Role of Next Generation Sequencing in the Etiological Diagnosis of Permanent Congenital Hypothyroidism With in Situ Thyroid

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

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.

Study Overview

• Status: Recruiting
• Conditions: Congenital Hypothyroidism

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.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

• Study Contact: Name: Rita Ortolano, MD; Phone Number: 00390512144816; Email: rita.ortolano@aosp.bo.it

Study Locations

• Italy
  • Bologna
    • Bologna, Bologna, Italy, 40138
      • Recruiting
      • IRCCS Azienda Ospedaliero-Universitaria di Bologna
      • Contact: Rita Ortolano, MD; Phone Number: 00390512144816; Email: rita.ortolano@aosp.bo.it
      • Principal Investigator: Rita Ortolano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NGS sequencing of a panel of target genes for thyroid pathology	DUOX2, DUOXA2, FOXE1, GLIS3, IGSF1, IYD, NIKX2-1, NIKX2-5, PAX8, SLC16A2, SLC26A4, SLC5A5, TG, THRA, THRB, TPO, TSHB, and TSHR genes	At the time of diagnostic reevaluation, on average 1 year after diagnosis, if permanent congenital hypothyroidism is confirmed

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TSH value at screening test, and at diagnostic confirmation	microU/ml	at baseline
ft4 values at diagnostic confirmation	pg/ml	at baseline

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Rita Ortolano, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: December 6, 2024
• First Posted (Actual): December 11, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Congenital Hypothyroidism
• Additional Relevant MeSH Terms: Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Thyroid Diseases; Bone Diseases, Endocrine; Bone Diseases, Developmental; Dwarfism; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypothyroidism; Congenital Hypothyroidism
• Other Study ID Numbers: IPOGEN2-20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No