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Thyroid Studies

For an overview of my approach to thyroid hormone replacement (and why it may differ from that of your doctor), please see the Thyroid Hormone page. Here is a sampling of the many research studies that explain why it is often not enough to simply ascertain that thyroid hormone levels are “within the normal range”, and why optimizing just T4 (levothyroxine, commonly as Synthroid) without T3 is also inadequate.


Archives of Internal Medicine, 2008

17,000 patients were followed for an average of 8.3 years to see if there was an association between fatal heart disease and thyroid levels that were somewhat low but still considered “normal” by traditional standards:CONCLUSIONS: Thyrotropin levels, even those within the reference range, were linearly associated with Coronary Heart Disease mortality in women. The results indicate that relatively low but clinically normal thyroid function may increase the risk of fatal Coronary Heart Disease.

Arch Intern Med. 2008 Apr 28;168(8):855-60.

Circulation--The Journal of the American Heart Association, 2003

The aim of this prospective study was to assess the role of thyroid hormones in the prognosis of patients with heart disease?. Conclusions: Low-T3 syndrome is a strong predictor of death in cardiac patients and might be directly implicated in the poor prognosis of cardiac patients.

Iervasi G et al. Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation 2003 Feb 11;107(5):708-13.

Atherosclerosis 2009

We have demonstrated that carotid intima-media thickness is independently associated with thyroid function within the normal reference range, which suggests an increased cardiovascular risk in subjects with low-normal thyroid function.

Thyroid function is associated with carotid intima-media thickness in euthyroid subjects. Atherosclerosis 2009; 204:77-81.

Annals of Internal Medicine, 2000

1149 women participated in a large study of chronic disease in older persons in Rotterdam, the Netherlands. All of the women in the study had been through menopause. Between 1990 and 1993, the researchers evaluated women in the study to see if they had blockages in their aorta (a large blood vessel leading from the heart to the body) or any evidence of a past heart attack. At the same time, the researchers collected blood tests of thyroid function.

RESULTS: Women with subclinical hypothyroidism (meaning T4 levels within “normal” range, but elevated TSH) were almost twice as likely as women without this condition to have blockages in the aorta. They were also twice as likely to have had heart attacks.

Subclinical Hypothyroidism Is an Independent Risk Factor for Atherosclerosis and Myocardial Infarction in Elderly Women: The Rotterdam Study. Ann Intern Med February 15, 2000 132:270-278

Maturitas, 2009

We found that TSH levels were associated with Metabolic syndrome in euthyroid postmenopausal women, independently of well known Metabolic Syndrome risk factors. LDL cholesterol and triglycerides were independently associated with TSH levels.

Subjects with high-normal TSH levels had a 1.95-fold increased risk of metabolic syndrome as compared to those with low-normal TSH levels.

Thyroid stimulating hormone is associated with metabolic syndrome in euthyroid postmenopausal women.

Maturitas 2009; 62:301-305

Cardiovascular Reviews and Reports, 2002

Thyroid hormone metabolism is frequently altered in patients with heart disease, leading to a fall in T3 levels potentially resulting in cellular hypothyroidism within the myocardium? Low serum T3 may contribute to contractile dysfunction.

Thyroid Hormone Therapy of Cardiovascular Disease. CVR&R. 2002;23:20-26

Journal of Cardiology, 1993 (Japan)

Decreased Free T3 levels? were associated with worse NYHA [New York Heart Association heart failure] class. ?Patients with ventricular tachycardia demonstrated significantly lower serum values of Free T3.

Shimoyama N et al. [Serum thyroid hormone levels correlate with cardiac function and ventricular tachyarrhythmia in patients with chronic heart failure]. J Cardiol 1993;23(2):205-13.

JAMA (The Journal of the American Medical Association), 2004

In our study, we found significant associations between low levels of Free T3, poor performance, and increased mortality.

Thyroid Status in Old Age. JAMA 2004 Vol 292, No. 21

Preventive Cardiology, Fall 2001

Evidence of an association between subclinical hypothyroidism and cardiovascular disease is mounting. The impact of thyroid hormone on lipid levels is mediated primarily through T3. Thus the decreased T3 seen in hypothyroidism may result in increased serum cholesterol.

An Association Between Varying Degrees of Hypothyroidism and Hypercholesterolemia in Women: The Thyroid-Cholesterol Connection. Preventive Cardiology, Vol. 4, Issue 4, pp 179-182, Fall 2001


Journal of Clinical Endocrinology and Metabolism, May 2005

Patients preferred combined T4/T3 therapy to usual T4 therapy. Decrease in weight was associated with satisfaction with study medication.

Combined Therapy with levothyroxine (T4) and liothyronine (T3) compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized clinical trial. J Clin Endocrinol Metab. 2005 May;90(5):2666-74. Epub 2005 Feb 10.

European Journal of Endocrinology, 2009

A double blind, randomized cross-over study was done to compare the effect of combination therapy with T4 and T3 versus T4 monotherapy in patients with hypothyroidism already being treated with T4 alone. Conclusion: Treatment with high dose of T3 was superior to (T4) monotherapy by evaluating several quality of life, depression and anxiety rating scales as well as patients own preference.

Effect of combination therapy with thyroxine (T4) and triiodothyronine (T3) versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. Eur. J. Endocrinol., December 1, 2009; 161(6): 895 ? 902.


The New England Journal of Medicine, 1999

Conclusions: In patients with hypothyroidism, partial substitution of triiodothyronine [T3] for thyroxine [T4] may improve mood and neuropsychological function; this finding suggests a specific effect of the T3 normally secreted by the thyroid gland.

Bunevicius R, et al. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med 1999;340:424-429.

Endocrine, 2002

Symptoms of hypothyroidism and of hyperthyroidism tended to decrease on a standard symptom scale after combined (T4 and T3) treatment. With combined hormone replacement, mental state tended to improve on some mood scales but not on cognitive tests?.These preliminary findings in a small group of patients with Graves’ disease are consistent with earlier findings that thyroid replacement with T4-T3 combination improves mental functioning.

Bunevicius R et al. Thyroxine vs thyroxine plus triiodothyronine in treatment of hypothyroidism after thyroidectomy for Graves’ disease. Endocrine 2002 Jul;18(2):129-3

International Journal of Neuropsychopharmacology, 2000

After combined (T3 and T4) hormone treatment there were clear improvements in both cognition and mood, the latter changes being greater.

Bunevicius R et al. Mental improvement after replacement therapy with thyroxine plus triiodothyronine (T3): relationship to cause of hypothyroidism. Int J Neuropsychopharmacol 2000 Jun;3(2):167-174.

International Journal of Neuropsychopharmacology, 2003

Addition of T3 was effective [for treating depression] in 10 out of 16 women (62.5%) while none of the 9 males responded. Although values were within the normal range, patients who responded to T3 had higher serum thyroid-stimulating hormone levels than those who did not?.The effect of T3 may be related to thyroid function even within the normal range.

Agid O et al. Algorithm-based treatment of major depression in an outpatient clinic: clinical correlates of response to a specific serotonin reuptake inhibitor and to triiodothyronine augmentation.Int J Neuropsychopharmacol 2003 Mar;6(1):41-49.

Annals of Pharmacotherapy, 2000

Depressed patients should be screened for hypothyroidism. In hypothyroid patients, depression may be more responsive to a replacement regimen that includes T3 rather than T4 alone. Therefore, inclusion of T3 in the treatment regimen may be warranted after adequate trial with T4 alone.

Rack SK et al. Hypothyroidism and Depression: A Therapeutic Challenge. Ann Pharmacother 2000 Oct;34(10):1142-5.

Journal of Clinical Psychiatry, 1992

We now report on the successful use of T3 augmentation therapy in seven of nine depressed patients who were also receiving T4 for thyroid disease?.Seven of the nine patients were judged to respond to T3 augmentation. CONCLUSION: These results are consistent with a report of differential effects for T3 versus T4 augmentation in depressed patients free of thyroid disease. The results have implications for the treatment of depression in the presence of thyroid disease and for the mechanism of thyroid hormone potentiation of antidepressants.

Cooke RG et al. T3 augmentation of antidepressant treatment in T4-replaced thyroid patients. J Clin Psychiatry 1992 Jan;53(1):16-8.

American Journal of Psychiatry, 2001

Does thyroid supplementation accelerate tricyclic antidepressant response?” Six studies were (reviewed). All were conducted with triiodothyronine (T3) and a tricyclic antidepressant. Five of the six studies found T3 to be significantly more effective than placebo in accelerating clinical response?.the effects of T3 (seemed to be greater in women).

Altshuler LL, et al. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry 2001 Oct;158(10):1617-22.

Encephale, 1996

?we concluded that Free T3 and TSH levels were significantly lower in the depressed group?and that Free T4 was slightly but not significantly increased in the depressed group. Free T3 decrease and the slight Free T4 increase in depression may be the consequence of (inadequate conversion of T4) into Free T3. Its link with intensity and polarity of depression suggests that it can be considered as a biological marker of this disease.

De Mendonca Lima CA, et al. [Thyroid function in depressed patients]. Encephale 1996 Mar-Apr;22(2):85-94.