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Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up
Beatriz Carmona-Hidalgo1, Estefanía Herrera-Ramos2,3,4, Rocío Rodríguez-López1
1Health Technology Assessment Area-AETSA, Andalusian Public Foundation for Progress and Health ("Fundación Progreso y Salud"-"FPS"), Seville, Spain.
Background:
NKX2-1, a crucial transcription factor in thyroid, lung, and brain development, is associated with rare disorders featuring thyroid dysfunction, neurological abnormalities, and respiratory symptoms. The primary challenge in managing NKX2-1-related disorders (NKX2-1-RD) is early diagnosis of the genetic defect and treating specific endocrine disorders. Levothyroxine (LT4) serves as the standard hypothyroidism treatment, with required dosages influenced by the severity of the individual's disorder, which varies widely among affected individuals.
Objectives:
This systematic review aims to assess the effectiveness of LT4 treatment in NKX2-1-RD and explore optimal dosing strategies. The primary focus is on the challenges associated with the prompt diagnosis of genetic defects, rather than the established treatment protocols for individual endocrine failures.
Methods:
Adhering to PRISMA guidelines, the review includes 42 studies involving 110 genetically confirmed NKX2-1-RD patients with hypothyroidism. The study investigates congenital hypothyroidism as the most prevalent endocrine alteration, along with gestational and overt hypothyroidism. The administration of LT4 treatment, dosages, and patient responses are analyzed.
Results:
Among the findings, congenital hypothyroidism emerges as the predominant endocrine alteration in 41% of patients. Notably, LT4 treatment is administered in only 10% of cases, with a mean dose of 52 μg/day. The variability in initiation and dosage is likely influenced by the age at diagnosis. Positive responses, characterized by TSH adjustments within normal ranges, are observed in 11 monitored patients.
Conclusions:
Early detection of congenital hypothyroidism is emphasized for timely LT4 initiation. Challenges in standardization are highlighted due to the variability in clinical manifestations and diagnostic procedures across NKX2-1-RD cases. While this review provides valuable insights into thyroid and pituitary disease treatment, limited details on LT4 treatment represent a significant study limitation. Key reporting points for future case studies are proposed to enhance the understanding and management of NKX2-1-RD hypothyroidism.
Insights
Early diagnosis of congenital hypothyroidism is key for treating NKX2-1-RD. Levothyroxine (LT4) treatment effectiveness varies, highlighting the need for standardized dosing strategies in these rare genetic disorders.
Area of Science:
- Genetics and Endocrinology
- Rare disease research
- Transcription factor function
Background:
- NKX2-1 transcription factor is vital for thyroid, lung, and brain development.
- NKX2-1-related disorders (NKX2-1-RD) present with thyroid dysfunction, neurological, and respiratory issues.
- Managing NKX2-1-RD requires early genetic diagnosis and tailored endocrine treatment, with Levothyroxine (LT4) as standard for hypothyroidism.
Purpose of the Study:
- To systematically review Levothyroxine (LT4) treatment effectiveness in NKX2-1-RD.
- To explore optimal LT4 dosing strategies for patients with NKX2-1-RD.
- To address challenges in the prompt diagnosis of genetic defects in NKX2-1-RD.
Main Methods:
- Systematic review adhering to PRISMA guidelines.
- Inclusion of 42 studies with 110 genetically confirmed NKX2-1-RD patients.
- Analysis of congenital, gestational, and overt hypothyroidism, LT4 administration, dosages, and patient responses.
Main Results:
- Congenital hypothyroidism is the most frequent endocrine alteration (41% of patients).
- LT4 treatment was administered in only 10% of cases, with a mean dose of 52 μg/day.
- Variability in LT4 initiation and dosage is linked to age at diagnosis; positive TSH responses noted in 11 patients.
Conclusions:
- Timely LT4 initiation is crucial upon early detection of congenital hypothyroidism in NKX2-1-RD.
- Standardization of treatment is challenging due to diverse clinical and diagnostic variability in NKX2-1-RD.
- Further research and standardized reporting are needed to improve understanding and management of hypothyroidism in NKX2-1-RD.
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