Interrelations Between FT3, FT4 and Pituitary TSH

Thyroid Clinical Trial

— IIFHT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01969552
• Other study ID #: IIFHT-161013
• Status: Completed
• Phase: N/A
• First received: October 16, 2013
• Last updated: September 1, 2014
• Start date: July 2013
• Est. completion date: June 2014

Study information

• Verified date: September 2014
• Source: Klinikum Lüdenscheid
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Observational

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1912
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Thyroid

Locations

Country	Name	City	State
Germany	Department of Nuclear Medicine Klinikum Luedenscheid	Luedenscheid	NRW

Sponsors (1)

Lead Sponsor	Collaborator
Klinikum Lüdenscheid

Country where clinical trial is conducted

Germany, 

References & Publications (6)

Clark PM, Holder RL, Haque SM, Hobbs FD, Roberts LM, Franklyn JA. The relationship between serum TSH and free T4 in older people. Postgrad Med J. 2012 Nov;88(1045):668-70. doi: 10.1136/postgradmedj-2011-200433rep. — View Citation

Dietrich JW, Landgrafe G, Fotiadou EH. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. J Thyroid Res. 2012;2012:351864. doi: 10.1155/2012/351864. Epub 2012 Dec 30. — View Citation

Hadlow NC, Rothacker KM, Wardrop R, Brown SJ, Lim EM, Walsh JP. The relationship between TSH and free T4 in a large population is complex and nonlinear and differs by age and sex. J Clin Endocrinol Metab. 2013 Jul;98(7):2936-43. doi: 10.1210/jc.2012-4223. Epub 2013 May 13. — View Citation

Hoermann R, Eckl W, Hoermann C, Larisch R. Complex relationship between free thyroxine and TSH in the regulation of thyroid function. Eur J Endocrinol. 2010 Jun;162(6):1123-9. doi: 10.1530/EJE-10-0106. Epub 2010 Mar 18. — View Citation

Hoermann R, Midgley JE, Larisch R, Dietrich JW. Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment? Eur J Endocrinol. 2013 Jan 17;168(2):271-80. doi: 10.1530/EJE-12-0819. Print 2013 Feb. — View Citation

Midgley JE, Hoermann R, Larisch R, Dietrich JW. Physiological states and functional relation between thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model. J Clin Pathol. 2013 Apr;66(4):335-42. doi: 10.1136/jclinpath-2012-201213. Epub 2013 Feb 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No