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7/31/2019 review thalassemia
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Endocrine Complication in
Thalassemia patient
.
..
autosomal recessive
globin chain
( developing
country )
free-radical formation peroxidation
membrane mitochondria, lysosome
sarcolemma
20 30
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hypogonadotropic hypogonadism impaired glucose
tolerance
hypothyroidism hypoparathyroidism
1861
50
(delayed puberty),
hypogonadism
amenorrhea (secondary
hypogonadism).
4-10 ,
, ,
. 10
18,
10 6.31
1.
(hemochromatosis)
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(iron overload)
, ,
, glomerulosa
, 2,
(
)
(non-invasive)2,
magnetic
resonance imaging (MRI),
,
(fibrosis),
,
,
.
,
.
ferritin
. ferritin
2000 ./.
.
2.
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(puberty)
3
3
10.5 /.
8.5 /.
4,5
8 /.
.
(growth hormone, GH) ,
(impaored glucose tolerance) ,
gonadotropin prolactin
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ferritin
3.
,
-
- desferrioxamine
,
.
-
,
(adrenalitis)
HIV
cytomegalovirus,
ketoconazole.
(adrenal insufficiency) .
1. (short stature)
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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%
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( 1)
( 2)
Heshmat 200613
158
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(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
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2. (Delayed Puberty and
Hypogonadism)
16 435
32.5
hypogonadotropic hypogonadism
hypothalamus
primary gonadol failure
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1
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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
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Hypogonatotrophic Hypogonadism
gonadotroph cell
adipose tissue leptin
/21
Heshmat13 2006
158
hypogonadism 69
hypogonadism
14 FSH LH
hypogonadism
ferritin
2000 /
0-1
1
(p
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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
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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
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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
,
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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
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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
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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
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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
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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
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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
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