Effect of Radioiodine Treatment on Quality of Life in Patients with Subclinical Hyperthyroidism: A Prospective Controlled Study.

Unlabelled: Radioiodine treatment (RIT) has a high success rate in both the treatment of hyperthyroidism and improving the quality of life (QoL) of symptomatic patients. In asymptomatic patients with subclinical hyperthyroidism thyroid related QoL outcomes are less well known.

Methods: Study aim was to evaluate thyroid-related QoL in patients with subclinical hyperthyroidism mostly due to toxic nodular goitre undergoing RIT, compared to a control group of euthyroid subjects.

Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change.

Endocrine regulation in the hypothalamic-pituitary-thyroid (HPT) axis is orchestrated by physiological circuits which integrate multiple internal and external influences. Essentially, it provides either of the two responses to overt biological challenges: to defend the homeostatic range of a target hormone or adapt it to changing environmental conditions. Under certain conditions, such flexibility may exceed the capability of a simple feedback control loop, rather requiring more intricate networks of communication between the system's components.

Heterogenous biochemical expression of hormone activity in subclinical/overt hyperthyroidism and exogenous thyrotoxicosis.

Background: Subclinical hyperthyroidism/thyrotoxicosis originates from different causes and clinical conditions, sharing the laboratory constellation of a suppressed TSH in the presence of thyroid hormone concentrations within the reference range.

Aim: Presentation of hyperthyroidism can manifest itself in several ways. We questioned whether there is either a consistent biochemical equivalence of thyroid hormone response to these diagnostic categories, or a high degree of heterogeneity may exist both within and between the different clinical manifestations.

Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma: A subgroup analysis of the PETAL trial.

The prospective randomized Positron Emission Tomography (PET)-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET-based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T-cell lymphoma.

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

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.

Functional and Symptomatic Individuality in the Response to Levothyroxine Treatment.

For significant numbers of patients dissatisfied on standard levothyroxine (LT4) treatment for hypothyroidism, patient-specific responses to T4 could play a significant role. To assess response heterogeneity to LT4 treatment, identifying confounders and hidden clusters within a patient panel, we performed a secondary analysis using data from a prospective cross-sectional and retrospective longitudinal study. Multivariate and multivariable linear models adjusted for covariates (gender, age, and BMI) were stratified by disease-specific treatment indication.

Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options.

Levothyroxine (LT4) therapy has a long history, a well-defined pharmacological profile and a favourable safety record in the alleviation of hypothyroidism. However, questions remain in defining the threshold for the requirement of treatment in patients with subclinical hypothyroidism, assessing the dose adequacy of the drug, and selecting the best treatment mode (LT4 monotherapy liothyronine [LT3]/LT4 combinations) for subpopulations with persisting complaints. Supplied as a prodrug, LT4 is enzymatically converted into the biologically more active thyroid hormone, triiodothyronine (T3).

Time for a reassessment of the treatment of hypothyroidism.

Background: In the treatment for hypothyroidism, a historically symptom-orientated approach has given way to reliance on a single biochemical parameter, thyroid stimulating hormone (TSH).

Main Body: The historical developments and motivation leading to that decision and its potential implications are explored from pathophysiological, clinical and statistical viewpoints. An increasing frequency of hypothyroid-like complaints is noted in patients in the wake of this directional shift, together with relaxation of treatment targets.

Lessons from Randomised Clinical Trials for Triiodothyronine Treatment of Hypothyroidism: Have They Achieved Their Objectives?

Randomised controlled trials are deemed to be the strongest class of evidence in evidence-based medicine. Failure of trials to prove superiority of T3/T4 combination therapy over standard LT4 monotherapy has greatly influenced guidelines, while not resolving the ongoing debate. Novel studies have recently produced more evidence from the examination of homeostatic equilibria in humans and experimental treatment protocols in animals.

The role of functional thyroid capacity in pituitary thyroid feedback regulation.

Background: Thyroid feedback regulation and equilibria between thyroid hormones differ in the presence or absence of a functioning thyroid remnant.

Materials And Methods: This study examines the relationship between the sensitivity of TSH feedback and thyroid capacity in untreated patients with thyroid autoimmune disease (n = 86) and healthy controls (n = 271). Functional capacity was estimated at maximum TSH stimulation, and pituitary TSH response was FT4-standardised with two established indices, the TSH index and the thyrotroph thyroid hormone resistance index.

Symptomatic Relief is Related to Serum Free Triiodothyronine Concentrations during Follow-up in Levothyroxine-Treated Patients with Differentiated Thyroid Cancer.

Aim: Patients on levothyroxine-treatment frequently have complaints although TSH is within the reference range. Moreover, FT3 is often low in these patients. The clinical significance of this disequilibrium is studied here.

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

In thyroid health, the pituitary hormone thyroid-stimulating hormone (TSH) raises glandular thyroid hormone production to a physiological level and enhances formation and conversion of T4 to the biologically more active T3. Overstimulation is limited by negative feedback control. In equilibrium defining the euthyroid state, the relationship between TSH and FT4 expresses clusters of genetically determined, interlocked TSH-FT4 pairs, which invalidates their statistical correlation within the euthyroid range.

Advances in applied homeostatic modelling of the relationship between thyrotropin and free thyroxine.

Introduction: The relationship between pituitary TSH and thyroid hormones is central to our understanding of thyroid physiology and thyroid function testing. Here, we generated distribution patterns by using validated tools of thyroid modelling.

Methods: We simulated patterns of individual set points under various conditions, based on a homeostatic model of thyroid feedback control.

Dual control of pituitary thyroid stimulating hormone secretion by thyroxine and triiodothyronine in athyreotic patients.

Background: Patient responses to levothyroxine (LT4) monotherapy vary considerably. We sought to differentiate contributions of FT4 and FT3 in controlling pituitary thyroid stimulating hormone (TSH) secretion.

Methods: We retrospectively assessed the relationships between TSH and thyroid hormones in 319 patients with thyroid carcinoma through 2914 visits on various LT4 doses during follow-up for 5.

Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function.

Thyroid hormone concentrations only become sufficient to maintain a euthyroid state through appropriate stimulation by pituitary thyroid-stimulating hormone (TSH). In such a dynamic system under constant high pressure, guarding against overstimulation becomes vital. Therefore, several defensive mechanisms protect against accidental overstimulation, such as plasma protein binding, conversion of T4 into the more active T3, active transmembrane transport, counter-regulatory activities of reverse T3 and thyronamines, and negative hypothalamic-pituitary-thyroid feedback control of TSH.

Relational Stability of Thyroid Hormones in Euthyroid Subjects and Patients with Autoimmune Thyroid Disease.

Background/aim: Operating far from its equilibrium resting point, the thyroid gland requires stimulation via feedback-controlled pituitary thyrotropin (TSH) secretion to maintain adequate hormone supply. We explored and defined variations in the expression of control mechanisms and physiological responses across the euthyroid reference range.

Methods: We analyzed the relational equilibria between thyroid parameters defining thyroid production and thyroid conversion in a group of 271 thyroid-healthy subjects and 86 untreated patients with thyroid autoimmune disease.

Derivation of a multivariate reference range for pituitary thyrotropin and thyroid hormones: diagnostic efficiency compared with conventional single-reference method.

Unlabelled: : Although pituitary thyrotropin (TSH) and thyroid hormones are physiologically interrelated, interpretation of measurements is conventionally done separately. Classification of subclinical thyroid dysfunction depends by definition solely on an abnormal TSH. This study examines a composite multivariate approach to disease classification.

Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment.

The long-held concept of a proportional negative feedback control between the thyroid and pituitary glands requires reconsideration in the light of more recent studies. Homeostatic equilibria depend on dynamic inter-relationships between thyroid hormones and pituitary thyrotropin (TSH). They display a high degree of individuality, thyroid-state-related hierarchy, and adaptive conditionality.

Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency.

Several influences modulate biochemical responses to a weight-adjusted levothyroxine (l-T4) replacement dose. We conducted a secondary analysis of the relationship of l-T4 dose to TSH and free T3 (FT3), using a prospective observational study examining the interacting equilibria between thyroid parameters. We studied 353 patients on steady-state l-T4 replacement for autoimmune thyroiditis or after surgery for malignant or benign thyroid disease.