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Title: Goiter: Pathophysiology and clinical aspects


1
Goiter Pathophysiology and clinical aspects
Joaquín Lado Abeal, MD, PhD
Department of Internal Medicine TTUHSC-SOM,
Lubbock
2
Iodine intake (goitrogens)
Gender
Genetic
3
From Iodine Satus Worldwide. WHO Global Data Base
on Iodine Deficiency. 2004
4
From Iodine Satus Worldwide. WHO Global Data Base
on Iodine Deficiency. 2004
5
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6
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7
Dr Gregorio Maranon
8
CRETINISM
Myxedematose
Neurological
9
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10
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11
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12
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13
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14
Thyroid Hormone Synthesis
15
TSH
Diferentiation
Proliferation
16
Pituitary TSHoma
TSH
17
Graves-Basedow disease
18
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19
Syndrome of Resistance to Thyroid Hormone Action
(SRTH)
37
36
Neck diameter (cm)
35
34
Weight (Kg)
33
32
31
30
November 2001
2
1
0.5
TSH (mU/L)
(µg/L)
TT4 (µg/dl)
TG
0.1
0.
05
L-T
dose
3
µg c.2.d.
Number of days
May 2003
20
TSH (µU/ml)
N Range Mean ? SE p p
Euthyroid (Buenos Aires) 20 2.4-3.6 3.2 ? 0.4 ? ?
Non goiter (Neuquen) 14 2.4-5.6 4 ? 0.8 lt0.01 ?
Goiter, grade I II 6 3.2-5.6 3.6 ? 0.8 NS NS
Goiter, grade III 8 2.4-5.6 4 ? 0.8 lt0.05 NS
Goiter, grado I II 7 2.4-4.8 4 ? 0.8 lt0.05 NS
Goiter, grado III 5 2.8-7.2 4 ? 0.8 lt0.05 NS
MA Pisarev, RD Utiger, JP Salvaneschi, N
Altschuler, LJ DeGroot. Serum TSH and thyroxine
in Goitrous Subjects in Argentina. J Clin Endocr.
30680-681. 1970.
21
MULTINODULAR GOITER
28.1.04
11.4.05
30.8.05
NORMAL
TSH µU/ml
0.42
0.10
0.08
0.35-5.50
1.08
FT4 ng/dl
0.88
0.80
0.85-1.86
3.29
3.89
3.65
2.20-4.70
FT3 pg/ml
Ab TPO
lt 33
AbTG
lt 100
22
Pendred Sydrome
23
Total Thyroidectomy (February 05)
50 µg/day T4 (starting March 04)
100 µg/day T4 Post surgery (starting February 05)
100 µg/day T4 (starting Nov 04)
24
rT3
D3
T3
MCT8
T4
T4
T3
D1, D2
T4
25
THYROGLOBULIN GENE MUTATIONS
Redgoiter
R277X
c.62051delG
p.R277X / c.62051delG
WT/ p.R277X
WT/ c.62051delG
WT / WT
WT/ c.62051delG
p.R277X / c.62051delG
p.R277X / c.62051delG
p.R277X / c.62051delG
WT/ c.62051delG
T
Exon 35
Intron 35
Exon 7
26
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27
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28
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29
p.R277X /c.62051delG
WT /c.62051delG
30
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31
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32
Thyroglobulin mutations
unfolded protein response
apoptosis
defective hormone synthesis
p53, NF-kB, MPAKs, VEGF
high serum TSH
Goiter
oxidative stress
BRAF mutations
Cancer
33
Afrikaner cow
9
TG
48
1
34
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35
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36
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37
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38
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39
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40
Normal Human Thyrocites
TTF-1
PAX-8
Tg
4 Days
3 Weeks
3 Weeks
H-RAS (V-12)
CONTROL
V Gire, D Wynford-Thomas. Oncogene.
19737-744.2000
41
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42
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43
PAX8-PPARG
t(23)(q13p25)
TG Kroll et al. Science. 2891357-1360.
2000 Placzkowski KA et al. PPAR Research. 2008
44
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45
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46
Chernobyl Disaster (April 26 1986)
47





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48
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49
Aneuploidy (33 Goiters)
66 XXX
From T Dettori et al. Genes, Chromosomes
Cancer. 38 22-31. 2003.
50
M Iliszko et al. Cancer Genetic and Cytogenetcis.
161 178-180. 2005
51
Cowden Syndrome
52
PI3K/AKT Pathway (cell proliferation and survival)
PIK3CA
PI3K
PTENPhosphatase and Tensin Homolog
I Vivanco, CL Sawyers. Nature Reviews. 2
489-501.2002
53
Wang Y et al. JCEM. 922387-2390. 2007
54
PAX8-PPARG
TSHR /GNAS
PAX8-PPARG
RAS
FollicularAdenoma
Follicular Carcinoma
PI3K/Akt
PI3K/Akt
PAX8-PPARG
mtDNA CD (mtDNA common deletion)
GRIM-19 (gene associated with
retinoid- interferon-induced mortality-19)
Hurthle Cell Adenoma
Hurthle Cell Carcinoma
55
Santiago de Compostela Cathedral
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