BRITISH

LONDON, SATURDAY 5 JULY 1980

MEDICAL

Br Med J: first published as 10.1136/bmj.281.6232.1 on 5 July 1980. Downloaded from http://www.bmj.com/ on 20 October 2018 by guest. Protected by copyright.
JOURNAL
Screening for congenital hypothyroidism
Congenital hypothyroidism requires early treatment to prevent TSH assay or TSH alone. Cord blood is easy to obtain and
mental retardation. Because newborn babies show no definitive does not need such cumbersome radioimmunoassay procedures
signs the diagnosis may be made only after weeks or months.' as the dried blood spot but it calls for special facilities, and the
Hulse et al in their paper in a recent BMJ2 report that in North screening cannot readily be combined with screening for other
London only 40% of cases of congenital hypothyroidism are inborn metabolic errors; moreover, up to 12% of all babies
recognised clinically before 3 months of age. Of 26 cases of screened for T4 need supplementary TSH determinations.7 '4
congenital hypothyroidism detected in their screening pro- Dried blood on filter paper has the advantages that it can
gramme, only two were diagnosed before results of the screen- be transported over a large area and that the screening can be
ing test were available. Experience has been similar in Zurich' incorporated into established programmes such as phenyl-
and in North America, where only eight of 277 cases of ketonuria screening.'9 The filter paper, however, needs to be
documented congenital hypothyroidism, from one million saturated on both sides and careful arrangements have to be
infants screened, were suspected clinically before 2 months of made for collection.
age.3 An -early diagnosis therefore clearly necessitates bio- Because of the high frequency of false-positive and false-
chemical screening. negative results, screening based on T4 measurement alone
The benefits of early treatment of this condition have been has been replaced by programmes using T4 assay with supple-
well documented by retrospective studies. A recent review4 mental TSH determinations or assay of TSH alone.'6 Ad-
showed that 55% of infants treated in the first 6 weeks of life mittedly, assay for TSH alone fails to detect both hypo-
had an IQ of 90 or more, but only 36% of those starting thalamic-pituitary disease, a rare condition (one in 100 000
treatment from 7 to 12 weeks of age. Klein et a15 found that births) that may not result in mental retardation, and con-
78% of those treated before 3 months of age achieved an IQ genital absence of thyroxine-binding globulins, where low T4
above 85. Similar findings have been recorded by Raiti and concentrations coexist with normal thyroid function. The
Newns.6 Preliminary data from prospective studies suggest recall rates and the incidence of false-positive results, however,
normal growth velocities and neuromuscular and psychological are lower than in programmes that assay both T4 and TSH.1 16
development in treated infants.' 7 8 But without early diagnosis We should not underestimate the emotional stress caused by
one-third of patients with congenital hypothyroidism require such recall. There is also some controversy about the appro-
special schooling and a quarter have an IQ less than 70.2 priate cut-off point for TSH measurements in programmes
Existing screening programmes, however, enable treatment to using initial T4 screening.7 20 Although the TSH assay itself
be started before 8 weeks of age and possibly as early as 2 is more expensive than the T4 assay, the lower recall rates in a
weeks.' 3 TSH screening programme make it more cost-effective. Hulse
Screening programmes for congenital hypothyroidism have et a12 convincingly show the effectiveness of such a pro-
already been established in North America, some European gramme. The dried blood assay for TSH, however, is tech-
countries, Japan, and Australia, and are being introduced in nically more difficult than for T4-an important consideration
several regions of the United Kingdom.9 The incidence of if the screening is to cover a large geographical area. Serum
primary hypothyroidism detected by such programmes is 3,3',5'-triiodothyronine (reverse T3) and thyroglobulin estima-
about one in 4400 live births (compared with one in 16 000 for tions may not detect all hypothyroid infants.2122 The serum T3
phenylketonuria), most cases resulting from thyroid dysgen- concentration is usually normal in these infants and not suitable
esis.9 This incidence is considerably higher than that based on as a basis for diagnosis.23
clinical studies'0 "-probably because sensitive thyrotrophin Nearly all false-negative results in existing screening pro-
(TSH) assays detect children with ectopic or hypoplastic grammes have arisen from human error, and such a programme
glands who may not present with obvious cretinism and those should handle from 30 000 to 150 000 samples a year.9 Since
with transient hypothyroidism.3 12 13 the annual birth rate in Britain is 700 000, a national screening
Screening can be performed on cord blood serum,14 capillary programme would need to be based on regional centres.
serum taken by heel prick on day 5,15 or a dried blood filter Centralised laboratories with adequate facilities for quality
paper spot taken by heel prick at 2-5 days.'6 18 Most pro- control and data collection for statistical analysis are of the
grammes use either assay of thyroxine (T4) with a supplemental utmost importance.
© BRITISH MEDICAL JOURNAL 1980. All reproduction rights reserved. NO 6232 PAGE 1
2 BRITISH MEDICAL JOURNAL 5 JULY 1980
In North America the cost of screening is estimated as the
equivalent of 28-64p per infant3; it would be even less if the Familial Mediterranean
screening were based on an established phenylketonuria
programme. The cost of institutional care or special schooling
fever
for those affected is undoubtedly higher than the cost of such
Familial Mediterranean fever is an inherited disease almost

Br Med J: first published as 10.1136/bmj.281.6232.1 on 5 July 1980. Downloaded from http://www.bmj.com/ on 20 October 2018 by guest. Protected by copyright.
programmes24-6-quite apart from the enormous emotional
costs. In view of the low clinical detection rate and the severity exclusively confined to populations originating on the south
of the untreated condition we cannot justify any further delay and east coasts of the Mediterranean Sea. It is rarely seen in
in implementing a national screening programme for con- Britain and Europe, but doctors in Israel and North Africa are
genital hypothyroidism. familiar with its features. The syndrome, consisting of irregular
episodes of fever with painful serositis and associated with
IIlig R. Congenital hypothyroidism. In: Evered D, Hall R, eds. Hypo-
insidiously developing amyloidosis, has been described many
thyroidism and goitre. Clinics in endocrinology and metabolism. Vol 8. times since the turn of the century' under the names of benign
London: WB Saunders, 1979:49-62. paroxysmal peritonitis, periodic peritonitis, and maladie
2 Hulse JA, Grant DB, Clayton BE, et al. Population screening for congenital
hypothyroidism. Br MedJ 1980;280:675-8.
periodique as well as familial Mediterranean fever.
3 Fisher DA, Dussault JH, Foley TP, et al. Screening for congenital hypo- Analysis of reported cases shows that families affected by
thyroidism: results of screening one million North American infants. familial Mediterranean fever originate in Morocco, Tunis,
J Pediatr 1979;94:700-5.
4Macfaul R, Grant DB. Early detection of congenital hypothyroidism. Algeria, Libya, Israel, Northern Egypt, and Iraq, though
Arch Dis Child 1977;52:87-8. occasional cases are seen elsewhere. Sephardic Jews are quite
5 Klein AH, Meltzer S, Kenny FM. Improved prognosis in congenital commonly affected, but Ashkenazic Jews hardly at all. Genetic
hypothyroidism treated before age three months. Jf Pediatr 1972;81: analysis of several hundred families has shown that the disease
912-5.
6 Raiti S, Newns GH. Cretinism: early diagnosis and its relation to mental closely follows the pattern of autosomal recessive inheritance.2
prognosis. Arch Dis Child 1971 ;46 :692-4. The clinical features of familial Mediterranean fever are
7 Walfish PG, Ginsberg J, Rosenberg RA, Howard NJ. Results of a regional
cord blood screening programme for detecting neonatal hypothyroidism. not present in the newborn, but may appear as early as the
Arch Dis Child 1979;54:171-7. first year of life. Over half of sufferers have had an attack by
8 Dussault JH, Glorieux J, Letarte J, Guyda H, Laberge C. Preliminary the age of 10 years, and 80-90% by the age of 20. Attacks of
report on psychological development at age one of treated hypothyroid
infants detected by the Quebec screening network for metabolic diseases. various types occur unpredictably, often once a month or
Clinical Research 1978;26 :169A. more, with occasional remissions lasting for a few months.
9 Fisher DA. Status of neonatal hypothyroid screening: report from the
Quebec International Conference on neonatal thyroid screening.
Remissions are sometimes associated with pregnancy. The
Proceedings of the eighth international thyroid congress, Sydney, Australia most common type of attack, affecting almost all patients
1980:IA (abst).
10 De Jonge GA. Congenital hypothyroidism in the Netherlands. Lancet
at some time, is abdominal. Pain may begin in any part of the
1976;ii :143. abdomen and spreads rapidly, peritonism, fever, vomiting, and
'1 Alm J, Larsson A, Zetterstr6m R. Congenital hypothyroidism in Sweden. absent bowel sounds developing within a few hours. The pain
Acta Paediatr Scand 1978;67 :1-3. and fever begin to abate, however, after a few hours and the
12 Delange F, Dodion J, Wolter R, et al. Transient hypothyroidism in the
newborn infant.J Pediatr 1978;92 :974-6. patient has usually recovered within 48 hours. Laparotomy
13 LaFranchi SH, Buist NRM, Murphey WH, Larsen PR, Foley TP. and appendicectomy are often carried out during a first attack.
Transient neonatal hypothyroidism detected by newborn screening
program. Pediatrics 1977;60:538-41.
This misplaced surgery does have the advantage that an acute
14 Walfish PG. Evaluation of three thyroid-function screening tests for appendicitis will not be mistaken for an attack later in life.
detecting neonatal hypothyroidism. Lancet 1976;i:1208-11. Attacks affecting the pleura on one or both sides of the chest
15 Delange F, Camus M, Winkler M, Dodion J, Ermans A-M. Thyrotrophin have a similar course, and a chest radiograph taken during
determination on day 5 of life as a screening procedure for congenital
hypothyroidism. Arch Dis Child 1977;52:89-96. the attack often shows a small, transient pleural effusion.
16 Newborn Committee of the European Thyroid Association. Neonatal Episodes of pleurisy are not as frequent as abdominal attacks,
screening for congenital hypothyroidism in Europe. Acta Endocrinol but synovitis is almost as common. The synovitis may persist
1979;90, suppl 223:5-29.
17 Dussault JH, Morissette J, Letarte J, Guyda H, Laberge C. Modification for only a day or two, with fever and painful effusion into a
of a screening program for neonatal hypothyroidism. J Pediatr 1978;92: large joint. Occasionally the effusion may be chronic, lasting
274-7. for several months with the development of osteoporosis
18 Mitchell ML, Larsen PR, Levy HL, Bennett AJE, Madoff MA. Screening
for congenital hypothyroidism. Results in the newborn population of around the affected joint; but recovery is almost always
New England.JAMA 1978;239:2348-51.
19 Dussault JH, Coulombe P, Laberge C, Letarte J, Guyda H, Khoury K.
spontaneous and complete. Sacroiliitis has been reported in
Preliminary report on a mass screening program for neonatal hypo- young sufferers,3 but it is not associated with the HLA-B27
thyroidism. J Pediatr 1975;86:670-4. tissue type.4 A characteristic feature of familial Mediterranean
20 Morissette J, Dussault JH. Commentary: the cut-off point for TSH fever during attacks of fever or synovitis is a sharply defined
measurement or recalls in a screening program for congenital hypo-
thyroidism using primary T4 screening. J Pediatr 1979 ;95 :404-6. erysipelas-like skin lesion. This occurs on the lower leg and
21 Ginsberg J, Walfish PG, Chopra IJ. Cord blood reverse T3 in normal, may be up to 15 cm in diameter.
premature, euthyroid low T4, and hypothyroid newborns. J Endocrinol No underlying cause for familial Mediterranean fever has
Invest 1978;56:633-42.
22 Osotimehin B, Black EG, Hoffenberg R. Thyroglobulin concentration in so far been discovered, despite extensive searches for infective,
ne-natal blood: a possible test for neonatal hypothyroidism. Br Med J
1978 ;ii: 1467-8.
metabolic, and toxic agents. Non-specific changes in circulating
23 Klein AH, Foley TP, Larsen PR, Agustin AV, Hopwood NJ. Neonatal complement components5 and in immunological responses6
thyroid function in congenital hypothyroidism. J Pediatr 1976;89: have been described, and during acute attacks the erythrocyte
545-9. sedimentation rate is raised; but no specific diagnostic test
24 Report of a Committee of the American Thyroid Association. Recom-
mendations for screening programs for congenital hypothyroidism. is yet available. Effusions may contain polymorphonuclear
Jr Pediatr 1976;89:692-4. leucocytes or other phagocytes, and occasionally these cells
25 Report of a Committee of the American Thyroid Association. Recom-
mendations for screening programs for congenital hypothyroidism. have small inclusion bodies, thought to be triglyceride.
AmJ Med 1976;61:932-4. The observation that acute attacks may disappear after
26 Report of a Committee of the American Thyroid Association. Recom- haemodialysis is begun7 supports the possibility of a
mendations for screening programs for congenital hypothyroidism.
Can Med Assoc J 1977;116:631-2. metabolic cause.