Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection

Abstract

Background/Aim: Congenital hypothyroidism (CH) is a heterogeneous entity. Neonatal screening programs based on thyrotropin (TSH) determination allow primary CH diagnosis but miss central CH (CCH). CCH causes morbidity, alerts to other pituitary deficiencies, and is more prevalent than previously thought. We aimed at developing a pilot neonatal screening program for CCH detection. Patients and Methods: A prospective 2-year pilot neonatal screening study based on simultaneous dried blood specimen TSH and thyroxine (T₄) measurements was implemented in term newborns aged 2–7 days. Those with T₄ ≤4.5 µg/dL (–2.3 SDS) and TSH <10 mIU/L were recalled (suspicious of CCH) and underwent clinical and biochemical assessment performed by expert pediatric endocrinologists. Results: A total of 67,719 newborns were screened. Primary CH was confirmed in 24 (1: 2,821). Forty-four newborns with potential CCH were recalled (recall rate 0.07%) at a mean age of 12.6 ± 4.8 days. In this group, permanent CCH was confirmed in 3 (1: 22,573), starting L-T₄ treatment at a mean age of 12.3 ± 6.6 days; 14 boys showed T₄-binding globulin deficiency (1: 4,837); 24 had transient hypothyroxinemia (21 non-thyroidal illness and 3 healthy); and 3 died before the confirmation stage. According to initial free T₄ measurements, CCH patients had moderate hypothyroidism. Conclusions: Adding T₄ to TSH measurements enabled the identification of CCH as a prevalent condition and contributed to improving the care of newborns with congenital hypopituitarism and recognizing other thyroidal disorders.

Determining Reference Ranges for Total T4 in Dried Blood Samples for Newborn Screening

“…Multiple studies underline the importance of C-CH detection by arguing that C-CH is more common than previously thought [4,32]. Also, according to Zwaveling-Soonawala et al, C-CH may fulfil the screening criteria because it is relatively frequent, testing methods are inexpensive, effective treatment is available, and the risks of an unfavorable outcome are well known [33].…”

Reference Percentiles and Changes over Time for Total Thyroxine in Preterm Infants: A Retrospective Cohort Study

“…Central congenital hypothyroidism (CCH) is less common than PCH, with a reported incidence of 1:16,000 to 1:21,600 [ 3 , 5 ]. This incidence is comparable to other conditions included in NS programs such as phenylketonuria or galactosemia [ 3 , 6 ].…”

“…CCH results from inappropriate thyroid hormone production caused by defective stimulation of a normal thyroid gland by the thyroid-stimulating hormone (TSH) [ 3 ]. CCH manifests with normal or subnormal TSH concentration despite subnormal thyroid hormone concentration [ 3 , 5 ]. Only the programs in which total thyroxine (tT4) or free thyroxine (fT4) are measured simultaneously with TSH or in a stepwise manner with an initial tT4 measurement are capable of detecting CCH [ 2 ].…”

Genome-wide methylation study of whole blood cells�DNA in men with congenital hypopituitarism disease

“…Prenatal or birth trauma and/or asphyxia and specific types of midline defect syndromes may additionally lead to CH ( 12 ); however, their association with CH are usually hard to determine. The underlying mechanisms for the clinical symptoms of patients with CH are due to the deficiency in pituitary hormones, including the growth hormone, adrenocorticotropin (ACTH), prolactin (PRL), thyroid stimulating hormone (TSH), luteinising hormone (LH) and follicle-stimulating hormone (FSH) ( 13 ). These deficiencies result in recurrent hypoglycemia and acute adrenal insufficiency with impairments of growth and neurodevelopment ( 13 ).…”

“…The underlying mechanisms for the clinical symptoms of patients with CH are due to the deficiency in pituitary hormones, including the growth hormone, adrenocorticotropin (ACTH), prolactin (PRL), thyroid stimulating hormone (TSH), luteinising hormone (LH) and follicle-stimulating hormone (FSH) ( 13 ). These deficiencies result in recurrent hypoglycemia and acute adrenal insufficiency with impairments of growth and neurodevelopment ( 13 ). Furthermore, due to the lack of gonadotropin hormones, spermatogenesis and/or testicular development are abnormal, resulting in infertility for male patients.…”