Although the normal thyroid gland secretes both levothyroxine (L-T4) and levotriiodothyronine (L-T3), normalization of serum TSH with L-T4-replacement therapy alone in hypothyroidism is generally believed to result in a normal serum L-T3 and to reflect a euthyroid state. However several recent studies suggest that this may not be the case. Accordingly, the relationship between serum free L-T4 and free L-T3 was examined in 20 normal individuals (group A) and in 53 patients with chronic autoimmune thyroiditis, 18 with normal TSH on no L-T4-replacement (group B), and 35 with normal TSH on L-T4-replacement therapy for hypothyroidism (group C).

Conflicting results have recently been published about the benefits of combined T4 and T3 in treating hypothyroid patients. However, these studies may have been underpowered to detect differences in psychological well-being specifically related to T4 replacement. We conducted a large, double-blind, randomized controlled trial of partial substitution of 50 µg T4 by 10 µg T3 vs. the original dose of T4 in 697 hypothyroid patients. Thyroid function showed a rise in TSH (132%), a fall in free T4 (35%, P < 0.001), and unchanged basal free T3 levels (P = 0.92). At 3 months, there was a large (39%) placebo effect improvement in psychiatric caseness defined by the General Health Questionnaire (GHQ) 12 score in the control group compared with baseline, and this was sustained at 12 months. Differences vs. the intervention (T3) group were more modest with improvements in GHQ caseness (odds ratio, 0.61; 95% confidence interval, 0.42, 0.90; P = 0.01) and Hospital Anxiety and Depression questionnaire-anxiety scores at 3 months (P < 0.03) but not GHQ Likert scores, Hospital Anxiety and Depression questionnaire-depression, thyroid symptoms, or visual analog scales of mood and the initial differences were lost at 12 months. These results may be consistent with a subgroup of patients showing transient improvement after partial substitution with T3 but do not provide conclusive evidence of specific benefit from partial substitution of T4 by T3 in patients on T4 replacement. They also emphasize the large and sustained placebo effect that can follow changes in thyroid hormone administration.

Abstract. "Replacement" is the most widely used approach to thyroid hormone therapy. Clinical practice guidelines define replacement therapy as: adjustment of a patient’s thyroid hormone dosage so that his or her TSH and thyroid hormone levels remain within current laboratory reference ranges. Overall, the endocrinology specialty endorses T4-replacement as the preferable approach to thyroid hormone therapy.

Chronic stress sufferers often have a significant problem with cold hands and feet by the time they consult me. Eventually all people suffering from unremitting stress develop temperature dysregulation and low body temperature—and with that lose the efficiency of their enzymes, much like a defect in the furnace reduces the efficiency of a home heating system. There are five core points in this discussion: