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Required section · Section 5 of 6

Learner decision: specimen B does not fit

Outpatient specimen B is from a 31-year-old on a stable levothyroxine prescription with a recent history of a hair, skin, and nail supplement, reported as feeling well with no hyperthyroid symptoms. The original-platform result: TSH 0.05 mIU/L (suppressed), FT4 0.9 ng/dL (mid-reference), total T3 110 ng/dL (mid-reference). TSH alone looks hyperthyroid. FT4 and T3 look ordinary. That is the discordance: a suppressed TSH with hormone measures that have not moved.

Classify this against the three drawn reference patterns first: it is not the concordant overt hyperthyroid pattern from specimen A, because FT4 and T3 are not elevated. It is not the primary hypothyroid pattern. It is not the central hypothyroid signature, because FT4 is not low. It does not cleanly fit any of the three, and that mismatch is itself the finding worth acting on.

The recent high-dose biotin-type supplement history is the lead to follow. Biotin can interfere with streptavidin-biotin-based immunoassays: in sandwich-format assays, often used for TSH, it can cause a falsely low result; in competitive-format assays, often used for T4/T3, it can cause a falsely high result. Together this can mimic a hyperthyroid or an over-replaced levothyroxine pattern without any real change in the patient's thyroid status. The exact washout duration and dose threshold are assay-specific and must be confirmed against the current package insert for the assay in use; the mechanism and direction are established, and the exact number is a local, declared value.

The defensible next action is to confirm or exclude recent high-dose biotin exposure and rerun the affected analyte, either on the current specimen after excluding interference by protocol or on a fresh draw after an appropriate washout, per this laboratory's biotin-interference protocol. Repeating only TSH without addressing the interference question would not resolve the mechanism. Assuming overtreatment and stopping the medication, or sending for imaging, would act on an unconfirmed number and are not defensible from this evidence alone.

The alternate-platform result after washout is TSH 2.10 mIU/L, within the reference interval and consistent with the unchanged FT4 and T3. This demonstrates resolution of the discordance and supports biotin interference as the working explanation. It does not, by itself, prove the exact mechanism without further confirmatory studies such as PEG precipitation; that limit is stated directly rather than overclaimed.

A TSH that disagrees with its own FT4 and T3, in a patient with a plausible interference history, earns a repeat before it earns a headline.

Illustrative drawing — this picture was drawn rather than captured.

Timeline for specimen B: a biotin-type supplement can affect susceptible streptavidin-biotin assays; the specimen has low TSH with unchanged mid-reference FT4 and T3, not elevated FT4/T3.
Figure 1Specimen B: low TSH with unchanged, mid-reference FT4/T3; susceptible streptavidin-biotin systems can distort results, but this specimen does not show elevated FT4/T3.

Illustrative drawing — this picture was drawn rather than captured.

Chart comparing specimen B's suppressed original TSH of 0.05 mIU/L to a concordant alternate-platform TSH of 2.10 mIU/L within the 0.40 to 4.50 mIU/L reference interval, alongside unchanged free T4 of 0.9 ng/dL and total T3 of 110 ng/dL, both within their reference intervals.
Figure 2Specimen B: original-platform TSH compared to the concordant alternate-platform TSH, with unchanged FT4 and T3.
Specimen B: original result versus alternate-platform result after biotin washout.
AnalyteReference intervalOriginal platformAlternate platform, post-washout
TSH0.40-4.50 mIU/L0.05 mIU/L (suppressed)2.10 mIU/L (within interval)
Free T40.8-1.8 ng/dL0.9 ng/dL (mid-reference)not repeated; unchanged clinically
Total T380-200 ng/dL110 ng/dL (mid-reference)not repeated; unchanged clinically

Ordering exercise

Put the steps of a macro-TSH or heterophile-antibody workup for an isolated, clinically discordant elevated TSH in the order this laboratory actually performs them.

  1. 1. Perform PEG precipitation with recovery calculation

    Estimates the proportion of immunoreactive TSH that is macro-TSH bound to immunoglobulin rather than free, active hormone.

  2. 2. Collect a fresh specimen

    Rule out a labeling, clotting, or specimen-integrity issue before assuming an analytical interference.

  3. 3. Escalate to a reference laboratory

    Protein A/G or gel-filtration chromatography confirms macro-TSH when local studies remain inconclusive.

  4. 4. Perform serial dilution

    Supportive but not definitive, because macro-TSH can dilute linearly and mimic a true elevated result.

  5. 5. Test on an alternate immunoassay platform

    A result that normalizes on a different platform points toward a platform-specific interference rather than true patient physiology.

Knowledge checks

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Knowledge check 1

Specimen B: TSH 0.05 mIU/L (suppressed), FT4 0.9 ng/dL (mid-reference), total T3 110 ng/dL (mid-reference), recent hair/skin/nail supplement history, no hyperthyroid symptoms. Which classification best fits?

Choose one option.

Knowledge check 2

For specimen B, which next laboratory action is best supported by the evidence?

Choose one option.

Knowledge check 3

Which statement is the defensible way to report specimen B's original result set?

Choose one option.

Knowledge check 4

The alternate-platform, post-washout TSH for specimen B is 2.10 mIU/L, within the reference interval, consistent with the unchanged FT4 and T3. What does this result support?

Choose one option.

Knowledge check 5

Select every method that is part of a standard investigation for suspected macro-TSH or heterophile-antibody interference.

Choose at least 2 options.

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