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Thyroid Function (T3, T4, Selenium)

Urine Thyroid Test

Importance of Thyroid Assessment

By some estimates, as many as 2 million Canadians could have undiagnosed thyroid disease. Thyroid disease refers to both hypo and hyperthyroidism, but hypothyroidism is by far the most common. Even mild hypothyroidism can have significant health consequences, so early detection is important.

Urinary Thyroid Assessment

The Urinary Thyroid Assessment measures unconjugated free triiodothyronine (T3), unconjugated free thyroxine (T4) and selenium in a 24 hour urine collection. There are several reasons why a urinary thyroid assessment may be beneficial:

  • A specimen collected over a 24 hour period may better reflect the average behaviour of the thyroid gland, since thyroid gland activity varies through the day.
  • Urinary thyroid hormone levels correlate well with classical symptoms of hypothyroidism. Baisier found that urinary T3 (in a 24 hour specimen) was better correlated to hypothyroid symptoms than serum TSH and Total T4.1 Urinary T3 also correlated well to dessicated thyroid dose.
  • Quantities of T3 and T4 in a 24 hour urine are significantly higher than those found in a spot serum sample, so levels can be more reliably measured.
  • Selenium is a cofactor for 5’-deiodinase, the enzyme required to convert T4 to T3. A low 24 hour urinary selenium level likely correlates with overall selenium deficiency and decreased tissue availability of T3 due to decreased conversion of T4 to T3.

    Note: The Urinary Thyroid Assessment does not replace serum testing in the diagnosis of thyroid illness; it is meant to assist clinicians in the evaluation of patients whose clinical presentation is not readily explainable by measurement of serum thyroid parameters alone.

Conditions and Symptoms Associated with Hypothyroidism

Cardiovascular Disease: Some studies suggest that total cholesterol rises incrementally with rises in TSH,2 while others refute that finding3. C-reactive protein and homocysteine levels are increased in hypothyroidism. Blood pressure is also often elevated.6 These laboratory changes are markers of increased cardiovascular disease risk.

Weight Gain/Fatigue: Hypothyroidism results in decreased metabolism, which in turn may lead to weight gain. Also, slow speech, slowing of physical functions, and dull facial expression can occur.

Skin, Hair Musculoskeletal: Dry skin, roughness and thickening of skin on hands, forearms or elbows, hair loss, thinning eye-brow hair, and/or a puffy, swollen face (particularly under the eyes) Muscle cramps in calves, toes, fingers, diaphragm, thighs and upper arms. Rheumatoid pain, joint, tendon and muscle swelling and stiffness.

Depression: General slowing of mental functions. Risk of depression is 4 times greater for elderly patients suffering from sub-clinical hypothyroidism than from overt hypothyroidism.

Headache: Migraine and tension headaches can be associated with hypothyroidism.

Constipation: A hard bowel movement less than once every 2 days may be an indicator of hypothyroidism.

Cold intolerance: Hands and feet are cold to touch, and patient frequently feels chilled.

Thyroid Hormone Treatments


Critical Considerations for
Low Levels

550 -825 pmol/24hrsh

Nutritional supplements
to consider

  • Iodine, tyrosine required to make T3 in thyroid gland
  • Selenium needed to convert T4 to T3 in kidney, liver and spleen
  • 7-keto DHEA has been shown to increase levels of free T3 in obese patients.8
  • Guggul (Indian frankincense) increases production of T3.9,10
  • Ashwaganda may increase T3 levels.
  • Adaptogens may normalize cortisol levels and prevent cortisol induced suppression of TSH.
  • Supplement with liothyronine (T3) sustained release compounded T3, or natural thyroid extracts.

Lifestyle considerations
Reduce stress as stress and high cortisol levels can suppress TSH release thereby reducing T3 production. Cortisol also stimulates conversion of T4 to inactive reverse T3.

Thyroxine (T4)
1400 - 2100 pmol/24 hrs

Nutritional supplements
to consider

  • Iodine, tyrosine required to make T4 in thyroid gland
  • Ashwaganda may increase
    T4 production.
  • Fucus (bladderwrack) is high in iodine. Contamination with cadmium and arsenic is possible.
  • Supplement with levothyroxine (T4), compounded combined T4 and T3, or natural thyroid extracts.

Lifestyle considerations
Reduce stress as high cortisol and high levels of stress can suppress TSH release and thereby reduce T4 production.
Dietary considerations
Reduce soy intake: soy can antagonize release of T4 from storage granules in thyroid.

Improving Conversion of T4 to T3

Nutritional supplements
to consider

  • Selenium is the cofactor required for 5’-deiodinase to convert T4 to T3. Supplementing with selenium may improve conversion of T4 to T3 and increase the T3/T4 ratio.
  • Zinc, vitamin C and vitamin E protect against cadmium toxicity.
  • Animal models suggest that free radicals may inhibit deiodination. Antioxidants may help improve T4 to T3 conversion that has been impaired by free radicals.
  • Adaptogens may normalize cortisol levels and prevent impairment of T4 to T3 conversion.
  • Detoxification program helps eliminate toxins that may impair conversion of T4 to T3.

Lifestyle considerations

  • Limit or eliminate exposure to toxic metals (e.g. cadmium, arsenic, mercury), environmental pollutants, and free radicals as these impair conversion of T4 to T3. Cadmium may also suppresses TSH production in the presence of low T3 and T4.
  • Reduce alcohol intake as alcohol increases cadmium uptake.

Other considerations

  • Use of estrogens, beta-blockers, cotrimoxazole, lithium, amiodarone, phenylbutazone, and certain psychotropic drugs may impair conversion of T4 to T3.
  • Conversion is impaired by aging, burns, starvation, chronic alcohol intake, diabetes, liver disease, kidney disease, systemic disease, stress, and surgery.

Selenium 22—240 µg/24 hrs

Nutritional supplements
to consider

  • Selenium supplementation may be necessary if selenium levels in 24 hour urine are low.


Symptoms of hyperthyroidism can include weight loss, increased appetite, nervousness, restlessness, heat intolerance, increased sweating, fatigue, frequent bowel movements, menstrual irregularities in women, and goiter. Approximately 75% of cases of hyperthyroidism are due to Grave’s disease. Hyperthyroidism is usually treated with anti-thyroid medications, radioactive iodine (which destroys the thyroid and stops the excess production of hormones), or surgery to remove the thyroid.

Elevated T3 or T4 in urine

  • High levels of T3 or T4 in urine may indicate hyperthyroidism where there is no supplementation with T3 or T4. High levels of T3 or T4 in urine in patients who are taking thyroid hormone likely indicate excessive supplementation. In either case, follow-up serum testing should be ordered.
  • Presence of proteins in urine may falsely elevate levels of T3 or T4 by increasing their excretion. Therefore, testing for proteinuria is worth consideration when confronted with an above range result.

Elevated selenium in urine

  • An above range result for selenium may indicate selenium overdose or toxicity. Follow-up serum or hair analysis for selenium levels should be considered.

What about Serum TSH?

Serum TSH is an excellent marker of thyroid function but has the following limitation

  • The normal ranges for serum TSH are quite broad. Most laboratories consider 0.35 mU/L to 5.0 mU/L to be normal, and some physicians will not treat a TSH less than 10mU/L. However, a British study showed that TSH >2.0 mU/L is associated with increased risk of developing overt hypothyroidism later in life. Thus, many instances of hypothyroidism could be missed because the range is so broad, and because the importance of having low TSH is overlooked.
  • Normal TSH may not represent optimal T3 levels in all tissues, particularly when supplementing with T4.
  • Saravanan found that patients whose TSH was lowered by T4 had significantly impaired psychological wellbeing compared to controls.20 And, Alevizaki showed that hypothyroid patients had low SHBG and low T3 (additional laboratory indicators of hypothyroidism) even after their serum TSH was normalized by T4 replacement.
  • High cortisol levels arising from physical or psychological stress or synthetic glucocorticoids may normalize TSH levels, thereby masking hypothyroidism. (TSH appears normal when it would be elevated in the absence of high cortisol).
  • Animal studies suggest that cadmium may lower TSH levels and mask hypothyroidism (TSH appears normal when it would be elevated in the absence of cadmium).

What about Serum Free T3 and T4?

Free T3 and T4 in serum should be good indicators of thyroid function since low levels trigger the pituitary to produce more TSH. However, the following factors may limit their usefulness:

  • levels of free T3 and T4 in serum are extremely low, and reliability of free T3 and T4 measurements at low levels is questionable.
  • free T3 is the active hormone, but levels change in response to fasting, presence of acute or chronic nonthyroid disease, and with age. This makes free T3 measurements too variable to be clinically useful.

Additional Laboratory Tests to Consider

  • Fasting insulin, fasting glucose, 13C breath test: high insulin levels and/or diabetes can impair TSH production.
  • Adrenal Function Panel: high levels of cortisol can impair TSH production.
  • Heavy metal toxicity screen: cadmium, mercury and arsenic can impair conversion of T4 to T3.
  • Cardiovascular Risk Panel: cholesterol, CRP, or homocysteine. Patients with subclinical or overt hypothyroidism are at greater risk for heart disease.

Test Limitations

Although unconjugated T3 and T4 levels in urine approximate serum free (non-protein bound) levels, urinary T3 and T4 concentrations can be affected by other disease states.

  • proteinuria can falsely elevate urinary T3 and T4 by increasing the overall excretion of hormone.
  • impaired renal function can reduce excretion of T3, T4 and selenium resulting in falsely low values.


  1. Baisier W. Hertoghe J. Eeckhaut W. Thyroid insufficiency. Is TSH the only diagnostic tool? J Nutr Environ ed. 2000;10:105-113.
  2. Canaris GL et al. The Colorado thyroid disease prevalence study. Arch Int Medicine. 2000;Feb 8;160(4):526-34
  3. Takashima N et al. Characterization of subclinical thyroid dysfunction from cardiovascular and metabolic viewpoints. Circ J. 2007 Feb;71(2):191-5
  4. Morris MS et al. Hyperhomocysteinemia and hypercholesterolemia associated with hypothyroidism in the third US National Health and Nutrition Examination Survey. Atherosclerosis. 2001;155:195-200
  5. Tuzcu A et al. Subclinical hypothyroidism may be associated with elevated high-sensitive c-reactive protein low grade inflammation) and fasting hyperinsulinemia. Endocr J. 2005;Feb;52(1):89-94.
  6. Asvold BO et al. Association between blood pressure and serum TSH concentration within the reference range: a population-based study. J Clin Endocrinol Metab. 2007 Jan 2; [Epub ahead of print]
  7. Chueire VB et al. Sublicinical hypothyroidism increase the risk for depression in the elderly. Arch Gerentol Geriatr. 2007 Jan-Feb;44(1):21-8
  8. Pharmacist’s Letter Natural Medicine Comprehensive Database; online access Jan 3, 2007 7-keto-DHEA
  9. Panda S, Kar A. Gugulu (Commiphora mukul) induces triiodothyronine production: possible involvement of lipid peroxidation. Life Sci 1999;65:PL137-41.
  10. Natural Medicine Comprehensive Database; online access Jan 2, 2007 Guggul
  11. Pharmacist’s Letter Natural Medicine Comprehensive Database; online access Jan 3, 2007 Ashwaganda
  12. Pharmacist’s Letter Natural Medicine Comprehensive Database; online access Jan 30, 2007 Fucus
  13. Yu HS Chan ST. Zinc amelioration of cadmium toxicity on preimplantation mouse zygotes in vitro. Teratology. 1988;37(1):13-9
  14. Gupta P Kar A. Role of ascorbic acid in cadmium-induced thyroid dysfunction and lipid peroxidation. J. Apppl Toxicol. 1998;18(5):317-20
  15. Gupta P Kar A. Cadmium induced thyroid dysfunction in chicken: hepatic type I iodothyronin 5’monodeiodinase activity and role of lipid peroxidation. Comp Biochem Physiol C Pharmacol Toxicol Endocriol. 1999;123(1):39-44
  16. Kelly G. Peripheral Metabolism of Thyroid Hormones: A Review. Alt Med Rev. 2000;5(4):306-33
  17. Pavia Junior MA et al. Evidence suggesting that cadmium induces a non-thyroidal illness syndrome in the rat. J Endocrinol. 1997;154(1):113-7
  18. Sharma G et al. Effect of ethanol on cadmium uptake and metabolism of zinc and copper in rats exposed to cadmium. J Nutr. 1991; 121(1):87-91.
  19. Tunbridge WM, Evered DC, Hall R et al. The spectrum of thyroid disease in the community. The Whickham survey. Clin Endocrinol1977;7:41–93
  20. Saravanan P, Chau WF, Roberts N et al. Psychological well-being in patients on 'adequate' doses of l thyroxine: results of a large, controlled community-based questionnaire study. Clin Endocrinol (Oxf). 2002 Nov;57(5):577-85.
  21. Alevizaki M, Mantzou E, Cimponeriu ATet al. TSH may not be a good marker for adequate thyroid hormone replacement therapy. Wien Klin Wochenschr. 2005 Sep;117(18):636-40.


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