Thyroid function testing in pregnancy:2017 ATA guidelines update

Dr Simon Forehan

Several factors are known to tax gravid thyroid economy:

• Increased plasma volume

• TBG – pool increased

• Renal clearance

• Feto-placental unit uptake

• Placental deiodination

• Homology of TSH and hCG• Same alpha sub-unit• 85% homology beta sub-unit

• hCG has thyromimetic effects and is responsible forthe hyperthyroidism associated with trophoblasticdisease.

HCG

TSH

Glinoer et al JCEM 1990

II: TSH reference range

ATA guidelines 2017

RECOMMENDATION 1

When possible, population-based trimester-specificreference ranges for serum TSH should be definedthrough assessment of local population datarepresentative of a health care provider’s practice.Reference range determinations should only includepregnant women with no known thyroid disease,optimal iodine intake, and negative TPOAb status.

Alexander THYROID 2017

Organisation TSH (mIU/L)American Thyroid Association,2011First trimester 0.1-2.5Second trimester 0.2-3.0Third trimester 0.3-3.0

Endocrine Society, 2012First trimester <2.5Second trimester <3.0Third trimester <3.0

European Thyroid Association,2014First trimester <2.5Second trimester <3.0Third trimester <3.5

ATA guidelines 2011

ATA guidelines 2011

5th to 95th percentiles

ATA guidelines 2011

Generation R study

Trimester TSH ≥2.5 mU/L 2.5th and 97.5th TSH(mU/L)

1st 8.6% 0.01-4.00

2nd 4.9% 0.05-4.05

Medici JCEM 2012

Of 19 studies, 97.5th TSH <2.5mU/L in only 1 study

14 studies 97.5th TSH >3 mU/L

ATA guidelines 2017

Question 31: What is the definition of hypothyroidism inpregnancy?

RECOMMENDATION 25In the setting of pregnancy, maternal hypothyroidism isdefined as a TSH concentration elevated beyond theupper limit of the pregnancy-specific reference range.

Strong recommendation, high-quality evidence.

ATA guidelines 2017RECOMMENDATION 26The pregnancy-specific TSH reference range should be defined as follows:

ATA guidelines 2017RECOMMENDATION 26The pregnancy-specific TSH reference range should be defined as follows:

When available, population- and trimester-specific reference ranges forserum TSH during pregnancy should be defined by a provider’s institute orlaboratory and should represent the typical population for whom care isprovided. Reference ranges should be defined in healthy TPOAb-negativepregnant women with optimal iodine intake and without thyroid illness.

Strong recommendation, high-quality evidence.

ATA guidelines 2017RECOMMENDATION 26The pregnancy-specific TSH reference range should be defined as follows:

When available, population- and trimester-specific reference ranges forserum TSH during pregnancy should be defined by a provider’s institute orlaboratory and should represent the typical population for whom care isprovided. Reference ranges should be defined in healthy TPOAb-negativepregnant women with optimal iodine intake and without thyroid illness.

Strong recommendation, high-quality evidence.

When this goal is not feasible, pregnancy-specific TSH reference rangesobtained from similar patient populations and performed using similar TSHassays should be substituted.

Strong recommendation, high-quality evidence.

ATA guidelines 2017RECOMMENDATION 26

If internal or transferable pregnancy-specific TSH reference ranges are notavailable, an upper reference limit of 4.0 mU/L may be used. For mostassays, this limit represents a reduction in the nonpregnant TSH upperreference limit of 0.5 mU/L.

Strong recommendation, moderate-quality evidence.

• Analytical method

• Ethnic differences

• Multiple pregnancy

• Iodine sufficiency

• Diurnal variation

• Predictable changes to thyroid function in pregnancy

• limited availability of trimester-specific reference rangescalculated for most ethnic and racial populations withadequate iodine intake who are free of thyroidautoantibodies

• Hierarchy:

i. Emphasis on population-based trimester-specificreference ranges for serum TSH

ii. Comparable population and assay

iii. Revision of prescriptive reference ranges• reduce lower range TSH by approx 0.4 mU/L• Reduced upper reference range is reduced by approx 0.5 mU/L• in early pregnancy, this corresponds to a TSH upper reference

limit of 4.0 mU/L• applied beginning with the late first trimester, weeks 7–12, with

a gradual return towards the non-pregnant range in the secondand third trimesters.

Taylor JCEM 2014

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

<0.2 0.2-2.5 2.51-4.5 4.51-10 >10

TSH mU/L

Adjusted OR

of Miscarriage

Euthyroid ab positive women

Negro JCEM 2006

Lui THYROID 2014

0

2

4

6

8

10

12

Euthyroid SCH Isolated TAI TAI + SCH

Miscarriage, %

ATA guidelines 2017

RECOMMENDATION 28

Pregnant women with TSH concentrations >2.5mU/L should beevaluated for TPOAb status.

ATA guidelines 2017

RECOMMENDATION 29

Subclinical hypothyroidism in pregnancy should be approached asfollows:

a) LT4 therapy is recommended for- TPOAb-positive women with a TSH greater than the pregnancy-specific reference range (see Recommendation 1).

Strong recommendation, moderate-quality evidence.

- TPOAb-negative women with a TSH greater than 10.0 mU/L.

Strong recommendation, low-quality evidence.

ATA guidelines 2017

RECOMMENDATION 29

Subclinical hypothyroidism in pregnancy should be approached asfollows:

(b) LT4 therapy may be considered for- TPOAb-positive women with TSH concentrations >2.5mU/L andbelow the upper limit of the pregnancy-specific reference range.

Weak recommendation, moderate-quality evidence.

- TPOAb-negative women and TPOAb-negative women with TSHconcentrations greater than the pregnancy- specific reference rangeand below 10.0 mU/L.

Weak recommendation, low-quality evidence.

ATA guidelines 2017

RECOMMENDATION 29

Subclinical hypothyroidism in pregnancy should be approached asfollows:

(c) LT4 therapy is not recommended for- TPOAb-negative women with a normal TSH (TSH within thepregnancy-specific reference range or <4.0 mU/L if unavailable).

Strong recommendation, high-quality evidence.