Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation
Condition: Secondary Hypothyroidism; Hypopituitarism; Hyperlipidemias
MeSH terms: Neoplasm Metastasis; Hypopituitarism; Hyperlipidemias; Hypothyroidism
Study type: Interventional
Phase: Phase 4

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.
    

Detailed 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.
    

Intervention name(s): Thyroxin, Triiodothyronine
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Treatment
Keywords: secondary hypothyroidism; body weight adjusted thyroxin dose; triiodothyronine supplementation