Total Thyroxine (T4)

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Total Thyroxine (T4) - Comprehensive Medical Test Information Guide

Section 1: Why is it done?
- Test Description: Measures the total concentration of thyroxine (T4) hormone in the blood, including both protein-bound and free T4. This test evaluates thyroid hormone production and helps assess thyroid gland function.
- Primary Indications: Diagnosing hypothyroidism (underactive thyroid) and hyperthyroidism (overactive thyroid); evaluating symptoms such as fatigue, weight changes, temperature sensitivity, and mood disturbances; monitoring thyroid replacement therapy effectiveness; screening for thyroid dysfunction in newborns; investigating goiter or thyroid nodules
- Typical Timing/Circumstances: Initial thyroid disorder evaluation; routine screening in patients with metabolic symptoms; annual monitoring of patients on thyroid medication; during pregnancy to assess maternal thyroid status; evaluation of infertility or menstrual irregularities; assessment of cardiac arrhythmias; newborn screening programs; before and after starting medications affecting thyroid function
Section 2: Normal Range
- Reference Ranges: Adults: 4.5 to 11.2 mcg/dL (58-145 nmol/L); Pregnant women: 5.5 to 16.0 mcg/dL (71-206 nmol/L); Newborns: 5.0 to 21.0 mcg/dL (64-271 nmol/L). Note: Reference ranges may vary between laboratories and testing methods.
- Units of Measurement: Micrograms per deciliter (mcg/dL) or nanomoles per liter (nmol/L)
- Normal Results Interpretation: T4 levels within the reference range indicate adequate thyroid hormone production and normal thyroid function; suggests no thyroid disorder is present; thyroid replacement therapy (if used) is appropriately dosed
- Low Results (Below Normal Range): May indicate hypothyroidism, undertreatment with thyroid replacement hormone, secondary hypothyroidism, or excessive antithyroid medication
- High Results (Above Normal Range): May indicate hyperthyroidism, Graves' disease, thyroiditis, overtreatment with thyroid replacement hormone, or thyroid hormone overdose
Section 3: Interpretation
- Clinical Significance of Results: Total T4 is not specific for thyroid disease; must be interpreted with TSH (Thyroid Stimulating Hormone) and clinical symptoms. Both high and normal total T4 can occur with abnormal protein-binding; free T4 or TSH may be more diagnostic in certain conditions
- Low T4 with High TSH: Indicates primary hypothyroidism (thyroid gland failure); common in Hashimoto's thyroiditis, iodine deficiency, radioactive iodine treatment, or thyroidectomy; requires thyroid hormone replacement therapy
- Low T4 with Low TSH: Suggests secondary or central hypothyroidism (pituitary or hypothalamic dysfunction); may indicate pituitary adenoma, head trauma, or hypopituitarism; requires investigation of pituitary function
- High T4 with Low TSH: Indicates hyperthyroidism; common in Graves' disease, toxic multinodular goiter, thyroiditis, or over-replacement with thyroid hormone; may cause tachycardia, tremor, and weight loss
- High T4 with Normal/High TSH: Suggests increased thyroxine-binding proteins (pregnancy, estrogen use, liver disease) or rarely TSH-secreting pituitary adenoma; free T4 testing helps clarify if hyperthyroidism is truly present
- Factors Affecting T4 Results: Medications (estrogen, lithium, amiodarone, beta-blockers, corticosteroids); pregnancy and oral contraceptives; liver disease; kidney disease; malnutrition; acute illness; acute psychiatric illness; changes in thyroxine-binding globulin levels; recent contrast dye or radioactive iodine administration
Section 4: Associated Organs
- Primary Organs Involved: Thyroid gland (produces T4); pituitary gland (produces TSH which stimulates thyroid); hypothalamus (produces TRH which stimulates pituitary)
- Diseases Diagnosed/Monitored: Hashimoto's thyroiditis (autoimmune hypothyroidism); Graves' disease (autoimmune hyperthyroidism); thyroid cancer; thyroid nodules; goiter; thyroiditis (subacute, postpartum, silent); iodine deficiency disorder; Plummer's disease (toxic multinodular goiter); sick euthyroid syndrome; secondary/central hypothyroidism (pituitary or hypothalamic disease)
- Associated Medical Conditions: Hypothyroidism symptoms: fatigue, weight gain, cold intolerance, constipation, dry skin, depression, bradycardia, elevated cholesterol; Hyperthyroidism symptoms: weight loss, heat intolerance, nervousness, palpitations, tremor, diarrhea, exophthalmos (in Graves' disease)
- Potential Complications of Abnormal Results: Hypothyroidism complications: myxedema, myxedema coma, infertility, increased cardiovascular disease risk, cognitive impairment, congenital hypothyroidism in infants (cretinism); Hyperthyroidism complications: atrial fibrillation and stroke, thyroid storm, heart failure, bone loss (osteoporosis), ophthalmopathy, thyrotoxic crisis
- Effects on Other Organ Systems: Thyroid hormones affect metabolism in all organs; cardiovascular system (heart rate and blood pressure); nervous system (mood, cognition); gastrointestinal system (motility); reproductive system (fertility); metabolic rate; thermoregulation; bone metabolism
Section 5: Follow-up Tests
- Recommended Follow-up Tests: TSH (Thyroid Stimulating Hormone) - primary confirmatory test; Free T4 (FT4) - distinguishes protein-binding from true thyroid dysfunction; Free T3 and Total T3 - assess if T3 thyrotoxicosis is present; Thyroid peroxidase antibodies (TPO-Ab) - diagnose autoimmune thyroiditis; Thyroglobulin antibodies - detect autoimmune thyroid disease; TSI (Thyroid Stimulating Immunoglobulin) - confirm Graves' disease
- Imaging Studies: Thyroid ultrasound - evaluate thyroid structure, detect nodules, assess vascularity; Thyroid radioiodine scan - assess thyroid function and activity; CT or MRI - evaluate pituitary if central hypothyroidism suspected
- Additional Tests Based on Clinical Context: Lipid panel - assess cardiovascular risk in hypothyroidism; TSH receptor antibodies - differentiate Graves' from other causes; Thyroglobulin level - monitor thyroid cancer; Liver function tests - if on antithyroid medications; Complete blood count - if taking PTU or methimazole; Pregnancy test - if applicable before thyroid imaging
- Monitoring Frequency: Initial hypothyroidism diagnosis: repeat TSH and T4 at 6-8 weeks after starting levothyroxine; Stable patients on thyroid replacement: annual TSH monitoring; During pregnancy: TSH every 6-8 weeks; Hyperthyroidism treatment: TSH and free T4 every 4-6 weeks initially; Post-thyroid cancer: variable intervals depending on cancer type and risk stratification; Newborn screening: follow-up if initial abnormal results
Section 6: Fasting Required?
- Fasting Requirement: NO - Fasting is not required for total T4 testing. The test can be performed at any time of day without regard to food intake.
- Optimal Timing: Morning collection preferred for consistency; if retesting, try to collect at same time as previous test for better comparison; best results obtained 4-6 hours after levothyroxine dose (if patient taking thyroid medication) to avoid peak absorption affecting results
- Medications to Avoid/Consider: If on levothyroxine, take on empty stomach 30-60 minutes before breakfast; wait 4-6 hours after dose before blood draw if possible; inform lab/provider of all medications: estrogen/oral contraceptives, lithium, amiodarone, beta-blockers, corticosteroids, antithyroid medications, iodine supplements; biotin supplements can interfere - discontinue 48 hours before test if possible; calcium, iron supplements, and proton pump inhibitors taken 4+ hours apart from thyroid medication
- Patient Preparation Requirements: Normal hydration acceptable; no special dietary restrictions; wear comfortable clothing for easy blood draw access; inform phlebotomist of recent contrast dye or radioactive iodine administration; report any acute illness, stress, or recent medications to provider; for baseline testing, note that medications affecting thyroid should be stable for at least 6 weeks prior to testing when possible; pregnancy status should be communicated as reference ranges differ

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