All-Cause and Disease-specific Mortality and Morbidity in Patients With Congenital Hypothyroidism Treated Since the Neonatal Period: A National Population-based Study

Univ Paris Diderot (J.L.), Sorbonne Paris Cité, F-75019 Paris, France
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 01/2013; 98(2). DOI: 10.1210/jc.2012-2731
Source: PubMed


Context:Little is known about the long-term health of patients treated for congenital hypothyroidism since the neonatal period.Objective:To evaluate the causes of mortality and comorbidity in a population-based registry of young adult patients.Design, Setting, and Participants:All 1772 eligible patients diagnosed during the first decade after the introduction of neonatal screening in France participated in the study. Follow-up data on vital status were available, in May 2010, for 99.5% of the patients. Completed questionnaires were obtained from 1202 of the selected patients.Main Outcome Measures:All-cause and cause-specific mortality and comorbidity.Results:All-cause mortality in the congenital hypothyroidism (CH) patients was slightly higher than expected on the basis of year, age, and sex (standardized mortality ratio [SMR] 1.24, 95% CI: 0.81-1.82). SMRs for each category of underlying cause of death showed mortality due to diseases of the central nervous system (SMR 5.22, 95% CI: 1.68-12.17) and congenital malformations (SMR 3.15, 95% CI: 1.86-6.49) to be significantly higher than expected in the CH patients. The risk of developing an associated chronic disease in the 1202 patients who completed the questionnaire was twice that for the reference population (odds ratio 2.0 [1.32-3.03]). Neurologic or mental diseases and congenital malformations were the most frequent (odds ratios 2.54 [1.12-5.86], 4.18 [1.27-13.76], and 4.36 [1.24-15.34], respectively). Overall, mortality and morbidity were not affected by sex, disease severity, cause of CH, or adequacy of treatment.Conclusion:Prognosis has improved considerably, but a few patients diagnosed during the first 10 years of screening in France nonetheless displayed comorbidity and mortality due to various neurodevelopmental disorders and associated malformations. These results reveal a continuing need for improvements in care and studies to provide knowledge about the full spectrum of the disease and the mechanisms underlying these developmental abnormalities.

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    ABSTRACT: O hipotireoidismo congênito (HC) é o distúrbio endócrino congênito mais frequente, com incidência variando de 1:2.000 a 1:4.000 crianças nascidas vivas e uma das principais causas de retardo mental que pode ser prevenida. Os Programas de Triagem Neonatal para a doença permitem a identificação precoce dos afetados e seu tratamento de modo a evitar as complicações da falta do hormônio. A maioria dos casos de hipotireoidismo congênito é decorrente de disgenesias tireoidianas (85%), entre elas a ectopia, hipoplasia ou agenesia tireoidianas, e os demais resultam de defeitos de síntese hormonal. As crianças afetadas (> 95%) geralmente não apresentam sintomas sugestivos da doença ao nascimento. Os sintomas e sinais mais comuns são: icterícia neonatal prolongada, choro rouco, letargia, movimentos lentos, constipação, macroglossia, hérnia umbilical, fontanelas amplas, hipotonia e pele seca. Várias estratégias são utilizadas para a triagem do HC. No Brasil, esta é obrigatória por lei e geralmente é feita com a dosagem de TSH em sangue seco coletado do calcanhar. A idade recomendada para sua realização é após as 48 horas de vida até o quarto dia. A confirmação diagnóstica é obrigatória com as dosagens de TSH e T4 livre ou T4 total.
    Arquivos Brasileiros de Endocrinologia & Metabologia 03/2013; 57(3). DOI:10.1590/S0004-27302013000300004 · 0.84 Impact Factor
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    ABSTRACT: Congenital hypothyroidism (CH) is the most common congenital endocrine disorder, with an incidence of 1:2,000 to 1:4,000 live births and it is a leading preventable mental retardation. Neonatal Screening Programs allow early identification of the disease and the adequate treatment of affected children can avoid the complications related to deprivation of the hormone. Most cases of primary congenital hypothyroidism (85%) are due to thyroid dysgenesis (ectopia, hypoplasia or agenesis) while the remaining result from defects in hormone synthesis. Affected children (> 95%) usually have no symptoms suggesting the disease at birth. The most frequent symptoms and signs are prolonged neonatal jaundice, hoarse cry, lethargy, slow movements, constipation, macroglossia, umbilical hernia, large fontanelle, hypotonia and dry skin. Around the world, various strategies are used for the screening of the CH. In Brazil, screening for CH is mandatory by law and usually done by serum TSH in dried blood collected from the heel. The recommended age for performing this test is after 48 hours of life until the 4th day. Diagnostic confirmation is required dosing TSH and free T4 or total T4 in serum.
    Arquivos brasileiros de endocrinologia e metabologia 04/2013; 57(3):184-192. · 0.84 Impact Factor
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    ABSTRACT: Context:Untreated hypothyroidism is known to impair hearing, but little is known about the long-term hearing of patients treated for congenital hypothyroidism (CH) since the neonatal period.Objective:To assess hearing and its determinants in a population-based registry of young adult patients with CH.Design, setting and participants:Self-declared hearing loss was evaluated in 1202 of the 1748 eligible patients with CH who completed a questionnaire on health status at a median age of 23.4 years. Audiograms were obtained for one third of the patients declaring hearing loss (37/107).Main outcome measures:Self-declared hearing loss and audiogram characteristics for patients reporting hearing impairment.Results:These patients had a risk of self-declared hearing loss more than three times higher than that for the reference population [RR= 3.7 (2.9-4.7)]. Hearing impairment was diagnosed at a median age of 7.0 (3.4-19.0) years and 17 % of affected patients required hearing support in early adulthood. Hearing loss was associated with the type of CH (patients with athyreosis and gland in situ being more frequently affected than those with ectopic gland [RR= 2.61 (1.77-3.88)]), disease severity, as assessed by bone maturation delay at the time of diagnosis, with at least one knee epiphyseal ossification center absent in the most severe form [RR= 2.29 (1.39-3.79)] and with other associated chronic diseases [RR= 3.64 (2.35-5.62)]. A trend for association with serum FT4 concentration at diagnosis was also observed [RR= 1.47 (0.96-2.23]. Hearing loss was mostly bilateral (90%), mild to moderate (96%), of the sensorineural type (76%) and concerned high or very high frequencies.Conclusion:Despite major improvements in prognosis, hearing loss remains a significant problem, particularly in patients with severe CH. Parents and primary care providers should be aware of this risk, as early diagnosis and intervention could improve the long-term prognosis of these patients.
    The Journal of Clinical Endocrinology and Metabolism 06/2013; 98(9). DOI:10.1210/jc.2013-1645 · 6.21 Impact Factor
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