Detecting Congenital Central Hypothyroidism by Newborn Screening

Difficulty in Distinguishing from Congenital Thyroxine-Binding Globulin Deficiency

Kara Connelly, Melinda J. Pierce, Cheryl Hanna, Stephen Lafranchi

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1 Citation (Scopus)

Abstract

Background/Aims: Congenital central hypothyroidism (CH-C) can be detected on newborn screening (NBS) by programs using thyroxine (T4)-reflex thyroid-stimulating hormone (TSH) test approach. CH-C must be distinguished from T4-binding globulin (TBG) deficiency. We sought to determine whether thyroid function tests reliably separate CH-C from TBG deficiency. Methods: We analyzed NBS and serum free and total T4, T3 resin uptake (T3RU) or TBG, and TSH for infants in the Northwest Regional NBS Program (NWRSP) between the years 2008 and 2015 with either CH-C or TBG deficiency. Results: We discovered a significant overlap in T3RU and TBG levels amongst 21 cases of CH-C and 250 cases of TBG deficiency. Mean serum TBG levels were lower in CH-C cases (20.3 µg/mL, range 14.2–33.3) than what is reported in healthy infants (28.6 µg/mL, range 19.1–44.6). Serum free T4 was lower in CH-C cases than TBG deficiency but did not always differentiate between the two conditions. Conclusion: CH-C benefits from detection on NBS but must be distinguished from TBG deficiency. The diagnosis of CH-C rests solely on subnormal serum free T4, but is supported by the demonstration of other pituitary hormone deficiencies. As an overlap exists, serum TBG (or T3RU) levels do not play a role in the diagnosis of CH-C.

Original languageEnglish (US)
JournalHormone Research in Paediatrics
DOIs
StateAccepted/In press - Sep 14 2017

Fingerprint

Congenital Hypothyroidism
Globulins
Newborn Infant
Serum
Thyrotropin
Thyroxine-Binding Globulin Deficiency
Thyroid Function Tests
Pituitary Hormones
Thyroxine
Reflex

Keywords

  • Congenital hypothyroidism
  • Newborn screening

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

@article{761389fb4b7140f6b79248b9c7f673db,
title = "Detecting Congenital Central Hypothyroidism by Newborn Screening: Difficulty in Distinguishing from Congenital Thyroxine-Binding Globulin Deficiency",
abstract = "Background/Aims: Congenital central hypothyroidism (CH-C) can be detected on newborn screening (NBS) by programs using thyroxine (T4)-reflex thyroid-stimulating hormone (TSH) test approach. CH-C must be distinguished from T4-binding globulin (TBG) deficiency. We sought to determine whether thyroid function tests reliably separate CH-C from TBG deficiency. Methods: We analyzed NBS and serum free and total T4, T3 resin uptake (T3RU) or TBG, and TSH for infants in the Northwest Regional NBS Program (NWRSP) between the years 2008 and 2015 with either CH-C or TBG deficiency. Results: We discovered a significant overlap in T3RU and TBG levels amongst 21 cases of CH-C and 250 cases of TBG deficiency. Mean serum TBG levels were lower in CH-C cases (20.3 µg/mL, range 14.2–33.3) than what is reported in healthy infants (28.6 µg/mL, range 19.1–44.6). Serum free T4 was lower in CH-C cases than TBG deficiency but did not always differentiate between the two conditions. Conclusion: CH-C benefits from detection on NBS but must be distinguished from TBG deficiency. The diagnosis of CH-C rests solely on subnormal serum free T4, but is supported by the demonstration of other pituitary hormone deficiencies. As an overlap exists, serum TBG (or T3RU) levels do not play a role in the diagnosis of CH-C.",
keywords = "Congenital hypothyroidism, Newborn screening",
author = "Kara Connelly and Pierce, {Melinda J.} and Cheryl Hanna and Stephen Lafranchi",
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language = "English (US)",
journal = "Hormone Research in Paediatrics",
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T1 - Detecting Congenital Central Hypothyroidism by Newborn Screening

T2 - Difficulty in Distinguishing from Congenital Thyroxine-Binding Globulin Deficiency

AU - Connelly, Kara

AU - Pierce, Melinda J.

AU - Hanna, Cheryl

AU - Lafranchi, Stephen

PY - 2017/9/14

Y1 - 2017/9/14

N2 - Background/Aims: Congenital central hypothyroidism (CH-C) can be detected on newborn screening (NBS) by programs using thyroxine (T4)-reflex thyroid-stimulating hormone (TSH) test approach. CH-C must be distinguished from T4-binding globulin (TBG) deficiency. We sought to determine whether thyroid function tests reliably separate CH-C from TBG deficiency. Methods: We analyzed NBS and serum free and total T4, T3 resin uptake (T3RU) or TBG, and TSH for infants in the Northwest Regional NBS Program (NWRSP) between the years 2008 and 2015 with either CH-C or TBG deficiency. Results: We discovered a significant overlap in T3RU and TBG levels amongst 21 cases of CH-C and 250 cases of TBG deficiency. Mean serum TBG levels were lower in CH-C cases (20.3 µg/mL, range 14.2–33.3) than what is reported in healthy infants (28.6 µg/mL, range 19.1–44.6). Serum free T4 was lower in CH-C cases than TBG deficiency but did not always differentiate between the two conditions. Conclusion: CH-C benefits from detection on NBS but must be distinguished from TBG deficiency. The diagnosis of CH-C rests solely on subnormal serum free T4, but is supported by the demonstration of other pituitary hormone deficiencies. As an overlap exists, serum TBG (or T3RU) levels do not play a role in the diagnosis of CH-C.

AB - Background/Aims: Congenital central hypothyroidism (CH-C) can be detected on newborn screening (NBS) by programs using thyroxine (T4)-reflex thyroid-stimulating hormone (TSH) test approach. CH-C must be distinguished from T4-binding globulin (TBG) deficiency. We sought to determine whether thyroid function tests reliably separate CH-C from TBG deficiency. Methods: We analyzed NBS and serum free and total T4, T3 resin uptake (T3RU) or TBG, and TSH for infants in the Northwest Regional NBS Program (NWRSP) between the years 2008 and 2015 with either CH-C or TBG deficiency. Results: We discovered a significant overlap in T3RU and TBG levels amongst 21 cases of CH-C and 250 cases of TBG deficiency. Mean serum TBG levels were lower in CH-C cases (20.3 µg/mL, range 14.2–33.3) than what is reported in healthy infants (28.6 µg/mL, range 19.1–44.6). Serum free T4 was lower in CH-C cases than TBG deficiency but did not always differentiate between the two conditions. Conclusion: CH-C benefits from detection on NBS but must be distinguished from TBG deficiency. The diagnosis of CH-C rests solely on subnormal serum free T4, but is supported by the demonstration of other pituitary hormone deficiencies. As an overlap exists, serum TBG (or T3RU) levels do not play a role in the diagnosis of CH-C.

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