Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.

<h4>Background</h4>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)...

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Main Authors: Beatriz Carmona-Hidalgo, Estefanía Herrera-Ramos, Rocío Rodríguez-López, Laia Nou-Fontanet, José C Moreno, Juan Antonio Blasco-Amaro, Juliane Léger, Juan Darío Ortigoza-Escobar, NKX2-1-Related Disorders Guideline Working Group
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0309064
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author Beatriz Carmona-Hidalgo
Estefanía Herrera-Ramos
Rocío Rodríguez-López
Laia Nou-Fontanet
José C Moreno
Juan Antonio Blasco-Amaro
Juliane Léger
Juan Darío Ortigoza-Escobar
NKX2-1-Related Disorders Guideline Working Group
author_facet Beatriz Carmona-Hidalgo
Estefanía Herrera-Ramos
Rocío Rodríguez-López
Laia Nou-Fontanet
José C Moreno
Juan Antonio Blasco-Amaro
Juliane Léger
Juan Darío Ortigoza-Escobar
NKX2-1-Related Disorders Guideline Working Group
author_sort Beatriz Carmona-Hidalgo
collection DOAJ
description <h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
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spelling doaj-art-dbbd3da4118a4b4f95af8185d101cb7e2025-08-20T02:50:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011910e030906410.1371/journal.pone.0309064Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.Beatriz Carmona-HidalgoEstefanía Herrera-RamosRocío Rodríguez-LópezLaia Nou-FontanetJosé C MorenoJuan Antonio Blasco-AmaroJuliane LégerJuan Darío Ortigoza-EscobarNKX2-1-Related Disorders Guideline Working Group<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0309064
spellingShingle Beatriz Carmona-Hidalgo
Estefanía Herrera-Ramos
Rocío Rodríguez-López
Laia Nou-Fontanet
José C Moreno
Juan Antonio Blasco-Amaro
Juliane Léger
Juan Darío Ortigoza-Escobar
NKX2-1-Related Disorders Guideline Working Group
Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.
PLoS ONE
title Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.
title_full Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.
title_fullStr Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.
title_full_unstemmed Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.
title_short Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.
title_sort systematic review of thyroid function in nkx2 1 related disorders treatment and follow up
url https://doi.org/10.1371/journal.pone.0309064
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