You're exhausted. You're gaining weight despite eating carefully. Your hair is thinning. You feel cold when everyone around you is comfortable. Your brain feels like it's running through fog.
You go to your doctor. They order a thyroid test. The TSH comes back at 3.8 mIU/L. "Normal," they say. "Your thyroid is fine."
But here's the problem: that single number may be telling you very little about what's actually happening inside your cells.
Thyroid-stimulating hormone (TSH) is produced by the pituitary gland in the brain. It sends a signal to your thyroid gland: make more hormone. When thyroid hormone levels drop, TSH rises to compensate. When levels are sufficient, TSH falls. This feedback loop makes TSH an excellent screening tool, it's sensitive to even small shifts in thyroid output. A 2-fold decrease in T4 produces roughly a 100-fold increase in TSH. [1]
This sensitivity is precisely why TSH is used as the first-line test. But sensitivity to the gland's output is not the same as sensitivity to what's happening at the tissue level, and this is where the standard testing paradigm breaks down.
Your thyroid gland produces mostly thyroxine (T4), a storage hormone that is largely inactive. Approximately 80% of T4 must be converted into triiodothyronine (T3): the biologically active form that your cells actually use, through enzymes called deiodinases, primarily in the liver, kidneys, and gut. [2] T3 is roughly five times more biologically potent than T4.
Here's the critical insight: TSH responds to T4 and T3 levels at the pituitary gland. But the pituitary has its own local deiodinase enzyme (D2), which is 1,000 times more efficient at converting T4 to T3 than the D1 enzyme used in the rest of the body. [3] This means the pituitary can be perfectly satisfied, producing a "normal" TSH, while peripheral tissues are starved for active T3.
This is why a person can have a normal TSH, a normal free T4, a low or low-normal free T3, and still present with every classic symptom of hypothyroidism: fatigue, weight gain, cold intolerance, brain fog, depression, hair loss, constipation, and muscle weakness. The pituitary is fine. The rest of the body is not.
There's an additional layer to this story that makes TSH-only testing even less reliable at the individual level.
In 2002, Andersen and colleagues published a landmark study in the Journal of Clinical Endocrinology & Metabolism showing that while thyroid hormone levels vary widely across the population, the variation within a single individual over time is remarkably narrow. [4] Each person has a unique hormonal "setpoint" — the TSH, T4, and T3 levels at which their hypothalamic-pituitary-thyroid axis is in equilibrium.
The standard TSH reference range (typically 0.4–4.5 mIU/L) represents the statistical distribution across an entire population. But your personal healthy range might be 0.8–1.4 mIU/L. If your setpoint TSH is 1.0 and it rises to 3.5, still "normal" by lab standards, that represents a significant shift in your thyroid function that a single test would classify as perfectly fine. [4]
This is why StatPearls, the standard medical reference, notes that although TSH shows wide variability across the population, intra-individual variation remains minimal, secondary to a unique individual setpoint. [5] And it's why subclinical hypothyroidism, where TSH is elevated but free T4 is still within range, affects between 3% and 15% of the population depending on the study. [5]
Without longitudinal data, your own baseline and trajectory over time, a single TSH measurement is far less informative than most people assume.
In 2023, the Thyroid Studies Collaboration published a massive individual-participant-data meta-analysis in The Lancet Diabetes & Endocrinology that fundamentally challenges how we think about "normal" thyroid function. [6]
The researchers pooled data from 26 prospective cohorts, 134,346 adults followed for an average of 11.5 years, and asked a simple question: within the "normal" reference range, which thyroid hormone levels are actually associated with the lowest risk of cardiovascular disease and death?
The findings were striking:
For free T4: Levels between the 20th and 40th percentiles of the normal range (median 13.5–14.8 pmol/L) carried the lowest risk. Above the 50th percentile, the risk of cardiovascular events and mortality increased in a largely linear fashion. People with free T4 in the 80th–100th percentile of the "normal" range had a 57% higher risk of cardiovascular death, a 34% higher risk of all-cause mortality, and a 22% higher risk of heart disease compared to those in the 20th–40th percentile. [6]
For TSH: The 60th–80th percentiles (approximately 1.9–2.9 mIU/L) were associated with the lowest composite risk. People with TSH in the lowest 20% of the normal range had a 9% higher risk of all-cause mortality compared to those in the 60th–80th percentile. [6]
In other words: the "normal" reference range is not a risk-free zone. The optimal healthy range is substantially narrower than what your lab report defines as normal. And the risk gradient is steep, particularly for older adults, in women and men over 70, free T4 above the 85th percentile of the normal range increased 10-year composite risk by more than 5%. [6]
Your thyroid tells a story. One number isn't enough to read it.Aniva measures TSH, free T4, and free T3, the complete thyroid output picture, plus the cofactors that drive conversion: selenium, zinc, iron/ferritin, and vitamin D. 140+ biomarkers per draw. No more guessing from a single number.
Of all the thyroid function issues that standard testing misses, the T4-to-T3 conversion problem is arguably the most common and the most consequential.
The pattern looks like this: TSH is in range. Free T4 is in range. Free T3 sits low or low-normal. Symptoms persist. If your doctor only tested TSH, or even TSH plus free T4, this pattern is invisible.
The conversion of T4 to T3 depends on three deiodinase enzymes (D1, D2, D3), and these enzymes are not decorative biochemistry. They are the control points of cellular thyroid activity, and they are profoundly influenced by nutrient status, inflammation, stress, and organ function. [3]
The deiodinase enzymes that convert T4 to T3 are selenoproteins, they literally cannot function without selenium. [2] A 1996 study measuring selenium status, zinc status, and thyroid hormones in 109 healthy subjects found that declining selenium levels in elderly subjects directly correlated with reduced T3/T4 ratios, meaning less T4 was being converted to active T3. [2]
Europe has variable selenium status. Unlike North America, where soil selenium levels are generally adequate, European soils, particularly in Germany, Scandinavia, and Eastern Europe, tend to be selenium-poor. This means dietary intake often falls below the levels needed for optimal deiodinase function. Without testing selenium alongside thyroid hormones, you're looking at the output without checking whether the machinery works.
Zinc is required for thyroid hormone receptor function — without adequate zinc, even sufficient T3 cannot bind effectively to cellular receptors. [2] Iron deficiency has been shown to significantly reduce T4-to-T3 conversion and increase reverse T3 levels. [3] Vitamin D deficiency is associated with higher rates of autoimmune thyroiditis. [7]
The pattern is familiar if you've read our vitamin D article: the nutrient you're testing depends on cofactors you're not measuring. If your thyroid numbers look "fine" but your selenium, zinc, ferritin, or vitamin D are suboptimal, conversion may be impaired — and you'll never know from TSH alone.
Under chronic stress, cortisol upregulates D3, the enzyme that converts T4 into reverse T3 (rT3) instead of active T3. [3] Reverse T3 is biologically inactive and competes with T3 at the receptor level. The body does this deliberately during acute illness or starvation as a protective mechanism to slow metabolism. But chronic stress, caloric restriction, insulin resistance, and liver dysfunction can create the same pattern persistently: low active T3, elevated rT3, and a TSH that remains stubbornly "normal" because the pituitary's own conversion is unaffected.
Approximately 60% of T4-to-T3 conversion occurs in the liver. [3] Another 20% occurs in the gut, facilitated by healthy intestinal bacteria. This means liver dysfunction and gut dysbiosis can directly impair thyroid hormone activation, connecting thyroid health to metabolic, digestive, and hepatic function in ways that a TSH test cannot capture.
Hashimoto's thyroiditis, autoimmune destruction of the thyroid gland, is the most common cause of hypothyroidism in iodine-sufficient countries. Its prevalence ranges from 4.8–25.8% in women and 0.9–7.9% in men, depending on the population. [7] A global meta-analysis of 48 studies found that the European prevalence was approximately 7.5%, with evidence of an increasing trend. [7]
Hashimoto's is diagnosed through thyroid peroxidase (TPO) antibodies, markers of autoimmune attack against the thyroid gland. The problem is that TPO antibodies are rarely tested in standard screening. A typical thyroid check includes TSH, possibly free T4. TPO antibodies are considered a "confirmatory" test ordered only when TSH is already abnormal. [8]
This creates a paradox: Hashimoto's is a progressive disease that destroys thyroid tissue gradually over years. In the early stages, the gland compensates by working harder, TSH may rise slightly but remain within the reference range, and free T4 stays normal. By the time TSH is clearly elevated, significant gland destruction has already occurred. Testing TPO antibodies early, before TSH becomes abnormal, can identify autoimmune thyroiditis years before it progresses to clinical hypothyroidism.
Approximately 30% of patients with TSH above 3.0 mIU/L have occult autoimmune thyroid disease. [9] In those with positive TPO antibodies and elevated TSH, the likelihood of progression to overt hypothyroidism increases significantly. [5]
The full thyroid picture requires more than one test.TSH tells you the pituitary's opinion. Free T4 tells you what the gland is producing. Free T3 tells you what your cells can actually use. TPO antibodies tell you whether autoimmunity is involved. Selenium, zinc, iron, and vitamin D tell you whether conversion is supported. Aniva's 140+ biomarker panel covers the complete picture, not just the screening test.
A 2019 systematic review and meta-analysis published in the European Thyroid Journal examined the prevalence of undiagnosed hypothyroidism across European populations. [10] The results: approximately 4.11% of the European population has undiagnosed subclinical hypothyroidism, plus an additional 0.65% with undiagnosed overt hypothyroidism, totaling nearly 5% of the population walking around with a thyroid problem they don't know about. [10]
The prevalence was higher in women, in those over 65, and in Eastern and Southern Europe. [10] A separate meta-analysis covering European data estimated the total prevalence of undiagnosed thyroid dysfunction at 6.71%, including both hypo- and hyperthyroidism. [11]
In Germany specifically, the Study of Health in Pomerania (SHIP), a longitudinal population-based study, found that self-reported diagnosed thyroid disorders increased from 7.6% to 18.9% between 2000 and 2010, while thyroid medication use nearly doubled from 6.2% to 11.1%. [12]
These numbers are significant because untreated hypothyroidism, even subclinical, correlates with increased risk of coronary artery disease, heart failure, cognitive decline, and metabolic dysfunction. [5] The 2023 Thyroid Studies Collaboration data makes this even more concerning: even within the "normal" range, suboptimal thyroid function carries measurable cardiovascular risk. [6]
A 2024 study analyzing 7.6 million TSH measurements and 2.2 million free T4 measurements from 13 Dutch medical institutions found that TSH levels naturally increase with age, particularly after age 50 in women and 60 in men. [13] The upper normal TSH limit for a 50-year-old woman was 4.0 mIU/L, but by age 90, it had risen to 6.0 mIU/L, a 50% increase. [13]
Using age-specific reference ranges significantly reduced the number of people diagnosed with subclinical hypothyroidism. [13] This matters in both directions: older adults may be overtreated based on reference ranges derived from younger populations, while younger adults with TSH values near the upper limit of "normal" may be undertreated.
Whether age-related TSH increases represent a protective adaptation or a sign of declining thyroid function is actively debated. Some evidence suggests that mild TSH elevation in the elderly may be associated with longevity. [1] The practical takeaway: context matters. Your age, sex, trajectory, antibody status, and symptom profile all influence what your thyroid numbers actually mean.
Based on the evidence, a comprehensive thyroid evaluation includes far more than a TSH check:
TSH — The screening gate. Sensitive to pituitary feedback, but tells you nothing about peripheral conversion, T3 availability, or autoimmune status. Optimal range based on cardiovascular outcomes: approximately 1.9–2.9 mIU/L (60th–80th percentile). [6]
Free T4 — What the thyroid gland is producing. Optimal range for cardiovascular risk: 20th–40th percentile of the reference range. The upper half of the "normal" range carries progressively higher cardiovascular risk. [6] Aniva measures free T4.
Free T3 — What your cells can actually use. The active hormone. A low or low-normal free T3 with adequate TSH and free T4 signals a conversion problem. This is the marker most commonly omitted from standard testing, and arguably the most important for understanding how you feel. Aniva measures free T3.
TPO Antibodies — Whether the immune system is attacking the thyroid. Identifies Hashimoto's thyroiditis years before TSH becomes abnormal. Positive in up to 25% of women. [7]
Selenium — Required for deiodinase enzyme function. Without it, T4 cannot become T3 regardless of gland output. European populations are frequently suboptimal. Aniva measures selenium.
Zinc — Required for thyroid hormone receptor binding and TSH production. Deficiency impairs both conversion and cellular response. Aniva measures zinc.
Ferritin/Iron — Iron deficiency reduces T4-to-T3 conversion and increases inactive reverse T3. Women of reproductive age are particularly vulnerable. Aniva measures ferritin and iron.
Vitamin D — Deficiency is associated with autoimmune thyroiditis. Critical cofactor for immune regulation. Aniva measures 25(OH)D.
hs-CRP — Chronic inflammation impairs deiodinase activity and diverts T4 toward reverse T3. Connects thyroid function to systemic inflammatory status. Aniva measures hs-CRP.
A thyroid "check" should be a thyroid panel.TSH, free T4, free T3, TPO antibodies, selenium, zinc, ferritin, vitamin D, hs-CRP — Aniva's 140+ biomarker panel covers the complete thyroid picture and the cofactor network that determines whether your thyroid hormones are actually working. One test. The whole story.
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Standard thyroid screening tests TSH — and sometimes free T4. This catches overt thyroid disease but misses the conversion problems, autoimmune patterns, cofactor deficiencies, and within-range suboptimal function that affect millions of Europeans.
A 134,346-person meta-analysis has shown that the "normal" reference range is not a risk-free zone. The optimal thyroid function ranges — based on actual cardiovascular and mortality outcomes — are narrower than what your lab report considers acceptable. [6]
Nearly 5% of Europeans have undiagnosed hypothyroidism. [10] Hashimoto's thyroiditis affects up to 1 in 4 women. [7] T4-to-T3 conversion depends on selenium, zinc, iron, and liver function — none of which appear on a standard thyroid screen. And each person has a unique hormonal setpoint that a single population-derived reference range cannot capture. [4]
The thyroid doesn't operate in isolation. It depends on nutrients, responds to inflammation, and connects to every organ system in the body. Testing it in isolation — with one number, one time — is a diagnostic artifact of a healthcare system built around efficiency, not comprehension.
You deserve the full picture.
Medical disclaimer: This content is for informational purposes only and is not medical advice. Thyroid conditions should be diagnosed and managed by a qualified healthcare professional.
