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Alterations of neonatal thyroid function
A Grüters1, H Krude, H Biebermann
1Department of Pediatrics, Charité University Hospital, Humboldt University, Berlin, Germany.
Insights
Genetic analysis advances neonatal thyroid disorder diagnosis and treatment. Understanding gene mutations like TSH receptor and PAX8 aids in identifying congenital hypothyroidism and hyperthyroidism, improving patient outcomes.
Area of Science:
- Endocrinology
- Medical Genetics
- Neonatology
Background:
- Neonatal thyroid disorders encompass hypothyroidism and hyperthyroidism with diverse etiologies.
- Genetic factors play a significant role in the pathogenesis of these conditions.
- Early diagnosis and intervention are crucial for optimal neurodevelopmental outcomes in affected infants.
Purpose of the Study:
- To review recent advancements in understanding the genetic basis of neonatal thyroid disorders.
- To highlight the clinical utility of molecular genetic analysis in diagnosing and managing these conditions.
- To emphasize the impact of genetic discoveries on patient care and therapeutic decision-making.
Main Methods:
- Review of recent scientific literature on neonatal thyroid disorders and their genetic underpinnings.
- Analysis of identified gene mutations (e.g., thyroid peroxidase, thyroglobulin, TSH receptor, PAX8) and their inheritance patterns.
- Correlation of molecular findings with clinical phenotypes and diagnostic/therapeutic strategies.
Main Results:
- Autosomal recessive mutations in thyroid peroxidase and thyroglobulin genes are linked to congenital hypothyroidism (CH).
- Mutations in the TSH receptor gene are associated with CH, thyroid hypoplasia, and non-autoimmune hyperthyroidism.
- Autosomal dominant PAX8 gene mutations are implicated in various forms of thyroid dysgenesis.
- Molecular genetic analysis enables rapid diagnosis of central CH missed by screening and guides treatment for hyperthyroidism.
Conclusions:
- Molecular genetic studies are essential for the comprehensive diagnostic work-up of neonatal thyroid alterations.
- Understanding the genetic etiology of neonatal thyroid disorders improves diagnostic accuracy and facilitates personalized therapeutic approaches.
- Genetic insights into neonatal thyroid disease are critical for guiding management, ensuring normal fertility, and preventing long-term complications.
Abstract:
Recent progress has been made in understanding the pathogenesis of neonatal thyroid disorders. Autosomal recessive inheritance of mutations of the thyroid peroxidase and thyroglobulin genes has been described in some patients with congenital hypothyroidism (CH) and a family history of CH. Autosomal recessive inheritance of mutations of the thyrotrophin (TSH) receptor gene has also been reported in patients with CH and thyroid hypoplasia, and autosomal dominant mutations of the PAX8 gene have been described in patients with different forms of thyroid dysgenesis. These discoveries are important for patients with CH diagnosed by neonatal screening, as these patients will have normal fertility. The molecular genetic analysis of mutations of the TSH gene in patients with familial and sporadic cases of isolated central CH, who are missed by TSH screening programmes, now enables rapid diagnosis and appropriate therapy in the neonate. In newborn infants with severe non-autoimmune hyperthyroidism, autosomal dominant gain-of-function mutations in the TSH receptor gene have been demonstrated. In these patients, molecular genetic studies are extremely helpful in therapeutic decision making, as early thyroid ablation is the only effective treatment that avoids the sequelae of long-term hyperthyroidism. Molecular genetic studies are therefore useful in the diagnostic work-up of neonatal thyroid alterations.