Predictors of transient congenital primary hypothyroidism: data from the German registry for congenital hypothyroidism (AQUAPE “HypoDok”)

Abstract

Neonatal screening for congenital primary hypothyroidism (CH) may not distinguish between transient (TCH) and permanent dysfunction (PCH), causing potential overtreatment and concerns in affected families. To specify the indication for interruption of therapy, we analysed the German registry “HypoDok” for infants with CH, which oversees 1625 patients from 49 participating centres in Germany and Austria from 1997 until today. A total of 357 patients with a thyroid gland in loco typico were identified and retrospectively grouped according to cessation (TCH, n = 24) or continuation (PCH, n = 333) of l-thyroxine (l-T4) treatment at 2 years of age. The receiver operating characteristic (ROC) analysis was performed to identify cutoffs predicting TCH by screening TSH concentrations and l-T4 dosages. Gestational ages, birth weights and prevalence of associated malformations were comparable in both groups. The cutoff screening TSH concentration was 73 mU/L. The cutoff daily l-T4 dosage at 1 year was 3.1 μg/kg (90% sensitivity, 63% specificity; 36 μg/day) and at 2 years of age 2.95 μg/kg (91% sensitivity, 59% specificity; 40 μg/day). At 2 years of age, specificity (71%) increased when both of these parameters were considered together.Conclusion: The decision to continue or cease l-T4 treatment at 2 years of age in CH patients diagnosed in neonatal screening may be based on their screening TSH concentrations and individual l-T4 dosages at 1 and 2 years of age. Thus, TCH and PCH may be distinguished; overtreatment avoided; and affected families reassured. What is Known:• The course of congenital primary hypothyroidism may be transient, causing potential overtreatment.• The dose ofl-thyroxine at 1 or 2 years of age may predict a transient course of primary congenital hypothyroidism. What is New:• TSH screening concentration andl-thyroxine dosages at 1 and 2 years of age represent reliable predictors for transient congenital primary hypothyroidism with higher sensitivity and specificity when considered together in order to select eligible patients who qualify for treatment withdrawal.

Primary Congenital Hypothyroidism in Children Below 3 Years Old - Etiology and Treatment With Overtreatment and Undertreatment Risks, a 5-Year Single Centre Experience

“…The important question is if the screening TSH test can be useful to select the patients who could be treated less extensively to avoid overtreatment and reduce parents’ anxiety and medical care costs ( 30 – 32 ). It is known from other data that screening TSH tends to be lower in neonates with TCH than in those with PCH ( 17 , 33 – 35 ). In our study, decreased screening TSH results were observed in newborns with birth weight below -2 SDS who are mostly burdened with TCH risk.…”

“…The diagnosis of CH is confirmed by the thyroid function tests (TFTs) and thyroglobulin (TG) analysis and subsequent immediate treatment implementation with oral, solid or liquid, levothyroxine (L-T4). In PCH the treatment will be life-long, but up to 35% of newborns diagnosed with CH reveal to have TCH, which allows for a trial of L-T4 dose reduction or withdrawal after the critical period of neurodevelopment ( 17 ).…”

Diagnostic Re-Evaluation and Potential Predictor Factors of Transient and Permanent Congenital Hypothyroidism in Eutopic Thyroid Gland

“…This variability can be explained by many factors, such as the inclusion/exclusion criteria, the cutoff of TSH at DBS for diagnosis or the recall strategy, the age of discontinuation of therapy. If the condition of CH due to ectopic gland or athyreosis is also considered, this rate is reduced to 6.7–60% [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. In our current study, the TCH rate was 47.3% when considering only subjects with eutopic thyroid, and 24.8% when considering the whole cohort.…”

“…Many authors have analyzed the risk factors for developing PCH by finding female gender, higher TSH and lower fT4 levels at diagnosis and higher levothyroxine requirement as predictors [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Our data confirm that the thyroid hormonal profile at diagnosis and the levothyroxine requirement upon discontinuation of treatment are predictive for the permanent condition, as well as the presence of extra-thyroid malformations.…”

“…Current data indicate TCH in 20–89% of cases of children with eutopic gland [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. The most important predictive factors of TCH appear to be TSH and fT4 levels at diagnosis and levothyroxine requirement in the first two years of life, but also gender, delivery, prematurity, low birth weight (LBW), maternal risk factors, family history of thyroid disease and consanguinity have been considered as risk factors [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”