Clinical trial NCT06728735: Role of Next Generation Sequencing in the Etiological Diagnosis of Permanent Congenital Hypothyroidism with in Situ Thyroid
Official title: Role of Next Generation Sequencing in the Etiological Diagnosis of Permanent Congenital Hypothyroidism with in Situ Thyroid: Preliminary Data in Patients Followed At the Regional Neonatal Screening Centre for Endrocrine-Metabolic Disease in Bologna
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Congenital Hypothyroidism
Keywords: Congenital Hypothyroidism
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
First posted: 2024-12-11
Enrollment: 350
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients born in Emilia-Romagna, Italy, between January 2003 and December 2023, recalled by the Regional Centre for Neonatal Screening for Endrocrine-Metabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy, for suspected congenital hypothyroidism and diagnosed with congenital hypothyroidism and in situ thyroid.

Brief summary: Retro-prospective, exploratory, single-centre observational study conducted at the Endrocrine-Metabolic Diseases Centre of the Pediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

The primary aim is to assess, by NGS sequencing of a panel of target genes, the frequency and type of variants with potential pathogenic significance in a patient population with congenital hypothyroidism and in situ thyroid, born between January 2003 and December 2023 identified through Neontal Screening at the Regional Centre for Neonatal Screening for Endrocrine-Metabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

Detailed description: The primary aim of this study is to assess by NGS sequencing of a panel of target genes, the frequency and type of variants with potential pathogenic significance in a patient population with congenital hypothyroidism and in situ thyroid, born between January 2003 and December 2023 identified through Neontal Screening at the Regional Centre for Neonatal Screening for Endrocrine-Metabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

The secondary aims are to identify possible associations between genotype and phenotype; assess the risk of familial recurrence by searching for specific familial mutations; estimate the frequency of congenital hypothyroidisms with thyroid in situ out of the total number of congenital hypothyroidisms at the time of diagnostic confirmation; estimate the percentage frequency of transient and permanent congenital hypothyroidisms in patients with a thyroid in situ at diagnostic re-evaluation; identify possible prognostic factors for transient or permanent congenital hypothyroidism.

The retrospective phase of the study consists of the collection and analysis of clinical, hormonal and instrumental data of the cohort of patients enrolled by consulting their clinical records. More in detail, data on complete medical history, family history, physical examination with evaluation of major associated malformations, and thyroid ecography will be retrospectively collected.

Among this cohort, patients who have been diagnosed with permanent congenital hypothyroidism following diagnostic re-evaluation, according to clinical practice, will undergo molecular analysis by NGS sequencing of a panel of target genes for thyroid pathology.

Eligibility criteria: Inclusion Criteria:

* Patients born in Emilia-Romagna region, Italy, between January 2003 and December 2023;
* Patients screened at the Regional Neonatal Screening Centre for Endrocrine-Metabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy, and recalled for suspected congenital hypothyroidism;
* Confirmed diagnosis of congenital hypothyroidism and in situ thyroid;
* Hormonal and clinical follow-up of at least 36 months at Centre for Endrocrine-Metabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy;
* Obtaining informed consent from parents/legal guardians of paediatric patients.

Exclusion Criteria:

• Patients with hypothyroidism associated with chromosomal syndromes.

Primary outcomes:
measure: NGS sequencing of a panel of target genes for thyroid pathology
timeFrame: At the time of diagnostic reevaluation, on average 1 year after diagnosis, if permanent congenital hypothyroidism is confirmed
Secondary outcomes:
measure: TSH value at screening test, and at diagnostic confirmation
timeFrame: at baseline
measure: ft4 values at diagnostic confirmation
timeFrame: at baseline
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Study officials:
affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna
name: Valeria Di Natale, MD
role: PRINCIPAL_INVESTIGATOR
References: