Effect of treatment with levothyroxine in a patient with thyroid hormone receptor *1 deficiency

Thyroid hormone receptor *1 (TR*1) deficiency is a recently identified syndrome
in which patients present with resistance to thyroid hormone at the tissue
level characterised by growth retardation, cognitive defects and delayed bone
development. The standard form of treatment for this disorder is levothyroxine.
The effects of TR*1 deficiency and levothyroxine treatment on innate immune
function, erythropoiesis, metabolomics and thyroid hormone target gene
expression have not yet been studied. We have recently identified a new patient
with TR*1 deficiency who has not yet started treatment. This patient presents a
unique opportunity to study the role of TR* and the effects of treatment with
levothyroxine in these physiological processes.

Objective: The primary objective of the study is to determine the effect of
standard treatment with levothyroxine in TR*1 deficiency on:
- Neutrophil and macrophage function
- Erythropoiesis
- Thyroid hormone target gene expression
- Plasma metabolome

Study design: Observational laboratory study

Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: The TR*1 deficient patient will undergo
venipuncture 4 times in total (max. 73,5 ml). Once prior to the start of
treatment and at 3, 6 and 12 months following the start of treatment.
Venipunctures after the start of treatment will be scheduled to coincide with
diagnostic venipunctures to avoid additional hospital visits. Healthy controls
will undergo venipuncture only once (18 ml). Venous blood collection may result
in minor discomfort and carries a small risk of bruising and bleeding.