Clinical Thyroidology® for the Public
Summaries for the Public from recent articles in Clinical Thyroidology
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THYROID FUNCTION
Is my TSH normal – for me?
BACKGROUND
Thyroid problems are very common and may affect 5-10% of people in the world. The best way to diagnose abnormal thyroid function is to use TSH (thyroid stimulating hormone) levels. The standard, population-based reference range for TSH is found by checking the TSH levels of healthy people who do not have thyroid disease or other problems that may affect the thyroid. Reference range is the range of values that are in the middle 95% of the results. Serum TSH levels can vary a lot between different people, so the reference range defining what is normal for the population is wide. However, for each person, their TSH levels usually stay within a smaller range, which means everyone has their own point where their thyroid works best. This means even the best of the currently available methods we have to diagnose thyroid disease may lead to incorrect diagnosis and potentially over- or under treatment. We know from the findings of past studies that many factors can affect TSH levels such as age, sex, ethnicity, weight, iodine intake, and most importantly genetic factors. Over the last 20 years, scientists have found many genetic differences that affect the TSH levels. However, no one has tried to use these measurable genetic variants to personalize TSH reference ranges.
The authors designed this study to learn more about the effects of genetic factors on TSH reference ranges by using a method for the first time to determine genetically determined reference ranges.
THE FULL ARTICLE TITLE
Kuś A, et al. Towards personalized TSH reference ranges: a genetic and population-based approach in three independent cohorts. Thyroid. Epub 2024 Jun 26; doi: 10.1089/thy.2024.0045. PMID: 38919119.
SUMMARY OF THE STUDY
The authors collected information from three separate groups of people from the Netherlands and Norway. They used polygenic score (PGS) which is a number calculated by adding up the effects of many small genetic variants that can affect the TSH level in a person and they factored the score into finding out the genetically determined reference ranges. They first studied 6834 individuals without thyroid disease from the Rotterdam study.
They used 59 genetic variants to calculate the PGS and genetically determined TSH reference ranges. They compared these TSH reference ranges with the standard reference ranges in this group. Then they studied 3800 individuals without thyroid disease from a second study to confirm their findings. A third separate large group of people were studied to find out the impact of using personalized reference ranges on 26321 individuals without thyroid disease and 1132 patients on thyroid hormone treatment.
They found that the TSH values were much better estimated by PGS than free thyroid hormone levels or other factors such as age, sex, or weight. PGS explained 9-11% of the difference in TSH compared to 2.4-2.7% that would be explained by the difference in free thyroid hormone level. Individuals whose PGS scores fell into higher ranges were more likely to be treated with thyroid hormone. Up to 25-30% of individuals who would be diagnosed with mild thyroid disease when standard population based reference range was used were classified as having normal thyroid function when the genetically based TSH reference ranges were used, while 0.6-0.8% of patients with normal TSH levels with standard ranges were reclassified as having mild thyroid disease.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The authors found that TSH reference ranges based on genetics differ from standard population-based reference ranges. By considering individual genetic profiles we could personalize TSH reference ranges which would lead to more accurate diagnosis and treatment decisions. These findings are very important for patients even though it is challenging to currently apply them in routine practice. This is an important study that opens the door for further studies to find additional genetic markers and factors to improve the reference ranges and to develop better personalized treatments for thyroid disease.
— Ebru Sulanc, MD
ATA RESOURCES
Thyroid Function Tests: https://www.thyroid.org/thyroid-function-tests/
ABBREVIATIONS & DEFINITIONS
Genes: a molecular unit of heredity of a living organism. Living beings depend on genes, as they code for all proteins and RNA chains that have functions in a cell. Genes hold the information to build and maintain an organism’s cells and pass g enetic traits to offspring.
Thyroid hormone therapy: patients with hypothyroidism are most often treated with Levothyroxine in order to return their thyroid hormone levels to normal. Replacement therapy means the goal is a TSH in the normal range and is the usual therapy.
TSH (Thyroid Stimulating Hormone): produced by the pituitary gland that regulates thyroid function; also the best screening test to determine if the thyroid is functioning normally.
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