Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment

Hoermann, Rudolf; Midgley, J. E. M.; Larisch, Rolf; Dietrich, Johannes W.

doi:10.3389/fendo.2017.00364

Cited by 51 publications

(68 citation statements)

References 105 publications

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“…1,36 Static assumptions in thyroid health may not hold for conditions of glandular stress. 3,38,40 Larger studies are needed to confirm and extend our findings towards a potential future clinical utility of such models, possibly app-based. In healthy subjects, T4-T3 conversion in extra-thyroidal organs is generally accepted as the main T3 source, the thyroidal contribution amounting to approx.…”

Section: Discussionmentioning

confidence: 69%

“…35 Our findings portray a more flexible view of the hypothalamic-pituitary-thyroid regulation, compared to the classical feedback model. 3,[38][39][40] Unlike univariate statistical range considerations for single parameters, set points, as modelled here, are fundamentally more well-founded and may be more suitable for individualised decision-making. This includes the relative importance of various contributions to the circulating T3 pool.…”

Section: Discussionmentioning

confidence: 99%

“…19,23 This is characteristic of a healthy individual, displaying far less variation, compared to the much wider reference ranges of the population's TSH and thyroid hormone concentrations. 3,[38][39][40] Unlike univariate statistical range considerations for single parameters, set points, as modelled here, are fundamentally more well-founded and may be more suitable for individualised decision-making. 3,38,40 Larger studies are needed to confirm and extend our findings towards a potential future clinical utility of such models, possibly app-based.…”

Section: Discussionmentioning

confidence: 99%

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Triiodothyronine secretion in early thyroid failure: The adaptive response of central feedforward control

Hoermann

Pekker

Midgley

et al. 2020

Eur J Clin Investigation

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Background: Defined by thyroid-pituitary feedback control, clinical diagnosis of hypothyroidism and hyperthyroidism has become synonymous with TSH measurement. We combined in silico analysis and in vivo data to explore the central influences on thyroidal T3 production. Materials & methods:A system of five coupled first-order nonlinear parameterised ordinary differential equations (ODEs) is used to model the feedback control of TSH and TRH by thyroid hormones together with the feedforward control of thyroidal T3 secretion and enzymatic T4-T3 conversion. Dependencies of the stable equilibrium solutions of this ODE system, that is the homeostasis of the underlying physiological process, on the system parameters were investigated whether they accounted for clinical observations. Results: During the modelled transition to hypothyroidism, central control imposed an increasing influence in maintaining serum FT3 levels, compared to peripheral conversion efficiency. Numerical continuation analysis revealed dependencies of T3 production on different elements of TSH feedforward control. While T4-T3 conversion provided the main T3 source in euthyroidism, this was overtaken by increasing glandular T3 secretion when thyroid reserve declined. The computational results were in good agreement with data from untreated patients with autoimmune thyroiditis. Conclusions: Dependencies revealed in the expression of control differ in thyroid health and disease, using a physiologically based mathematical model of combined feedback-feedforward control of the hypothalamic-pituitary-thyroid regulation.Strong T3-protective mechanisms of the control system emerge with declining thyroid function, when glandular T3 secretion becomes increasingly influential over conversion efficiency. This has wide-ranging implications for the utility of TSH in clinical decision-making. K E Y W O R D Sautoimmune thyroiditis, mathematical model, personalised medicine, set point, subclinical hypothyroidism, T3 secretion

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Triiodothyronine secretion in early thyroid failure: The adaptive response of central feedforward control

Hoermann

Pekker

Midgley

et al. 2020

Eur J Clin Investigation

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“…An abnormal hypothalamic‐pituitary‐thyroid feedback was often observed in the patients with hypothyroidism . Pituitary TSH cannot be readily interpreted as a sensitive mirror image of thyroid function because the negative TSH‐FT4 correlation is frequently broken, even inverted, by common conditions . FT4 and FT3 are not affected by serum thyroxine‐binding globulin in theory.…”

Section: Discussionmentioning

confidence: 99%

Effect of l‐thyroxine administration before breakfast vs at bedtime on hypothyroidism: A meta‐analysis

Pang

et al. 2020

Clinical Endocrinology

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Hypothyroidism is resulting from a deficiency of thyroid hormones, which is common condition with potentially devastating health consequences that affect all populations worldwide. 1 Thyroid hormones are essential for growth, neuronal development, reproduction and the regulation of energy metabolism. The prevalence of hypothyroidism varies considerably across the general population, ranging between 0.2% and 5.3% in Europe, 2 0.3% and 3.7% in the USA, 3 11% in India 4 and 17.8% in China (overt hypothyroidism: 1.1%; subclinical hypothyroidism: 16.7%). 5 Longitudinal studies from large UK cohorts report an incidence rate of spontaneous hypothyroidism of 3.5-5.0 per 1000 and 0.6-1.0 per 1000 in women and men, respectively. 6The clinical presentation of hypothyroidism is nonspecific and variable. Therefore, the diagnosis of hypothyroidism is based primarily on biochemical abnormalities. The pituitary hormone thyrotropin (TSH) has a complex inverse relationship with the thyroid hormones thyroxine (T4) and triiodothyronine (T3). 7 Accordingly, overt hypothyroidism is defined as serum TSH concentrations above the reference range with low free T4 (FT4) levels, while subclinical hypothyroidism is diagnosed when TSH levels are high and circulating Abstract Purpose: To compare the effects of l-thyroxine (L-T4) administration before breakfast and administration at bedtime on hypothyroidism. Methods: The PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing L-T4 administration before breakfast to the administration at bedtime in patients with hypothyroidism were included in the analysis. Results: Initially, 2884 articles were retrieved from the databases, and 10 articles were included in the quantitative analysis. The effect of L-T4 administration before breakfast compared with administration at bedtime had no statistically significant association with hormone thyrotropin (TSH) (Standardized mean differences [SMD] = 0.09, 95% confidence intervals (CI): −0.12, 0.30; P = .39), or free triiodothyronine (FT3) (SMD=−0.19, 95% CI: −0.53, 0.15; P = .28) in patients with hypothyroidism. However, the result of FT4 level was favourable for L-T4 bedtime administration group (SMD=−0.27, 95% CI: −0.52, −0.02; P = .03). Conclusion:Our meta-analysis revealed that L-T4 administration at bedtime is as effective as administration before breakfast for patients with hypothyroidism. Taking L-T4 at bedtime may be an attractive option for patients with hypothyroidism. K E Y W O R D Sadministration timing, hypothyroidism, l-thyroxine, meta-analysis How to cite this article: Pang X, Pu T, Xu L, Sun R. Effect of l-thyroxine administration before breakfast vs at bedtime on hypothyroidism: A meta-analysis. Clin Endocrinol (Oxf).

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“…We did, however, find a correlation between baseline ThyPRO-39 composite score and baseline free T 3 (r s = 0.481; p = 0.02), indicating that higher free T 3 levels were associated with poorer QoL, and that those with the smallest increase had the largest increase in QoL. This could be a type 1 error, but could also be an argument to refute the claim that high levels of free T 3 are essential for optimal QoL [15].…”

Section: Discussionmentioning

confidence: 98%

Levothyroxine/Liothyronine Combination Therapy and Quality of Life: Is It All about Weight Loss?

Michaelsson¹,

Cour²,

Medici³

et al. 2018

Eur Thyroid J

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Objectives: According to one hypothesis, the popularity of levothyroxine (L-T₄)/liothyronine (L-T₃) combination therapy relates to weight loss. The purpose of this study was to detect a possible correlation between thyroid-related quality of life (QoL) and weight loss in hypothyroid patients switched from L-T₄ monotherapy to L-T₄/L-T₃ combination therapy. Methods: In an open-label cohort study, all hypothyroid patients referred to the University Hospital endocrine clinic due to persistent symptoms despite adequate L-T₄ monotherapy (without other explanations for the symptoms) were switched from L-T₄ monotherapy to L-T₄/ L-T₃ combination therapy at a ratio of approximately 17/1. At baseline and after 3 months of treatment we measured: QoL by the Thyroid Patient-Reported Outcome (ThyPRO-39) questionnaire, thyroid hormones, body weight, body composition by a DEXA-scan, and cognitive function by evaluating participants’ reaction time as well as working memory by the California Computerized Assessment Package (CalCAP®). QoL was re-evaluated after 12 months. Results: Twenty-three patients participated (91% women, median age 47 years). The ThyPRO-39 composite score decreased from a median of 54 (quartiles: 34, 74) to 15 (11, 28) after 3 months (p < 0.0001), and 20 (14, 26) after 12 months, indicating a better QoL. There was no change in body weight, and no correlations between QoL and weight. There was a slight improvement in cognitive function, whereas body composition, heart rate, and serum TSH did not change. Conclusion: Our study on hypothyroid patients switched from L-T₄ monotherapy to L-T₄/L-T₃ combination therapy showed a substantial improvement in QoL measured by the ThyPRO-39. This improvement could not be explained by weight loss.

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Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment

Cited by 51 publications

References 105 publications

Triiodothyronine secretion in early thyroid failure: The adaptive response of central feedforward control

Triiodothyronine secretion in early thyroid failure: The adaptive response of central feedforward control

Effect of l‐thyroxine administration before breakfast vs at bedtime on hypothyroidism: A meta‐analysis

Levothyroxine/Liothyronine Combination Therapy and Quality of Life: Is It All about Weight Loss?

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