this might be overkill...but here is a compilation of stuff i've gotten from medline on hypothyroidism. There is tons more, i pulled these cause most of them have a reference to t3 and/or what happens to thyroid hormones during exercise or at altitude. you can read the abstracts to the ones i didn't include at:
http://www.ncbi.nlm.nih.gov./entrez/query.fcgi
Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism.
Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ Jr.
Institute of Endocrinology, Kaunas Medical University, Lithuania.
BACKGROUND: Patients with hypothyroidism are usually treated with thyroxine (levothyroxine) only, although both thyroxine and triiodothyronine are secreted by the normal thyroid gland. Whether thyroid secretion of triiodothyronine is physiologically important is unknown. METHODS: We compared the effects of thyroxine alone with those of thyroxine plus triiodothyronine (liothyronine) in 33 patients with hypothyroidism. Each patient was studied for two five-week periods. During one period, the patient received his or her usual dose of thyroxine. During the other, the patient received a regimen in which 50 microg of the usual dose of thyroxine was replaced by 12.5 microg of triiodothyronine. The order in which each patient received the two treatments was randomized. Biochemical, physiologic, and psychological tests were performed at the end of each treatment period. RESULTS: The patients had lower serum free and total thyroxine concentrations and higher serum total triiodothyronine concentrations after treatment with thyroxine plus triiodothyronine than after thyroxine alone, whereas the serum thyrotropin concentrations were similar after both treatments. Among 17 scores on tests of cognitive performance and assessments of mood, 6 were better or closer to normal after treatment with thyroxine plus triiodothyronine. Similarly, among 15 visual-analogue scales used to indicate mood and physical status, the results for 10 were significantly better after treatment with thyroxine plus triiodothyronine. The pulse rate and serum sex hormone-binding globulin concentrations were slightly higher after treatment with thyroxine plus triiodothyronine, but blood pressure, serum lipid concentrations, and the results of neurophysiologic tests were similar after the two treatments. CONCLUSIONS: In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.
AND THE ARTICLE WITH THE CONFLICTING CONCLUSION.....
JAMA. 2003 Dec 10;290(22):2952-8.
Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial.
Clyde PW, Harari AE, Getka EJ, Shakir KM.
Department of Endocrinology and Metabolism, Nation Naval Medical Center, Bethesda, Md 20889-5600, USA.
pwclyde@mar.med.navy.mil
CONTEXT: Standard therapy for patients with primary hypothyroidism is replacement with synthetic thyroxine, which undergoes peripheral conversion to triiodothyronine, the active form of thyroid hormone. Within the lay population and in some medical communities, there is a perception that adding synthetic triiodothyronine, or liothyronine, to levothyroxine improves the symptoms of hypothyroidism despite insufficient evidence to support this practice. OBJECTIVE: To evaluate the benefits of treating primary hypothyroidism with levothyroxine plus liothyronine combination therapy vs levothyroxine monotherapy. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled trial conducted from May 2000 to February 2002 at a military treatment facility that serves active duty and retired military personnel and their family members. The trial included a total of 46 patients aged 24 to 65 years with at least a 6-month history of treatment with levothyroxine for primary hypothyroidism. INTERVENTION: Patients received either their usual dose of levothyroxine (n = 23) or combination therapy (n = 23), in which their usual levothyroxine dose was reduced by 50 micro g/d and substituted with liothyronine, 7.5 micro g, taken twice daily for 4 months. MAIN OUTCOME MEASURES: Scores on a hypothyroid-specific health-related quality-of-life (HRQL) questionnaire, body weight, serum lipid levels, and 13 neuropsychological tests measured before and after treatment. RESULTS: Serum thyrotropin levels remained similar and within the normal range in both treatment groups from baseline to 4 months. Body weight and serum lipid levels did not change. The HRQL questionnaire scores improved significantly in both the control group (23%; P<.001) and the combination therapy group (12%; P =.02), but these changes were statistically similar (P =.54). In 12 of 13 neuropsychological tests, outcomes between groups were not significantly different; the 1 remaining test (Grooved Peg Board) showed better performance in the control group. CONCLUSION: Compared with levothyroxine alone, treatment of primary hypothyroidism with combination levothyroxine plus liothyronine demonstrated no beneficial changes in body weight, serum lipid levels, hypothyroid symptoms as measured by a HRQL questionnaire, and standard measures of cognitive performance.
THIS ONE IS INTERESTING...- OF OF THE TISSUES IT REFERS TO IS MUSCLE TISSUE
J Clin Invest. 1995 Dec;96(6):2828-38.
Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats.
J. T. van der Heyden, R. Docter, H. van Toor, J. H. Wilson, G. Hennemann and E. P. Krenning AJP - Effects of caloric deprivation on thyroid hormone tissue uptake and generation of low-T3 syndrome. Endocrinology and Metabolism, Vol 251, Issue 2 156-E163.
B. Loucks and R. Callister AJP - Induction and prevention of low-T3 syndrome in exercising women
Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 5 924-R930
Baylor LS, Hackney AC. Eur J Appl Physiol. 2003 Jan;88(4-5):480-4. Epub 2002 Nov 22.
Resting thyroid and leptin hormone changes in women following intense, prolonged
exercise training.
Humpeler E, Skrabal F, Bartsch G. Influence of exposure to moderate altitude on the plasma concentraton of cortisol, aldosterone, renin, testosterone, and gonadotropins
Eur J Appl Physiol Occup Physiol. 1980;45(2-3):167-76.
.
Loucks AB, Callister R. Induction and prevention of low-T3 syndrome in exercising women.
Am J Physiol. 1993 May;264(5 Pt 2):R924-30.
Connors JM, Martin LG.J Appl Physiol. Altitude-induced changes in plasma thyroxine, 3,5,3'-triiodothyronine,and thyrotropin in rats. 1982 Aug;53(2):313-5.
Mordes JP, Blume FD, Boyer S, Zheng MR, Braverman LE. High-altitude pituitary-thyroid dysfunction on Mount Everest. N Engl J Med. 1983 May 12;308(19):1135-8.
Clyde, P. Harari, A. Getka, E., Shakir, M. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism. A randomized controlled trial.
JAMA, December 10, 2003 – Vol 290, No 22.
Clin Endocrinol (Oxf). 2004 Jun;60(6):750-7.
Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14 : 1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism.
Siegmund W, Spieker K, Weike AI, Giessmann T, Modess C, Dabers T, Kirsch G, Sanger E, Engel G, Hamm AO, Nauck M, Meng W.
Thyroid. 2004 Apr;14(4):271-5.
Thyroxine plus low-dose, slow-release triiodothyronine replacement in hypothyroidism: proof of principle.
Hennemann G, Docter R, Visser TJ, Postema PT, Krenning EP.
Clin Endocrinol (Oxf). 2003 Aug;59(2):162-7.
Musculoskeletal manifestations in patients with thyroid disease.
Cakir M, Samanci N, Balci N, Balci MK.
Endocrinology. 1996 Jun;137(6):2490-502.
Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat.
Escobar-Morreale HF, del Rey FE, Obregon MJ, de Escobar GM.
Escobar-Morreale HF, Obregon MJ, Escobar del Rey F, Morreale de Escobar G.
Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientificas y Universidad Autonoma, Madrid, Spain.
We have studied whether, or not, tissue-specific regulatory mechanisms provide normal 3,5,3'-triiodothyronine (T3) concentrations simultaneously in all tissues of a hypothyroid animal receiving thyroxine (T4), an assumption implicit in the replacement therapy of hypothyroid patients with T4 alone. Thyroidectomized rats were infused with placebo or 1 of 10 T4 doses (0.2-8.0 micrograms per 100 grams of body weight per day). Placebo-infused intact rats served as controls. Plasma and 10 tissues were obtained after 12-13 d of infusion. Plasma thyrotropin and plasma and tissue T4 and T3 were determined by RIA. Iodothyronine-deiodinase activities were assayed using cerebral cortex, liver, and lung. No single dose of T4 was able to restore normal plasma thyrotropin, T4 and T3, as well as T4 and T3 in all tissues, or at least to restore T3 simultaneously in plasma and all tissues. Moreover, in most tissues, the dose of T4 needed to ensure normal T3 levels resulted in supraphysiological T4 concentrations. Notable exceptions were the cortex, brown adipose tissue, and cerebellum, which maintained T3 homeostasis over a wide range of plasma T4 and T3 levels. Deiodinase activities explained some, but not all, of the tissue-specific and dose related changes in tissue T3 concentrations. In conclusion, euthyroidism is not restored in plasma and all tissues of thyroidectomized rats on T4 alone. These results may well be pertinent to patients on T4 replacement therapy.
J Clin Endocrinol Metab. 1999 Mar;84(3):924-9.
Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism.
Ferretti E, Persani L, Jaffrain-Rea ML, Giambona S, Tamburrano G, Beck-Peccoz P.
Department of Endocrinology, University La Sapienza, Rome, Italy.
As there are few data on the evaluation of the adequacy of levothyroxine (L-T4) therapy in patients with central hypothyroidism (CH), a prospective study was performed to assess the accuracy of various parameters in the follow-up of 37 CH patients. Total and free thyroid hormones, TSH, and a series of clinical and biochemical indexes of peripheral thyroid hormone action have been evaluated off and on L-T4 therapy. Samples were taken before the daily administration of L-T4. In all patients off therapy, clinical hypothyroidism and low levels of free T4 (FT4) were observed, whereas values of FT3, total T4, and total T3 were below the normal range in 73%, 57%, and 19% of cases, respectively. Most of the indexes of thyroid hormone action were significantly modified after L-T4 withdrawal and exhibited significant correlation with free thyroid hormone levels. During L-T4 replacement therapy, 32 patients had circulating levels of FT4 and FT3 and indexes within the normal range with a mean L-T4 daily dose of 1.5 +/- 0.3 microg/kg BW. Despite normal serum FT4, 3 patients had borderline high values of FT3 and a clear elevation of serum-soluble interleukin-2 receptor concentrations, suggesting overtreatment. Low or borderline low FT4/FT3 levels indicated undertreatment in 2 patients. The clinical parameters lack the required specificity for the diagnosis or follow-up of CH patients. The L-T4 daily dose should be established, taking into account the weight, the age, and the presence of other hormone deficiencies or pharmacological treatment of CH patients. In conclusion, our results indicate that the diagnosis of CH is reached at best by measuring TSH and FT4 concentrations. In the evaluation of the adequacy of L-T4 replacement therapy, both FT4 and FT3 serum levels together with some biochemical indexes of thyroid hormone action are all necessary to a more accurate disclosure of over- or undertreated patients.
...THE ARTICLE I FOUND THAT
J Rheumatol. 1990 Aug;17(8):1025-8.
Triiodothyronine treatment for Raynaud's phenomenon: a controlled trial.
Dessein PH, Morrison RC, Lamparelli RD, van der Merwe CA.
Rheumatology Unit, University of the Witwatersrand Medical School, Johannesburg, South Africa.
The effects of 80 micrograms triiodothyronine (T3) daily were compared with placebo in a double blind controlled crossover trial in 18 patients with Raynaud's phenomenon. Reductions in the frequency, duration and severity of attacks while taking T3 were gradual but highly significant. Four of 6 subjects had skin ulcer healing. Skin temperatures in the hands increased significantly. The skin temperature recovery times after cold exposure were significantly shorter during T3 therapy compared with placebo. Although large dosages of T3 were well tolerated, 6 patients experienced episodic palpitations, and slight but significant increases in heart rate and pulse pressure were observed. Evaluation of the use of physiological doses of T3 (60 micrograms daily or less) in the treatment of Raynaud's phenomenon is suggested.