Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patients with Hypothyroidism

Bunevičius, Robertas; Kazanavičius, Gintautas; Žalinkevičius, R; Aj, Prange

doi:10.1056/nejm199902113400603

Cited by 427 publications

(309 citation statements)

References 13 publications

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“…Our patient initially received 200 µg of T4 intravenously, followed by a combination of T3 and T4 given orally. The combination of T4 and T3 has been reported to benefit some patients with myxedema madness (29). As in most reported cases, our patient was also treated with antipsychotic drugs.…”

Section: Discussionsupporting

confidence: 60%

Myxedema madness complicating postoperative follow-up of thyroid cancer

Allo

Rosmarin

Urrutia

et al. 2015

Arch. Endocrinol. Metab.

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SUMMARYAlthough hypothyroidism is associated with an increased prevalence of psychiatric manifestations, myxedema madness is rarely observed. We report the case of a 62-year-old woman with no prior history of psychiatric disorders, who presented to the emergency department with psychomotor agitation 6 weeks after total thyroidectomy for papillary thyroid cancer. Serum thyroid stimulating hormone (TSH) on admission was 62.9 mIU/L and free T4 was < 0.35 ng/dL, indicating severe hypothyroidism. After ruling out other possible causes, the diagnosis of myxedema madness was considered; hence, antipsychotic drug treatment and intravenous levothyroxine were prescribed. Behavioral symptoms returned to normal within 4 days of presentation, while levels of thyroid hormones attained normal values 1 week after admission. Recombinant TSH (Thyrogen ® ) was used successfully to prevent new episodes of mania due to thyroid hormone withdrawal in further controls for her thyroid cancer. This case illustrates that myxedema madness can occur in the setting of acute hypothyroidism, completely reverting with levothyroxine and antipsychotic treatment. Recombinant TSH may be a useful tool to prevent myxedema madness or any severe manifestation of levothyroxine withdrawal for the follow-up of thyroid cancer.

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Section: Discussionsupporting

confidence: 60%

Myxedema madness complicating postoperative follow-up of thyroid cancer

Allo

Rosmarin

Urrutia

et al. 2015

Arch. Endocrinol. Metab.

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“…This may be explained by the lack of direct thyroidal T 3 production, which accounts for approximately 20% of circulating T 3 , and/or a reduced 5 0 deiodinase activity in patients with a defective thyreotrope axis. It remains to be determined whether adding small doses of T 3 would be beneficial in CH patients, as has been proposed in primary hypothyroidism (22). Alternatively, targeting higher fT 4 levels would likely lead to normalisation of fT 3 concentrations.…”

Section: Discussionmentioning

confidence: 99%

Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients

et al. 2004

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Objective: We studied the clinical and hormonal profiles of patients with central hypothyroidism (CH), the adequacy of levothyroxine (L-T4) treatment and the influence of other pituitary hormone replacement therapies. Methods: We reviewed medical records of 108 adult patients with child-onset (CO; n ¼ 26) or adultonset (AO; n ¼ 82) CH. Results: At diagnosis, the most frequently reported symptoms were fatigue and headaches in AO patients, and growth retardation in CO patients. Serum TSH was normal in a majority of CH patients, low in 8% and elevated in 8%. Serum free thyroxine (fT 4 ) was usually reduced, but remained within the low normal range in 28% of the study population (mostly CO patients). Similarly, serum total T 4 (tT 4 ), total triiodothyronine (tT 3 ) and free T 3 (fT 3 ) were found to be within the normal range in significant subsets of patients. Interestingly, the clinical and biochemical characteristics of CH patients with normal f/t T 4 levels were not different from those of the patients with low fT 4 values. The thyroid hormonal profile was not influenced by gender, etiology or by the number of hormone deficiencies. At last evaluation, the mean dose of L-T 4 was 1.6^0.5 mg/kg/day and was negatively correlated to current age (P , 0.001) but positively correlated to the number of hormone deficiencies (P , 0.05). Treatment suppressed TSH in 75% of the patients, induced normal fT 4 in 94%, but normal fT 3 in only 49% of them. Male GH-treated patients and estrogen-treated females needed a higher L-T 4 dose compared with non-treated patients. Conclusions: fT 4 is clearly the best indicator of CH, but remains in the low normal range in a significant subset of patients, especially in those with CO disease. Adequacy of therapy is mostly reflected by the combination of upper normal fT 4 and low normal fT 3 levels. Pituitary hormone replacement therapy may require an adjustment of T 4 treatment, as female patients under estrogen treatment and male patients under GH treatment will need a higher T 4 dose in order to remain in the euthyroid range.European Journal of Endocrinology 150 1-8

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“…In spite of apparently optimal T 4 substitution therapy (securing normal serum TSH levels), reduced quality of life (QOL) has been described in these patients as compared to the healthy subjects (7). In 1999, Bunevicius described an increase in wellbeing in substituted hypothyroid subjects when comparing combination therapy with T 4 and T 3 to monotherapy with T 4 (8). Later, ten studies have been performed including a total of w1000 patients, and based on these studies a recent meta-analysis concluded that there seems to be no evidence supporting superior effect of combination treatment (9).…”

Section: Introductionmentioning

confidence: 99%

Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study

Nygaard¹,

Jensen²,

Kvetny³

et al. 2009

European Journal of Endocrinology

140

156

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Background: Treatment of hypothyroidism with 3,5,3 0 -triiodothyronine (T 3 ) is controversial. A recent meta-analysis concludes that no evidence is present in favour of using T 3 . However, the analysis included a mixture of different patient groups and dose-regimens. Objective: To compare the effect of combination therapy with thyroxine (T 4 ) and T 3 versus T 4 monotherapy in patients with hypothyroidism on stable T 4 substitution. Study design: Double-blind, randomised cross-over. Fifty micrograms of the usual T 4 dose was replaced with either 20 mg T 3 or 50 mg T 4 for 12 weeks, followed by cross-over for another 12 weeks. The T 4 dose was regulated if needed, intending unaltered serum TSH levels. Evaluation: Tests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods. Inclusion criteria: Serum TSH between 0.1 and 5.0 mU/l on unaltered T 4 substitution for 6 months. Results: A total of 59 patients (55 women); median age 46 years. When comparing scores of QOL and depression on T 4 monotherapy versus T 4 /T 3 combination therapy, significant differences were seen in 7 out of 11 scores, indicating a positive effect related to the combination therapy. Forty-nine percent preferred the combination and 15% monotherapy (PZ0.002). Serum TSH remained unaltered between the groups as intended. Conclusion: In a study design, where morning TSH levels were unaltered between groups combination therapy, (treated with T 3 20 mg once daily) was superior to monotherapy by evaluating several QOL, depression and anxiety rating scales as well as patients own preference.

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Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patients with Hypothyroidism

Abstract: 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.

Cited by 427 publications

References 13 publications

Myxedema madness complicating postoperative follow-up of thyroid cancer

Myxedema madness complicating postoperative follow-up of thyroid cancer

Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients

Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study

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