Reference Levels for TSH in Iodine-Sufficient Low-Risk Pregnant Women

[helvella]

Just don't be different!

If TSH levels are, as stated, population specific because of differences in ethnicity, then we need a rather more significant changes than just making the top of the TSH reference interval a bit higher.

I think it easy to imagine a clinic in the north of India. They pick up this 0.59 and 4.48 mIU/L interval. And then apply it to those who come to them.

Can you seriously imagine the clinic applying a pre-test check on ethnicity? (Difficult to be sure of ethnicity in many cases without significant genetic testing and interpretation.) Nor can I. So we can be pretty sure this reference interval will be applied to everyone - whatever their ethnicity.

I mean, can you imagine UK clinics using a north Indian ethnicity reference interval for any patients who have that ethnicity?

Doesn't failure to consider subgroups (different ethnicities) have the potential to be a motorway to Simpson's Paradox?

Mind, it is important to pick up and understand things like ethnicity, iodine levels, etc., as factors which need to be considered.

J Obstet Gynaecol India

. 2021 Dec;71(6):596-599.

doi: 10.1007/s13224-021-01477-y. Epub 2021 Apr 2.

Reference Levels for TSH in Iodine-Sufficient Low-Risk Pregnant Women

Bharti Goel 1 , Poonam Goel 1 , Jasbinder Kaur 2

Affiliations

• PMID: 34898897

• PMCID: PMC8617113 (available on 2022-12-01)

• DOI: 10.1007/s13224-021-01477-y

Abstract

Background: Recent evidence suggests that thyrotropin (TSH) levels are population specific because of differences in ethnicity. As a result, the 2017 ATA guidelines state that treatment may be tailored as per the laboratory-specific reference ranges of TSH for the local population instead of using a fixed upper limit of 2.5 mIU/L during pregnancy.

Methodology: This was a cross-sectional study in which we collected detailed clinical data of 604 pregnant women along with their TSH and spot urinary iodine excretion levels. Reflex testing for thyroid peroxidase antibodies (TPOAb) was done in women with TSH levels > 2.5 mIU/L in 1st trimester and 3.0 mIU/L in 2nd and 3rd trimester. After excluding 295 women who had high risk factors as per ATA 2017 guidelines and those who were TPOAb positive, we calculated the reference range for TSH in an iodine-sufficient low-risk cohort of 309 women.

Results: With median urinary Iodine of 255 µg/l, our population had more than required iodine levels. The 5th and 95th percentiles of TSH in our study cohort of 604 women were 0.64 and 7.81 mIU/L, respectively, while the 5th and 95th percentiles of TSH for the low-risk cohort of 309 women were 0.59 and 4.48 mIU/L, respectively.

Conclusion: An upper limit of 4.5 mIU/L for TSH level during pregnancy can be used to guide management decisions for low-risk North Indian women.

Keywords: Hypothyroidism; Pregnancy; Reference range; TSH.

© Federation of Obstetric & Gynecological Societies of India 2021.

Abstract here:

pubmed.ncbi.nlm.nih.gov/348...

Looks like the paper will be released for access in about a year - currently behind paywall:

link.springer.com/article/1...

Please re-read any comments you write before posting. It would be very easy to inadvertently write something that could be read the wrong way. I just hope I haven't done so.

[tattybogle]

i wonder if anybody recorded how the north indian pregnant women with TSH 4. 48 actually felt ....

[helvella Administrator Thyroid UK in reply to tattybogle]

Afraid that sarcasm comes to the fore. Since when was that of any importance whatsoever?

[jimh111]

There's a danger we reinforce the TSH dogma by looking too closely at TSH reference intervals. The TSH assay counts molecules, whether or not they are dud, or as Dr Skinner put it 'a graveyard has a high level of presence but little activity'.

In 2000 before I started thyroid medication, I was severely hypothyroid with RTH, my blood test results then were: -

TSH 1.0 (0.4 - 5.5), fT3 4.9 (3.5 - 6.5), fT4 13.3 (9.0 - 20.0)

A few years ago when I tried coming off thyroid hormone for quite some time: -

TSH 2.55 (0.27 - 4.2), fT3 4.2 (3.1 - 6.8), fT4 13.4 (12.0 - 22.0)

I did a crude 'set point indicator' calculated as fT4 + 4*fT3 based on T3 being about 4 times as potent at T4 (in the blood) expressed as a percentage of mid-interval results. This gave results of 95% for 2000 and 82% for the later results. The lower set point results in profound hypothyroidism.

These results reveal a more important issue than just a down-regulated axis causing lower hormone levels and reduced peripheral deiodinase. In the first case 1.0 mU/l of TSH is able to stimulate my thyroid into producing close to average levels of T3 and T4. Subsequent to down-regulation more than two and half times as much TSH (2.55 mU/l) has much less stimulatory effect on my (healthy) thyroid. The later TSH has much less bioactivity.

Thus, there is a danger in trying to analyse TSH too closely, creating the illusion that it is a precise marker. When there is thyroid failure low hormone levels produce high levels of TRH which stimulate not only higher levels of TSH but also highly glycosylated TSH which has full bioactivity. These TSH levels are informative, although so high (e.g. 20 or 50) that we don't care about the exact number. As TRH stimulation of the pituitary falls different and less potent TSH molecules are formed making the TSH assay of little relevance.

It's important to look at TSH, fT3 and fT4 all together so that meaningful interpretation can be made. If all three are low to low-normal the axis is not intact and TSH will be composed of isoforms with greatly reduced effect.

[jimh111]

Just noticed they refer to the 2.5 upper limit for pregnant women. This relates to women with hypothyroidism, those with a healthy thyroid will be able to respond to mildly higher TSH levels with adequate thyroid hormone. This illustrates that the research team have little understanding of thyroid issues and any peer review was a sham. Studies such as this should not be published as they dilute the benefits of genuine research.