Subclinical Thyroid Dysfunction in the First Trimester of Pregnancy

Disease' Versus Physiological (Pulsatile) Variation in TSH Concentrations

Krzysztof C. Lewandowski; Karolina Garnysz; Wojciech Horzelski; Joanna Kawalec; Karolina Budzen; Mariusz Grzesiak; Andrzej Lewinski


Clin Endocrinol. 2020;93(6):739-745. 

In This Article

Abstract and Introduction


Background: There is no universal consensus regarding cut-off points for TSH in pregnancy, so concentrations of 2.5 or 4.0 mIU/L were suggested for first trimester (Endocrine Society [2012] and ATA [2017] guidelines, respectively). Yet, the impact of physiological variation in TSH secretion has not been assessed.

Subjects and Methods: We assessed baseline concentrations of free T4, free T3 and TSH at 30-minute intervals (between 7.00 and 9.00 hours) in 110 healthy pregnant women, age 30.2 ± 6.0 years, 9.9 ± 2.4 weeks of gestation, and in 19 female controls, age 28.9 ± 10.7.

Results: Mean TSH concentrations in pregnant women were 1.62 ± 1.26 mIU/L and on average varied by 39.5% (dispersion between the highest and the lowest TSH), with no difference in TSH variation between pregnant women and controls. Taking into account the highest TSH out of five consecutive measurements, TSH >2.5 mIU/L and TSH above 4.0 mIU/L were found in 23 (20.9%) and 10 (9.1%) pregnant women, respectively. In contrast, when the lowest TSH value was considered, then concentrations of TSH >2.5 mIU/L and >4.0 mIU/L were found in 14 (12.7%) and 4 (3.6%) women, respectively. This discrepancy was even more pronounced in aTPO-negative subjects (21 [21.2%] vs 8 [8.1%] women, for TSH >2.5 mIU/L, and six [6.06%] vs one [1.01%], for TSH >4.0 mIU/L). Furthermore, either six (5.4%) or 10 (9.1%) women had TSH concentrations below 0.1 mIU/L.

Conclusions: In a significant number of patients, diagnosis of subclinical thyroid dysfunction could be erroneously made not as a result of 'disease', but as a result of physiological variation in TSH concentrations.


There is no universal agreement regarding reference ranges for TSH and thyroid hormones during pregnancy. For instance, 2011 American Thyroid Association (ATA) guidelines[1] suggested that if trimester-specific reference ranges for TSH are not available, the following reference ranges are recommended: first trimester, 0.1–2.5 mIU/L; second trimester, 0.2–3.0 mIU/L; and third trimester, 0.3–3.0 mIU/L. Such position was repeated in the Endocrine Society[2] and European Thyroid Association guidelines,[3] while subsequent 2017 ATA guidelines[4] suggested a higher cut-off point of TSH 4.0 mIU/L.

What is often not realised is the fact that TSH is also secreted in a pulsatile manner,[5–7] where nocturnal TSH concentrations may be even twice as high as during the day.[7] There are approximately 10 TSH pulses per 24 hours,[7] while TSH pulse amplitude appears to be increased in nonthyroidal illness.[8] Any decisions to instigate treatment, particularly during such a sensitive period like pregnancy, should be based on clear data that define what TSH and thyroid hormone concentrations are abnormal and evidence of definite benefit of treatment. Furthermore, assessment of thyroid function should be performed during the first trimester of pregnancy, as foetal development is then almost entirely dependent on maternal thyroid hormone concentrations. In such circumstances, it is mandatory to ascertain that one is dealing with a genuine abnormality and not with physiological variation in hormone concentrations. We have therefore endeavoured to assess physiological variation in TSH secretion in the first trimester of pregnancy in order to estimate to what extent the 'diagnosis' of subclinical thyroid dysfunction in the first trimester of pregnancy might be influenced by physiological variation in TSH concentrations.