Laboratory medicine : Endocrinology and thyroid disorders
Thyroid Workup
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A thyroid panel is a set of blood tests used to assess the function of the thyroid gland, an endocrine organ located at the base of the neck that regulates the metabolism of the entire body by secreting thyroid hormones. The panel is based mainly on measuring thyroid-stimulating hormone (TSH), a pituitary hormone that is the central regulatory signal for thyroid production, supplemented, depending on the context, by measuring free thyroxine (free T4) and free triiodothyronine (free T3). Additional markers, including anti-thyroid antibodies and thyroglobulin, are added based on specific clinical indications. The thyroid panel is among the most frequently ordered laboratory tests in primary care in Quebec. It is indicated in cases of unexplained fatigue, unexplained weight gain or loss, heart rhythm disorders, menstrual cycle abnormalities or treatment-resistant depression, or as part of the follow-up of a known thyroid disease and its treatments. Rigorous interpretation of the thyroid panel requires taking into account all of the results at the same time, along with the clinical context and potential interfering factors.
Thyroid storm and myxedema coma: endocrine emergencies
Thyrotoxic crisis (acute decompensation of hyperthyroidism) and myxedematous coma (severe decompensation of profound hypothyroidism) are two potentially fatal endocrine emergencies. The former presents with high fever, extreme tachycardia, agitation and confusion. The second presents with hypothermia, bradycardia, altered consciousness and hypoventilation. Both conditions require immediate intensive care hospitalization.
Call 911 immediately.
Thyroid workup components
Thyroid workup is modular: TSH is the universal first-line screening test, supplemented by other assays depending on initial results and clinical context.
| Marker | Abbreviation | Usual values | Role and origin |
|---|---|---|---|
| Thyroid-stimulating hormone | TSH | 0.4 to 4.0 mIU/L | Pituitary hormone that regulates the thyroid; first-line screening test; inversely related to thyroid function: rises in hypothyroidism, falls in hyperthyroidism |
| Free thyroxine | Free T4 (FT4) | 10 to 25 pmol/L | Main hormone secreted by the thyroid; the free fraction is the biologically active one; a more reliable measurement than total T4, independent of carrier proteins |
| Free triiodothyronine | Free T3 (FT3) | 3.5 to 6.5 pmol/L | Most biologically active thyroid hormone; produced partly by the thyroid and largely through peripheral conversion of T4; useful in T3-predominant hyperthyroidism |
| Anti-thyroperoxidase antibodies | Anti-TPO | Less than 34 IU/mL (varies by laboratory) | Marker of thyroid autoimmunity; positive in Hashimoto's thyroiditis and Graves' disease; present in 10 to 15% of the general population without thyroid dysfunction |
| Anti-thyroglobulin antibodies | Anti-TG | Less than 115 IU/mL (varies by laboratory) | Complementary marker of thyroid autoimmunity; useful when anti-TPO antibodies are negative and clinical suspicion persists; interfere with thyroglobulin measurement |
| TSH receptor antibodies | TRAK (TRAb) | Less than 1.75 IU/L (varies by laboratory) | Specific marker of Graves' disease; stimulate the TSH receptor autonomously, causing autoimmune hyperthyroidism |
| Thyroglobulin | Tg | 1.6 to 59.9 ng/mL (varies with thyroid status) | Storage protein for thyroid hormones; used as a tumour marker in the follow-up of differentiated thyroid cancer after total thyroidectomy and radioactive iodine treatment |
| Calcitonin | CT | Less than 5 to 10 pg/mL depending on sex | Secreted by parafollicular C cells; tumour marker for medullary thyroid carcinoma; measured in cases of a suspicious thyroid nodule or a family history of MEN2 |
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TSH is the first-line thyroid screening test recommended by all endocrinology professional societies. Because of the log-linear relationship between TSH and free thyroid hormones, small changes in T4 or T3 levels lead to large changes in TSH, making it a much more sensitive indicator of early thyroid dysfunction than the peripheral hormones themselves.
Indications for thyroid assessment
| Clinical context | Recommended first-line markers |
|---|---|
| Screening for thyroid dysfunction (suggestive symptoms) | TSH alone as the first-line test; free T4 if TSH is abnormal |
| Unexplained chronic fatigue, treatment-resistant depression | TSH, free T4, anti-TPO |
| Unexplained weight gain, cold intolerance, constipation, bradycardia | TSH, T4 libre (suspicion d'hypothyroïdie) |
| Weight loss, palpitations, tremors, heat intolerance, nervousness | TSH, T4 libre, T3 libre, TRAK (suspicion d'hyperthyroïdie) |
| Goitre or thyroid nodule | TSH, free T4, anti-TPO, calcitonin according to context |
| Menstrual disorders, infertility, recurrent miscarriage | TSH, free T4, anti-TPO |
| Pregnancy (screening or follow-up) | TSH, free T4, anti-TPO; trimester-specific reference values |
| Monitoring of treated hypothyroidism (levothyroxine) | TSH alone on a stable regimen; free T4 after a recent adjustment |
| Monitoring of treated hyperthyroidism (antithyroid drugs, radioactive iodine) | TSH, free T4, free T3 |
| Post-thyroidectomy follow-up for differentiated cancer | TSH, thyroglobulin, anti-TG (to detect interference with Tg) |
| Starting a treatment with potential thyroid toxicity (amiodarone, lithium, interferon, immunotherapy) | TSH, free T4 at baseline, then regular monitoring |
| New-onset atrial fibrillation or unexplained tachycardia | TSH, free T4, free T3 |
Interpretation of thyroid biology profiles
Interpretation of the thyroid work-up is based on the combination of markers measured and their correlation with the clinical picture. TSH is at the heart of any interpretation.
| TSH / T4L profile | Interpretation | Common causes |
|---|---|---|
| TSH normal / T4L normal | Fonction thyroïdienne euthyroïdienne | No biochemical thyroid dysfunction |
| High TSH / normal free T4 | Hypothyroïdie fruste (subclinique) | Early Hashimoto's thyroiditis, mild iodine deficiency, recovery phase after thyroiditis, medications (lithium, amiodarone) |
| High TSH / low free T4 | Hypothyroïdie franche (clinique) | Advanced Hashimoto's thyroiditis, post-thyroidectomy or post-radioactive iodine hypothyroidism, severe iodine deficiency, medications with thyroid toxicity |
| TSH low / T4L normal | Hyperthyroïdie fruste (subclinique) | Early Graves' disease, toxic adenoma, early toxic multinodular goitre, excess levothyroxine, physiologically low TSH in early pregnancy |
| Low TSH / high free T4 | Hyperthyroïdie franche (clinique) | Graves' disease, toxic adenoma, toxic multinodular goitre, subacute thyroiditis in the hyperthyroid phase, iodine overload (amiodarone, contrast agent) |
| TSH low / T4L low | Central hypothyroidism (pituitary or hypothalamic) | Pituitary insufficiency, Sheehan's syndrome, pituitary tumor, craniopharyngioma, autoimmune hypophysitis |
| Normal or high TSH / high free T3 | T3-predominant hyperthyroidism | Early-phase Graves' disease, T3-secreting toxic adenoma, resistance to thyroid hormones |
| TSH normal / T4L low (T3 low syndrome) | Euthyroid sick syndrome (non-thyroidal illness) | Severe systemic illness, malnutrition, major surgery, sepsis: reduced peripheral conversion of T4 to T3; does not require thyroid treatment |
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During pregnancy, normal TSH values differ from those of the general population and vary by trimester. In the first trimester, TSH is physiologically lowered because of the thyroid-stimulating effect of beta-hCG, and can drop as low as 0.1 mIU/L without any pathological significance. Interpretation of the thyroid panel in pregnant women must always use pregnancy-specific reference intervals.
Factors that may affect results
Numerous factors external to thyroid pathology can influence workup values, leading to falsely abnormal or falsely normal results. Their identification is essential before any therapeutic decision is taken.
| Interfering factor | Balance sheet impact |
|---|---|
| Amiodarone | Raises free T4 and lowers free T3 by inhibiting deiodinase; can cause true hypothyroidism or hyperthyroidism depending on the context |
| Lithium | Inhibits thyroid secretion and can induce overt hypothyroidism, particularly in the presence of pre-existing anti-TPO antibodies |
| High-dose glucocorticoids | Transiently lower TSH and inhibit peripheral conversion of T4 to T3; can mimic central hypothyroidism |
| High-dose biotin (vitamin B7) | Interferes with immunoassays that use biotin-streptavidin technology, which can mimic hyperthyroidism (falsely low TSH, falsely high T4 and T3); stop supplementation 48 to 72 hours before the blood collection |
| Pregnancy | Physiological change in reference intervals by trimester; increase in carrier proteins (TBG) under the effect of estrogens, physiological lowering of TSH in the first trimester |
| Oral contraceptives and estrogens | Increase TBG, raising total T4 without changing free T4; warrant measuring free T4 rather than total T4 |
| Severe systemic illness (euthyroid sick syndrome) | Lowered free T3, sometimes free T4, with normal or slightly low TSH; does not reflect primary thyroid disease |
| Heterophile antibodies | Rare immunological interference that can produce discordant results (high TSH with high T4, or vice versa); to be suspected whenever clinical and laboratory findings are discordant |
| Levothyroxine (Synthroid) | Ideally, the blood sample is taken in the morning before the tablet is taken, for a measurement that reflects the therapeutic steady state; a recent dose can transiently raise free T4 |
Recommended frequency of check-ups depending on the context
- First-line screening in symptomatic adults: TSH alone; check at 6 weeks if slightly abnormal before treating.
- Initiation of levothyroxine therapy: TSH checked 6-8 weeks after each dosage adjustment, then annually during stable therapy
- Treatment with synthetic antithyroid drugs (Tapazole, PTU): TSH and free T4 every 4 to 6 weeks at the start of treatment, then every 3 months in the stabilization phase
- Pregnancy with known hypothyroidism: TSH and free T4 every trimester, or every 4 weeks in the first trimester in the event of recent dosage adjustment
- Post-thyroidectomy follow-up for differentiated cancer: TSH, thyroglobulin and anti-TG according to oncology protocol (frequency varies from 3 to 12 months depending on risk level)
- Amiodarone treatment: thyroid check-up before initiation, then every 6 months for the duration of treatment and up to 12 months after discontinuation.
- Systematic screening of at-risk individuals without symptoms (family history, known positive anti-TPO, Down syndrome, Turner syndrome): Annual TSH
Conditions requiring a full thyroid workup with antibodies
- Confirmed hypothyroidism: anti-TPO assay to identify autoimmune origin (Hashimoto's thyroiditis) and stratify risk of progression to frank hypothyroidism
- Confirmed hyperthyroidism: TRAK assay to distinguish Graves' disease from other causes (toxic adenoma, thyroiditis) and guide the choice of treatment.
- Pregnancy with abnormal TSH or personal or family history of autoimmune thyroid disease
- Recurrent miscarriages or unexplained infertility: anti-TPO positives are associated with an increased risk of obstetrical complications even in euthyroidism
- Diffuse goiter or thyroid nodule in a clinical setting suggestive of autoimmunity
- Initiation of immunotherapy with immune checkpoint inhibitors (pembrolizumab, nivolumab): risk of immune thyroiditis and autoimmune thyroid dysfunction
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Isolated positive anti-TPO antibodies with a normal TSH do not, in the absence of symptoms, justify starting treatment. They do, however, indicate the need for annual TSH monitoring, as the risk of progression to clinical hypothyroidism is about 2 to 4% per year in this situation.
Particularities of thyroid assessment in specific populations
| Population | Specific considerations for interpretation and follow-up |
|---|---|
| Newborn | Systematic newborn screening for congenital hypothyroidism in Quebec through TSH measurement on filter paper on days 3 to 5 of life; TSH values are physiologically very high in the first hours of life (physiological peak) |
| Children and teenagers | Reference values differ from those of adults depending on age; Hashimoto's thyroiditis is the main cause of acquired hypothyroidism in school-age children |
| Pregnant woman | Trimester-specific reference intervals; untreated hypothyroidism is associated with risks of miscarriage, preterm birth and impaired fetal neurological development; screening recommended from the first trimester when risk factors are present |
| Older adult (over 70) | The upper limit of normal TSH rises physiologically with age (some experts tolerate a TSH of up to 6 to 7 mIU/L without treatment in asymptomatic octogenarians); symptoms of hypothyroidism are often atypical or attributed to normal aging |
| Patient on levothyroxine | Target TSH varies by indication: 0.5 to 2.5 mIU/L in uncomplicated hypothyroidism; 0.1 to 0.5 mIU/L after thyroidectomy for intermediate- or high-risk cancer; lower TSH values tolerated in pregnancy |
| Patients on cancer immunotherapy | Mandatory thyroid monitoring before each cycle; immune-related thyroiditis may first present as a transient hyperthyroid phase followed by permanent hypothyroidism |
Consult at Clinique Omicron
A complete thyroid panel can be prescribed and interpreted by the physicians and nurse practitioners (IPS) at Clinique Omicron as part of a preventive health assessment, an investigation of symptoms suggestive of thyroid dysfunction, or the follow-up of a known thyroid disease and its treatment. Results are analyzed taking into account the overall clinical context, current medications and potential interfering factors. When abnormalities require further investigation, such as a thyroid ultrasound or an endocrinology consultation, a referral is provided from Clinique Omicron's service points in Quebec. Book an appointment online or by phone at one of our service points in Quebec.
The content of this page is provided for informational purposes only and is not intended to replace the advice of a qualified healthcare professional. Consult a physician for any symptoms, questions or decisions you may have regarding your health.
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