Newborn screening for central congenital hypothyroidism: past, present and future

Area of Science:

• Pediatrics
• Endocrinology
• Genetics

Background:

• Congenital hypothyroidism (CH) is a leading cause of preventable intellectual disability.
• Central CH results from impaired pituitary or hypothalamic thyroid control, often occurring with other pituitary hormone deficiencies (MPHD).
• MPHD at birth (congenital hypopituitarism) can be life-threatening due to potential adrenal and growth hormone deficiencies.

Purpose of the Study:

• To review the historical development, current status, and future directions of newborn screening (NBS) for central CH.
• To emphasize the importance of early detection of central CH for timely intervention.
• To discuss the challenges and opportunities associated with implementing NBS for central CH.

Main Methods:

• Review of existing literature and historical NBS programs for CH.
• Analysis of biochemical markers used in NBS (T4-based vs. TSH-based methods).
• Discussion of the clinical implications of central CH and MPHD.

Main Results:

• Central CH is a rare cause of CH but is the only pituitary hormone deficiency suitable for NBS.
• Early NBS programs using T4-based methods could detect central CH, but TSH-based methods, now widely adopted, have a high false-positive rate for central CH.
• Only a limited number of countries have NBS programs capable of detecting central CH 50 years after NBS for CH began.

Conclusions:

• Early detection of central CH through NBS is critical for preventing severe health consequences, including intellectual disability and life-threatening conditions.
• Current NBS strategies face challenges in accurately identifying central CH, necessitating advancements in screening technology and protocols.
• Future NBS programs should aim to incorporate reliable methods for detecting central CH to ensure comprehensive newborn screening.