Randomized Crossover Trial for the Evaluation of the Possible Effects in the Intestine of Two Different Pharmaceutical Forms of L - Thyroxine in Patients With Primary Acquired Hypothyroidism
Randomized Crossover Trial for the Evaluation of the Possible Effects in the Intestine of Two Different Pharmaceutical Forms of L - Thyroxine in Patients With Primary Acquired Hypothyroidism
Thyroid disorders, in particular hypothyroidism, are associated with gastrointestinal
 impairment, such as celiac disease. A study reported an increased prevalence of celiac
 disease in a large cohort of children affected by congenital hypothyroidism, underlying the
 relationship between these two conditions. The hypothesis of our study is that the onset of
 celiac disorder may be related to the gut concentration of thyroid hormone (TH) in
 hypothyroidism patients treated with replacement therapy. In fact, TH replacement therapy
 showed a low bioavailability with a consequent high gut concentration. Two different
 pharmaceutical formulations (liquid and solid, per os) are available. The liquid one has a
 better absorption profile and bioavailability than the solid; therefore, it is associated
 with a low TH intestinal concentration. According to our hypothesis, the solid TH formulation
 could increase the microbial diversity in the gut instead of the liquid form, due to the high
 local TH concentration. Based on these findings, the purpose of this study is to evaluate the
 effect of two different pharmaceutical formulations of TH on the gut in terms of modification
 of gut microbiota, inflammatory parameters and gut absorption.
Inclusion Criteria:

 -  Children with primary acquired hypothyroidism that require Levothyroxine therapy
 (naïve patients, < 18 years)

 -  Informed consent from parents and patient

 Exclusion Criteria:

 -  Age < 3 years

 -  Patients with secondary hypothyroidism, euthyroid sick syndrome or thyroid hormone
 resistant

 -  Patients with celiac disease, type I diabetes or other known autoimmune diseases

 -  Patients with genetic diseases or syndromes, such as Down, Williams-Beuren, Turner

 -  Assumption of antibiotics, probiotics, prebiotics, or other medications that could
 affect the gut microbiota in the month before the beginning of the study

 -  Gastrointestinal infectious diseases in the month before the beginning of the study

 -  Hypersensitivity to levothyroxine or any of the ingredients contained in the two
 pharmaceutical formulations

 -  Untreated adrenal insufficiency, untreated pituitary insufficiency and untreated
 thyrotoxicosis.

 -  Patients with cardiovascular disease

 -  Patients who show with impaired pancreatic function measured using the assay in faecal
 fat (steatocrit) at the screening visit