Rationale: The internal observational data on 514 children and adolescents with ADHD suggest
that 16-28% of them have an abnormal thyroid profile in immuno-analysis: normal free
thyroid-stimulating hormone TSH and T4 but abnormally high free T3. Several
pathophysiological hypotheses can be formulated, some of which relate to possible
polymorphisms of the deiodase or transmembrane carriers of thyroid hormones, and also with
other suspected biological markers of ADHD reported in the literature (low ferritin, atopic
disease and oxidative stress). This abnormal thyroid profile may be an endophenotype of a
subgroup of children and adolescents with ADHD. However, the reference technique for the
determination of free fractions of hormones is chromatography with mass spectrometry and not
immuno-analysis.
Main objective : To confirm by chromatography with mass spectrometry the existence of a
subgroup of children and adolescents with ADHD with this abnormal thyroid profile.
Secondary objectives:
Describe this subgroup by sex (male/female) and age (before 12 and after 12 years)
clinically and neuropsychologically (Attention Network Task and Tower of London coupled
with eye-tracking) and compare it with the rest of the sample.
Dose thyroid hormones and TSH levels with 4 different techniques of immuno-analysis
Calculate the classification concordance (abnormal profile / normal profile) between all
pairs of dosage methods (chromatography and 4 immuno-analysis based techniques)
Calculate 95% reference intervals for all assays and techniques throughout the sample.
Main evaluation criterion: free T3 greater than the 97.5 percentile of the reference interval
in chromatography, free T4 between the 2.5 percentile and the 97.5 percentile with this same
technique, and free TSH between the 2.5 percentile and the 97.5 percentile of the
immuno-analytical reference interval.
Secondary evaluation criteria:
Describe the subgroup and compare it to the rest of the sample:
Number of criteria for inattention, hyperactivity-impulsivity and therefore
clinical presentation of ADHD (Predominant Inattentive, Predominant
Hyperactive-Impulsive, Combined)
Scores for inattention, hyperactivity-impulsivity and their sum on the ADHD-Rating
Scale and score on the Clinical Global Impression - Severity
Pattern of comorbidities diagnosed with Kiddie-SADDS-PL, manual, ocular and
pedestrian preference, presence of atopic disease
Performance at the Attention Network Task and Test of the Tower of London coupled
with eye-tracking
Calculate the classification concordance all pairs of dosage methods (chromatography and
4 immuno-analysis based techniques): correlation, concordance indices 2x2 (for example,
Cohen's kappa)
Calculate 95% reference intervals with age as co-variable and separately for boys and
girls.
Study duration: 30 months (24 months for inclusion and 6 months for data analyses) Study
design: Open-label, cross-sectional (category 2 : interventional research with minimal risks
or constraints), multicentre, no treatment or placebo administration.
Selection criteria:
Inclusion criteria: Boys or girls aged 7 to 17 with ADHD (as per Diagnostic and
Statistical Manual DSM-5 criteria).
Criteria for Non-Inclusion:
Known or concurrent diagnosis of Autism Spectrum Disorder, Schizophrenia or
Psychotic Disorder (as determined by DSM-5), thyroid disease of any origin, genetic
disease known to affect thyroid function.
Any psychotropic treatment (for ADHD or others) in the month before inclusion or
any treatment that may affect thyroid function
Exclusion criteria: Withdrawal of informed consent by at least one of the child's
parents or their legal representative.
Course of the study: The criteria for non-inclusion are checked, the diagnosis is confirmed
using the Kiddie-SADS-PL before the child can be included. The patient's participation stops
after the venous blood collection and the administration of two neuropsychological tests
(Attention Network Task and Tower of London). The tubes are transported to the biochemistry
laboratory of the CHU of Nice which prepares five aliquots (4 for assays in immuno-analysis
including 2 on site, and one for assay in chromatography with mass spectrometry at the CHU of
Toulouse).
Expected outcomes: The identification and clinical characterization of a subgroup of children
and adolescents with ADHD with an abnormal thyroid profile will support the clinical
diagnosis for these at least. Ancillary studies will investigate genetic physiopathological
mechanisms (polymorphisms of deiodases or transmembrane carriers of thyroid hormones) and
link this profile to other biological markers proposed in the literature (low ferritinemia,
higher oxidative stress, atopic comorbid disease). The clinical trajectory of this subgroup
and the persistence of this abnormal thyroid profile in adulthood will be relevant in the
future