with Hypothyroidism during Pregnancy Show Abnormal Corpus Callosum - - PowerPoint PPT Presentation

▶
with hypothyroidism during
SMART_READER_LITE
LIVE PREVIEW

with Hypothyroidism during Pregnancy Show Abnormal Corpus Callosum - - PowerPoint PPT Presentation

Sep 06, 2023 22 likes •394 views

Children Born to Women with Hypothyroidism during Pregnancy Show Abnormal Corpus Callosum Development Arash Samadi, Jovanka Skocic, Joanne Rovet A MERICAN T HYROID A SSOCIATION A NNUAL M EETING S AN J UAN P UERTO R ICO , O CTOBER 2013

slide-1
SLIDE 1

Children Born to Women with Hypothyroidism during Pregnancy Show Abnormal Corpus Callosum Development

AMERICAN THYROID ASSOCIATION ANNUAL MEETING SAN JUAN PUERTO RICO, OCTOBER 2013

Arash Samadi, Jovanka Skocic, Joanne Rovet

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-2
SLIDE 2

Arash Samadi

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-3
SLIDE 3

Disclosure

I have nothing to disclose

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-4
SLIDE 4

Maternal Thyroid Hormone Deficiency in Pregnancy

  • Hypothyroxinemia (low T4)
  • Subclinical hypothyroidism

(high TSH)

  • Clinical hypothyroidism (low

T4/high TSH)

  • Iodine deficiency

4

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-5
SLIDE 5

Maternal Thyroid Hormone Deficiency Effects on Offspring

  • Reduced IQ
  • Attention problems
  • Memory weaknesses
  • Visual & visuomotor difficulties
  • Poor language, auditory, &

literacy skills

  • Behavior problems

5

e.g., Haddow J et al 1999 NEJM; Henrichs et al 2010 JCEM; Ghassabian et al 2011 Pediatr Res; Ghassabian et al 2012, Thyroid; Hynes KL et al JCEM 2013; Mirabella G et al 2000 J Ped Endo Metab; Mirabella G et al 2005 Ped Res; Pharoah & Connelly 1990, Early Hum Develop; Pop V et al 1999 Clin Endo; Smit BJ et al 2000 Acta Paed; Roman G et al Ann Neurol, 2013: Vermiglio F et al 2004 JCEM; Willoughby K et al 2013 JINS

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-6
SLIDE 6

HYPO > CON HYPO Willoughby K et al, 2013, Thyroid, in press ATA 2011 ITC 2011 ATA 2012 Control

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-7
SLIDE 7

Thyroid hormone is essential for corpus callosum development

Berbel P et al (1994) Behav Brain Res 64: 9-14

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-8
SLIDE 8

Thyroid hormone is essential for corpus callosum development

Powell M.H. et al (2012) Neurotoxicol 33: 1322-1329

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-9
SLIDE 9

Thyroid hormone is essential for corpus callosum development

Pettigrew, R., et al (2007) Vet Pathol 44:50-56

wild type

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-10
SLIDE 10

Corpus Callosum

  • Largest white matter

(WM) tract in brain

  • Transfers information

between hemispheres

Hofer & Frahm (2006) NeuroImage 32:989-994

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-11
SLIDE 11

Corpus Callosum

  • Largest white matter

(WM) tract in brain

  • Transfers information

between hemispheres

  • Needed for many

functions (e.g., bimanual coordination, social communication, complex reasoning)

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-12
SLIDE 12

Corpus Callosum Abnormalities

Raybaud, C. (2010) Neuroradiol 52:447-477

Turner syndrome Fetal alcohol syndrome Autism

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-13
SLIDE 13
  • Exuberant axonal growth in first 2

trimesters

  • Exuberant pruning in third trimester
  • Myelination from birth to adulthood

Corpus Callosum Development

13 wk 12 wk 14 wk 30 wk 22 wk

maternal thyroid hormones

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-14
SLIDE 14

Morreale de Escobar G et al, 2000

maternal thyroid hormones maternal thyroid hormones

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-15
SLIDE 15

Abnormal Corpus Callosum Morphology in Congenital Hypothyroidism

Control

Ibrahim F et al, ATA 2013

Congenital Hypothyroidism

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-16
SLIDE 16

CH have smaller genus

p<0.01

CH Control

p<0.01

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-17
SLIDE 17

Is corpus callosum development abnormal in children born to women with thyroid hormone insufficiency during pregnancy?

17

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-18
SLIDE 18
  • 1. Is the corpus callosum (CC)

abnormal in size and/or shape in

  • ffspring of hypothyroid women

(HYPO)?

  • 2. Are CC abnormalities related to

severity or duration of maternal hypothyroidism?

  • 3. Do CC abnormalities predict
  • utcome in HYPO?

Research Questions

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-19
SLIDE 19
  • N=20
  • 9 to 12 yrs (mean=10.3 yrs)
  • Born 1996-2001 to women with

hypothyroidism diagnosed prior to (83%) or during pregnancy

  • Inclusion criterion: mothers not given L-

T4 dose increase in pregnancy

  • Excluded if mothers had normal TSH

levels in all trimesters

Sample: HYPO

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-20
SLIDE 20

Sample: Controls

  • 22 children, mostly from same birth

cohort as HYPO

  • Matched with HYPO for sex, age,

socioeconomic status

  • Mean age = 10.9 years
  • All mothers claimed no

hypothyroidism during pregnancy

  • r since

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-21
SLIDE 21
  • Day 1: 4-hour

neuropsychological evaluation

  • Day 2: 1-hour MRI scan in 1.5

Tesla magnet

  • 7-min axial T1 FSPGR

sequence (TR/TE=10.3/4.2 ms,

inversion time=400 ms, flip angle = 200, slice thickness = 1.5mm)

  • Corpus callosum manually

traced and measured using Analyze 9.0

Procedures

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-22
SLIDE 22

Quantitative Approach

genu splenium

rostrum

isthmus anterior midbody posterior midbody

genu splenium Hofer & Frahm (2006) NeuroImage 32:989-994

VI

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-23
SLIDE 23

Quantitative Approach

genu splenium

rostrum

isthmus anterior midbody posterior midbody

genu splenium

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-24
SLIDE 24
  • Curvature (d)
  • Droop (e)
  • Peak (a)

Qualitative Approach

Gabrielli O et al (1993) Neuroradiol 35:109-112

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-25
SLIDE 25
  • Shape of genu (A/B) and splenium

(C/D)

Qualitative Approach

A B C D

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-26
SLIDE 26

HYPO Have Smaller Genu/Larger Splenium

Group X Region Interactions

Raw areas: F=4.49, p=0.05 Proportions: F=5.15, p=0.02

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-27
SLIDE 27

Linear Measurements

  • No significant group differences in

lengths or widths

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-28
SLIDE 28

Angles

  • No significant group differences in

curvature or orientation of genu

  • r splenium

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-29
SLIDE 29

Shape of Genu & Splenium

B A D C

HYPO have shorter/wider genus than controls HYPO have longer/narrow spleniums than controls

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-30
SLIDE 30

Correlations with Maternal Hypothyroidism

  • Corpus callosum size/shape not

correlated with any trimester maternal TSH/T4

  • Size of anterior and posterior

segments correlated with duration of maternal hypothyroidism in pregnancy

Anterior Posterior

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-31
SLIDE 31
  • Larger anterior CC

(posterior midbody) associated with better reading ability

  • Larger genu with

better cognitive flexibility

Structure/Function Correlations

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-32
SLIDE 32
  • Smaller isthmus with

better nonverbal memory

  • Smaller splenium

with better verbal ability

Structure/Function Correlations

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-33
SLIDE 33

In Summary

  • HYPO relative to controls show:
  • Reduced size of genu and

increased size of splenium

  • Abnormal splenium and genu

shapes

  • Normal lengths & thickness of CC
  • Normal CC shape

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-34
SLIDE 34

In Summary

  • No effect of maternal hypothyroidism

severity

  • More severe effects reflect duration
  • f hypothyroidism
  • Size of specific CC regions

associated performance in different cognitive abilities in HYPO

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-35
SLIDE 35

Morreale de Escobar G et al, 2000

HYPO

  • Normal shaped CC
  • Smaller & wider genu
  • Larger (longer, skinnier)

splenium CH

  • Flatter CC
  • Smaller & narrower genu
  • Abnormally oriented but normal

size splenium Effects on axonal growth & pruning? Effects on axonal pruning & myelination?

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-36
SLIDE 36

Conclusion

  • Inadequately treated hypothyroidism

in pregnancy disturbs corpus callosum development by disrupting the patterning of axonal growth and pruning

  • These effects are associated with

reduced cognitive abilities

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)

slide-37
SLIDE 37

Thank You

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Arash Samadi, Jovanka Skocic, Joanne Rovet)