review thalassemia ล่าสุด

7/31/2019 review thalassemia

1/31

Endocrine Complication in

Thalassemia patient

.

..

autosomal recessive

globin chain

( developing

country )

free-radical formation peroxidation

membrane mitochondria, lysosome

sarcolemma

20 30


2/31

hypogonadotropic hypogonadism impaired glucose

tolerance

hypothyroidism hypoparathyroidism

1861

50

(delayed puberty),

hypogonadism

amenorrhea (secondary

hypogonadism).

4-10 ,

, ,

. 10

18,

10 6.31

1.

(hemochromatosis)


3/31

(iron overload)

, ,

, glomerulosa

, 2,

(

)

(non-invasive)2,

magnetic

resonance imaging (MRI),

,

(fibrosis),

,

,

.

,

.

ferritin

. ferritin

2000 ./.

.

2.


4/31

(puberty)

3

3

10.5 /.

8.5 /.

4,5

8 /.

.

(growth hormone, GH) ,

(impaored glucose tolerance) ,

gonadotropin prolactin


5/31

ferritin

3.

,

-

- desferrioxamine

,

.

-

,

(adrenalitis)

HIV

cytomegalovirus,

ketoconazole.

(adrenal insufficiency) .

1. (short stature)


6/31

9 10

multifactorial6,7

chronic anemia

chronic hypoxia, chronic liver desease,

, , chelating

agent , , endocrine-pathies

(hypogonadism, delayed puberty, hypo-thyrodism)

Growth Hormone Insulin-like growth factor (IGF-1)

0-10

Hb

9 g/dl

6,8

desferioxamine 9,10

2-5 desferioxamine9,11,12

DNA, Fibroblast proliferation, collagen

desferioxamine 50 ./.

(short trunk)

(normal)

15-40%


7/31

( 1)

( 2)

Heshmat 200613

158


8/31

(short stature) 62

Growth hormone

insulin like growth factor 1

Growth hormone insulin like growth factor

1 38 42

ferritin

2000 /

0-

1

1 (p


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curve,

3. Growth Hormone,

deferoxamine

15

1. Recombinant humanGrowth Hormone ( rhGH )

GH 0.6 0.9

iu/kg/wk GH

GH resistance

GH GH

insulin sensitivity glucose tolerance

2. Zine Sulphate

3. Desferioxamine

risk/benefit Desferioxamine


10/31

2. (Delayed Puberty and

Hypogonadism)

16 435

32.5

hypogonadotropic hypogonadism

hypothalamus

primary gonadol failure


11/31

1


12/31

Delayed Puberty

13-14 (breast

enlargement or testicular enlargement)

Hypogonadotrophic Hypogonagism

Arrested puberty

1

6 8 .

Tanner stage 3

Hypogonadism

15-16

Secondary hypogonadism

hypogonadism

hypothalamus

impotence ejaculation

secondary amenorrhea

hot flush,

17

Hypogonadotrophic

Hypogonadism phenotype

18-20

18


13/31

Hypogonatotrophic Hypogonadism

gonadotroph cell

adipose tissue leptin

/21

Heshmat13 2006

158

hypogonadism 69

hypogonadism

14 FSH LH

hypogonadism

ferritin

2000 /

0-1

1

(p


14/31

3. hypogonadism

,

testosterone estradiol

DHEA-S

4. secondary hypoganadism ,

impotence infertility

22

hypothalamo-pituitary-gonadal axis

hypogonadism

depot-

testosterone 25-5. .

6 100 mg

1 1

14

ethiyl estradiol 2.5 5 mcg 6

1

ethinyl estradiol 5 10

mcg 12

(breakthrough uterine bleeding)

medroxy progesterone acetate


15/31

5 . 12

estrogen-progesterone

patche

3. Hypothyroidism

granule follicular

epithelium macrophage interstitium

fibrosis primary

hypothyroidism secondary

preclinical, mild overt hypothyroidism

pericardial effusion

thyroid-stimulating hormone (TSH)

T4 free T4 antibody thyrolobulin

8823 alteration

thyroglobulin membrane

homogeneous echo pattern capsule

electrocardiogram (ECG) prolongedQT interval pericardial effusion ECG

Voltage secondary hypothyroidism serum T4

TSH thyrotropin-

releasing hormone (TRH) stimulation

Hypothyroidism & Cardiac dysfunction


16/31

adenosine triphosphatase

hypothyroidism cardiac output 24

peripheral

vascular resistance

hypothyroidism peripheral vascular

resistance tissue perfusion oxygen utilization

,

bradycardia, hypertension, nonpitting edema pleural

pericardial effusion

dyslipidemia Cholesterol LDL

De Sanctis 200823

50 hypothyriod

arrhythmia

4

L-thyroxine

Hypothyroidism & hypogonadism

Subclinical hypothyroidism

gonad dysfunction

,


17/31

Treatment

overt hypothyroidism sodium-L-thyroxine

25 2-3

100 mcg/m2/day

mild hypothyroidism

preclinical hypothyroidism

Biondi Cooper

200825

L-thyroxine

Bauer 26 thyroid hormone

Trokoudes 200627

thyroxine hormone subclinical hypothyroidism ovulatory

dysfunction

Kallistheni28

2011

52 FT4

(p < 0.001) combine

chelation treatment ( DFO and DFP ) TSH

(p < 0.001)

mono chelation

treatment

Intervention

1. TSH 1

12


18/31

2. hypothyroidism

thyroid hormone replacement

4. Hypoparathyroidism

hypoparathyroidism

hypoparathyroidism

1.2 1429 16-20

( 18.7)

induce reabsorption

hematopoiesis

hypoparathyroidism

tetany, seizures, carpopedal

spasm paresthesi30

mild parathesia

tetany

, genu valgum

1,25-dihydroxy

24

(osteoporosis) trabecule

codfishdeformities

analogue

Calcitriol 0.25-1.0

2

3


19/31

24 3

phosphate binder tetany

60 /

turnover

resorptive phase neoformation phase

31 bone density

-2.5 SD

hypertransfusion

(hormonal

replacement therapy,HRT) resorption

bisphosphonate 31

Hamidieh 29 2009

130

hypoparathyroidism

14.6 serum ferritin

(p=0.95)

hypoparathyroidism cardiac

diastolic dysfunction

hypoparathyroidism

(p=0.04)

hypoparathyroidism abnormal

glucose metabolism


20/31

hypoparathyroidism

(p=0.03)

Nicholas 32 2006

243

hypoparathyroidism 14.6

serum parathyroid hormone

calcium (total and ionized form)

(p=0.03)

phosphorus

(p=0.007)

hypoparathyroidism abnormal glucose

metabolism (p


21/31

cell ,

, ,

, , blood transfusion

, serum ferritin, 35-36

blood transfusion 10

2:5 37

interstitial cell collagen

microcirculation

supply

impaired glucose tolerance

ketoacidosis IGT

(intensive chelation therapy)

IGT

fructosamine

glycosylated hemoglobin

hemolysis glycosylation

threshold

hypogonadism

hypothyroidism life expectancy

acidosis

thromboembolism

IGT


22/31

10

glucose tolerance test

Jimmy 38

transfusion dependent beta-thalassemia

89 19.5

8.5

abnormal glucose tolerance transfusion

dependent beta-thalassemia serumm ferritin

hepatitis C infection

Mehrvar 39

437

5.4

Intervention

1. fasting plasma glucose test

1

75-g2-h OGTT

40

2.

insulin resistance glucose intolerance 41


23/31

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review thalassemia ล่าสุด