scholarly journals THERAPY OF ENDOCRINE DISEASE: T4 + T3 combination therapy: is there a true effect?

2017 ◽  
Vol 177 (6) ◽  
pp. R287-R296 ◽  
Author(s):  
Wilmar M Wiersinga
Keyword(s):  
Combination Therapy ◽  
Thyroid Function ◽  
Healthy Subjects ◽  
Randomized Clinical Trials ◽  
Peripheral Tissue ◽  
Thyroid Function Tests ◽  
Peripheral Tissues ◽  
Persistent Symptoms ◽  
Function Tests ◽  
Number Of Patients

About 5%–10% of hypothyroid patients on T4 replacement therapy have persistent symptoms, despite normal TSH levels. It was hoped that T4 + T3 combination therapy might provide better outcomes, but that was not observed according to a meta-analysis of 11 randomized clinical trials comparing T4 monotherapy with T4 + T3 combination therapy. However, the issue is still subject of much research because normal thyroid function tests in serum may not necessarily indicate an euthyroid state in all peripheral tissues. This review evaluates recent developments in the field of T4 + T3 combination therapy. T4 monotherapy is associated with higher serum FT4 levels than in healthy subjects, and subnormal serum FT3 and FT3/FT4 ratios are observed in about 15% and 30% respectively. T4 + T3 combination therapy may mimic more closely thyroid function tests of healthy subjects, but it has not been demonstrated that relatively low serum FT3 or FT3/FT4 ratios are linked to persistent symptoms. One study reports polymorphism Thr92Ala in DIO2 is related to lower serum FT3 levels after thyroidectomy, and that the D2-Ala mutant reduces T4 to T3 conversion in cell cultures. Peripheral tissue function tests such as serum cholesterol reflect thyroid hormone action in target tissues. Using such biochemical markers, patients who had a normal serum TSH during postoperative T4 monotherapy, were mildly hypothyroid, whereas those with a TSH 0.03–≤0.3 mU/L were closest to euthyroidism. Peripheral tissue function tests suggest euthyroidism more often in patients randomized to T4 + T3 rather than that to T4. Preference for T4 + T3 combination over T4 monotherapy was dose-dependently related to the presence of two polymorphisms in MCT10 and DIO2 in one small study. It is not known if persistent symptoms during T4 monotherapy disappear by switching to T4 + T3 combination therapy. The number of patients on T4 + T3 therapy has multiplied in the last decade, likely induced by indiscriminate statements on the internet. Patients are sometimes not just asking but rather demanding this treatment modality. It creates tensions between patients and physicians. Only continued research will answer the question whether or not T4 + T3 combination therapy has true benefits in some patients.

scholarly journals MON-478 Impaired Sensitivity to Thyroid Hormone - A Diagnostic and Therapeutic Challenge

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jorge Pedro ◽  
Vanessa Gorito ◽  
Cristina Ferreras ◽  
Ferreira João Silva Maria ◽  
Sofia Ferreira ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Function ◽  
Thyroid Function Tests ◽  
Pediatric Endocrinology ◽  
Free T4 ◽  
Peripheral Tissues ◽  
Free T3 ◽  
Function Tests ◽  
Trh Stimulation ◽  
History Of

Abstract Background: Impaired sensitivity to thyroid hormone refers to any process that negatively affects its action, including defects in its transport, metabolism and action on the receptor. Resistance to thyroid hormone due to beta-receptor mutations (RTH-beta) is the most common form of this entity and is characterized by reduced response of peripheral tissues to the action of thyroid hormone. The genetic variability of cofactors involved in the action of thyroid hormone explains the heterogeneity of resistance among affected individuals. Generally, patients with this disorder, have increased levels of free T4 and free T3 in association with normal or high TSH. Clinical case: 11-year-old boy, with personal history of Attention-deficit/hyperactivity disorder (ADHD). A pediatric endocrinology consultation was requested to evaluate abnormalities in his thyroid function tests. A few months earlier, his father was referred to endocrinology consultation because of thyroid function tests abnormalities: TSH - 3.01 μIU / mL (N: 0.35 - 4.94); Free T4 1.7 ng / dL (N: 0.7-1.48); Free T3 4.77 pg / mL (N: 1.71-3.71). Initially, two diagnostic hypotheses were considered: central hyperthyroidism or impaired sensitivity to thyroid hormone. The adult underwent pituitary magnetic resonance, which raised the hypothesis of a pituitary microadenoma, and TRH stimulation test, whose result was strongly suggestive of the second diagnostic possibility. A genetic study was requested and the presence of the c700 G> A variant (p. Ala 324 trh) in the THRB gene was identified, which confirmed the most likely hypothesis. At the time of the pediatric endocrinology consultation, the 11-year-old boy had the results of his lab tests: TSH - 6.67 μIU / mL (N: 0.35 - 5); T4L 2.27 ng / dL (N: 0.88-1.58); T3L 7.79 pg / mL (N: 2-4.20). Given his perfect height and weight evolution and the absence of symptoms suggestive of hypo or hyperthyroidism, it was decided not to start any medication, keeping only periodic surveillance. Conclusion: This case exemplifies unusual thyroid function tests. This discordance between serum thyroid hormone and TSH concentrations should raise the possibility of impaired sensitivity to thyroid hormone. In this condition, patients may present with symptoms of hypo or hyperthyroidism and the etiology of thyroid function tests abnormalities are not easily recognized. This can lead to misdiagnosis and consequently unnecessary treatment.

scholarly journals Analytical and Clinical Evaluation of Three Sensitive Thyrotropin Assays

1989 ◽  
Vol 26 (6) ◽  
pp. 508-516 ◽  
Author(s):  
H A Bonte ◽  
I Vermes ◽  
G V D Sluijs Veer
Keyword(s):  
Thyroid Function ◽  
Clinical Evaluation ◽  
Healthy Subjects ◽  
Clinical Utility ◽  
Matrix Effects ◽  
High Dose ◽  
Thyroid Function Tests ◽  
Good Precision ◽  
First Line ◽  
Function Tests

Three sensitive assays (Behring, Organon and LKB-Pharmacia) for measurement of serum thyrotropin (TSH) were evaluated. All three assays showed good precision, sensitivity, linearity and for practical purposes negligible high dose hook effects. The correlations between the assays were excellent, but due to standardisation and/or matrix effects there were incomplete recoveries in two kits and the kits showed systematic differences of up to 20% in the TSH values obtained. The clinical utility of the three assays was investigated in patients with thyroidal and non-thyroidal illnesses and in healthy subjects with thyroxine binding abnormalities. According to the results of the analytical and clinical evaluation, all three kits are acceptable and reliable as first-line thyroid function tests.

scholarly journals SAT-443 Impact of Fasting on Plasma Thyrotropin in Hypothyroid Patients Taking Levothyroxine During Ramadan (IFT-R Study)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Samer El-Kaissi ◽  
Laila AbdelWareth ◽  
Ruba Dajani ◽  
Terrence Lee St John ◽  
Sherry Ann Santarina ◽  
...  
Keyword(s):  
Thyroid Function ◽  
P Value ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Fasting Period ◽  
Function Tests ◽  
Number Of Patients ◽  
The Mean ◽  
Group 2 ◽  
Hypothyroid Patients

Abstract Background and Aim: We previously showed in a retrospective analysis that the plasma TSH rises significantly post-Ramadan in levothyroxine-treated hypothyroid patients, possibly as a result of changes in the eating habit during the non-fasting period from dusk until dawn. The aim of this study is to determine the best time for taking levothyroxine during Ramadan in order to minimize changes in thyroid function tests. Methods: in a randomized prospective design, hypothyroid patients taking levothyroxine for greater than 6-months were randomized to take levothyroxine at one of the following 3 times during Ramadan: (group 1) at dusk after a prolonged fast and 30-minutes before the Iftar meal, (group 2) ≥ 3-hours after the Iftar meal, or (group 3) at dawn 30-minutes before Suhur meal. Patients were instructed to allow a minimum of 3-hours between the last meal and levothyroxine and to refrain from eating and drinking for at least 30-minutes after taking levothyroxine. Thyroid function tests were performed within 3-months before Ramadan and within 6-weeks post Ramadan. To estimate intent-to-treat effects, we examined pre- and post-Ramadan thyroid function tests in relation to the assigned levothyroxine administration times. Results: 147 patients were randomized into the study and the respective number of patients in groups 1, 2 and 3 were 50, 46 and 51. The mean age of participants was 43.5±12.4 years [range 21.0-86.0] and 78% were females with no statistical differences in the mean age or gender distribution between the 3 groups. The respective pre-Ramadan mean TSH values for the 3 groups were 2.49 mIU/L, 2.16 mIU/L and 3.37 mIU/L with no significant differences at baseline. Post-Ramadan mean TSH values were 2.47 mIU/L, 4.26 mIU/L and 3.85 mIU/L for groups 1, 2 and 3 respectively. The pre- and post-Ramadan mean TSH differences were significant only for group 2, who took levothyroxine 3-hours post-Iftar (P-value 0.041). There were no significant differences in the free-T4 levels across the 3-groups before and after Ramadan. In a subset of 85 patients, the preferred times for levothyroxine administration during Ramadan were 44.7% before Iftar, 50.6% post-Iftar and only 4.7% were in favor of taking the medication before Suhur meal. Conclusions: Levothyroxine-treated hypothyroid patients who took levothyroxine 3-hours after the main Iftar meal showed a significant increase in plasma TSH post-Ramadan, possibly reflecting a reduced time period between levothyroxine administration and the previous meal. There was no significant change in the mean plasma TSH for patients taking levothyroxine at dusk before Iftar or at dawn before Suhur. The least patient-preferred time for taking levothyroxine was at dawn before Suhur possibly due to time constraints before the start of fasting.

scholarly journals T4 + T3 combination therapy: any progress?

Endocrine ◽  
2019 ◽  
Vol 66 (1) ◽  
pp. 70-78 ◽  
Author(s):  
Wilmar M. Wiersinga
Keyword(s):  
Combination Therapy ◽  
Randomized Clinical Trials ◽  
Normal Serum ◽  
Thyroid Function Tests ◽  
Pressure Groups ◽  
Persistent Symptoms ◽  
House Of Lords ◽  
Serum T3 ◽  
With Memory ◽  
Serum Tsh

Abstract Guidelines on T4 + T3 combination therapy were published in 2012. This review investigates whether the issue is better understood 7 years later. Dissatisfaction with the outcome of T4 monotherapy remains high. Persistent symptoms consist mostly of fatigue, weight gain, problems with memory and thinking and mood disturbances. T4 monotherapy is associated with low serum T3 levels, which often require TSH-suppressive doses of L-T4 for normalization. Peripheral tissue thyroid function tests during T4 treatment indicate mild hyperthyroidism at TSH < 0.03 mU/L and mild hypothyroidism at TSH 0.3–5.0 mU/L; tissues are closest to euthyroidism at TSH 0.03–0.3 mU/L. This is explained by the finding that whereas T4 is usually ubiquinated and targeted for proteasomal degradation, hypothalamic T4 is rather stable and less sensitive to ubiquination. A normal serum TSH consequently does not necessarily indicate a euthyroid state. Persistent symptoms in L-T4 treated patients despite a normal serum TSH remain incompletely understood. One hypothesis is that a SNP (Thr92Ala) in DIO2 (required for local production of T3 out of T4) interferes with its kinetics and/or action, resulting in a local hypothyroid state in the brain. Effective treatment of persistent symptoms has not yet realized. One may try T4 + T3 combination treatment in selected patients as an experimental n = 1 study. The 2012 ETA guidelines are still valid for this purpose. More well-designed randomized clinical trials in selected patients are key in order to make progress. In the meantime the whole issue has become rather complicated by commercial and political overtones, as evident from skyrocketing prices of T3 tablets, aggressive pressure groups and motions in the House of Lords.

In a bind: abnormal thyroid function tests

2019 ◽  
Author(s):  
Catriona Hilton ◽  
Farhan Ahmed ◽  
Asif Ali
Keyword(s):  
Thyroid Function ◽  
Thyroid Function Tests ◽  
Function Tests
Sign in / Sign up

Export Citation Format

Share Document