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Part 26-1. The Endocrine System

³»ºÐºñ p1567-1577

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¸¦ Àڱؠ

          - 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 Å°¿¡ 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 Àº 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¿ëÇϸ鼭 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 È¯ÀÚµéÀÇ 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¯¸¦ ¸ÔÀÌ¸é ¸¸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 personÀº 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´ëÈ­µÊ

 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ȭ°¡ 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°¡ ¸í¹éÇÏ°Ô 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

    ÀӽŠ10-12ÁÖ 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 : ÀӽŠ20ÁÖ 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 ÀӽŽà 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¿äÇϹǷΠirreversible 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¡·áÁߴܽà 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  fluctuationÇϸ鼭 ¸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°úÇϹǷΠȿ°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 ÀӽŽà 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"