Part 26-3. The Endocrine System

623.10 Toe Deformities

Syndactly

; aysmptomatic, positive family history

# Classification

    ; zygosyndactly

           - complete or incomplete webbing

           - between 2nd and 3rd toe

    ; polysyndactly

           - duplication of fifth toe and syndactly between 4th and 5th toes

           - synostosis of lateral metatarsals

Treatment

    ; zygosyndactly

           - no treatment

    ; polysyndactly

           - associated anomalies

Chapter 629. The Neck

629.1 Torticollis

★Table 629-1

# muscular torticollis

    ; *▲common

    ; *resulting from injury to SCM muscle

Clinical Manifestation

# muscular torticolis

    ; palpable mass in inferior aspect of SCM muscle

    ; normal neurologic sign

Radiographic Evaluation

Treatment

# muscular torticolis

    ; passive stretching

Chapter 647. Metabolic Bone Disease

 1) bone의 특징

   1.dynamic organ capable of rapid turnover, weight bearing, and withstanding the stresses 

     of a variety of physical activities

   2.끊임없이 modeling(being formed) and remodeling(reformed)을  진행함.

   3. major body reservoir for calcium, phosphorus, and magnesium

 2)human skeleton 구성

   1. protein matrix

      90% of bone protein은 collagen-containing osteoid이며 , 그 외 osteocalcin 등

   2.crystalline mineral phase

 3)bone growth in children

    :by the process of calcification of the cartilage cells present at the ends of bone

 4)main function of the vitamin D-PTH-endocrine axis

    :to maintain the ECF calcium and phosphate concentrations

 5) 그 외 growth and mineralization of cartilage를 조절하는 hormone

   1. GH acting through somatomedins, thyroid H, insulin, androgens, and estrogens during

       the pubertal growth spurt.

   2.반대로 supraphysiologic concentrations of glucocorticoids는 cartilage function과 bone

       growth를 억제함.

 

 

24.60 rickets (see also Sec. 4.29.)

 

 1)rates of bone formation은 intestine과 kidney의 mineral metabolism의 변화에 의해서

     조절된다

   1.calcium homeostasis

    a. calcium homeostasis는 intestine에서 조절됨.

    b. inadequate dietary intake or intestinal absorption of calcium은 serum calcium과 ionized

       fraction을 저하시켜, PTH의 synthesis와 secretion을 증가시킴

     a) greater bone resorption to raise serum calcium

     b)enhanced distal tubular reabsorption of calcium

     c) higher rates of synthesis by the kidney of 1, 25-dihydroxy V-D (the most active

          V-D)

   2.phosphate homeostasis

    a. phosphate homeostasis는 kidney에서 조절됨.

     이유  a)intestinal phosphate absorption is nearly complete

           b)renal excretion determines the serum level.

    b.excessive intestinal phosphate absorption은 serum ionized calcium을 저하시키고 , PTH

      secretion을 증가시킨다.  

      :phosphaturia, lowering serum phosphate, and permitting calcium to rise

    c.hypophosphatemia: PTH secretion을 억제하고 renal 1,25(OH)2 synthesis를 증가시킴 .

       이는 intestinal phosphate aabsorption을 증가시킴

 2)An understanding of the metabolism of vitamin D (Fig 24-38)

   1. in skin

    a. 7-dehydrocholesterol이 있으며 , UV radiation에 의해서 vitamin D3 로 전환

         (그러므로 reduced skin exposure UV light는 rickets를 초래)

   b. vitamin D3 는 blood stream을 통하여 vitamin D binding protein (DBP)에 의해서

      liver까지 전달  

  2. in GI tract

   a. dietary vitamin D2(ergocalciferol) or vitamin D3 (cholecalciferol)의 ingestion은 bile

      salts에 의해서 다른 fat-soluble vitamin 과 함께 장에서 흡수됨

   b. absorption후 chylomicrons에 의해서 liver에 까지 전달

  3.liver에서 hepatic microsomal enzyme에 의해서 25-hydroxy vitamin D로 변환.

   (이때 oxygen, NADPH, and magnesium이 필요)

  4.다음 25(OH)D는  DBP에 의해서 kidney에 전달.

   (참고  : 25(OH)D )

       a. main circulating vitamin D metabolite in humans(20-80ng/mL)(Table 24-16)

       b. weakly regulated by feedback

       c. its plasma level rises in summer and falls in winter

  5.kidney에서 further hydroxylation됨

   a. reduced calcium or phosphate, elevated PTH 시는 1,5(OH)2D형성 

     a)only 0.1% of the level of 25(OH)D

     b)tightly regulated by feedback

     c)작용  :  intestine에서 calcium , phosphate 흡수를 증가시킴

     d)특징  :  1.higher in children than in adults

               2.not subject to seasonal variability

               3.peak in the 1st yr of life and again during the adolescent

   b. normal or elevated serum calcium or phosphate 시는 24,25(OH)2D형성

      a) pathway for the removal of excess vitamin D

      b) serum level of 1-5 ng/mL and becomes higher after ingestion of large amounts of

         vitamin D

 3)mineral deficiency는 normal process of bone mineral deposition을  억제함 

  1. mineral deficiency at the growth plate

    :growth slows and bone age is retarded ( a condition called rickets )

  2. poor mineralization of trabecular bone

    :osteomalacia

    (참고) osteoporosis

      1. a condition of equal loss of bone volume and mineral

      2. caused in childhood by steroid administration

      3. found in Turner and Klinefelter syndromes, or as an idiopathic

 4)Rickets 분류 :calcium-deficient or phosphate deficient rickets (Table 24-17)

Chapter 648. Familial Hypophosphatemia

(=vitamin D resistant rickets X-Linked Hypophosphatemia)

 1)개요

   1.the most commonly encounted form of rickets

   2.유전양식

    a. X-linked dominant : usual mode of inheritance

       환아의 mother는 bowing, short stature 혹은 only fasting hypophosphatemia를 보일 수

        있음 

    b. 그 외 AR, sporadic forms 등

 2)PATHOGENESIS

   1.defects in the proximal tubular reabsorption of phosphate

   2.defects in the conversion of 25(OH)D to 1,25(OH)2D

 3)임상 소견

   1,bowing of the lower extremities related to weight bearing at the age of walking

   2.waddling gait, smooth(rather than angular) bowing of the lower extremities coxa vara,

     genu varus, genu valgum, and short stature

   3."intraglobular dentin"(특징적인 tooth abnormalities) : pulp deformities enamel defects는

     는 가끔 발견되며 이는 Calcium-deficient rickets의 특징이다.

   4.tetany is not present

   5. adult height of untreated patients : 10 -165 cm

 4)방사선학적 소견

   1.metaphyseal widening and fraying and coarse-appearing trabecular bone

   2.cupping of the metaphysis at the proximal and distal tibia and at the distal femur,

     radius, and ulna

 5)검사실 소견

   1.normal or slightly reduced serum calcium level(9-9.4mg/dL;2.24-2.34 mM/L)

   2.a moderately reduced serum phosphate level(1.5-3mg/dL; 0.48-0.9 mM/L)

   3.elevated alkaline phosphates activity

   4.no evidence of secondary hyperparathyroidism

   5.large urinary phosphate excretion, despite hypophosphatemia

   6.typical of pure phosphate-deficient ricket since aminoaciduria, glucosuria bicarbonaturia,

     and kaliuria are never found

 6)치료

   1.oral phosphate supplements coupled with a vitamin D analog to offset the secondary

     hyperparathyroidism that may accompany an oral phosphate load

    a. oral phosphate : usually given every 4 hr for at least 5 times a day

      a)young children : .5-1 g/24hr, older children  : 1-4g/24hr

      b)Joulie solution (dibasic sodium phosphate 136 g/L, and Phosphoric acid, 58.8 g/L)

           which contains 30.4mg of phosphate/mL

      c)main side effect : diarrhea (which often improves spontaneously)

    b. vitamin D analog : important for complete bone healing and prevention of secondary

                        hyperparathyroidisn

      a)classically : vitamin D2 was used at 2000IU/Kg/24hr

      b)more recently :dihydrotachysterol at a dosage of 0.02mg/kg/24hr

                     1,25(OH)2D at dosage of 20-50ng/kg/24hr

    c .vitamin D가 효과가 없고 serum phosphate가 감소되면, metaphyseal dysplasia를

      의심해야 함 

   2.corrective osteotomies

    a. surgery should always be deferred

     a) until rickets appears healed roentgenographically

     b) until serum ALP level is in the normal range

    b. surgery prior to bone healing은 redevelopment of deformity and bowing가 나타날 수

     있음

    c.osteotomy를 시행하는 환자는 수술 전에 ahems vitamin D preparation을 중지해야 하며, 

       ambulation할 때까지는 다시 투약하지 말아야 한다.

      a)1,25(OH)2D

        장점 ; 1. short half-life이므로 수술 바로 직전에 중단할 수있음

               2.augmentation of intestinal phosphate absorption and may improve phosphate

                 balance

        단점 :concomitant oral phosphate없이 사용해서는 안됨

      b)vitamin D2는 적어도 수술 1개월 전에 중단해야 함

 7)hypophosphatemic bone disease

   1.hypophosphatemia and hyperphosphaturia but X-ray evidence of rickets

   2.AD disease

   3. 임상 소견

    a, serum concentration of 1,25(OH)2D: normal

    b, renal tubular phosphate excretion defect, short stature

      ; not as marked as in familial hypophosphatemic rickets

   4. 치료 : oral phosphate and 1,25(OH)2D

Chapter 649. Vitamin D Dependent Rickets

    (pseudovitamin D deficiency hypocalcemic  vitamin D resistant rickets )

  1)개요

   1,호발연령 : 3-6 mo in children

   2, AR disorder

  2)원인 : deficiency or greatly reduced in the enzyme activity of 25(OH)2D-1-hydroxylase

          그러므로 hypocalcemia, hypophosphatemia, elevated PTH level 에도 불구하고

           low serum levels of 1,25(OH)2D나타냄

  3)검사 소견

   1,low serum calcium and phosphate levels, and elevated ALP activity

   2,calcium deficient form 이므로 2ndary hyperparathyroidism, aminoaciduria,glucosuria

     renal tubular bicarbonate wasting, and renal tubular acidosis를 나타냄

  4)임상소견 :dental enamel hypoplasia

  5)치료

   1.massive dosage of vitamin D2(200,000-1million IU/24hr)

   2.the use of relatively low-dose 1,25(OH)2D at 1-2ug/24hr

  6)vitamin D dependency type II or hereditary resistancy  to 1,25(OH)2D

   1,개요

     a, vitamin D dependent rickets의 몇몇 환자에서는 high dose vitamin D2 or

        1,25(OH)2D치료에도 회복 없음

     b, extremely high circulating levels of 1,25(OH)2D에도 불구하고, hypocalcemia

          hypophosphatemia aminoaciduria가 계속됨 

     c. particularly prevalent among children of 1st-cousin marriage

   2.patophysiologic mechanism :defect in the binding of 1,25(OH)2D to either cytoplasmic or

      nuclear receptors in skin and bone cells

     (by a single amino acid substitution in an important DNA-binding site in the receptor)

   3. some patients have short stature and alopecia totalis

   4 치료 :15-30ug/24hr 1,25(OH)2D

Chapter 650. Hepatic Rickets

 1)not uncommon in children with hepatic disorders, particularly in extrahepatic biliary

   atresia 

 2)원인 :neonatal hepatitis and following hepatocellular damage induced by total parenteral

         nutrition

 3)기전

   1,과거 :impair 25-hydroxylation and thus reduce serum 25(OH)D

   2현재 :failure of bile salt secretion은 vitamin D의 흡수에 장애

 4)검사 소견

   reduced serum 25(OH)D values hypocalcemia, X-ray evidence

   elevated serum ALP activity (raised bone and heptic isoenzyme levels)

 5)치료 : high enough vitamin D doses to overcome malabsorption along with oral calcium

   1. 4,000 -10,000 IU of vitamin D2 (100-250ug)

   2 50 ug of 5(OH)D or 0.2ug/kg of 1,25(OH)2D

Chapter 651. Rickets Associated With Anticonvulsant Therapy

 1)개요

   1,calcium-deficient rickets , despite apparently adequate vitamin D intake

   2,more common after the combination of p-b and phenytoin

 2)원인

   1,이 anticonvulsant가 hepatic cytochrome P-450 hydroxylation enzyme activity를 자극하여

    25(OH)D를 more polar, inactive metabolites로 전환 따라서 reduced serum levels of

    1,25(OH)2D가 됨  

   2,low intake of daily products (the major dietary source of calcium)

   3,very poor exposure  to sunlight

 3)치료

   1 주기적인 serum values of calcium, phosphate and alkaline phosphatase activity측정 

   2예방 a, providing an extra 500-1,000 IU of vitamin D2 each day

         b, ensuring that the dietary intake of calcium is adequate

Chapter 652. Oncogenic Rickets

    (primary hypophosphatemic rickets associated with tumor)

 1)rickets  associated with a tumor of mesenchymal origin,

   resolution upon removal of the tumor

 2)이러한 tumor의 특징

  1,phosphate deficient form of rickets 야기

  2,mostly benign

  3,may become apparent only years  after the development of rickets

  4,may be located in sites difficult to detect, such as the small bones of the hands and feet,

    abdominal sheath, nasal antrum, and pharynx

  5,also associated with the epidermal nevus syndrome, neurofibromatosis, and linear nevus

    syndrome  

 3)검사 소견 : hypophosphatemia, hyperphosphaturia, glycinemia, glycinuria

 4)기전 :tumor가 still-unidentified substance를 생성하여 phosphaturia를 야기하고

        conversion of 25(OH)D to 1,25(OH)2D를 방해  

        (normal serum 25(OH)D level, 그러나 1,25(OH)2D는 low but rapidly rise to normal

            after tumor excision)

 5)children with acquired or late-appearing hypophosphatemic rickets가 있을 경우 반드시 tumor유무를 확인하기 위해서 X-ray, bone scan을 실시

 

24.66        RICKETS ASSOCIATED WITH RENAL TUBULAR ACIDOSIS

 

 1)type II or proxymal RTA

  1.rickets may be present

  2.hypophosphatemia and phosphaturia are common

  3.특징 :hyperchloremic metabolic acidosis

         varing degrees of bicarbonaturia

         frequently hypercalciuria and hyperkaliuria

         lowered renal threshold for bicarbonate

         impaired urinary acidification at normal levels of serum bicarbonate

  4. 치료

      a, both bicarbonate and oral phosphate supplements to heal bone disease

      b, vitamin D(to offset the 2ndary hyperparathyroidism that complicates oral

         phosphate therapy)

 2)type I and distal RTA

  1, usually bone demineralization without overt rickets

     (due to dissolution of bone)

  2,an inability to form an  adequately acid urine t all levels of serum bicarbonate

  3,치료 :administration of sufficient bicarbonate to reverse acidosis

       (bone dissolution and the hypercalciura 중지시킴 )

 3)in both types

  1.metabolic bone diseases 초래

   bone pain , growth retardation, osteopenia, and occasionally pathologic fractures

 2.circulating levels of 1,25(OH)2D :N

Chapter 653. Hypophosphatasia

 

 1)개요

  1,AR disorder that roentgenographically resembles rickets and is defined by low serum ALP

    activity

  2.now recognized to be an inborn error of metabolism

   :deficient activity of the tissue-nonspecific(liver/bone/kidney) ALP

  3.간혹 출생시 나타나며, diagnosis in utero by X-ray examination of the fetus 될 수 있음

  4.분류는

   a. lethal neonatal or perinatal form (congenital lethal hypophosphatasia)

   b. a severe infantile form

   c. a milder form occurring in childhood or late adolescence

     (hypophosphatasia tarda)

 2)congenital lethal hypophosphatasia

  1.  lethal neonatal or perinatal form

  2.  특징 :moth-eaten appearance at the ends of the long bones

           severe deficiency of ossification throughout the skeleton

           marked shortening of the long bone

  3.neonatal or infantile form 에서는 hypercalcemia에 의한 nephrocalcinosis를 야기할 수 있음

 3)patients with the mild disease

  1. bowing of the legs and variable statural shortening

  2. calcium accumulation by mature chondrocytes dl 되지 않으므로 rickets 가 나타날 수 있음

  3.unusual clinical manifestration

    a)wormian bones in the calvarium

    b)poor calcification of the frontal , parietal and occipital bones

    c)premature loss of deciduous or permanent teeth owing to hypoplasia of dental cementum

  4.bone pain frequent fractures and milder skeletal deformities

  5.irregular ossification punched-out areas. and metaphyseal cupping in metaphysis

 4)검사소견

  1. large quantities of phosphoethanolamine in urine (이는 ALP에 의해 분해됨 )

  2. elevated plasma inorganic pyrophosphate and pyridoxal-5-phosphate

 5)치료 : no satisfactory therapy

         but infusion of plasma rich in ALP activity 가 도움됨

 6)예후

  1,mild disease : often improves spontaneously as the child matures

  2. severe infantilie form : early death from renal failure, flail chest, or Pn

 7)pseudohypophosphatsia

  1,rare patients presenting identical clinical and X-ray patterns but normal serum-ALP

     activity

  2.may present the presence of a mutant ALP isozyme that reacts to artificial substrates in

    alkaline environment

Chapter 654. Primary Chondrodystrophy (Meaphyseal Dysplasia)

 

1)bowing of the legs , short stature, and a waddling gait in the absence of abnormalities of

  serum calcium, phosphate, ALP activity, or citamin D metabolites

2)Jasen type of metaphyseal chondrodysplasia

  1.typified by cupped and ragged metaphyses

  2.mottled calcification at the distal ends of bone over time

  3.hypercalcemia, with serum values of 13-15mg/dL

  4.deformed spine by the irregular growth

 3)Schmidt type of metaphyseal chondrodysplasia

  1. less severe

  2. familial hypophosphatemia 와 유사한 X-ray appearance of the knees and extreme bowing

    of the lower limbs

  3.more debilitating hip abnormalities

  4.Jasen type과 함께 life-long short stature

 4)metaphyseal dysotosis or Pyle disease

  1.defects in endochondral bone formation and metaphyseal modeling

  2. "Erlen-meyer flask" defect: splayed 된 long ends of bones

  3. not present short stature, normal serum chemical levels

  4. meonine features if the facial bones are involved

 5)치료 : no effective forms of treatment

Chapter 655. Idiopathic Hypercalcemia

 

 1)제 2차 대전 직후 , 영국 영아에서 excessive quantities of vitamin D를 food에 강화시켰을 때

  hypercalcemia가 나타나는 데 대한 의학적인 이목이 처음으로 집중하였다 비록 많은 영아가 높은 level의 vitamin D에 노출되었지만 소수에서만 hypercalcemia, failure to thrive, and decline in renal function이 나타났다.

 X-ray상 osteosclerosis and dende bones at the metaphyses를 나타냈으며, vitamin D content of milk를 감소한 후로 이 질환이 줄었다.

  다음은 three forms of hypercalcemia of unknown origin 의 기술이다

  2)Williams syndrome or the elfin facies syndrome

   1.hypercalcemia : an infrequent finding

   2.sporadic

     a. some children: hypervitaminosis D without evidence of increased maternal or infantile

          vitamin D intake

     b. most cases : the circulating values for vitamin D metabolites 는 normal

   3. slowly excretion of an infused calcium load

     evidence for increased production of 25(OH)D from vitamin D

   4.a constellation of manifestations

     a. characteristics facial features: small mandible, prominent maxilla, upturned nose,

       upper lip of Cupid's bow crve, and small peg-like teeth with numerous caries

     b, feeding problems and failure to thrive during the 1st  yr of life

     c. mild mental retardation

     d, unusual "cocktail party patter" personality : typical

     e. cardiac lesions : supravalvular aortic stenosis , peripheral pulmonary stenosis,

        hypoplasia of the aorta and ASD or VSD

     f. in hypercalcemic patients nephrocalcinosis and sclerotic long bones

 3)mild idiopathic hypercalcemia

   1. usually transient

   2phenotypic features of Williams syndrome은 없음

   3 hypercalceuria and sometimes nephrocalcinosis, possibly resembling the English infants

      who received excessive vitamin D after World War II

   4. no evidence for abnormalities in vitamin D metabolism

 4) familial hypocalciuric hypercalcemia

   1.개요

    a, AD condition

    b, asymptomatic hypercalcemia without hypercalciuria

    c. pancreatitis in some families

      neonates of life-threatening parathyroid hyperplasia in a few kindreds

   2 검사소견

    a serum calcium levels : exceeding 18 mg/dL

    b. mild parathyroid hyperplasia despite hypercalcemia

    c. normal vitamin D metabolism

   3.치료

    a only the infants with serious hyperparathyroidism

      :an emergency parathyroidectomy

    b. serum magnesium이 증가될 수 있지만 , 이는 not a serious concern

Chapter 656. Hyperphosphatasia

 1)특징 :excessive dldvaion of the bone isozyme of ALP in serum significant growth

        failure

 2)임상소견

   1.osteoid proliferation in the subperiosteal portion of bone 은 periosteum과 bone

    cortex의 분리를 초래함

   2. bowing and thickening of the diaphyses, along with osteopenia

   3. 2-3세경 onset하며 painful deformity in the extremities , abnormal gait, and sometimes

        fractures로 나타난다 .

   4other common findings : pectus carinatum, kyphoscoliosis, and rib fraying

   5.large skull, thickened and deformed cranium

 3)방사선학적 소견

   1.variable bony testure : dense areas with radiolucent areas and general demineralization

         (showing a teased cotton-wool appearance)

   2. long bone은 sylindric metaphyseal modeling 소실 , pseudocysts showing a dense body

        halo를 나타냄

 4)검사소견

   1.serum levels of both calcium and phosphate : normal

   2. urinary leucine amino acid peptidase activity and serum acid phosphatase :increased

 5)종종 juvenile Paget disease라고 하는 데 이는  adult-onset Paget disease와 같이

   1calcitonin이 이 질환에서 나타나는 srapid bone turnover를 감소시키기 때문임

   2.그리고 소아에서는 more generalized and symmetric 하다

 6)Transient hyperphosphatemia

   1.2mo-2yr사이에 나타나며, 증상이 없어 routine 검사에서 우연히 발견됨

   2.elevated both liver and bone isoenzyme fractions

    but no other manifestations of hepatic or bone dysfunction

   3.unknown etiology

   4.usually resolution within 4-6 mo

 7)Familial hyperphosphatemia

   1.AD trait benign condition

   2. transient infantile form과의 구별은 persistent and asymptomatic elevations of serum

    ALP levels에 의함