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.

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

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.

Adult subjects presenting for thyroid testing or treatment to the Department of Nuclear Medicine, Klinikum Luedenscheid, Luedenscheid, Germany.