Thyroid Stimulating Hormone

What is TSH?

Thyroid stimulating hormone (TSH) is a hormone released by the pituitary gland at the base of the brain, not by the thyroid itself. Its job is to tell the thyroid to make and release thyroxine (T4) and triiodothyronine (T3). Because the pituitary raises TSH when thyroid hormone is scarce and lowers it when there is plenty, the TSH level is read backwards: it reports how hard the pituitary is having to push, which is an unusually sensitive measure of whether the thyroid is keeping up.

What is TSH made of, and where does it come from?

TSH is a glycoprotein of about 28 kDa made of two chains: an alpha subunit that it shares with LH, FSH and the pregnancy hormone hCG, and a beta subunit that is unique to TSH and gives it its activity. Modern third-generation immunoassays measure it down to about 0.01 mIU/L, which is what allows a suppressed TSH to be distinguished from a merely low one. The shared alpha subunit matters in practice, because very high hCG in early pregnancy can weakly stimulate the thyroid and push TSH down.

What does TSH do in the body?

TSH sits in the middle of a feedback loop: the hypothalamus releases TRH, which prompts the pituitary to release TSH, which prompts the thyroid to release T4 and T3, which in turn switch TRH and TSH off. The relationship is not linear but logarithmic — a fall in free T4 of only 20% roughly doubles TSH — so TSH amplifies small changes in thyroid output and changes long before T4 leaves its reference range. This amplification is why TSH is the usual first test of thyroid function and why, in most adults, a normal TSH makes a primary thyroid problem unlikely. The loop is slow: after any change in thyroid hormone supply, TSH takes six to eight weeks to settle at its new level.

What does a high TSH mean?

A high TSH usually means the thyroid is underactive and the pituitary is pushing harder to compensate — this is primary hypothyroidism, and it is far more common than any other explanation. When TSH is raised but free T4 is still normal, the state is called subclinical hypothyroidism; it is common, often transient, and the 2012 ATA/AACE guideline treats a TSH above 10 mIU/L differently from a milder elevation, which it suggests confirming on repeat testing before drawing conclusions. A single raised value therefore means 'look again', not 'the thyroid has failed' — non-thyroidal illness, assay interference and normal ageing all produce transient or mild elevations.

Common causes:

• Hashimoto's autoimmune thyroiditis, the most common cause of an underactive thyroid in iodine-sufficient regions; thyroid peroxidase antibodies are usually positive.
• Iodine deficiency, or, less intuitively, iodine excess from kelp supplements or iodine-rich medications, which can shut thyroid hormone production down.
• The recovery phase of a significant illness, when TSH rebounds above normal for a few weeks.
• Medications that suppress the thyroid, including lithium, amiodarone, interferon and some cancer immunotherapies, or previous thyroid surgery or radioiodine treatment.
• In people taking thyroid hormone replacement, a dose that no longer covers their needs, missed doses, or the tablet being taken together with iron, calcium, coffee or a proton-pump inhibitor, all of which reduce its absorption.
• Laboratory artefacts: heterophile antibodies or 'macro-TSH' complexes that give a high reading without any thyroid problem. Suspected when the TSH makes no clinical sense.

What does a low TSH mean?

A low TSH usually means there is more thyroid hormone in circulation than the pituitary wants, so it has gone quiet — either the thyroid is overactive, or thyroid hormone is being taken in a higher dose than the body needs. Low TSH with normal free T4 and T3 is called subclinical hyperthyroidism, and Biondi and Cooper's 2008 review in Endocrine Reviews links a persistently suppressed TSH, particularly below 0.1 mIU/L, with atrial fibrillation and bone loss in older adults. Two exceptions run the other way: in early pregnancy a mildly low TSH is physiological, and in the rare condition of central hypothyroidism the pituitary itself is failing, so TSH is low or misleadingly normal while free T4 is low.

Common causes:

• Graves' disease, in which antibodies stimulate the thyroid directly, or one or more autonomously overactive thyroid nodules.
• Thyroiditis — after a viral illness, after childbirth, or drug-induced — which leaks stored hormone and suppresses TSH for weeks, then often swings to a high TSH before recovering.
• Thyroid hormone replacement at a dose above current needs, including deliberate suppression after thyroid cancer surgery.
• First-trimester pregnancy, where hCG stimulates the thyroid; severe non-thyroidal illness; and treatment with glucocorticoids or dopamine.
• High-dose biotin supplements, which produce a falsely low TSH together with a falsely high free T4 — a pattern that mimics Graves' disease on paper.

What moves TSH apart from disease?

Time of day either direction

TSH follows a daily rhythm, peaking around midnight to the early hours and reaching its lowest point in the late afternoon. Values drawn in the afternoon can run 20-30% below a morning value from the same person, which is enough to move a borderline result across a threshold.

Biotin supplements lowers it

Biotin does not change thyroid function, but many TSH assays use a biotin-streptavidin link, and biotin in the blood competes with it. A 2017 JAMA study found that a week of 10 mg/day biotin produced falsely abnormal thyroid results in healthy volunteers. Doses in hair, skin and nail products are often far above this.

Recent illness, surgery or hospitalisation either direction

During any significant illness the body dials thyroid signalling down, so TSH can read low; in the weeks of recovery it rebounds and can read high. Neither reflects the thyroid itself, and the pattern is called non-thyroidal illness or sick euthyroid syndrome. Thyroid function measured during an acute illness is generally regarded as uninterpretable.

Pregnancy either direction

In the first trimester hCG stimulates the thyroid and TSH falls, sometimes below the non-pregnant range; it rises again in the second and third trimesters. The 2017 ATA pregnancy guideline calls for trimester-specific reference ranges, so a pregnant result read against the general adult range is easily misjudged in both directions.

Glucocorticoids, dopamine and other medications either direction

Glucocorticoids (including prednisone courses and high-dose inhaled steroids), dopamine and somatostatin analogues suppress TSH release. Amiodarone, lithium, interferon and immune checkpoint inhibitors disturb the thyroid itself and can push TSH either way. Metformin slightly lowers TSH in people with hypothyroidism.

Sleep loss, age and body weight either direction

A night without sleep blunts the nocturnal TSH surge and lowers the next morning's value. Independently, the normal TSH distribution shifts upward with age — a mildly raised TSH in someone over 70 is often not a disease — and obesity raises TSH modestly through leptin, with the value falling after weight loss without any thyroid treatment.

Which other tests are read together with TSH?

Free Thyroxine downstream

Free T4 is the hormone TSH is regulating. Read together they separate primary thyroid disease (TSH and FT4 move in opposite directions) from a pituitary cause (both low or both high) and define the subclinical grey zones (TSH abnormal, FT4 normal).

Free Triiodothyronine downstream

Free T3 is the active hormone and rises earliest in hyperthyroidism, so it is the value that explains a suppressed TSH when FT4 is still normal. It adds little in suspected hypothyroidism, where it stays normal until late.

Anti-TPO Antibodies same panel

Thyroid peroxidase antibodies identify the autoimmune cause behind a raised TSH and predict which subclinical elevations will progress — in the Whickham cohort, antibody-positive people progressed to overt hypothyroidism several times more often.

Anti-Thyroglobulin Antibodies same panel

Thyroglobulin antibodies are the second marker of autoimmune thyroiditis and occasionally positive when TPO antibodies are not.

LDL Cholesterol downstream

An underactive thyroid slows LDL receptor activity and raises LDL cholesterol; a raised TSH is one of the reversible causes checked before a new high LDL-C is treated as a lipid problem.

Heart Rate downstream

Resting heart rate tracks thyroid hormone: a suppressed TSH with a fast or irregular resting pulse is the combination that raises concern for atrial fibrillation, while an unexplained slow pulse can accompany hypothyroidism.

Which foods affect TSH?

• Adequate iodine from iodised salt, dairy, eggs, fish and seafood — supports strong evidence
• Large amounts of kelp, seaweed snacks or seaweed broth — iodine excess suppresses thyroid hormone production in susceptible people — raises moderate evidence
• Selenium-containing foods such as Brazil nuts, fish, eggs and whole grains — supports moderate evidence
• Soy and raw cruciferous vegetables — only meaningful when iodine intake is already low — raises emerging evidence

Which supplements are studied for TSH?

Iodine strong evidence

Iodine is the raw material of thyroid hormone, and where intake is genuinely low, restoring it normalises TSH. The relationship is U-shaped: intake well above need is as capable of raising TSH as deficiency is, because a large iodine load temporarily switches hormone synthesis off. Whether any given person needs more depends on their diet and region, which is why no general dose is stated here.
Typical dose: no general dose given
Cautions: In people with Hashimoto's or nodular thyroid disease, added iodine can trigger either hypothyroidism or hyperthyroidism. Kelp and seaweed capsules contain wildly variable and often very large iodine amounts; the label rarely reflects the content. Pregnancy raises iodine requirements, and the 2017 ATA pregnancy guideline addresses this specifically — a clinician's advice applies rather than a general rule.

Selenium emerging evidence

Selenium is built into the deiodinase enzymes that activate thyroid hormone and into the antioxidant enzymes that protect the gland. In autoimmune thyroiditis, trials show it lowers thyroid peroxidase antibody levels, but there is little evidence that it changes TSH or prevents progression, and the effect on antibodies has not been shown to matter clinically.
Typical dose: up to 200 µg/day
Cautions: The margin between enough and too much is narrow: chronic intake above about 400 µg/day causes hair and nail loss, nausea and nerve symptoms. A large prevention trial found more type 2 diabetes in people randomised to selenium, so long-term supplementation in people who are not deficient is not obviously benign.

Biotin (vitamin B7) strong evidence

Biotin has no effect on the thyroid and is listed here only as a warning. High-dose biotin, sold for hair, skin and nails and used medically in multiple sclerosis, interferes with the immunoassays used for TSH and thyroid hormones, producing a falsely low TSH and falsely high free T4 that together look exactly like hyperthyroidism.
Typical dose: no general dose given
Cautions: Laboratories and assay manufacturers commonly advise stopping biotin for at least 48-72 hours before a thyroid blood test, longer at very high doses. Multivitamins and B-complex products usually contain amounts too small to interfere, but 'hair and nail' formulas often carry 5-10 mg, hundreds of times the daily requirement.

How does exercise affect TSH?

Regular moderate aerobic exercise moderate evidence

How much: 150 minutes a week at moderate intensity, in line with general health guidance.
What to expect: Exercise does not meaningfully change TSH in people with a healthy thyroid, and it does not treat thyroid disease. Its value here is indirect: it counteracts the weight gain, fatigue and raised LDL-C that accompany an underactive thyroid, and it improves the insulin resistance that nudges TSH upward in obesity.

Very high training loads with low energy intake moderate evidence

How much: A pattern to recognise rather than a prescription: endurance athletes and dieters combining heavy training with restricted eating.
What to expect: Sustained energy deficiency lowers T3 and can lower TSH as the body conserves energy — the same adaptive response seen in starvation. The values normalise when energy intake matches training load, and this is not thyroid disease.

Which lifestyle factors affect TSH?

Smoking strong evidence

Smoking lowers TSH slightly in the general population, roughly doubles the risk of Graves' disease, and is the strongest modifiable risk factor for thyroid eye disease. Stopping is the single lifestyle change with the clearest evidence for thyroid health.

Sleep regularity moderate evidence

TSH is released mostly at night, so night shifts, jet lag and short sleep flatten its rhythm and can shift a morning value. Consistent sleep timing makes serial TSH results comparable with each other.

Body weight moderate evidence

Obesity raises TSH modestly without the thyroid being at fault, and the value tends to fall with weight loss. A mildly raised TSH in someone with a high BMI and negative thyroid antibodies is more often a consequence of weight than a cause of it.

How should you prepare for a TSH test?

• Morning samples, taken at a consistent time, give the most comparable results because of the daily rhythm; fasting is not required.
• Biotin supplements taken within the previous two to three days can corrupt the result. Laboratories generally ask for them to be paused before the draw and for the clinician to be told.
• Thyroid function measured during or within about six weeks after a significant illness, surgery or hospital stay reflects the illness, not the thyroid.
• The 2012 ATA/AACE guideline recommends re-checking TSH four to eight weeks after any change in thyroid hormone dose, because the feedback loop takes that long to settle. Testing sooner measures the transition, not the new steady state.
• In pregnancy, the result belongs against trimester-specific ranges; pregnancy is worth stating on the request form.
• A first abnormal TSH is confirmed by a repeat, usually with free T4 and antibodies added, before it is treated as a diagnosis.

References

1. Garber JR et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid 2012 — https://doi.org/10.1089/thy.2012.0205
2. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008 — https://doi.org/10.1210/er.2006-0043
3. Ross DS et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016 — https://doi.org/10.1089/thy.2016.0229
4. Li D et al. Association of biotin ingestion with performance of hormone and nonhormone assays in healthy adults. JAMA 2017 — https://doi.org/10.1001/jama.2017.13705
5. Alexander EK et al. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017 — https://doi.org/10.1089/thy.2016.0457