Interrelations Between FT3, FT4 and Pituitary TSH

Study Overview
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Brief Summary
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TSH plays a central role in current thyroid function testing both as a diagnostic tool and therapeutic target. Recent studies have suggested a more complex and hierarchical relationship between logTSH and FT4 over the entire functional spectrum than the widely assumed single log linear gradient (1-4). Our group has also shown a disjoint between pituitary TSH and FT3 serum levels being operative under conditions of levothyroxine monotherapy (5). The present prospective observational study aims at confirming some of these findings and exploring additional factors other than TSH that may be important in shaping the interrelation of thyroid parameters and modulating thyroidal activity in health and disease. To this purpose, unselected patients presenting for thyroid testing or treatment to a specialised unit at a teaching hospital will be prospectively studied to assess the interplay of FT3, FT4 and TSH under various conditions, and to evaluate various thyroidal and non-thyroidal influences, such as disease entity, thyroid volume, deiodinase activity, thyroid medication, surgery, radioiodine treatment, age, BMI, smoking on pituitary set-point and homeostatic equilibria.

Detailed Description
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Study Design: Prospective observational cross-sectional monocentre study Eligible Patients: Adult subjects presenting for thyroid testing or treatment to the Department of Nuclear Medicine, Klinikum Luedenscheid, Luedenscheid, Germany. Inclusion criteria: All consecutively seen subjects who consent to precipitate and to fill out a questionnaire, which represent the full functional spectrum, as seen in a praxis setting. Exclusion criteria from analysis: Missing consent, severe illness that may be associated with euthyroid sick syndrome (non-thyroidal illness syndrome), pregnancy, pituitary and hypothalamic disorders as well as medication that may impair pituitary thyroid hormone feedback Methods: Except for a detailed questionnaire the study includes routine work-up, established standard procedures for diagnosis and standard care for treatment of thyroid disease Patient history and physical examination Detailed questionnaire on disease history and medication Measurement of thyroid function parameters and autoantibodies Ultrasound of thyroid gland and scintigraphy where required Statistical analysis includes group comparisons, correlations, generalised linear models with multiple covariates and more advanced modelling techniques of feedback control and FT3- FT4-TSH interrelations, as previously described (4, 5, 6). Outcome Measures: Group comparisons among treated patients and untreated subjects and various disease entities, modelling of lnTSH interactions with FT4 and FT3,influence of clinically relevant covariates on FT3-FT4-TSH interrelations and equilibria. Estimated Enrolment : approx. 1500 patients Estimated Duration: approx. 12 months Ethical approval: Ethical Committee of the University of Muenster, Muenster, Germany Sponsor: none Financial Support: none Conflicts of Interest: none

Official Title
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Interrelations Between FT3, FT4 and Pituitary TSH and Implications For Thyroid Hormone Treatment (IIFHT-Study)

Conditions
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Thyroid

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All consecutively seen subjects who consent to precipitate and to fill out a questionnaire, which represent the full functional spectrum, as seen in a praxis setting. Exclusion Criteria: Missing consent, severe illness that may be associated with euthyroid sick syndrome (non-thyroidal illness syndrome), pregnancy, pituitary and hypothalamic disorders as well as medication that may impair pituitary thyroid hormone feedback.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Thyroid testing<br>Adult subjects presenting for thyroid testing or treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pituitary setpoint and thyroid hormone equilibria | According to our previous work, the states of hypothyroidism, euthyroidism and hyperthyroidism can be regarded as differently regulated entities. The present study assesses modulators that influence pituitary thyroid feedback control and impact on the pituitary setpoint and hormonal equilibria. The measure is change in circulating levels of TSH (mU/L) per change in FT4 (nmol/L) or FT3 (pmol/L). | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TSH, thyroid hormones, thyroid tresting, levothyroxine