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At least 19 recordsLinked to original sources
PubMed2005

REVIEW: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine.

CONTEXT: Combined infusion of levothyroxine plus liothyronine, as opposed to levothyroxine alone, is the only way of restoring the concentrations of circulating TSH, T4, and T3 as well as those of both T4 and T3 in all tissues of thyroidectomized rats. Considering the substantial differences in thyroid hormone secretion, transport, and metabolism between rats and humans, whether or not combined levothyroxine plus liothyronine replacement therapy has advantages over treatment with levothyroxine alone in hypothyroid patients is still questioned. EVIDENCE ACQUISITION: We conducted a systematic review of all the published controlled studies comparing treatment with levothyroxine alone with combinations of levothyroxine plus liothyronine in hypothyroid patients, identified through the Entrez-PubMed search engine. EVIDENCE SYNTHESIS: Nine controlled clinical trials were identified that compared treatment with levothyroxine alone and treatment with combinations of levothyroxine plus liothyronine and included a sufficient number of adult hypothyroid patients to yield meaningful results. In only one study did the combined therapy appear to have beneficial effects on the mood, quality of life, and psychometric performance of the patients over levothyroxine alone. These results have not been confirmed by later studies using either T3 substitution protocols or approaches with fixed combinations of levothyroxine plus liothyronine, including those based on the physiological proportion in which T3 and T4 are secreted by the human thyroid. However, in some of these studies the patients preferred levothyroxine plus liothyronine combinations, for reasons not explained by changes in the psychological and psychometric tests employed. Yet patients' preference should be balanced against the possibility of adverse events resulting from the addition of liothyronine to levothyroxine, even in the small doses used in these studies. CONCLUSIONS: Until clear advantages of levothyroxine plus liothyronine are demonstrated, the administration of levothyroxine alone should remain the treatment of choice for replacement therapy of hypothyroidism.

Drug Therapy, Combination↗
PubMed2005

Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone.

BACKGROUND: Substituting part of the dose of l-thyroxine with small but supraphysiologic doses of liothyronine in hypothyroid patients has yielded conflicting results. OBJECTIVE: To evaluate combinations of L-thyroxine plus liothyronine in hypothyroid patients that match the proportions present in normal secretions of the human thyroid gland. DESIGN: Randomized, double-blind, crossover trial. SETTING: Academic research hospital. PARTICIPANTS: 28 women with overt primary hypothyroidism. INTERVENTION: Crossover trial comparing treatment with l-thyroxine, 100 microg/d (standard treatment), versus treatment with L-thyroxine, 75 microg/d, plus liothyronine, 5 microg/d (combination treatment), for 8-week periods. All patients also received L-thyroxine, 87.5 microg/d, plus liothyronine, 7.5 microg/d (add-on combination treatment), for a final 8-week add-on period. MEASUREMENTS: Primary outcomes included serum thyroid hormone levels, results of quality-of-life and psychometric tests, and patients' preference. Multiple biological thyroid hormone end points were studied as secondary outcomes. RESULTS: Compared with standard treatment, combination treatment led to lower free thyroxine levels (decrease, 3.9 pmol/L [95% CI, 2.5 to 5.3 pmol/L]), slightly higher serum levels of thyroid-stimulating hormone (increase, 0.62 mU/L [CI, 0.01 to 1.23 mU/L]), and unchanged free triiodothyronine levels. No improvement was observed in the other primary and secondary end points after combination treatment, with the exception of the Digit Span Test, in which the mean backward score and the mean total score increased slightly (0.6 digit [CI, 0.1 to 1.0 digit] and 0.8 digit [CI, 0.2 to 1.4 digits], respectively). The add-on combination treatment resulted in overreplacement. Levels of thyroid-stimulating hormone decreased by 0.85 mU/L (CI, 0.27 to 1.43 mU/L) and serum free triiodothyronine levels increased by 0.8 pmol/L (CI, 0.1 to 1.5 pmol/L) compared with standard treatment; 10 patients had levels of thyroid-stimulating hormone that were below the normal range. Twelve patients preferred combination treatment, 6 patients preferred the add-on combination treatment, 2 patients preferred standard treatment, and 6 patients had no preference (P = 0.015). LIMITATIONS: Treatment with L-thyroxine, 87.5 microg/d, plus liothyronine, 7.5 microg/d, was an add-on regimen and was not randomized. CONCLUSIONS: Physiologic combinations of L-thyroxine plus liothyronine do not offer any objective advantage over l-thyroxine alone, yet patients prefer combination treatment.

Adolescent↗
PubMed1975

The time course of changes in TRH responsiveness in man following a single dose of liothyronine.

The serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH, 100 mug i.v.) was evaluated prior to and at various times following the oral administration of single doses of liothyronine (100 mug) given at weekly intervals. The TSH response to TRH was mildly depressed when TRH was given 1 hr after liothyronine administration when the serum triiodothyronine (T3) concentration was strikingly elevated, was markedly reduced 16 and 24 hr after liothyronine, was essentially abolished 3 days after liothyronine when the serum T3 concentration was normal, and was normal 7 days after liothyronine administration. These findings suggest that the more prolonged suppression of TRH responsiveness, observed following the withdrawal of long-term excess endogenous or exogenous thyroid hormones, cannot be ascribed to the intrinsic duration of action of the hormone present at the time of withdrawal, but rather to the prolonged extent of the suppression itself.

Administration, Oral↗
PubMed2003

Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial.

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.

Adult↗
PubMed1979

Differential pulse polarographic analysis of thyroid hormone: determination of iodine, thyroxine, and liothyronine.

A differential pulse polarographic method for the analysis of thyroid and thyroid tablets for total iodine, thyroxine, and liothyronine is described. The procedure for iodine, which is also applicable to individual tablet assay, consists of ashing the sample, coverting iodide to iodate, and analyzing by differential pulse polarography. The procedure for thyroxine and liothyronine involves hydrolysis of the sample with barium hydroxide and isolation and separation of the iodoamino acids using ion exchangers, followed by differential pulse polarographic determination in a supporting electrolyte composed of 0.5 N Na2CO3 in 20% 2-propanol containing 1% tetrabutylammonium bromide. The differential pulse polarographic results for iodine agree with values obtained using the USP XIX procedure, and the quantities of thyroxine and liothyronine found agree with literature values.

Iodine↗
PubMed1964

THE FORMATION OF (14C)-HISTAMINE IN VIVO IN NORMAL RATS AND IN RATS TREATED WITH LIOTHYRONINE.

Female rats treated with liothyronine or its solvent (control rats) were given an intravenous injection of [(14)C]-L-histidine. The amount of [(14)C]-histamine in various tissues was measured at 10 min, 60 min and 22 hr after the injection. In control rats the glandular stomach contained large amounts of [(14)C]-histamine at 10 and 60 min, with a sharp decline at 22 hr. The skin contained small amounts at 10 and 60 min, with a slight rise at 22 hr. In rats treated with liothyronine there was more [(14)C]-histamine in the stomach at 10 and 60 min, but not at 22 hr after the injection of [(14)C]-L-histidine. The results support the following conclusions: (1) The glandular stomach in the intact rat forms more histamine than do other tissues; the gastric histamine is in a rapid state of turnover and is likely to contribute substantially to the urinary output of histamine. (2) After treatment with liothyronine the rat has an increased histamine formation in the stomach; this is probably the main cause of the raised urinary histamine excretion in such a rat.

Carbon Isotopes↗
PubMed1981

Reversed-phase high-performance liquid chromatographic analysis of liothyronine sodium and levothyroxine sodium in tablet formulations: preliminary studies on dissolution and content uniformity.

Levothyroxine sodium was estimated from tablet formulations of levothyroxine sodium and liotrix (liothyronine sodium-levothyroxine sodium combination tablet). The procedures consisted of the addition of 3,3-,5-triiodothyronine as the internal standard to the pulverized sample, followed by an acidic butanol extraction, evaporation, and injection onto a muBondapak reversed-phase high-performance liquid chromatographic column. The eluent was methanol-water-phosphoric acid (50:50:0.1), and the effluent was monitored by UV detection at 254 nm. A standard linear calibration curve was obtained for direct standard solutions equivalent to 18-225 micrograms of levothyroxine sodium/tablet. The procedure is sensitive enough for single-tablet analysis. Using this procedure, content uniformity studies were performed on liothyronine sodium tablets, levothyroxine sodium tablets, and liotrix tablets. The procedure also was adapted for conducting dissolution studies on levothyroxine sodium tablets in deionized water using the rotating-paddle method.

Chromatography, High Pressure Liquid↗
PubMed1986

Determination of liothyronine and levothyroxine in thyroid preparations by liquid chromatography.

Liothyronine and levothyroxine were quantitatively determined in samples of commercial thyroid tablets and bulk powders. Samples were first hydrolyzed using a bacterial protease and then analyzed by high-performance liquid chromatography. Various hydrolysis conditions were investigated. The liothyronine and levothyroxine contents of commercial tablets and bulk powders were found to be approximately 8-11 micrograms and 25-43 micrograms, respectively, per 65 mg of thyroid. The stability of the iodothyronines in thyroid tablets was also investigated.

Chromatography, High Pressure Liquid↗
PubMed1977

Detection and semiquantitative estimation of thyroxine and diiodothyronine in liothyronine sodium.

A method is presented for the detection and semiquantitative estimation of thyroxine and diiodothyronine in liothyronine sodium. Thyroxine is detected by thin layer chromatography, using silica gel H plates developed in butanol-acetone-ammonia (30 + 55 + 15) and sprayed with a 2,7-dichlorofluorescein solution, and estimated by comparison with standard spots. For quantitative results, a larger amount of sample is applied as a streak on a fluorescent silica gel H plate. After a 5 hr development, the band is scraped off and extracted in a small volume of 0.1N NaOH; the extract is centrifuged, transferred to a 2 cm microcell, and examined spectrophotometrically. The diiodothyronine content of liothyronine sodium is estimated by liquid chromatography on a Bondapak C18 column with 0.01N sodium perchloratebutanol-acetonitrile (1000 +62 + 188) as the eluting solvent.

Chromatography, Liquid↗
PubMed1997

Behavioral effects of liothyronine (L-T3) in children with attention deficit hyperactivity disorder in the presence and absence of resistance to thyroid hormone.

Evidence that the thyroid may play a role in the pathogenesis of attention deficit hyperactivity disorder (ADHD) comes from observations that 48% to 73% of children with the syndrome of resistance to thyroid hormone (RTH) have ADHD. Casual observations in subjects with RTH have suggested that treatment with thyroid hormone may improve the symptoms of ADHD. The aim of this study was to determine whether thyroid hormone has a beneficial effect on the behavior of children with RTH. A prospective, randomized, double-blinded, placebo-controlled, cross-over study was conducted to evaluate the effect of the rapid acting thyroid hormone, liothyronine (L-T3), on the behavior of 8 children with ADHD + RTH, and 9 children with ADHD and normal thyroid function (ADHD Only). Parent and teacher ratings of hyperactivity (Conners scale) and a computerized continuous performance test (CPT) were used as objective measures of hyperactivity, attention and impulsivity. L-T3 had no effect on Conners Hyperactivity Index in 7 of 9 children with ADHD Only; it caused improvement and deterioration in 1 subject each. In contrast, the rating in 5 of 8 subjects with ADHD + RTH showed improvement, whereas 3 of 8 subjects remained unchanged. L-T3 was associated with increased commission errors in 5 of 8 children with ADHD Only and decreased commission errors in 4 of 7 with ADHD + RTH. In children with RTH and ADHD, particularly those that exhibit hyperactivity, L-T3 in supraphysiological doses may be beneficial in reducing hyperactivity and impulsivity. In the majority of children with ADHD who do not have RTH, L-T3 treatment has no effect or may be detrimental.

Attention Deficit Disorder with Hyperactivity↗
PubMed1981

The separation and determination of liothyronine and levothyroxine in tablets by reversed-phase high performance liquid chromatography.

A high performance liquid chromatographic (HPLC) system is described for the determination of liothyronine sodium (NaT3) and levothyroxine sodium (NaT4) in tablets using an octadecylsilane reversed-phase (RP-18) column packing with a mobile phase consisting of potassium dihydrogen phosphate, methanol, and water at 44 degrees C. After extracting the active ingredient from the excipients with dilute sodium hydroxide, an aliquot was chromatographed and the components were detected and quantitated by their UV spectrophotometric response at 254 nm.

Chromatography, High Pressure Liquid↗
PubMed2005

Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial.

Controversy remains about the value of combined treatment with levothyroxine (LT4) and liothyronine (LT3), compared with LT4 alone in primary hypothyroidism. We compared combined treatment with LT4 and LT3 in a ratio of 5:1 or 10:1 with LT4 monotherapy. We conducted a double-blind, randomized, controlled trial in 141 patients (18-70 yr old) with primary autoimmune hypothyroidism, recruited via general practitioners. Inclusion criteria included: LT4 treatment for 6 months or more, a stable dose for 6 wk or more, and serum TSH levels between 0.11 and 4.0 microU/ml (mU/liter). Randomization groups were: 1) continuation of LT4 (n = 48); 2) LT4/LT3, ratio 10:1 (n = 46); and 3) LT4/LT3, ratio 5:1 (n = 47). Subjective preference of study medication after 15 wk, compared with usual LT4, was the primary outcome measure. Secondary outcomes included scores on questionnaires on mood, fatigue, psychological symptoms, and a substantial set of neurocognitive tests. Study medication was preferred to usual treatment by 29.2, 41.3, and 52.2% in the LT4, 10:1 ratio, and 5:1 ratio groups, respectively (chi2 test for trend, P = 0.024). This linear trend was not substantiated by results on any of the secondary outcome measures: scores on questionnaires and neurocognitive tests consistently ameliorated, but the amelioration was not different among the treatment groups. Median end point serum TSH was 0.64 microU/ml (mU/liter), 0.35 microU/ml (mU/liter), and 0.07 microU/ml (mU/liter), respectively [ANOVA on ln(TSH) for linear trend, P < 0.01]. Mean body weight change was +0.1, -0.5, and -1.7 kg, respectively (ANOVA for trend, P = 0.01). Decrease in weight, but not decrease in serum TSH was correlated with increased satisfaction with study medication. Of the patients who preferred combined LT4/LT3 therapy, 44% had serum TSH less than 0.11 microU/ml (mU/liter). Patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy. Decrease in body weight was associated with satisfaction with study medication.

Adolescent↗
PubMed1976

The importance of growth hormone and liothyronine in induced hypocalcaemia in hypophysectomized animals.

The resistance to hypocalcaemia induced by synthetic salmon calcitonin (SCT) was studied in intact and hypophysectomized rats. The recovery from hypocalcaemia was greatly impaired in the latter group, but this was normalised by small doses of purified human growth hormone (GH). The initial hypocalcaemic response to SCT was delayed in the hypophysectomized rats. This was not affected by treatment with GH, but normalised by substitution with liothyronine. We conclude that GH accelerates the recovery from hypocalcaemia in hypophysectomized animals, perhaps by a stimulation of parathyroid activity, while thyroid hormone accelerates the initial hypocalcaemic response to SCT, probably by restoring the reduced rate of bone resorption.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Substitution of liothyronine at a 1:5 ratio for a portion of levothyroxine: effect on fatigue, symptoms of depression, and working memory versus treatment with levothyroxine alone.

OBJECTIVE: To attempt to confirm a previous report of superior effectiveness of using two thyroid hormones rather than one hormone to treat hypothyroidism. METHODS: This trial attempted to replicate prior findings, which suggested that substituting 12.5 microg of liothyronine (LT(3)) for 50 microg of levothyroxine (LT(4)) might improve mood, cognition, and physical symptoms in patients with primary hypothyroidism. Additionally, this trial aimed to extend the previous findings to fatigue and to assess for differential effects in subjects with low fatigue and high fatigue at baseline. A randomized, double-blind, two-period, crossover design was used. At an endocrinology and diabetes clinic, 30 adult subjects with primary hypothyroidism stabilized on LT(4) were recruited. Patients randomly assigned to treatment sequence 1 received their standard LT(4) dose in one capsule and placebo in another. Patients assigned to sequence 2 received their usual LT(4) dose minus 50 microg in one capsule and 10 microg of LT(3) in the other. At the end of the first 6 weeks, subjects were crossed over to receive the other treatment. Carryover and treatment effects were assessed by t tests. RESULTS: Of the 30 enrolled study subjects, 27 completed the trial. The mean LT(4) dose was 121 +/- 26 microg/day at baseline. No significant differences in fatigue and symptoms of depression were found between treatments. Measures of working memory were unchanged. During substitution treatment, the free thyroxine index was reduced by 0.7 (P<0.001), total serum thyroxine was reduced by 3.0 microg/dL (P<0.001), and total serum triiodothyronine was increased by 20.5 ng/dL (P = 0.004). CONCLUSION: With regard to the outcomes measured, substitution of LT(3) at a 1:5 ratio for a portion of baseline LT(4) yielded no better results than did treatment with the original dose of LT(4) alone.

Adult↗
PubMed2002

Hypothyroidism and muscular respiratory failure successfully treated with liothyronine.

After total thyroidectomy because of hyperthyroidism, hypothyroidism developed in a 78-year-old woman. Despite replacement therapy with levothyroxine sodium in continuously increasing doses, worsening hypothyroidism led to respiratory failure, necessitating artificial ventilation. The addition of liothyronine resulted in complete recovery. Impaired conversion of thyroxine to triiodothyronine by the dejodase was responsible for the manifestations of hypothyroidism.

Aged↗
PubMed1979

Reverse phase high pressure liquid chromatographic determination of some iodoamino acid contaminants in sodium liothyronine or sodium levothyroxine.

Some iodoamino acids have been separated and determined by high pressure liquid chromatography on octadecylsilane reverse phase packing with a mobile phase consisting of methanol, potassium phosphate monobasic, and orthophosphoric acid at 44 degrees C. The method separates and quantitates mixtures of 3,5-diiodothyronine, liothyronine, isoliothyronine, and levothyroxine. The procedure provides an accurate, sensitive, and rapid estimation of decomposition and/or impurities in standards in approximately 30 min, at the less than 75 pmole level, using an ultraviolet detector at 254 nm.

Amino Acids↗