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 for the hyperthyroidism associated with trophoblastic disease.
TSH HCG Glinoer et al JCEM 1990
II: TSH reference range
ATA guidelines 2017 RECOMMENDATION 1 When possible, population-based trimester-specific reference ranges for serum TSH should be defined through assessment of local population data representative of a health care provider s practice. Reference range determinations should only include pregnant women with no known thyroid disease, optimal iodine intake, and negative TPOAb status. Alexander THYROID 2017
Organisation American Thyroid Association, 2011 TSH (miu/l) First trimester 0.1-2.5 Second trimester 0.2-3.0 Third trimester 0.3-3.0 Endocrine Society, 2012 First trimester <2.5 Second trimester <3.0 Third trimester <3.0 European Thyroid Association, 2014 First trimester <2.5 Second trimester <3.0 Third trimester <3.5
ATA guidelines 2011
ATA guidelines 2011
ATA guidelines 2011 5 th to 95 th percentiles
Generation R study Trimester TSH 2.5 mu/l 2.5 th 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 <2.5 mu/l in only 1 study 14 studies 97.5th TSH >3 mu/l
ATA guidelines 2017 Question 31: What is the definition of hypothyroidism in pregnancy? RECOMMENDATION 25 In the setting of pregnancy, maternal hypothyroidism is defined as a TSH concentration elevated beyond the upper limit of the pregnancy-specific reference range. Strong recommendation, high-quality evidence.
ATA guidelines 2017 RECOMMENDATION 26 The pregnancy-specific TSH reference range should be defined as follows:
ATA guidelines 2017 RECOMMENDATION 26 The pregnancy-specific TSH reference range should be defined as follows: When available, population- and trimester-specific reference ranges for serum TSH during pregnancy should be defined by a provider s institute or laboratory and should represent the typical population for whom care is provided. Reference ranges should be defined in healthy TPOAb-negative pregnant women with optimal iodine intake and without thyroid illness. Strong recommendation, high-quality evidence.
ATA guidelines 2017 RECOMMENDATION 26 The pregnancy-specific TSH reference range should be defined as follows: When available, population- and trimester-specific reference ranges for serum TSH during pregnancy should be defined by a provider s institute or laboratory and should represent the typical population for whom care is provided. Reference ranges should be defined in healthy TPOAb-negative pregnant women with optimal iodine intake and without thyroid illness. Strong recommendation, high-quality evidence. When this goal is not feasible, pregnancy-specific TSH reference ranges obtained from similar patient populations and performed using similar TSH assays should be substituted. Strong recommendation, high-quality evidence.
ATA guidelines 2017 RECOMMENDATION 26 If internal or transferable pregnancy-specific TSH reference ranges are not available, an upper reference limit of 4.0 mu/l may be used. For most assays, this limit represents a reduction in the nonpregnant TSH upper reference 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 ranges calculated for most ethnic and racial populations with adequate iodine intake who are free of thyroid autoantibodies
Hierarchy: i. Emphasis on population-based trimester-specific reference 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 second and third trimesters.
Adjusted OR of Miscarriage 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 <0.2 0.2-2.5 2.51-4.5 4.51-10 >10 TSH mu/l Taylor JCEM 2014
Euthyroid ab positive women Negro JCEM 2006
12 Miscarriage, % 10 8 6 4 2 0 Euthyroid SCH Isolated TAI TAI + SCH Lui THYROID 2014
ATA guidelines 2017 RECOMMENDATION 28 Pregnant women with TSH concentrations >2.5mU/L should be evaluated for TPOAb status.
ATA guidelines 2017 RECOMMENDATION 29 Subclinical hypothyroidism in pregnancy should be approached as follows: a) LT4 therapy is recommended for - TPOAb-positive women with a TSH greater than the pregnancyspecific 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 as follows: (b) LT4 therapy may be considered for - TPOAb-positive women with TSH concentrations >2.5mU/L and below the upper limit of the pregnancy-specific reference range. Weak recommendation, moderate-quality evidence. - TPOAb-negative women and TPOAb-negative women with TSH concentrations greater than the pregnancy- specific reference range and below 10.0 mu/l. Weak recommendation, low-quality evidence.
ATA guidelines 2017 RECOMMENDATION 29 Subclinical hypothyroidism in pregnancy should be approached as follows: (c) LT4 therapy is not recommended for - TPOAb-negative women with a normal TSH (TSH within the pregnancy-specific reference range or <4.0 mu/l if unavailable). Strong recommendation, high-quality evidence.