitation due to
papillary m. dysfunction
-
apical systolic murmur
; increased systolic BP &
pulse pressure resulting from hyperactivity of sympathetic nervous system
4)
thyroid "crisis" or "storm"