Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation

Hyperlipidemias Clinical Trial

Official title:

A Randomised, Controlled, Crossover Study: Treatment With Thyroxin Compared to Thyroxin + Triiodothyronin in Patients With Secondary Hypothyroidism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00360074
• Other study ID #: FH 326/03
• Status: Completed
• Phase: Phase 4
• First received: August 2, 2006
• Last updated: June 6, 2008
• Start date: February 2004
• Est. completion date: April 2007

Study information

• Verified date: June 2008
• Source: University Hospital Freiburg
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether a body weight adjusted dose of thyroxin is superior to treatment guided by laboratory results of thyroxin hormones in patients with central hypothyroidism. Moreover beneficial effects of triiodthyronine supplementation are investigated.

Description:

Backround: A normal thyroid function is critical for metabolism, well-being and cognitive function. It is now well accepted that primary subclinical hypothyroidism, characterized by normal circulating thyroid hormones (fT3 and fT4) and elevated TSH, should be treated to improve reduced quality of life and abnormalities of lipid metabolism. In central hypothyroidism (CH) the dose of replacement therapy aims to achieve normal thyroxin (T4) concentrations as defined by appropriate reference populations. Adequate thyroxin treatment is especially challenging, as T4 cannot be titrated according to endogenous TSH levels because of the impaired hypothalamic-pituitary unit. The majority of untreated CH patients show normal (40 %) or elevated TSH levels (35 %) while only a minority has reduced concentrations (25 %) {Faglia, 1979 #1}. These findings are explained by the lack of pulsatile secretion and nocturnal TSH surge, which has been attributed to impaired thyrotroph function in CH patients {Caron, 1986 #2}. Moreover, impaired biological activity of TSH itself due to reduced glycosylation has been described in secondary hypothyroidism.

In a cross sectional study performed in patients with central hypothyroidism, we found elevated cholesterol levels and increased ankle reflex time suggesting subtle hypothyroidism, though fT3 and fT4 serum concentrations were within the normal range. The average dose of thyroxin (T4) applied in these patients with central hypothyroidism was 1.1 µg/kg bw, which is below the average dose recommended in primary hypothyroidism (1.6 µg/kg bw). We hypothesized that these results might indicate suboptimal T4 replacement therapy, not detectable by current laboratory testing.

Hypothesis: To investigate the effects of a body weight adjusted T4 or T3T4 dose on metabolism, well-being and cognitive function.

Study design: Placebo controlled trial in patients with central hypothyroidism following a double blind cross-over design.

Intervention: Three different treatment regimes (5 weeks each) were compared: "CON-T4", empirically chosen, current dose of T4 (1 ± 0.05 μg/kg body weight (bw); "OPT-T4", optimized T4 treatment (1.6 μg/kg bw T4); "T3T4", combination of triiodothyronine (T3, 0.16) and T4 (1.44 μg/kg bw). Biochemical parameters, ankle reflex time and neurocognitive functions were assessed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• hypopituitarism of at least 3 axes (TSH plus gonadotropin, somatotropin, corticotropin or ADH deficiency)

• termination of surgical or radiation treatment of pituitary tumors at least six month before study entry

• BMI of 20 - 39.9 kg/m2

• non-smoking status.

Exclusion Criteria:

• history of cardiovascular or pulmonary diseases

• current thyroxin dosage > 1.6 µg/kg bw

• pregnancy

• epilepsy

• cerebrovascular diseases

• nodular goiter

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperlipidemias
• Hypopituitarism
• Hypothyroidism
• Neoplasm Metastasis
• Secondary Hypothyroidism

Intervention

Drug:
• Thyroxin, Triiodothyronine

Locations

Country	Name	City	State
Germany	University Hospital Freiburg, Department of Medicine	Freiburg	Baden-Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Freiburg

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Slawik M, Klawitter B, Meiser E, Schories M, Zwermann O, Borm K, Peper M, Lubrich B, Hug MJ, Nauck M, Olschewski M, Beuschlein F, Reincke M. Thyroid hormone replacement for central hypothyroidism: a randomized controlled trial comparing two doses of thyro — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	well-being		3 weeks of treatment
Primary	cognitive function		3 weeks of treatment
Secondary	lipid metabolism		3 weeks of treatment
Secondary	muscle function / ankle reflex time		3 weeks of treatment