To screen, or not to screen?

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About this transcript

This is a verbatim machine transcript of the full 60-minute recording, rebuilt for this file. It differs from the earlier auto-transcript in four ways: (1) every paragraph carries a video timestamp in HH:MM:SS form, converted to session wall-clock time in the section headings; (2) speakers are identified by voice — ECAPA speaker embeddings clustered into the three voices and anchored on each speaker's solo stretches — not by guessing from content; (3) every distinct screen state (65 slides, 88 on-screen states) is reproduced in place, with chart/table descriptions where the slide was graphical; (4) known speech-recognition errors in names, acronyms, units and clinical terms were corrected against the slides, the speakers' own published papers and the guideline documents, and material that the recording does not contain was removed rather than guessed at.

Disfluencies (um, uh, false starts) are preserved because this is a verbatim record. Obvious recognition repetition artifacts were removed. Text marked [V] or † is flagged in Appendix D: [V] = wording is reconstructed/uncertain and must be checked against the audio before quotation; † = a short passage reconstructed from the earlier transcript where the audio is partly unintelligible.

Speakers and timing

Recording starts 11:45 AM Central. Add the video timestamp to 11:45 AM for wall-clock time (e.g. 00:22:14 = 12:07 PM — which is why Dr. Boelaert says “Good afternoon”). The session was 60 minutes; the audio file is 60:12.7 and the final 12 seconds are a recording artifact.

00:00 — Opening and screening primer

11:45 AM CT

On screen · 00:00–00:38 · S01

Endocrine Debate: Thyroid Disease in Pregnancy: To Screen, or Not to Screen?

For - Alex Stagnaro-Green, MD, MHPE, MHA
Against - Kristien Boelaert, MD, PhD
Moderator - David S. Cooper, MD

Plain royal-blue title slide with a small green arrow pointer (presenter cursor); no charts.

On screen · 00:38–01:18 · S02

What is screening? (WHO definition)

Screening refers to the use of simple tests across a healthy population in order to identify individuals who have disease, but do not yet have symptoms.
Example: breast cancer screening using mammography.
For this morning: will screening (and treating) pregnant women for thyroid disease improve obstetrical and neurodevelopmental outcomes?

World Health Organization logo (top left); clip-art of a crowd under a magnifying glass with one figure highlighted in red (top right).

Note: incremental build: second bullet added

On screen · 01:18–02:22 · S03

Screening Criteria

• Thyroid disease in pregnancy
  ** Serum TSH; Serum TPO Ab
  Adapted from:
  Wilson JMG, Jungner G. Principles and Practice of Screening for Disease, World Health Organization, 1968

Same slide with only the title visible (the 5 criteria have not yet appeared); WHO logo and crowd/magnifying-glass clip-art present.

Note: incremental build: title-only state

On screen · 02:22–02:48 · S04

The Debaters

For screening
Dr.. Alex Stagnaro-Green is the Regional Dean of the University of Illinois College of Medicine Rockford and is Professor of Medicine, Obstetrics and Gynecology, and Medical Education.
Against screening
Dr.. Kristien Boelaert is a Reader in Endocrinology at the University of Birmingham and a Consultant Endocrinologist at University Hospitals Birmingham, UK.

Two small portrait photos at left: Dr. Alex Stagnaro-Green (above 'For screening') and Dr. Kristien Boelaert (above 'Against screening'); green arrow pointer.

02:47 — Format, rules, and the pre-debate poll

11:47 AM CT

On screen · 02:48–03:38 · S05

Endocrine Debate: Thyroid Disease in Pregnancy: To Screen, or Not to Screen?

Audience Poll
Frame the Position/Share Evidence
Advocate For the Motion (Dr. Stagnaro-Green)
Advocate Against the Motion (Dr. Boeleart)
Rebuttals
Advocate For the Motion
Advocate Against the Motion
Questions from Audience

Agenda bullet list on solid blue background; green arrow pointer.

Note: keyframe is before the 'Final Statements' sub-bullets were added (~t=200s, not captured in the 95-state list - see report)

On screen · 03:38–03:52 · S06

SESSION PARTICIPATION AND EVALUATIONS USING THE ENDO 2019 APP

STEP 1 Find the session
STEP 2 Tap the Participate Evaluate button
Complete session evaluations by clicking Evaluate This Session

Two smartphone screenshots of the ENDO 2019 app (session OR07 Growth, Puberty, and Insulin Action and Resistance; Room 356; Saturday, March 23 11:30 AM - 1:00 PM; CME/MOC 1.50), blue arrows with STEP 1 'Find the session' / STEP 2 'Tap the Participate Evaluate button'; app tags: Evaluate This Session, Polls, Question 1, Social Q&A, Ask, ADD TO MY SCHEDULE; ENDO 2019 logo.

On screen · 03:52–04:02 · S07

Question

1. Are you in favor of screening all pregnant women for thyroid dysfunction?
   – Yes
   – No

Plain purple question slide; red banner at the bottom reads 'LIVE POLLING IS THE NEXT SLIDE'; green arrow pointer.

On screen · 04:03–04:14 · S08

1. Are you in favor of screening all pregnant women for thyroid dysfunction?

Yes
No
6 (yellow countdown box, bottom-right)

White live-poll screen of the ENDO 2019 app: question at top, 'Yes'/'No' options, large yellow countdown box bottom-right showing '6'.

On screen · 04:15–04:20 · S09

1. Are you in favor of screening all pregnant women for thyroid dysfunction?

Yes 71%
No 29%
Poll is Locked

White live-poll results screen of the ENDO 2019 app: question at top, Yes/No rows with percentages and horizontal bars (yellow for Yes, green for No), grey label 'Poll is Locked' bottom-right.

On screen · 04:20–04:30 · S07

Question

2. Are you in favor of screening all pregnant women for thyroid autoimmunity?
   – Yes
   – No

Plain purple question slide; red banner at the bottom reads 'LIVE POLLING IS THE NEXT SLIDE'; green arrow pointer.

On screen · 04:32–04:42 · S08

2. Are you in favor of screening all pregnant women for thyroid autoimmunity?

Yes
No
6 (yellow countdown box, bottom-right)

White live-poll screen of the ENDO 2019 app: question at top, 'Yes'/'No' options, large yellow countdown box bottom-right showing '6'.

On screen · 04:42–04:47 · S09

2. Are you in favor of screening all pregnant women for thyroid autoimmunity?

Yes 35%
No 65%
Poll is Locked

White live-poll results screen of the ENDO 2019 app: question at top, Yes/No rows with percentages and horizontal bars (yellow for Yes, green for No), grey label 'Poll is Locked' bottom-right.

On screen · 04:50–05:01 · S11

Select your presentation

Menu screen; the 'David Cooper 11:45 AM - 12:45 PM' card is highlighted/selected with 'Start' and 'My Files' buttons; cards also list Kristien Boelaert and Alex Stagnaro-Green sessions.

Note: Operator screen: 'Select your presentation' list (the session is listed as 11:45 AM – 12:45 PM).

04:55 — Handover and slide setup

11:49 AM CT

On screen · 05:06–05:33 · S12

UNIVERSAL SCREENING FOR THYROID DISEASE IN PREGNANCY SHOULD BE PERFORMED

Alex Stagnaro-Green, MD, MHPE, MHA
University of Illinois College of Medicine Rockford

Red title slide with a cropped Renaissance-style painting of a mother and child with an older woman (Madonna and Child); green arrow pointer.

05:08 — Stagnaro-Green: presentation for universal screening

11:50 AM CT

On screen · 05:40–06:12 · S13

To Screen or Not to Screen: That is the Question

Collage of 7-8 full-page journal-article screenshots (Clinical Thyroidology 'Comparison of universal...', Eur J Endocrinol 'Universal screening detects two times more thyroid disorders in early pregnancy...', BMJ 'Universal screening...', Lancet 'Universal screening in early pregnancy and treatment of overt and subclinical thyroid dysfunction...', NEJM 'Universal screening...', a Perspectives/Editorial, Frontiers in Endocrinology 'Thyroid Screening in Early Pregnancy: Pros and Cons'); green boxes/arrows and 'Free' tags highlight supportive sentences.

On screen · 06:12–06:39 · S14

Terry Davies quote: “You can't sit on the fence forever” (2007)

"You can't sit on the fence forever. It is very uncomfortable for the backside."
-Terry Davies - 2007

Red quote slide over a photo of a wrought-iron fence in front of a building, decorated with red ribbon graphics and three logos (stylised 'M', a blue square emblem, and the AACE seal).

On screen · 06:39–06:56 · S15

Criteria for Screening

1. The condition is common.
2. Screening tool is readily available, reliable, inexpensive and acceptable.
3. Intervention favorably influences the disease with limited adverse effects.
4. Screening and intervention are cost-effective.
5. Agreed-upon policy on whom to treat.
   Wilson and Junger (1968)

Red slide: white box listing the 5 Wilson-Junger screening criteria at left; large blue UN/World Health Organization emblem at right.

On screen · 06:56–07:28 · S16

Prevalence in the Published Literature

Condition | Reported Prevalence Range
Overt Hypothyroidism - 0 - 13.1%
Subclinical Hypothyroidism - 1.5 - 42.9%
Isolated Hypothyroxinemia - 0.18 - 31%
Overt Hyperthyroidism - 0 - 2.5%
Subclinical Hyperthyroidism - 0.3 - 13%

Two-column table with dark-blue header (Condition | Reported Prevalence Range), 5 rows alternating white/light-blue.

On screen · 07:28–08:08 · S17

Differences in Diagnostic Criteria Mask the True Prevalence of Thyroid Disease in Pregnancy

Need consistent criteria to determine true prevalence
Meta analysis of all previously available data
Studies grouped based on criteria for diagnosis
For Hypothyroidism:
Gold-standard 97.5th percentile TSH cutoff is most accurate
For Hyperthyroidism:
Thyroid function testing done in 2nd trimester is most accurate
Dong & Stagnaro-Green, Thyroid 2019

Text slide, no chart: 5 bullets (two with sub-bullets for Hypo- and Hyperthyroidism) and citation line.

On screen · 08:08–08:45 · S18

Prevalence of Overt Hypothyroidism Based on TSH Cutoff Values

% Prevalence (y-axis 0.00% - 3.00%)
All N = 43 - 0.61%
97.5th Percentile N = 19 - 0.50%
95th Percentile N = 4 - 1.50%
ATA 2011^ N = 12 - 1.33%
TSH > 4* N = 9 - 0.80%
TSH Cutoff Criteria
Dong and Stagnaro-Green, Thyroid 2019

Vertical bar chart, % prevalence y-axis 0-3%, red '% Prevalence' label; bars: All 0.61% (N=43), 97.5th Percentile 0.50% (N=19; highlighted with red border), 95th Percentile 1.50% (N=4), ATA 2011^ 1.33% (N=12), TSH >4 0.80% (N=9); red banner 'TSH Cutoff Criteria'.*

On screen · 08:45–09:18 · S19

Prevalence of Subclinical Hypothyroidism Based on TSH Cutoff Values

% Prevalence (y-axis 0.00% - 25.00%)
All N = 56 - 5.10%
97.5th Percentile N = 24 - 3.47%
95th Percentile N = 4 - 3.89%
ATA 2011^ N = 25 - 14.39%*
TSH > 4^ N = 8 - 4.05%
TSH Cutoff Criteria
Dong and Stagnaro-Green, Thyroid 2019

Vertical bar chart, % prevalence y-axis 0-25%; bars: All 5.10% (N=56), 97.5th Percentile 3.47% (N=24; highlighted with red border), 95th Percentile 3.89% (N=4), ATA 2011^ 14.39% (N=25), TSH >4^ 4.05% (N=8); red banner 'TSH Cutoff Criteria'.*

On screen · 09:18–09:38 · S20

Prevalence of Overt Hyperthyroidism Based on Timing of Screening

% Prevalence (y-axis 0.00% - 1.60%)
All* N = 21 - 0.64%
1st Trimester^ N = 14 - 0.91%
2nd Trimester^ N = 6 - 0.65%
TSH Cutoff Criteria
Dong and Stagnaro-Green, Thyroid 2019

Vertical bar chart, % prevalence y-axis 0-1.6%; bars: All 0.64% (N=21), 1st Trimester^ 0.91% (N=14), 2nd Trimester^ 0.65% (N=6; highlighted with red border); red banner 'TSH Cutoff Criteria'.*

On screen · 09:38–10:30 · S21

Thyroid Disease Prevalence in Pregnancy

Prevalence Rates:
Overt Hypothyroidism 0.50%
Subclinical Hypothyroidism 3.47%
Isolated Hypothyroxinemia 2.05%
Overt Hyperthyroidism T1 0.91%
Overt Hyperthyroidism T2 0.65%
Subclinical Hyperthyroidism T1 2.18%
Subclinical Hyperthyroidism T2 0.98%
Thyroid Autoimmunity: TPOAb 5-14%; TgAb 3-18% (De Leo & Pearce, 2018)
Dong & Stagnaro-Green, Thyroid 2019

Two boxes: left table 'Prevalence Rates:' (rows Overt Hypothyroidism 0.50%, Subclinical Hypothyroidism 3.47%, Isolated Hypothyroxinemia 2.05%, Overt Hyperthyroidism T1 0.91%, Overt Hyperthyroidism T2 0.65%, Subclinical Hyperthyroidism T1 2.18%, Subclinical Hyperthyroidism T2 0.98%; first row outlined red); right box 'Thyroid Autoimmunity' (TPOAb 5-14%, TgAb 3-18%, De Leo & Pearce, 2018).

On screen · 10:30–11:02 · S22

Wilson–Jungner scorecard (progressive build)

(table) rows = screening criteria; columns = Overt Hypo, Subclinical Hypo, Isolated Hypothyroxinemia, Overt Hyper, Subclinical Hyper, Thyroid Auto-immunity
Row 1 'The condition is common.': + for all six columns (only row filled so far)

Checklist table build state: only criterion 1 row has green '+' cells across all six condition columns; rows 2-5 still empty.

Note: build state 1 of 5

On screen · 11:02–11:13 · S15

Criteria for Screening

1. The condition is common.
2. Screening tool is readily available, reliable, inexpensive and acceptable.
3. Intervention favorably influences the disease with limited adverse effects.
4. Screening and intervention are cost-effective.
5. Agreed-upon policy on whom to treat.
   Wilson and Junger (1968)

Red slide: white box listing the 5 Wilson-Junger screening criteria at left; large blue UN/World Health Organization emblem at right.

Note: near-duplicate of state 19 (same slide re-shown; only cursor position differs)

On screen · 11:13–11:42 · S23

Test Acceptable to Population

Blood Draw at 1st Prenatal/Preconception Visit
Type and Screen
CBC
Rubella & Varicella IgG, RPR, HBsAg, HIV
Thyroid Screening
TSH

Red slide with photos of blood-collection tubes: 'Blood Draw at 1st Prenatal/Preconception Visit' showing Type and Screen (pink/red tube), CBC (lavender tube), and bottom row of yellow tubes for Rubella & Varicella IgG, RPR, HBsAg, HIV; 'Thyroid Screening' column shows a single TSH (yellow) tube.

On screen · 11:42–12:04 · S22

Wilson–Jungner scorecard (progressive build)

Row 1 'The condition is common.': + all columns
Row 2 'Screening tool-readily available, reliable, cheap and acceptable.': + all columns

Checklist table build state: rows 1 and 2 filled with green '+' across all six columns; rows 3-5 empty.

Note: build state 2 of 5

On screen · 12:04–12:13 · S15

Criteria for Screening

1. The condition is common.
2. Screening tool is readily available, reliable, inexpensive and acceptable.
3. Intervention favorably influences the disease with limited adverse effects.
4. Screening and intervention are cost-effective.
5. Agreed-upon policy on whom to treat.
   Wilson and Junger (1968)

Red slide: white box listing the 5 Wilson-Junger screening criteria at left; large blue UN/World Health Organization emblem at right.

Note: near-duplicate of state 19 (same slide re-shown)

On screen · 12:15–12:52 · S24

Overt Hypothyroidism Correlation Studies

GH/Preeclampsia: Correlation found - Davis et al. 1988, Leung et al. 1993, Buckshee et al. 1997, Sahu et al. 2010, Sharmeen et al. 2014
Placental Abruption: Davis et al. 1988
Low Birth Weight: Leung et al. 1993, Su et al. 2011
Premature Birth: Buckshee et al. 1997, Yang et al. 2018 | No correlation: Abalovich et al. 2002, Nambiar et al. 2011
Offspring Cognitive Delay/Deficits: Haddow et al. 1999, Klein et al. 2001
Miscarriage: Abalovich et al. 2002, Hallengren et al. 2009, Nambiar et al. 2011, Aguayo et al. 2013, Taylor et al. 2014
GDM: Sahu et al. 2010, Sharmeen et al. 2014

Table: Outcome Studied | Correlation Found | No Correlation Found. Rows GH/Preeclampsia (Davis 1988, Leung 1993, Buckshee 1997, Sahu 2010, Sharmeen 2014), Placental Abruption (Davis 1988), Low Birth Weight (Leung 1993, Su 2011), Premature Birth (Buckshee 1997, Yang 2018 | Abalovich 2002, Nambiar 2011), Offspring Cognitive Delay/Deficits (Haddow 1999, Klein 2001), Miscarriage (Abalovich 2002, Hallengren 2009, Nambiar 2011, Aguayo 2013, Taylor 2014), GDM (Sahu 2010, Sharmeen 2014).

On screen · 12:52–13:06 · S25

Overt Hypothyroidism Treatment Studies

GH/Preeclampsia: Treatment benefit - Tan et al. 2006 | No benefit - Wolfberg et al. 2005
Offspring Cognitive Delay/Deficits: Treatment benefit - Haddow et al. 1995, Downing et al. 2012 | No benefit - Liu et al. 1994, Lazarus et al. 2012, Hales et al. 2018
Miscarriage: Treatment benefit - Abalovich et al. 2002, Hallengren et al. 2009, Hirsch et al. 2013, Taylor et al. 2014

Table: Outcome Studied | Treatment Benefit | Treatment No Benefit. Rows GH/Preeclampsia (Tan 2006 | Wolfberg 2005); Offspring Cognitive Delay/Deficits (Haddow 1995, Downing 2012 | Liu 1994, Lazarus 2012, Hales 2018); Miscarriage (Abalovich 2002, Hallengren 2009, Hirsch 2013, Taylor 2014).

On screen · 13:06–13:28 · S26

Overt Hyperthyroidism Correlation Studies

Low Birth Weight: Correlation found - Davis et al. 1989, Momotami et al. 1991, Millar et al. 1994, Phoojaroenchanachai et al. 2001, Luewan et al. 2011, Andersen et al. 2013
Miscarriage: Davis et al. 1989, Momotami et al. 1991, Andersen et al. 2014, Yang et al. 2018
Congenital Abnormalities: Davis et al. 1989, Momotami et al. 1991
Preterm Delivery: Davis et al. 1989, Luewan et al. 2011
Preeclampsia: Millar et al. 1994 | No correlation: Luewan et al. 2011
Heart Failure: Davis et al. 1989

Table: Outcome Studied | Correlation Found | No Correlation Found. Rows Low Birth Weight (Davis 1989, Momotami 1991, Millar 1994, Phoojaroenchanachai 2001, Luewan 2011, Andersen 2013); Miscarriage (Davis 1989, Momotami 1991, Andersen 2014, Yang 2018); Congenital Abnormalities (Davis 1989, Momotami 1991); Preterm Delivery (Davis 1989, Luewan 2011); Preeclampsia (Millar 1994 | Luewan 2011); Heart Failure (Davis 1989).

On screen · 13:28–13:48 · S27

Overt Hyperthyroidism Treatment Studies

Low Birth Weight: Treatment benefit - Davis et al. 1989, Millar et al. 1994, Phoojaroenchanachai 2001, Aggarawal et al. 2014
Miscarriage: Momotami et al. 1991
Preterm Delivery: Davis et al. 1989, Momotami et al. 1991

Table: Outcome Studied | Treatment Benefit | Treatment No Benefit. Rows Low Birth Weight (Davis 1989, Millar 1994, Phoojaroenchanachai 2001, Aggarawal 2014); Miscarriage (Momotami 1991); Preterm Delivery (Davis 1989, Momotami 1991).

On screen · 13:48–14:15 · S28

Thyroid Autoimmunity Correlation Studies

Miscarriage: Correlation found - Stagnaro-Green et al. 1990, Glinoer et al. 1991, Lejeune et al. 1993, Netto et al. 2004, Negro et al. 2006, Ghafoor et al. 2006, Nambiar et al. 2011, Lepoutre et al. 2012, Liu et al. 2014, Iqbal et al. 2016 | No correlation: Iijima et al. 1996, Plowden et al. 2016
Preterm Delivery: Correlation found - Stagnaro-Green et al. 2005, Negro et al. 2006, Ghafoor et al. 2006, Karakosta et al. 2012, Kumru et al. 2015, Saki et al. 2015, Iqbal et al. 2016, Meena et al. 2016, Han et al. 2018 | No correlation: Iijima et al. 1996, Haddow et al. 2010, Nambiar et al. 2011
Offspring Cognitive Delay: Pop et al. 1995, Wasserman et al. 2012

Table: Outcome Studied | Correlation Found | No Correlation Found. Rows Miscarriage (Stagnaro-Green 1990, Glinoer 1991, Lejeune 1993, Netto 2004, Negro 2006, Ghafoor 2006, Nambiar 2011, Lepoutre 2012, Liu 2014, Iqbal 2016 | Iijima 1996, Plowden 2016); Preterm Delivery (Stagnaro-Green 2005, Negro 2006, Ghafoor 2006, Karakosta 2012, Kumru 2015, Saki 2015, Iqbal 2016, Meena 2016, Han 2018 | Iijima 1996, Haddow 2010, Nambiar 2011); Offspring Cognitive Delay (Pop 1995, Wasserman 2012).

On screen · 14:15–14:30 · S29

Thyroid Autoimmunity Treatment Studies

Miscarriage: Treatment benefit - Negro et al. 2006, Negro et al. 2016, Lepoutre et al. 2012 | No benefit: Dhillin-Smith, March 23, 2019
Preterm Delivery: Treatment benefit - Negro et al. 2006, Negro et al. 2016, Nazarpour et al. 2017

Table: Outcome Studied | Treatment Benefit | Treatment No Benefit. Rows Miscarriage (Negro 2006, Negro 2016, Lepoutre 2012 | Dhillin-Smith, March 23, 2019); Preterm Delivery (Negro 2006, Negro 2016, Nazarpour 2017).

On screen · 14:30–14:58 · S22

Wilson–Jungner scorecard (progressive build)

Row 1: + all columns
Row 2: + all columns
Row 3 'Intervention favorably influences the disease': Overt Hypo +, Subclinical Hypo +/-, Isolated Hypothyroxinemia -, Overt Hyper +, Subclinical Hyper -, Thyroid Autoimmunity +/-

Checklist table build state: rows 1-3 filled; row 3 shows + for Overt Hypo and Overt Hyper, +/- for Subclinical Hypo and Thyroid Autoimmunity, - for Isolated Hypothyroxinemia and Subclinical Hyper; rows 4-5 empty.

Note: build state 3 of 5

On screen · 14:58–15:02 · S15

Criteria for Screening

1. The condition is common.
2. Screening tool is readily available, reliable, inexpensive and acceptable.
3. Intervention favorably influences the disease with limited adverse effects.
4. Screening and intervention are cost-effective.
5. Agreed-upon policy on whom to treat.
   Wilson and Junger (1968)

Red slide: white box listing the 5 Wilson-Junger screening criteria at left; large blue UN/World Health Organization emblem at right.

Note: near-duplicate of state 19 (same slide re-shown)

On screen · 15:02–16:04 · S30

Cost Effectiveness Analysis

CEA-analytic tool comparing relative costs and benefits of at least two courses of action
COST (intervention A- B): Blood Test, Extra Visits, Treatment
BENEFIT (effectiveness A-B): Decrease miscarriage, Decrease preterm delivery, Improve IQ of child

Red slide: CEA definition; a balance-beam diagram: COST (intervention A- B) list = Blood Test, Extra Visits, Treatment; BENEFIT (effectiveness A-B) list = Decrease miscarriage, Decrease preterm delivery, Improve IQ of child; blue beam with white triangle fulcrum.

On screen · 16:04–17:26 · S31

Incremental Cost Effectiveness Ratio

(Cost of Intervention A-Cost of Intervention B)
/ (Effectiveness of A-Effectiveness of B)
Effectiveness measured in Quality Adjusted Life Years (QALYs),
QALY calculated = (0 death, 1=optimal life) X (years)
ICER in US < $50,000/QALY deemed cost effective

Formula slide: ICER = (Cost of Intervention A - Cost of Intervention B) / (Effectiveness of A - Effectiveness of B); QALY definitions; bottom line 'ICER in US < $50,000/QALY deemed cost effective'.

On screen · 17:26–18:28 · S32

Cost-Effectiveness of Universal Screening

Dosiou et al. 2008 - USA - Universal TSH VS No Screening - Dominant
Thung et al. 2009 - USA - Universal TSH VS No Screening - Cost-Effective
Dosiou et al. 2012 - USA - Universal TSH and TPO VS Targeted - Cost-Effective
Donnay Candil et al. 2015 - Spain - Universal TSH and TPO VS Targeted - Dominant
Dosiou, 2012. Universal screening was cost-effective compared to both no screening and targeted screening even when eliminated any benefit of identifying and treating SCH

Table: Study | Location | Comparison | Universal Screening Was...; rows Dosiou et al. 2008 USA Universal TSH VS No Screening Dominant; Thung et al. 2009 USA Universal TSH VS No Screening Cost-Effective; Dosiou et al. 2012 USA Universal TSH and TPO VS Targeted Cost-Effective (highlighted row); Donnay Candil et al. 2015 Spain Universal TSH and TPO VS Targeted Dominant. Bottom red text: 'Dosiou, 2012. Universal screening was cost-effective compared to both no screening and targeted screening even when eliminated any benefit of identifying and treating SCH'.

On screen · 18:28–18:58 · S33

Cost-Effectiveness - Overt Hyperthyroidism Logic Argument

Treatment of Overt Hyperthyroidism is beneficial
Screening method for Overt Hyperthyroidism is the same as for hypothyroidism
Screening for and treatment of Overt Hypothyroidism - shown to be cost-effective
Therefore Screening for Overt Hyperthyroidism can be assumed to be even more cost-effective

Bulleted logic argument (4 bullets) on red background; no chart.

On screen · 18:58–19:26 · S22

Wilson–Jungner scorecard (progressive build)

Row 1: + all columns
Row 2: + all columns
Row 3: Overt Hypo +, Subclinical Hypo +/-, Isolated Hypothyroxinemia -, Overt Hyper +, Subclinical Hyper -, Thyroid Autoimmunity +/-
Row 4 'Screening and intervention are cost-effective': Overt Hypo +, Subclinical Hypo +/-, Isolated Hypothyroxinemia -, Overt Hyper +, Subclinical Hyper -, Thyroid Autoimmunity +/-

Checklist table build state: rows 1-4 filled; row 5 still empty.

Note: build state 4 of 5

On screen · 19:28–20:04 · S34

Agreement To Treat Meter

Never Treat: Isolated Hypothyroxinemia, Subclinical Hyperthyroidism
Unclear if Should Treat: Subclinical Hypothyroidism, Thyroid Autoimmunity
Always Treat: Overt Hypo, Overt Hyper

Horizontal blue meter with a blue dot: left 'Never Treat', centre 'Unclear if Should Treat', right 'Always Treat'; below: Never Treat = Isolated Hypothyroxinemia, Subclinical Hyperthyroidism; Unclear = Subclinical Hypothyroidism, Thyroid Autoimmunity; Always Treat = Overt Hypo, Overt Hyper.

On screen · 20:04–20:17 · S22

Wilson–Jungner scorecard (progressive build)

Row 1: + all columns
Row 2: + all columns
Row 3: Overt Hypo +, Subclinical Hypo +/-, Isolated Hypothyroxinemia -, Overt Hyper +, Subclinical Hyper -, Thyroid Autoimmunity +/-
Row 4: Overt Hypo +, Subclinical Hypo +/-, Isolated Hypothyroxinemia -, Overt Hyper +, Subclinical Hyper -, Thyroid Autoimmunity +/-
Row 5 'Agreed-upon policy on whom to treat': Overt Hypo +, Subclinical Hypo -, Isolated Hypothyroxinemia -, Overt Hyper +, Subclinical Hyper -, Thyroid Autoimmunity +/-

Checklist table build state: all 5 rows filled (complete table).

Note: build state 5 of 5 (final)

On screen · 20:17–20:46 · S35

Recommended Universal Screening

AACE (1999) - Pre-Pregnancy - TSH
AACE (2002) - Pre-Pregnancy or 1st Trimester - TSH
Endocrine Society (Minority) (2007) - 1st Visit - TSH
Italian Thyroid Association & Italian Association of Clinical Endocrinologists (2011) - 1st Visit - TSH, fT4
Endocrine Society (Minority) (2012) - 1st Visit - TSH
Spanish Society of Endocrinology and Nutrition jointly with Spanish Society of Gynecology and Obstetrics (2012) - Pre-Pregnancy or 1st Trimester - TSH, fT4 Reflex
European Thyroid Association (Majority) (2014) - 1st Trimester - TSH, fT4 Reflex

Table: Professional Society | Timing | TSH | fT4 (check marks); rows AACE 1999 Pre-Pregnancy TSH ✓; AACE 2002 Pre-Pregnancy or 1st Trimester TSH ✓; Endocrine Society (Minority) 2007 1st Visit TSH ✓; Italian Thyroid Association & Italian Association of Clinical Endocrinologists 2011 1st Visit TSH ✓ fT4 ✓; Endocrine Society (Minority) 2012 1st Visit TSH ✓; Spanish Society of Endocrinology and Nutrition jointly with Spanish Society of Gynecology and Obstetrics 2012 Pre-Pregnancy or 1st Trimester TSH ✓ fT4 Reflex; European Thyroid Association (Majority) 2014 1st Trimester TSH ✓ fT4 Reflex.

On screen · 20:46–21:06 · S36

ATA 2017 Recommendation - Targeted Screening

History of or current signs of thyroid dysfunction
Known thyroid antibody positivity or presence of goiter
History of head/neck radiation or thyroid surgery
Age > 30
Type 1 diabetes or other autoimmune disorders
History of pregnancy loss, preterm delivery or infertility
2 or more prior pregnancies
Family history of autoimmune thyroid disease or thyroid dysfunction
Morbid obesity (BMI >= 40)
Use of amiodarone, lithium, or recent administration of iodinated contrast
Residing in an area of known moderate - severe iodine insufficiency

Bullet list of 10 risk factors for targeted screening; no chart.

On screen · 21:06–21:14 · S37

Women with overt and/or subclinical disease in pregnancy missed with targeted screening

y-axis 0%-100%; 12 vertical bars with no value labels
x-axis studies: Vaidya et al. 2007 [142]; Horacek et al. 2010 [143]; Jiskra et al. 2011 [144]; Chang et al. 2013 [145]; Akafajsi et al. 2013 [146]; Goel et al. 2012 [147]; Altomare et al. 2013 [148]; Kian et al. 2013 [149]; Granfors et al. 2014 [151]; Ahmed et al. 2014 [152]; Nazarpour et al. 2016 [153]; Akram et al. 2017 [154]

Vertical bar chart (y-axis 0-100%): 12 bars, no numbers printed, roughly 15-90%; x-axis lists 12 studies: Vaidya et al. 2007 [142], Horacek et al. 2010 [143], Jiskra et al. 2011 [144], Chang et al. 2013 [145], Akafajsi et al. 2013 [146], Goel et al. 2012 [147], Altomare et al. 2013 [148], Kian et al. 2013 [149], Granfors et al. 2014 [151], Ahmed et al. 2014 [152], Nazarpour et al. 2016 [153], Akram et al. 2017 [154] (some x labels partly unreadable - see report).

Note: some x-axis study labels are small/blurred - see report for uncertainty

On screen · 21:14–21:29 · S38

Where We Are Today: Prevalence of Universal Screening Practices

y-axis 0%-100%, x-axis years
2004 Maine Survey ~48%
2009 ACOG Survey ~13%
2010 European Survey ~42%
2012 ATA Survey ~73%
2013 Latin America, Asian and East Asian Surveys ~28%
2014 Brazilian Survey ~83%
2016 Israeli Survey ~62%

Vertical bar chart (y-axis 0-100%) by year: 2004 Maine Survey ~48%, 2009 ACOG Survey ~13%, 2010 European Survey ~42%, 2012 ATA Survey ~73%, 2013 Latin America, Asian and East Asian Surveys ~28%, 2014 Brazilian Survey ~83%, 2016 Israeli Survey ~62%.

Note: percentages read approximately from bar heights - see report

On screen · 21:29–21:50 · S39

SUMMARY

1. Overt thyroid disease is an important health problem in pregnancy
2. Simple and reliable screening tests are available
3. Untreated overt disease causes demonstratable harms
4. Effective treatment is available for these conditions
5. Targeted screening misses a significant number of women needing treatment
6. Universal screening has been shown to be cost-effective
7. A large proportion of providers already do universal screening

Bulleted summary, numbered 1-8 with number 6 missing on the slide (jump from 5 to 7); no chart.

Note: slide numbering skips 6 (as printed; 'demonstratable' is the slide spelling)

On screen · 21:50–21:56 · S40

It's time to get off the fence (cartoon)

Red slide with a photo of white gulls perched along a black metal fence; joke following the screening-criteria theme.

21:58 — Handover

12:06 PM CT

On screen · 22:00–22:18 · S11

Select your presentation

Menu screen; the 'Alex Stagnaro-Green 11:45 AM - 12:45 PM' card is highlighted/selected with Start and My Files buttons.

Note: Operator screen: 'Select your presentation' list (the session is listed as 11:45 AM – 12:45 PM).

22:14 — Boelaert: presentation against universal screening

12:07 PM CT

On screen · 22:23–22:42 · S41

Thyroid Disease in Pregnancy: To Screen or Not to Screen - AGAINST the MOTION

Endocrine Debate
Thyroid Disease in Pregnancy: To Screen or Not to Screen
AGAINST the MOTION
Kristien Boelaert
Reader in Endocrinology
Consultant Endocrinologist
University of Birmingham
k.boelaert@bham.ac.uk

Boelaert title slide: ENDO 2019 banner top-left; University of Birmingham and IMSR logos top-right; three photos of Birmingham buildings along the bottom.

On screen · 22:42–22:46 · S42

Disclosure

Nothing to disclose

Mostly white slide with only the title and the sentence 'Nothing to disclose'; ENDO 2019 banner bottom-left; ENB/AACE-style flower graphics bottom-right.

On screen · 22:46–24:02 · S43

(1) Thyroid dysfunction in pregnancy

Increased maternal total T4 and total T3
Declining free T4 and free T3 with advancing gestation
Overt Hypothyroidism: High TSH low FT4 0.2-0.6%
Overt Hyperthyroidism: Low TSH high FT4 0.2-0.4%
Subclinical Hypothyroidism: High TSH normal T4 2-18%
Isolated Hypothyroxinemia: Normal TSH low FT4 ~2%
Transient Gestational Thyrotoxicosis 1-3%
Chan and Boelaert Clin Endo 2015 82: 313-326
Korevaar et al. Nature Reviews 2017 13: 610-622
Taylor et al. Frontiers in Endocrinology 2018 9: 1-7

Physiology diagram: central pregnant-woman silhouette with arrows labelled TSH, TBG, Estrogen, HCG, maternal thyroxine (T4); boxes 'Increased maternal total T4 and total T3' and 'Declining free T4 and free T3 with advancing gestation'; labels 'Placental development and D3 metabolism', 'Fetal development'; title above diagram 'Physiological changes during pregnancy'.

Note: incremental build: right-hand prevalence column added

On screen · 24:02–25:16 · S44

(1) Thyroid autoimmunity in pregnancy

TPO abs: 5-14% of unselected pregnancies (10-30% in subfertile/recurrent miscarriage population)
TABLET Trial: 9.5% TPO-positive (N = 19,237 screened)
TPO status affects treatment thresholds for starting levothyroxine
4 line charts: FT4 in pmol/L and TSH in mU/L vs hCG in IU/L, for TPOAb negative vs positive; p<0.0001 for FT4/TSH decline in negatives, p=0.79 / p=0.92 in positives.
Korevaar et al. JCEM 2017 102: 69-77

Bullet slide (3 bullets); citation Korevaar et al. JCEM 2017; in the later state 4 small line charts appear (see per-state note).

Note: incremental build: 4 charts added below bullets

On screen · 25:16–26:24 · S45

(2) Screening tool: TFT and TPO testing

Interpretation of thyroid function tests not straightforward
Use of gestation-specific reference ranges recommended - not readily available
Continued debate and changes on "normal reference ranges"
Reference ranges derived from cross-sectional samples not considering longitudinal trajectories
FT4 concentration measurements often problematic

Red bullet slide (5 bullets); no chart.

On screen · 26:24–27:11 · S46

(3) Intervention favorably influences disease? - CATS TRIAL

CATS TRIAL
Treatment of sub. hypothyroidism or hypothyroxinemia with 150ug LT4
Start treatment median week 13, IQ test at age 3 years
Mean offspring IQ: LT4 99.2 | Placebo 100.0 | Difference -0.8 | P 0.40 | (N/groups) (323/326)
No differences in obstetric outcomes
Lazarus et al. N Engl J Med. 2012 366: 493-5

Table 'Mean offspring IQ': LT4 | Placebo | Difference | P | (N/groups); row Subcl. Hypo OR Hypothyroxinemia 99.2 | 100.0 | -0.8 | 0.40 | (323/326); note 'No differences in obstetric outcomes'.

On screen · 27:11–27:42 · S47

(3) Intervention favorably influences disease - NICHD TRIAL

NICHD TRIAL
Treatment of women with sub. hypothyroidism (100ug LT4) or hypothyroxinemia (50ug LT4)
Mean treatment start week 17, IQ test age 3/5 yrs
Powered to detect a 5 point IQ difference
Mean offspring IQ - Subclinical hypothyroidism: LT4 97 | Placebo 94 | Difference +3 | P 0.71 | (323/326)
Mean offspring IQ - Hypothyroxinemia: LT4 94 | Placebo 91 | Difference +3 | P 0.30 | (254/253)
No differences in obstetric outcomes
Casey et al. N Engl J Med 2017 376: 815-25

Table 'Mean offspring IQ': LT4 | Placebo | Difference | P | (N/groups); rows Subclinical hypothyroidism 97 | 94 | +3 | 0.71 | (323/326); Hypothyroxinemia 94 | 91 | +3 | 0.30 | (254/253); note 'No differences in obstetric outcomes'.

On screen · 27:42–28:19 · S48

(3) Intervention favorably influences disease - TABLET results

Primary outcome - Livebirth >=34 weeks: Levothyroxine 176/470 (37.4%) | Placebo 178/470 (37.9%) | Comparison 0.97 (0.83, 1.14) | p=0.74
Secondary pregnancy outcomes (as a proportion of women who achieved pregnancy within 12 months; N=266 vs N=274):
Clinical pregnancy at 7 weeks: 237/266 (89.1%) vs 248/274 (90.5%); 0.98 (0.93, 1.04)
On-going pregnancy at 12 weeks: 194/266 (72.9%) vs 200/274 (73.0%); 1.00 (0.90, 1.11)
Miscarriage <24 weeks: 75/266 (28.2%) vs 81/274 (29.6%); 0.95 (0.73, 1.23)
Livebirth >=34 weeks: 176/266 (66.2%) vs 178/274 (65.0%); 1.02 (0.90, 1.15)
Dhillon-Smith et al. N Engl J Med 2019: epub

Table: Outcome | Levothyroxine | Placebo | Comparison; primary outcome Livebirth >=34 weeks 176/470 (37.4%) vs 178/470 (37.9%), 0.97 (0.83, 1.14), p=0.74 (red oval highlights this row); secondary pregnancy outcomes (N=266 vs N=274): clinical pregnancy at 7 weeks 237/266 (89.1%) vs 248/274 (90.5%) 0.98 (0.93, 1.04); on-going pregnancy at 12 weeks 194/266 (72.9%) vs 200/274 (73.0%) 1.00 (0.90, 1.11); miscarriage <24 weeks 75/266 (28.2%) vs 81/274 (29.6%) 0.95 (0.73, 1.23); livebirth >=34 weeks 176/266 (66.2%) vs 178/274 (65.0%) 1.02 (0.90, 1.15).

On screen · 28:19–28:42 · S49

(3) Intervention favorably influences disease - TABLET subgroup forest plot

Subgroups: maternal age (<35, >=35 yr); No. of previous miscarriages (0, 1 or 2, >=3); Thyrotropin concentration at baseline (<=2.5, >2.5 mIU/liter); Infertility treatment at time of randomization (Yes/No); Thyroid peroxidase antibody concentration at baseline (Low/High); Race or ethnic group (White, South Asian, Chinese/black/other); BMI (<25, >=25)
All participants: Levothyroxine 176/470 vs Placebo 178/470; Relative Risk 0.97 (0.83-1.14); P for interaction 0.74
Relative risk axis 0.50 / 0.75 / 1.00 / 1.50 / 2.50 with 'Placebo Better' and 'Levothyroxine Better'
Dhillon-Smith et al. N Engl J Med 2019: epub

Forest plot of relative risk (95% CI) by subgroup (maternal age, number of previous miscarriages, thyrotropin concentration at baseline <=2.5 vs >2.5 mU/L [highlighted row], infertility treatment, TPO antibody, race/ethnic group, BMI) plus 'All participants' 176/470 vs 178/470, 0.97 (0.83-1.14), p interaction 0.74; axis 0.50-2.50 with 'Placebo Better' / 'Levothyroxine Better'.

Note: dense table - subgroup rows condensed; individual cell values omitted

On screen · 28:42–29:22 · S50

(3) Intervention favorably influences disease - TABLET trial (survival curve)

TABLET trial - line graph: Pregnancy (%) (0-100%) vs Weeks from Conception to Pregnancy End; two nearly identical curves (Levothyroxine, Placebo); number-at-risk table below (Levothyroxine 470, 324, 310, 301, 255, ...; Placebo 470, 324, 303, 291, 242, ...)
Dhillon-Smith et al. N Engl J Med 2019: epub

Line graph: pregnancy (%) y-axis 0-100% vs weeks from conception to pregnancy end; two nearly overlapping lines (Levothyroxine blue, Placebo pink); below the axis a 'number at risk' table (Levothyroxine/Placebo rows, ~470 starting) with counts at 0,3,6,9,12,15,20,25,30,35,40,45+ weeks.

Note: number-at-risk values approximate - see report

On screen · 29:22–30:30 · S51

(3) Intervention may cause harm - optimal vs overtreatment

c Optimal treatment scenario
d Overtreatment scenario
y-axis: Mean cortex volume (cm3) 530-550
x-axis: Maternal free T4 (pmol/l) - 7.4, 12.2, 20.1, 33.1, 54.6
Shaded normal range band; blue fitted curve with pink observed points; overtreatment curve declines steeply at high maternal free T4
Korevaar et al. Nature Reviews 2017 13: 610-622

Two line graphs (c 'Optimal treatment scenario', d 'Overtreatment scenario'): y-axis Mean cortex volume (cm3) 530-550, x-axis Maternal free T4 (pmol/l) 7.4, 12.2, 20.1, 33.1, 54.6; shaded 'Normal range' band; blue fitted curve with pink observed points; the overtreatment curve declines at high fT4.

On screen · 30:30–31:46 · S52

(3) Intervention may cause harm - FT4 >97.5th percentile and verbal IQ

FT4 >97.5th percentile
INMA: High FT4 n=31, Reference n=628, beta -0.1 (-3.6, 3.7)
Generation R: n=78 vs 1,569, beta -2.4 (-5.8, 1.1)
ALSPAC: n=61 vs 1,162, beta -0.1 (-3.6, 3.3)
Overall: n=170 vs 3,359, beta -0.8 (-2.9, -1.2)
Forest plot: Lower verbal IQ <-> Higher verbal IQ
Right chart: Adjusted mean difference in verbal IQ (95% CI) vs Free T4 (pmol/L) categories <10.0, 10.0-10.99, 11.0-11.99, 12.0-12.99, 13.0-18.99, 19.0-19.99, >20.0
Increased risk of ADHD in proportion of women overtreated in CATS (unpublished)
High fT4 associated with autism in offspring
Levie et al. JCEM 2018 103: 2967-2979
Andersen et al. Thyroid 2018; 28: 537-546

Left table: Cohort | High FT4 (n) | Reference (n) | beta (95% CI); INMA 31/628 -0.1 (-3.6, 3.7); Generation R 78/1,569 -2.4 (-5.8, 1.1); ALSPAC 61/1,162 -0.1 (-3.6, 3.3); Overall 170/3,359 -0.8 (-2.9, -1.2), with forest plot 'Lower verbal IQ / Higher verbal IQ'. Right: adjusted mean difference in verbal IQ (95% CI) by free T4 category (<10.0, 10.0-10.99, 11.0-11.99, 12.0-12.99, 13.0-18.99, 19.0-19.99, >20.0 pmol/l).

On screen · 31:46–32:25 · S53

(3) Intervention may cause harm - Maraka adverse outcomes table

Pregnancy loss: 89 (10.6) vs 614 (13.5); Unadjusted 0.76 (0.60 to 0.96); Adjusted 0.62 (0.48 to 0.82); P 0.01
Preterm delivery: 60 (7.1) vs 236 (5.2); 1.41 (1.05 to 1.88); 1.60 (1.14 to 2.24); 0.01
Preterm labor: 111 (13.2) vs 569 (12.5); 1.08 (0.87 to 1.34); 1.14 (0.89 to 1.46); 0.29
Premature rupture of membranes: 42 (5.0) vs 220 (4.8); 1.04 (0.74 to 1.45); 0.97 (0.66 to 1.42); 0.87
Placental abruption: 7 (0.8) vs 36 (0.8); 1.05 (0.47 to 2.37); 1.60 (0.65 to 3.93); 0.30
Gestational diabetes: 101 (12.0) vs 401 (8.8); 1.41 (1.12 to 1.78); 1.37 (1.05 to 1.79); 0.02
Gestational hypertension: 49 (5.8) vs 221 (4.8); 1.24 (0.90 to 1.70); 1.27 (0.88 to 1.82); 0.21
Pre-eclampsia: 46 (5.5) vs 177 (3.9); 1.43 (1.03 to 2.00); 1.61 (1.10 to 2.37); 0.01
Poor fetal growth: 78 (9.3) vs 397 (8.7); 1.07 (0.83 to 1.38); 1.12 (0.84 to 1.50); 0.45
Tachycardia: 18 (2.1) vs 90 (2.0); 1.08 (0.65 to 1.81); 1.77 (1.00 to 3.11); 0.05
Maraka et al. BMJ 2017, 356: i6865

Table: No. (%) events for thyroid hormone treatment (n=843) vs no thyroid hormone treatment (n=4562); Odds ratio (95% CI) unadjusted and adjusted; P value; outcomes pregnancy loss (89 (10.6) vs 614 (13.5); 0.76 (0.60 to 0.96); 0.62 (0.48 to 0.82); 0.01), preterm delivery (60 (7.1) vs 236 (5.2); 1.41 (1.05 to 1.88); 1.60 (1.14 to 2.24); 0.01), preterm labor, premature rupture of membranes, placental abruption, gestational diabetes (101 (12.0) vs 401 (8.8); 1.41 (1.12 to 1.78); 1.37 (1.05 to 1.79); 0.02), gestational hypertension, pre-eclampsia (46 (5.5) vs 177 (3.9); 1.43 (1.03 to 2.00); 1.61 (1.10 to 2.37); 0.01), poor fetal growth, tachycardia; several rows outlined in red.

On screen · 32:25–33:34 · S54

(4) Cost-effectiveness

Economic model demonstrating incremental cost-effectiveness ratio of 7258 USD per QUALY
Based on 2 small RCT in area of mild iodine deficiency
Overall costs of personnel training, public education, establishment of healthcare infrastructure
Burden of over-diagnosis and over-treatment

Bullet slide (4 bullets); later state adds a pasted image of Munch's 'The Scream' with the label 'Anxiety and inconvenience for patients'.

On screen · 33:34–34:37 · S55

(5) No agreed policy on whom to treat - ATA 2017 Guidance

ATA 2017 Guidance:
Use trimester-specific reference ranges, similar assays or TSH > 4 mU/L
Consider levothyroxine if TSH > 2.5 mU/L in TPO+ or > 4.0 mU/L in TPO- women
Don't routinely treat isolated hypothyroxinemia
ETA 2014 Guidance:
Ideally trimester and population-specific ranges, otherwise (2.5 mU/L, 3.0 mU/L and 3.5 mU/L in different trimesters
Treat SCH before and during pregnancy
Consider treatment of isolated hypothyroxinemia in 1st trimester
Alexander et al. 2017 ATA guidelines, Thyroid 2017 27: 315-389
Lazarus et al. 2014 ETA guidelines Eur Thyroid J 2014;3: 76-94

Red slide with ATA 2017 Guidance bullets; later state adds a second green sub-heading 'ETA 2014 Guidance' with 3 more bullets.

Note: incremental build: ETA 2014 Guidance section added

On screen · 34:37–35:48 · S56

Conclusions

Criteria
Condition is common - V
Screening tool available, reliable, inexpensive and acceptable - X
Intervention favourably influences disease and does not cause harm - X
Screening and intervention cost-effective - X
Agreed upon policy on whom to treat - X
PREGNANT WOMEN SHOULD NOT UNDERGO UNIVERSAL SCREENING FOR THYROID FUNCTION AND THYROID ANTIBODIES

Table 'Criteria' with right-hand check/cross marks: Condition is common ✓; Screening tool available, reliable, inexpensive and acceptable ✗; Intervention favourably influences disease and does not cause harm ✗; Screening and intervention cost-effective ✗; Agreed upon policy on whom to treat ✗. Large green text: 'PREGNANT WOMEN SHOULD NOT UNDERGO UNIVERSAL SCREENING FOR THYROID FUNCTION AND THYROID ANTIBODIES'.

35:40 — Handover

12:20 PM CT

On screen · 35:48–35:55 · S11

Select your presentation

Menu screen; the 'Kristien Boelaert 11:45 AM - 12:45 PM' card is highlighted/selected.

Note: Operator screen: 'Select your presentation' list (the session is listed as 11:45 AM – 12:45 PM).

35:55 — Stagnaro-Green: rebuttal

12:20 PM CT

On screen · 36:02–38:22 · S57

Confusion on How to Monitor/Treat Women with SCH

Confusion on How to Monitor/Treat Women with SCH
AVOID UNCERTAINTY AT ALL COSTS
Targeted Screening Yields SCH
Ethical Concept of Autonomy

Red slide: 'AVOID UNCERTAINTY AT ALL COSTS' plus a photo of an ostrich with its head buried in the sand; bottom lines 'Targeted Screening Yields SCH' and 'Ethical Concept of Autonomy'.

On screen · 38:22–39:15 · S58

Subclinical Hyperthyroidism Correlation Studies

Obstetrical Outcomes: No correlation - Casey et al. 2006, Rosario et al. 2016, Fraenkel et al. 2018
Neonatal Outcomes: No correlation - Rosario et al. 2016, Fraenkel et al. 2018
Decreased Offspring IQ/Cognitive Delay: Correlation found - Korevaar et al. 2015 | No correlation - Nelson et al. 2018, Pakkila et al. 2018
Decreased risk of gestational hypertension: Correlation found - Casey et al. 2006

Table: Outcome Studied | Correlation Found | No Correlation Found. Rows Obstetrical Outcomes (none | Casey 2006, Rosario 2016, Fraenkel 2018); Neonatal Outcomes (none | Rosario 2016, Fraenkel 2018); Decreased Offspring IQ/Cognitive Delay (Korevaar 2015 | Nelson 2018, Pakkila 2018); Decreased risk of gestational hypertension (Casey 2006).

On screen · 39:15–39:56 · S59

Treatment of Graves' Disease - ATA Thyroid & Pregnancy Guidelines Recommendation 48

ATA Thyroid & Pregnancy Guidelines Recommendation 48
"Antithyroid medication during pregnancy should be administered at the lowest effective dose of MMI or PTU, targeting maternal serum FT4/TT4 at or moderately above the reference range"
Strong Recommendation, High Quality Evidence

Quote slide: 'Antithyroid medication during pregnancy should be administered at the lowest effective dose of MMI or PTU, targeting maternal serum FT4/TT4 at or moderately above the reference range'; 'Strong Recommendation, High Quality Evidence'.

On screen · 39:56–40:43 · S60

Screening Algorithm - Pre-conception or First Trimester

Screening Algorithm - Pre-conception or First Trimester
TSH: Low <0.1 mU/L -> Reflex fT4
TSH: Normal 0.1-4.0 -> No Further Workup
TSH: High >4.0 mU/L -> Reflex fT4 + TPO

Flowchart: green TSH box; Low (<0.1 mU/L) -> yellow 'Reflex fT4'; Normal (0.1-4.0) -> red 'No Further Workup'; High (>4.0 mU/L) -> yellow 'Reflex fT4 + TPO'.

On screen · 40:43–40:58 · S11

Select your presentation

Menu screen; the 'Alex Stagnaro-Green 11:45 AM - 12:45 PM' card is highlighted/selected and shows a 'Slides' button.

Note: Operator screen: 'Select your presentation' list (the session is listed as 11:45 AM – 12:45 PM).

40:48 — Handover

12:25 PM CT

40:54 — Boelaert: rebuttal

12:25 PM CT

On screen · 41:02–42:10 · S61

TABLET prevalence data

Total number of women who had thyroid function tested n = 19,213
Euthyroid n = 18,293 (95.2%)
Isolated Hypothyroxinaemia n = 46 (0.3%)
Overt thyroid dysfunction n = 85 (0.4%)
SC thyroid dysfunction n = 694 (3.6%)
Other n = 95 (0.5%)
Euthyroid subgroup TSH<2.5 n = 14,919 (77.7%); TSH 2.5-4.5 n = 3,374 (17.6%)
Overt Hypothyroid n = 36 (0.2%); Overt Hyperthyroid n = 49 (0.3%)
SC Hypo TSH>4.5 n = 451 (2.4%); SC Hyper n = 243 (1.3%)
TPOAb positive: 9.5%
SC Hypo TSH>=2.5 n = 3,825 (19.9%); Moderate SCH TSH 4.5-10 n = 421 (2.2%); Severe SCH TSH>10 n = 30 (0.2%)
Dhillon-Smith et al. N Engl J Med 2019: epub

Flowchart of participants: total n=19,213 tested -> Euthyroid n=18,293 (95.2%), Isolated Hypothyroxinaemia n=46 (0.3%), Overt thyroid dysfunction n=85 (0.4%), SC thyroid dysfunction n=694 (3.6%), Other n=95 (0.5%); Euthyroid subgroup TSH<2.5 n=14,919 (77.7%) / TSH 2.5-4.5 n=3,374 (17.6%); Overt Hypothyroid n=36 (0.2%); Overt Hyperthyroid n=49 (0.3%); SC Hypo TSH>4.5 n=451 (2.4%); SC Hyper n=243 (1.3%); TPOAb positive 9.5%; SC Hypo TSH>=2.5 n=3,825 (19.9%), Moderate SCH 4.5-10 n=421 (2.2%), Severe SCH >10 n=30 (0.2%).

On screen · 42:10–42:49 · S62

CATS Results

Overall: N 390 vs 404; Mean IQ (SD) 99.2 (13.3) vs 100.0 (13.3); difference 0.8 (-1.1 to 2.6); p 0.40; IQ<85 12.1% vs 14.1% (2.1% (-2.6 to 6.7%))
Positive on TSH1: N 209 vs 219; 100.4 (13.7) vs 100.7 (13.0); 0.3 (-2.2 to 2.8); p 0.82; IQ<85 11.0% vs 13.7%
Positive on FT4?: N 204 vs 207; 97.8 (12.7) vs 99.2 (13.3); 1.3 (-1.3 to 3.8); p 0.28; IQ<85 13.2% vs 14.5%
Positive on TSH and FT4: N 23 vs 22; 97.7 (11.6) vs 99.4 (11.4); 1.7 (-5.2 to 8.6); p 0.61; IQ<85 13.0% vs 13.6%
Lazarus et al. N Engl J Med. 2012 366: 493-5

Table of mean offspring IQ and IQ<85 by subgroup (Overall N=390/404, mean IQ 99.2 (13.3) / 100.0 (13.3), difference 0.8 (-1.1 to 2.6), p=0.40; Positive on TSH1 N=209/219 100.4 / 100.7, 0.3 (-2.2 to 2.8), p=0.82; Positive on FT4? N=204/207 97.8 / 99.2, 1.3 (-1.3 to 3.8), p=0.28; Positive on TSH and FT4 N=23/22 97.7 / 99.4, 1.7 (-5.2 to 8.6), p=0.61), with IQ<85 percentages; last subgroup outlined in red.

On screen · 42:49–54:41 · S63

TABLET Results

Levothyroxine | Placebo
No. of women withdrawn from trial medication due to abnormal TFT: 46 (9.8%) | 45 (9.6%)
No. of SAEs: 28 (5.9%) | 18 (3.8%)
No. of women with pre-eclampsia: 9 (5%) | 5 (3%)
No. of women with gestational diabetes: 20 (11%) | 16 (9%)
Dhillon-Smith et al. N Engl J Med 2019: epub

Two-column table: Levothyroxine | Placebo; rows No. of women withdrawn from trial medication due to abnormal TFT 46 (9.8%) vs 45 (9.6%); No. of SAEs 28 (5.9%) vs 18 (3.8%); No. of women with pre-eclampsia 9 (5%) vs 5 (3%); No. of women with gestational diabetes 20 (11%) vs 16 (9%).

44:53 — Audience questions

12:29 PM CT

54:23 — Final statements

12:39 PM CT

On screen · 54:41–56:24 · S11

Select your presentation

Menu screen; the 'Alex Stagnaro-Green 11:45 AM - 12:45 PM' card is highlighted/selected (green arrow points at it).

Note: Operator screen: 'Select your presentation' list (the session is listed as 11:45 AM – 12:45 PM).

On screen · 56:28–57:10 · S64

Universal screening

It's cost-effective
Intervention does not cause harm
Screening tool is easy to use
There is an agreed treatment policy

Four portraits of UK political figures, each with an off-white speech bubble: 'It's cost-effective', 'Intervention does not cause harm', 'Screening tool is easy to use', 'There is an agreed treatment policy'; later state adds a photo of Theresa May with a thought bubble 'We must screen all pregnant women!'.

On screen · 57:10–57:54 · S65

Targeted case-finding

Let's treat women who need Rx appropriately
Let's re-assess cost-effectiveness
Let's agree a policy
Let's conduct RCTs early in pregnancy

Photo of Michelle Obama at centre; four off-white thought bubbles around it: 'Let's treat women who need Rx appropriately', 'Let's re-assess cost-effectiveness', 'Let's agree a policy', 'Let's conduct RCTs early in pregnancy'.

57:40 — Re-poll, results, and close

12:42 PM CT

On screen · 57:54–58:02 · S11

Select your presentation

Menu screen; the 'Kristien Boelaert 11:45 AM - 12:45 PM' card is highlighted/selected.

Note: Operator screen: 'Select your presentation' list (the session is listed as 11:45 AM – 12:45 PM).

On screen · 58:05–58:12 · S06

SESSION PARTICIPATION AND EVALUATIONS USING THE ENDO 2019 APP

STEP 1 Find the session
STEP 2 Tap the Participate Evaluate button
Complete session evaluations by clicking Evaluate This Session

Same ENDO 2019 app instructions slide, but the right-hand phone screenshot now shows the purple 'ENDO 2019' banner

Note: near-duplicate of state 08 (same slide, slightly different app screenshot)

On screen · 58:12–58:26 · S07

Question

1. Are you in favor of screening all pregnant women for thyroid dysfunction?
   – Yes
   – No

Plain purple question slide; red banner at the bottom reads 'LIVE POLLING IS THE NEXT SLIDE'; green arrow pointer.

On screen · 58:28–58:39 · S08

1. Are you in favor of screening all pregnant women for thyroid dysfunction?

Yes
No
6 (yellow countdown box, bottom-right)

White live-poll screen of the ENDO 2019 app: question at top, 'Yes'/'No' options, large yellow countdown box bottom-right showing '6'.

On screen · 58:40–58:45 · S09

1. Are you in favor of screening all pregnant women for thyroid dysfunction?

Yes 54%
No 46%
Poll is Locked

White live-poll results screen of the ENDO 2019 app: question at top, Yes/No rows with percentages and horizontal bars (yellow for Yes, green for No), grey label 'Poll is Locked' bottom-right.

On screen · 58:47–59:04 · S10

1. Are you in favor of screening all pregnant women for thyroid dysfunction?

Yes 71% (Pre-Test) / 55% (Post-Test)
No 29% (Pre-Test) / 45% (Post-Test)
Pre-Test | Post-Test toggle buttons

Live-poll comparison screen of the ENDO 2019 app on black background: Pre-Test / Post-Test toggle buttons, Yes/No rows with grey (pre-test) and blue (post-test) horizontal bars and percentages.

On screen · 59:04–59:12 · S07

Question

2. Are you in favor of screening all pregnant women for thyroid autoimmunity?
   – Yes
   – No

Plain purple question slide; red banner at the bottom reads 'LIVE POLLING IS THE NEXT SLIDE'; green arrow pointer.

On screen · 59:14–59:24 · S08

2. Are you in favor of screening all pregnant women for thyroid autoimmunity?

Yes
No
6 (yellow countdown box, bottom-right)

White live-poll screen of the ENDO 2019 app: question at top, 'Yes'/'No' options, large yellow countdown box bottom-right showing '6'.

On screen · 59:24–59:32 · S09

2. Are you in favor of screening all pregnant women for thyroid autoimmunity?

Yes 11%
No 89%
Poll is Locked

White live-poll results screen of the ENDO 2019 app: question at top, Yes/No rows with percentages and horizontal bars (yellow for Yes, green for No), grey label 'Poll is Locked' bottom-right.

On screen · 59:34–01:00:01 · S10

2. Are you in favor of screening all pregnant women for thyroid autoimmunity?

Yes 35% (Pre-Test) / 11% (Post-Test)
No 65% (Pre-Test) / 89% (Post-Test)
Pre-Test | Post-Test toggle buttons

Live-poll comparison screen of the ENDO 2019 app on black background: Pre-Test / Post-Test toggle buttons, Yes/No rows with grey (pre-test) and blue (post-test) horizontal bars and percentages.

Appendix A — Session timeline

Appendix B — Slide index (every distinct screen)

A complete slide-by-slide transcript, including each build state and every chart description, is in the companion file ENDO2019_Slide_Appendix.md.

Appendix C — Audience poll results

The one-point difference in the first poll is a projection-slide inconsistency in the original deck (the live board reads 54%, the comparison slide 55%); both are reproduced on screen below.

Appendix D — Verification notes and quotations requiring a check

D.1 Passages marked [V] or † in the transcript

These are the only places where the wording is not secured by the audio plus the slides. Quote them only after checking the recording.

D.2 Material removed because it is not in the recording

• Recognition garbage at 10:01, 19:51–20:22, 29:49–30:13 and 59:11–60:12 (recogniser hallucination over silence/applause/slide changes) was deleted; the real speech was recovered by re-transcribing those windows continuously.
• About 50 spurious one-word “No.” segments during the re-poll (audience noise) were deleted.
• Prompts leaked into the recogniser output at the 49:40 chunk boundary (“Dr. David Cooper-…”); the false prefixes were stripped.

D.3 Corrections applied (summary)

• Names: Christian Bollard / Bullard / Borler → Kristien Boelaert; Stegner / Stegnero / Stagnero / Sagnawa → Stagnaro-Green; Christy Dissau → Kristi Dosiou; Dylan Smith → Dhillon-Smith; Tim Korova → Tim Korevaar; “core of our study” → “Korevaar study”; Gacy's → Casey; Wilson and younger → Wilson and Jungner; ACE → AACE (where the society is meant).
• Trials and tests: tablet/TABLA/Tabla → TABLET; TPU/TPR/DPO → TPO; ICR → ICER; NIH trials → NICHD trials.
• Clinical terms: 3T4 / 3D4 / 3-T4 → free T4; hyperthyroxenemia → hypothyroxinemia; thyroid toxicosis → thyrotoxicosis; growth hormone → gestational hypertension; main cortex volume → mean cortex volume; over thyroid → overt thyroid; paternal → maternal; function deaths → function tests; home to treat → whom to treat.
• Numbers/units: 97.5th-percentile TSH cutoff; ATA-2011 cutoff 2.5 mU/L; 1 million units per litre → 1 mU/L; 7,558 → 7,258 USD/QALY (see V7); quality saved → QALY saved.

D.4 Provenance of the session date

The presentation screen in the recording reads “Saturday, March 23 11:30 AM – 1:00 PM”, but that is the stale advertised slot in the ENDO 2019 app. The Endocrine Society session archive for E22, the HCPLive report on the session, and the internal evidence in the recording (MLB Opening Day “starts in two days” = 26 March; the TABLET trial “presented here on Saturday” = 23 March; the NEJM paper “three days ago”) all date the session to Tuesday 26 March 2019, 11:45 AM–12:45 PM CT. Cite 26 March.

D.5 What the earlier transcript got wrong or missed (for the record)

• Its “Speaker 1 / 2 / 3” labels were mostly right but were never named, and they broke down in the Q&A and the final statements.
• It contained no timestamps and no on-screen text.
• Named errors: “Christian Ballard” (Boelaert), “Kristi Dzau” (Dosiou), “Dylan Smith” (Dhillon-Smith), “Wilson and younger” (Jungner), “KC trial” (NICHD/Casey), “tablet” (TABLET), “TPO” read as “TPU”.
• It silently dropped the audience-poll percentages, the published cost-effectiveness numbers and the entire slide sequence — all of which are restored above.

Transcript produced from the ENDO 2019 recording (60:00.93, 640×360). Speech recognition: Whisper large-v3-turbo; speaker attribution: ECAPA-TDNN voice embeddings; screen capture: scene-change detection at 2 fps plus visual transcription of all 95 detected states.

The eight key moments remain available as ordinary links with JavaScript off. Filtering does not change the transcript.