Patient Details: 29 year-old female, from Mumbai.
Medical History: No major systemic disorder, healthy patient.
Clinical presentation: The patient presented to her family physician to get basic lab tests done as she wanted to conceive shortly and evaluate her fitness.
Clinical Action: The doctor ordered basic blood tests. In particular, the doctor was keen to assess thyroid function prior to conception. Thyroid assessment was also done as it is a key parameter for women who want to conceive.
Tests done: CBC, LFT, Blood sugar, HbA1c, AMH, urinalysis and lipid profile. Thyroid tests included free T3/T4 and TSH. She gave the sample for TSH testing at one of our centres in the morning.
Results: We performed TSH testing on the CLIA platform. The patient’s result was 7.6 microIU/mL and reported as elevated as per the reference range of the CLIA platform. No other tests showed any derangements.
Clinical Problem: As the patient did not have any symptoms, the clinician was not sure whether the TSH result was correct. The same patients, 2 days later, gave another sample for TSH testing at another lab. The sample was given in the evening. The other lab performed the test by the CMIA method. As per that platform, the patient was reported to have a normal TSH level with a value of 4.5 microIU/mL.
Clinical Question: The clinician and the patient were confused and did not know which report to consider true and correct as there was a 40% difference in the TSH values between the 2 reports.
Points to Note: The patient gave samples for TSH testing in the two labs at different times of the day (morning and evening). Besides, the second sample was given two days later. Both labs used a different method to test TSH levels. Diurnal variations can cause large fluctuations in TSH levels. So also, different platforms that labs use for testing TSH can cause wide variations in the result.
Let’s delve deeper to precisely understand the reasons for TSH variations and why is it that a large number of hypothyroid patients may actually have elevated TSH and not show any apparent features
In the context of the clinical and laboratory diagnosis of hypothyroidism, the frequent variations that occur in the levels of TSH need to be factored in.
Ref: Biological Variation: From Principles to Practice-Callum G Fraser (AACC Press)
Let’s take a closer look at commonly known causes that bring about changes in TSH levels
At Suburban Diagnostics, we report TSH values by the Chemiluminescence Immunoassay (CLIA). The other commonly used methodology is Chemiluminescent Microparticle Immunoassay (CMIA).
What are the reference ranges of the CLIA and CMIA platforms used for measuring TSH?
CLIA reference range for TSH (0.27–4.20 µIU/mL) is actually on the narrower side than the range of the CMIA assay (0.35–4.94 µIU/mL) Indian J Clin Biochem 2014 Apr; 29(2): 189–195 (Note: The lab uses its own derived ranges)
The CLIA platform used at Suburban diagnosticsis based on a 95% central interval limit which means that while determining the biological reference range for this assay, 95% central values of the general population were taken into consideration – excluding 2.5% values at the bottom and 2.5% values at the top of the range, from the general population.
This is the central interval limit recommended by the regulating authority – Clinical Laboratory Standards Institute (CLSI)
On the other hand, the CMIA platform is based on a 99% central interval which means that while determining the biological reference range for this assay, 99% central values of the general population were taken into consideration – excluding 0.5% values at the bottom and 0.5% values at the top of the range, from the general population.
Ref: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory, 3rd Edition
TREATMENT ALGORITHM FOR SUBCLINICAL HYPOTHYROIDISM
Ref: Harrison – Textbook of Medicine As per recommendations, treatment need not be initiated if TSH levels are below 10 mU/L
Any elevations above this level can be considered for treatment. However, lab-based evidence of such elevations above 10 mU/L, sustained for at least a period of 3 months; should be available before treatment is begun.