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Thyroid Disorders
Consequences of the Use of Low Blood-spot Thyroid-stimulating Hormone
Cut-offs for the Neonatal Screening of Congenital Hypothyroidism
Luca Persani
1
and Davide Calebiro
2
1. Associate Professor of Endocrinology; 2. Post-doctoral Research Fellow, Department of Medical Sciences, University of Milan, and
Laboratory of Experimental Endocrinology, IRCCS Istituto Auxologico Italiano
Abstract
The consequences of using low blood-spot thyroid-stimulating hormone (b-TSH) cut-off values for newborn screening of congenital
hypothyroidism (CH) are largely unknown. Therefore, the impact on CH epidemiology and classification generated by the introduction in our
Italian region of a low b-TSH cut-off during 1999–2005 was retrospectively examined. This work was recently performed in collaboration
with the Laboratory for Neonatal Screening and the Principal Follow-up Centre of the Lombardy region. The incidence of CH in this Italian
population was 1:1,446 live births, with a predominance of functional over morphogenetic defects. The use of low b-TSH cut-offs allowed
the detection of an unsuspected number of children with neonatal hypothyroidism, evolving to mild permanent thyroid dysfunction later
in life. Premature birth was associated with a three- to five-fold increased risk of CH with gland in situ.
Keywords
Newborn screening, congenital hypothyroidism, thyroid-stimulating hormone, thyroid dyshormogenesis, thyroid dysgenesis, premature birth
Disclosure: The authors have no conflicts of interest to declare.
Received: 25 May 2009 Accepted: 21 July 2009
Correspondence: Luca Persani, Department of Medical Sciences, University of Milan, Laboratory of Experimental Endocrinology, IRCCS Istituto Auxologico Italiano,
Via Zucchi, 18, 20095 Cusano, Milan, Italy. E:
luca.persani@unimi.it
Congenital hypothyroidism (CH) is the most common congenital milder CH forms are devoid of neurological consequences.
endocrine disease and avoidable cause of severe mental retardation. However, definitive proof for this hypothesis is lacking.
L-thyroxine supplementation started by two to three weeks of age
can prevent severe neurological damage. Thus, in economically Considerable advances in the analytical performance of TSH
advanced countries, neonatal screening programmes have been measurements have been made during recent years, and highly
instituted to allow early CH detection and initiation of therapy. sensitive TSH assays are now largely employed as the first-line test
for thyroid function.
9
As a direct consequence of such analytical
In the mid-1970s, a newborn screening programme for CH was improvements, lowering of the upper limit of normal range for TSH
started in Quebec and rapidly developed in other countries.
1–4
Two determination has been recommended.
9,10
Thus, all of these
principal screening strategies have been followed: a primary considerations justify studies aimed at investigating the impact that
thyroid-stimulating hormone (TSH) method, more common in more sensitive screening strategies may have on the incidence and
Europe, Japan and Oceania, and a primary T4 method, more clinical classification of the disease.
common in North America. The use of these strategies has allowed
the early detection of a larger number of CH cases, with a currently The screening centre in the Lombardy region uses a primary TSH
reported incidence of 1:3,000–4,000 newborns.
1–4
A recent method for the screening of about 89,000 newborns per year. This
European survey on about 6 million newborns, mostly screened reference centre chose to shift the blood-spot TSH (b-TSH) cut-off
using a primary TSH method, reported an overall incidence of level from 20mU/l down to 12mU/l in 1999 and to 10mU/l in 2002.
1:2,709.
5
In 1987–2003, the Italian CH Registry reported a national The thyroid function parameters and clinical features at birth of all
incidence of 1:2,500 out of about 7,520,000 live newborns.
6
children born over a seven-year period in Lombardy were
retrospectively analysed with the aim of verifying the impact of
The current understanding of CH indicates that morphogenetic lower b-TSH cut-off values on the epidemiology and clinical
defects (athyreosis, ectopy, hemiagenesis or hypoplasia) account classification of CH.
11
for about 75% of total cases. The remainder have a thyroid gland in
situ (GIS) that may be associated with either transient or permanent Results and Discussion
functional defects.
1–8
This classification is based on the experience During 1999–2005, in Lombardy 629,042 newborns were screened
with screening programmes using primary T4 determination or TSH for CH using low b-TSH cut-offs (12/10mU/l). The main results are
cut-off values of 20–40mU/l in the dry blood-spot. These strategies illustrated in Table 1 and Figure 1. We found a CH incidence of
have been followed mainly in order to avoid excessive recall rates 1:1,446 live newborns, which is at least double that currently
and limit costs, and were justified by the general assumption that reported in textbooks.
1–8
Indeed, using the virtual cut-off values of
64 © TOUCH BRIEFINGS 2009
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