Dr. Ron’s Research Review – September 16, 2015

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This week’s research review focuses on Armour thyroid vs Synthroid (levothyroxine).

The standard treatment of hypothyroidism (central and primary) consists of thyroxine (T4) administration alone, usually with Synthroid (levothyroxine, synthetic T4). T4 is converted into triiodothyronine (T3), the active thyroid hormone. (Sesmilo et al., 2011)
Ratios in dessicated thyroid products (e.g. Armour, NatureThroid) and drugs (Thyrolar) are based on pig thyroids, which contain approximately 80% T4 and 20% T3 (4:1). In humans, the ratio is 11:1. (Snyder and Listecki, 2012)

A recent study compared desiccated thyroid extract (DTE) with levothyroxine in the treatment of hypothyroidism. (Hoang et al., 2013)
Patients (n = 70, age 18-65 years) were randomized to either DTE or L-T₄ for 16 weeks and then crossed over for the same duration. There were no differences in symptoms and neurocognitive measurements between the 2 therapies.
Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001). At the end of the study, 34 patients (48.6%) preferred DTE, 13 (18.6%) preferred L-T₄, and 23 (32.9%) had no preference.
In the subgroup analyses, those patients who preferred DTE lost 4 lb during the DTE treatment, and their subjective symptoms were significantly better while taking DTE as measured by the general health questionnaire-12 and thyroid symptom questionnaire (P < .001 for both).

 

Dr. Ron


 

Articles

Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study.
            (Hoang et al., 2013) Download
CONTEXT:  Patients previously treated with desiccated thyroid extract (DTE), when being switched to levothyroxine (L-T₄), occasionally did not feel as well despite adequate dosing based on serum TSH levels. OBJECTIVE:  Our objective was to investigate the effectiveness of DTE compared with L-T₄ in hypothyroid patients. DESIGN AND SETTING:  We conducted a randomized, double-blind, crossover study at a tertiary care center. PATIENTS:  Patients (n = 70, age 18-65 years) diagnosed with primary hypothyroidism on a stable dose of L-T₄ for 6 months were included in the study. INTERVENTION:  Patients were randomized to either DTE or L-T₄ for 16 weeks and then crossed over for the same duration. OUTCOME MEASURES:  Biochemical and neurocognitive tests at baseline and at the end of each treatment period were evaluated. RESULTS:  There were no differences in symptoms and neurocognitive measurements between the 2 therapies. Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001). At the end of the study, 34 patients (48.6%) preferred DTE, 13 (18.6%) preferred L-T₄, and 23 (32.9%) had no preference. In the subgroup analyses, those patients who preferred DTE lost 4 lb during the DTE treatment, and their subjective symptoms were significantly better while taking DTE as measured by the general health questionnaire-12 and thyroid symptom questionnaire (P < .001 for both). Five variables were predictors of preference for DTE. CONCLUSION:  DTE therapy did not result in a significant improvement in quality of life; however, DTE caused modest weight loss and nearly half (48.6%) of the study patients expressed preference for DTE over L-T₄. DTE therapy may be relevant for some hypothyroid patients.

Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism.
            (Sesmilo et al., 2011) Download
UNLABELLED:  The standard treatment of hypothyroidism (central and primary) consists of thyroxine (T4) administration alone. However, the normal thyroid gland produces a small proportion of triiodothyronine (T3) directly into the circulation. AIM:  We aimed to study the free T3 to free T4 ratio in treated central hypothyroidism compared with euthyroidism and treated primary hypothyroidism. METHODS:  Eighty-three subjects were included in this cross-sectional study: 36 with central hypothyroidism, 20 with primary hypothyroidism and 27 healthy controls. A clinical history and a physical examination, including height and weight measurement, were performed and body mass index (BMI) was calculated. Fasting blood was drawn to measure T3, T4, free T3, free T4 and TSH. RESULTS:  The free T3 to free T4 ratio was lower in treated central hypothyroidism than in euthyroidism but was similar to treated primary hypothyroidism. Free T4 was higher in treated central and primary hypothyroidism than in euthyroidism. Age, sex and BMI did not affect the free T3 to free T4 ratio. CONCLUSIONS:  Treated patients with central hypothyroidism had a lower free T3 to free T4 ratio, similar free T3 levels and higher free T4 concentrations than euthyroid controls, whereas all these parameters were similar in central and primary hypothyroid patients treated with T4. The question of whether these findings translate into adequate tissue concentrations of free thyroid hormones in all tissues remains to be answered. Further studies should aim to determine whether clinical outcomes could be improved by a treatment achieving more physiological plasma concentrations.

Bioidentical thyroid replacement therapy in practice: Delivering a physiologic T4:T3 ratio for improved patient outcomes with the Listecki-Snyder protocol.
            (Snyder and Listecki, 2012) Download
Effective thyroid replacement therapy may be elusive to some patients, and compounding pharmacists have an opportunity to deliver more effective therapy. Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th edition states that the body usually secretes T4:T3 in an 11:1 ratio but cautions against pursuing combined thyroid replacement due to the short halflife of T3 that necessitates multiple daily dosing; no commercial availability and lack of benefit were shown in trials. Commercial combinations of T4/T3 such as Armour Thyroid and Nature-Throid have a 4.22:1 T4:T3 ratio. Applying the same concept as bioidentical hormone replacement therapy, compounding pharmacists can deliver an 11:1 ratio using a commercial T4 product and taking into account oral bioavailability of each entity. The short half-life of T3 can be remedied by taking the patient's daily T3 dose and dividing it into two slow-release capsules to be dosed every 12 hours.

 


 

References

Hoang, TD, et al. (2013), ‘Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study.’, J Clin Endocrinol Metab, 98 (5), 1982-90. PubMedID: 23539727
Sesmilo, G, et al. (2011), ‘Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism.’, Endocrinol Nutr, 58 (1), 9-15. PubMedID: 21195684
Snyder, S and RE Listecki (2012), ‘Bioidentical thyroid replacement therapy in practice: Delivering a physiologic T4:T3 ratio for improved patient outcomes with the Listecki-Snyder protocol.’, Int J Pharm Compd, 16 (5), 376-80. PubMedID: 23072197