2 I 2009

 published by:

edited by: Peter PASmyth, UCD, Dublin Merck KGaA, Darmstadt, Germany

Epidemiology of Thyroid Dysfunction

Hypothyroidism and Hyperthyroidism
Mark PJ Vanderpump
Thyroid International 2 2009

Epidemiology of Thyroid Dysfunction

Hypothyroidism and Hyperthyroidism
Mark PJ Vanderpump
Consultant Physician and Honorary Senior Lecturer in
Endocrinology and Diabetes

Correspondence:
Mark PJ Vanderpump
Department of Endocrinology
Royal Free Hampstead NHS Trust
Pond Street
London
NW3 2QG
United Kingdom
Tel: +44 207 4726280
Fax: +44 207 4726487
Email: mark.vanderpump@royalfree.nhs.uk
2 Thyroid International 2 2009

Dr Mark Vanderpump Description of Picture

has been a Consultant
Physician and Honorary
Senior Lecturer in Diabetes
and Endocrinology at the
Royal Free Hampstead
NHS Trust in London
since 1999. Having quali-
fied at the University of
Birmingham, his training
was completed at posts in
North East England and
North Staffordshire. Whilst in Newcastle-upon-Tyne
he was responsible for the 20-year follow-up of the
Whickham survey. He has published on various aspects
of thyroid disease and has been Secretary of the British
Thyroid Association.
for Front Page
The famous Champions
Statue, commemorating
three of West Ham's play-
ers who helped to win the
1966 World Cup for
England. Captain Bobby
Moore is held aloft with
the cup. Geoff Hurst and
Martin Peters, together
with Ray Wilson (Fulham)
are alongside him. It is located just outside Upton Park,
the home ground of West Ham United Football Club in
Newham, East London, near the site of the Olympic
Stadium being built for 2012.

Thyroid International
Editor-in-Chief: Peter PA Smyth, UCD,Dublin
This is the title of a publication series by Merck KGaA,
Darmstadt, Germany. We are publishing p apers from
renowned international thyroid experts in order to pass
on the extensive experience which the a uthors possess
in their field to a wide r ange of physicians dealing with

H t Thyr idology
the diagnosis and therapy ofthyroid dis eases.
Responsible at M
erck KGaA, Darmstadt, Germany:
Sigrid Butz, M.D.
ETAs journal on hot and controversial topics

Free access:
Thyroid International 22009
erck KGaA, Darmstadt, Germany, D-64271 Darmstadt
M www.hotthyroidology.com
ISSN 0946-5464

1. Introduction
Thyroid disorders are amongst the most prevalent of
medical conditions. Their manifestations vary consider-
ably from area to area and are determined principally
by the availability of iodine in the diet. Epidemiological
studies of thyroid dysfunction have limitations, for
example the definition of overt hypothyroidism and
subclinical hypothyroidism, the selection criteria of the
sample used, the influence of age, sex, genetic and envi-
ronmental factors and the different techniques used for
the measurement of thyroid hormones and the relative
paucity of incidence data.1
Almost one-third of the world's population lives in areas
of iodine deficiency.2 In areas where the daily iodine
intake is below 50g, goitre is usually endemic, and
when the daily intake falls below 25g, hypothyroid-
ism is seen. The prevalence of goitre in areas of severe
iodine deficiency can be as high as 80%. Populations at
particular risk tend to be remote and live in mountain-
ous areas in South-East Asia, Latin America and Central
Africa. Iodisation programmes are of proven value in
reducing goitre size and in preventing goitre develop-
ment and cretinism in children. Goitrogens in the diet,
such as thiocyanate in incompletely cooked Cassava
or thioglucosides in Brassica vegetables, can explain
some of the differences in prevalence of endemic goi-
tre in areas with similar degrees of iodine deficiency.
2. Hypothyroidism
In persons living in iodine-replete areas, the cause of
acquired hypothyroidism is either chronic autoimmune
disease (atrophic autoimmune thyroiditis or goitrous
autoimmune thyroiditis [Hashimoto's thyroiditis]) or
destructive treatment for thyrotoxicosis, but this is
rarely discussed in the available studies. In iodine-
deficient countries a daily iodine intake below 25g,
particularly in preterm infants, is a more frequent
cause of hypothyroidism accounting for many cases in
Europe, Asia and Africa.
Iodine Deficiency Disorders: Silent Pandemic 3
Autonomy can develop in nodular goitres leading occa-
sionally to thyrotoxicosis and iodisation programmes
can also induce thyrotoxicosis, especially in those aged
over 40 years with nodular goitres. Autoimmune thy-
roiditis or hypothyroidism has not been reported to
complicate salt iodisation programmes. Little preva-
lence data exists for autoimmune thyroid disease in
areas of iodine deficiency.3
In iodine-replete areas, most persons with thyroid
disorders have autoimmune disease, ranging through
primary atrophic hypothyroidism, Hashimoto's thy-
roiditis to thyrotoxicosis caused by Graves' disease.
Cross-sectional studies in Europe, the United States
and Japan have determined the prevalence of hyper-
thyroidism and hypothyroidism and the frequency
and distribution of thyroid autoantibodies in differ-
ent, mainly Caucasian, communities.1 Recent data
from studies screening large population samples in
the United States4,5 have revealed differences in the
frequency of thyroid dysfunction and serum thyroid
antibody concentrations in different ethnic groups,
whereas studies from Europe have shown the influence
of dietary iodine intake on the epidemiology of thyroid
dysfunction.6 However studies of incidence of autoim-
mune thyroid disease have only been conducted in a
small number of developed countries.7
2.1 Congenital hypothyroidism
Congenital hypothyroidism affects about one newborn
in 3,500 to 4,000 births and is the most treatable cause
of mental retardation.1 There is an inverse relationship
between age at diagnosis and intelligence quotient
(IQ) in later life. In iodine-replete areas, 85% of the
cases are due to sporadic developmental defects of the
thyroid gland (thyroid dysgenesis) such as the arrested
migration of the embryonic thyroid (ectopic thyroid)
or a complete absence of thyroid tissue (athyreosis).
The remaining 15% have thyroid dyshormonogenesis
defects transmitted by an autosomal recessive mode of
4 Thyroid International 2 2009
inheritance. Clinical diagnosis occurs in less than 5% of
newborns with hypothyroidism because symptoms and
signs are often minimal. As a result it is not possible to
predict which infants are likely to be affected. Without
prompt diagnosis and treatment most affected children
gradually develop growth failure, irreversible mental
retardation and a variety of neuropsychological deficits.
The value of screening for congenital hypothyroidism
in heel-prick blood specimens is unquestioned, and it
is now done routinely in many countries.
2.2 Asymptomatic autoimmune thyroiditis
The presence of high serum concentrations of thy-
roid antibodies (anti-thyroid peroxidase [microsomal]
[TPOAb] and anti-thyroglobulin [TGAb]) correlates
with the presence of focal thyroiditis in thyroid tis-
sue obtained by biopsy and at autopsy from patients
with no evidence of hypothyroidism during life. Early
post-mortem studies confirmed histological evidence
of chronic autoimmune thyroiditis in 27% of adult
women, with a rise in frequency over 50 years, and 7%
of adult men, and diffuse changes in 5% of women
and 1% of men.1 Patients with hypothyroidism caused
by either atrophic or goitrous autoimmune thyroiditis
usually have high serum concentrations of these same
antibodies. These antibodies also are often detected in
serum of patients with Graves disease and other thyroid
diseases, but the concentrations are usually lower.
There is considerable variation in the frequency and
distribution of thyroid antibodies because of variations
in techniques of detection, definition of abnormal titres,
and inherent differences in the populations tested. In
the UK Whickham survey, the mean serum TSH con-
centrations were significantly higher in both men and
women with positive serum antithyroid antibody tests,
and 3% of the subjects (5% of women, 1% of men) lence of newly diagnosed overt hypothyroidism was
had both positive antibody tests and a serum TSH value
greater than 6mU/L.8 In the Third National Health and
Nutrition Examination Survey (NHANES III) in the USA,
the percentage of subjects with high serum TPOAb
and TGAb concentrations increased with age in both
men and women, and high concentrations were more
prevalent in women than in men and less prevalent in
blacks than in other ethnic groups.5 Using a competi-
tive immunoassay procedure, the reported prevalence of
detectable TGAb and TPOAb levels were 10% and 12%
of the healthy population. A hypoechoic ultrasound
pattern or an irregular echo pattern may precede TPOAb
positivity in autoimmune thyroid disease, and TPOAb
may not be detected in more than 20% of individuals
with ultrasound evidence of thyroid autoimmunity.9
2.3 Prevalence of hypothyroidism
In iodine-replete communities, the prevalence of spon-
taneous hypothyroidism is between 1% and 2%, and it
is more common in older women and ten times more
common in women than in men.1 In the Whickham
survey, the prevalence of newly diagnosed overt hypo-
thyroidism was 3 per 1000 women.8 The prevalence of
previously diagnosed and treated hypothyroidism was
14 per 1000 women, increasing to 19 per 1000 women
when possible but unproven cases were included. The
overall prevalence in men was less than 1 case per
1000. One third had been previously treated by surgery
or radioiodine for thyrotoxicosis. Excluding iatrogenic
causes, the prevalence of hypothyroidism was 10 per
1000 women, increasing to 15 per 1000 when pos-
sible but unproven cases were included. The mean age
at diagnosis was 57 years. Other studies in Northern
Europe, Japan and the USA have found the prevalence
to range between 0.6 and 12 per 1000 women and
between 1.3 and 4.0 per 1000 in men investigated (see
Table 1 and [1] for references). In the Colorado and
NHANES III studies, the prevalence of newly diag-
nosed hypothyroidism was 4 per 1000 and 3 per 1000
respectively.4,5
In Pescopagano, Italy, an area of mild iodine deficiency
(median urinary iodine excretion 55g/L), the preva-
0.3% of 573 women (autoimmune thyroiditis confirmed
as aetiology) (there were no cases among 419 men), and
no subject had been diagnosed and treated for hypothy-
roidism.10 In borderline iodine-deficient Copenhagen,
Denmark, 6 per 1000 of the women and 2 per 1000 men
had overt but undiagnosed hypothyroidism, and 1% of
all subjects were taking thyroxine.11
 Iodine Deficiency Disorders: Silent Pandemic 5

Table 1. Prevalence of previously undiagnosed overt hypothyroidism and incidence of overt hypothyroidism in selected
epidemiological surveys of thyroid dysfunction (see reference 1 unless stated)

Study Name N Age (Years) Test Prevalence n/1000 Incidence n/1000/year

Men Women Follow-up Men Women
Whickham, UK8,15 2779 18+ TSH, T4 0 3.3 20 years 0.6 3.5
(0.31.2) (2.84.5)
Colorado, USA4 25,862 18+ TSH 4.0
NHANES III, USA5 16,533 12+ TSH 2.0
Pescopagano, Italy10 992 15+ TSH, FT4 0 3.0
Sapporo, Japan 4110 25+ TSH 2.4 8.5
Copenhagen, Denmark11 2656 4171 TSH, FT4 2.0 5.0
Memphis/Pitttsburgh, USA14 2797 7079 TSH, FT4 5.4 13.0
Leiden, Netherlands12 558 8589 TSH, FT4 70
Tayside, UK (19931997)16 390,000 0+ Treatment 4 years 0.88 4.98
for hypo- (0.800.95) (4.815.17)
thyroidism
Tayside, UK (1997-2001)17 390,000 0+ As above 4 years 1.09 4.75
(0.951.25 (4.465.07)
Gteborg, Sweden 1283 4466 TSH 6.4 4 years 12
Birmingham, UK 1210 60+ TSH 7.8 20.5 1 year 11.1
Gothenburg, Sweden 1148 70+ TSH 10 years 2

The prevalence is higher in surveys of the elderly in the
community.1 The overall prevalence of hypothyroidism,
including those already taking T4, in Birmingham, UK,
of 1210 subjects aged 60 and over was 4% of women
and 0.8% of men aged over 60 years. In subjects aged
60 years or more in Framingham, 4% had serum TSH
concentration greater than 10mU/L, of whom one-third
had low serum T4 concentrations.7 Overt hypothyroid-
ism was found in 7% of 558 subjects aged between 85
and 89 years in Leiden, Netherlands.12
2.4 Subclinical hypothyroidism
The term subclinical hypothyroidism is used to describe
the finding of a raised serum TSH but a normal FT4 in
an asymptomatic patient. In the community, the most
common aetiology is chronic autoimmune thyroiditis.1,9
In the original Whickham survey, 8% of women (10% of
women over 55 years of age) and 3% of men had sub-
clinical hypothyroidism.8 In the Colorado, USA, study,
9.4% of the subjects had a high serum TSH concentra-
tion, of whom 9.0% had subclinical hypothyroidism.4
Among those with a high serum TSH concentration,
74% had a value between 5.1mU/L and 10mU/L and
26% had a value greater than 10mU/L. The percentage
of subjects with a high serum TSH concentration was
higher for women than men in each decade of age, and
ranged from 4 to 21% in women and 3 to 16% in men.
An increase in serum TSH concentrations was also found
in men in the NHANES III study. In the same study serum
TSH concentrations increased with age in both men and
women and were higher in whites than blacks, inde-
pendent of serum antithyroid antibody concentrations.5
Community studies of elderly persons have confirmed
the high prevalence of subclinical hypothyroidism in
this age group, with approximately 10% of subjects
over 60 years having serum TSH values above the nor-
mal range.6,9 A further analysis of the NHANES III data
demonstrated that the 97.5 centile for those subjects
aged over 80 was 7.49mU/L and 70% had a serum TSH
greater than the population defined upper limit of the
reference range of 4.5mU/L of whom only 40% were
anti-thyroid antibody positive.13 Data from a US cohort
aged 70 to 79 years found that black subjects had a
significantly lower prevalence of subclinical hypothy-
roidism (2% in men, 3% in women), as compared with
white subjects (4% in men, 6% in women).14
6 Thyroid International 2 2009

In Pescopagano, there was a slightly lower prevalence ratios (with 95% CI) of developing spontaneous hypo-
of subclinical hypothyroidism (4% of women and 3% thyroidism in surviving women are shown in Table 2.
of men), but high serum antithyroid antibody concen- Either raised serum TSH or positive thyroid antibodies
trations were as prevalent, although at lower titres, as in alone or in combination are associated with a signifi-
iodine-replete communities. In Copenhagen (median
10 cantly increased risk of hypothyroidism. The odds are
urinary iodine excretion 70g/L), only 0.7% of subjects greatly increased when both risk factors are present
had subclinical hypo- and each had a similar
Table 2. D  evelopment of spontaneous hypothyroidism in surviving
thyroidism, and 83% effect. The smaller
women and men at 20-year follow-up of Whickham survey:
of them had serum number of observed
odds ratios (with 95% CI)7
antithyroid antibody cases in men resulted
concentrations greater Women in wide but highly
than 200kU/L. Other TSH raised, regardless of thyroid antibody status
11 14 (924) significant confidence
studies of elderly per- Thyroid antibody + , regardless of TSH status 13 (819) limits but also did not
sons in iodine-deficient If thyroid antibody - , effect of raised TSH alone 8 (320) allow the independent
areas have suggested a If thyroid antibody + , additional effect of raised TSH 5 (211) effects of these risk
high prevalence of sub- If TSH normal, effect of thyroid antibody + alone 8 (515) factors to be calcu-
clinical hypothyroid- If TSH raised, additional effect of thyroid antibody + 5 (115) lated. In the surviving
ism with approximate- TSH raised and thyroid antibody + combined 38 (2265) women the annual risk
ly 10% of subjects over of spontaneous overt
60 years having serum Men hypothyroidism was
TSH values above TSH raised, regardless of thyroid antibody status 44 (19104) 4% in those who had
the normal range. Thyroid antibody + , regardless of TSH status 25 (1063) both high serum TSH
Subclinical hypothy- TSH raised and thyroid antibody + combined 173 (81-370) and antithyroid anti-
roidism is found at body concentrations,
higher frequency (18% in Iceland and 24% in Hungary) 3% if only their serum TSH concentrations was high,
in areas where iodine intake is high, but most cases are and 2% if only their serum thyroid antibody concentra-
not of autoimmune origin.1 tion was high; at the time of follow up the respective
rates of hypothyroidism were 55%, 33%, and 27%. The
2.5 Incidence of overt hypothyroidism probability of developing hypothyroidism was higher
in those women who had serum TSH concentrations
The 20 year follow up of the Whickham cohort pro- above 2.0mU/L and high serum titres of antithyroid
vided incidence data and allowed the determination microsomal antibodies during the first survey.
of risk factors for spontaneous hypothyroidism in this
period.15 The mean annual incidence of spontaneous The other incidence data for hypothyroidism are from
hypothyroidism in the surviving women during the short (and often small) follow-up studies.7 In elderly sub-
20 year follow up period was 3.5 per 1000 (95% con- jects, the annual incidence rate of hypothyroidism varies
fidence interval [CI] 2.8 to 4.5), increasing to 4.1 per widely between 0.2 and 7% in the available studies (see
1000 (95% CI 3.3 to 5.0) if all cases including those Table 1 and [1] for references). Data from the large popu-
who had received destructive treatment for thyrotoxi- lation study in Tayside, UK, has demonstrated that the
cosis were included. The mean annual incidence during standardised incidence of primary hypothyroidism varied
the 20-year follow-up period in men (all spontaneous between 3.90 and 4.89 per 1000 women per year between
except for one case of lithium-induced hypothyroidism) 1993 and 2001. The incidence of hypothyroidism in men
was 0.6 per 1000 (95% CI 0.3 to 1.2). The risk of having significantly increased from 0.65 to 1.01 per 1000 per year
developed hypothyroidism was examined with respect (P=0.0017). The mean age at diagnosis of primary hypo-
to risk factors identified in the first survey. The odds thyroidism decreased in women from 1994 to 2001.16,17

Spontaneous recovery has also been described in sub-
jects with subclinical hypothyroidism, although the
frequency of this phenomenon is unclear. In one study,
37% of patients normalised their serum TSH levels over
a mean follow-up time of 31.7 months. Normalisation
of serum TSH concentrations were more likely to occur
3. Hyperthyroidism
The most common causes of hyperthyroidism are Graves'
disease, followed by toxic multinodular goitre, whilst
rarer causes include an autonomously functioning thy-
roid adenoma, or thyroiditis. In epidemiological studies,
however, the aetiology is rarely ascertained.
3.1 Prevalence of hyperthyroidism
The prevalence of hyperthyroidism in women is between
0.5 and 2%, and is ten times more common in women than
in men in iodine-replete communities. In the Whickham
survey, the prevalence of undiagnosed hyperthyroidism
was 4.7 per 1000 women.8 Hyperthyroidism had been
previously diagnosed and treated in 20 per 1000 women,
rising to 27 per 1000 women when possible but unproven
cases were included, as compared with 1.6 to 2.3 per 1000
men, in whom no new cases were found at the survey.
The mean age at diagnosis was 48 years. Other available
cross-sectional studies of the adult population provide
comparable data (see Table 3 and [1] for references).
In NHANES III, in those subjects who were neither tak-
ing thyroid medication nor reported histories of thyroid
disease, 2 per 1000 had clinically significant hyperthy-
roidism, defined as a serum TSH concentration less than
0.1mU/L and a serum total T4 concentration greater than
170nmol/L.5 Overt hyperthyroidism, defined as serum
TSH concentration less than 0.01mU/L, was present in
only 1 per 1000 of those not taking thyroid medication
in the cross-sectional survey of 25,682 subjects aged over
18 years attending the Health Fair in Colorado.4
The prevalence data in elderly persons show a wide
range between 0.4% to 2.0%.1 A cross-sectional study
of 2799 healthy community-dwelling adults aged 70 to
Iodine Deficiency Disorders: Silent Pandemic 7
in patients with negative antithyroid antibodies and
serum TSH levels less than 10mU/L, and within the first
two years after diagnosis.9 However, all studies indicate
that the higher the serum TSH value, the greater the
likelihood of development of overt hypothyroidism in
subjects with chronic autoimmune thyroiditis.
79 years in the US found evidence of hyperthyroidism
(defined biochemically as a serum TSH concentration
less than 0.1mU/L and a serum free T4 concentration
greater than 23pmol/L in only five subjects (one man
and four women).14 In Leiden only 2 of 558 subjects
aged between 85 and 89 years had newly diagnosed overt
hyperthyroidism.12
The prevalence of undiagnosed hyperthyroidism in
Pescopagano was higher, at 2%, with a further 1% of
adults there having a history of toxic nodular goitre.10
Approximately one-third had a diffuse goitre; the fre-
quency in men and women was similar. In a population
sample of 2656 from Copenhagen, another area of mild
iodine deficiency, newly diagnosed thyrotoxicosis was
found in 1.2% of women and no men, and the prevalence
of known thyrotoxicosis was 1.4%.11
3.2 Subclinical hyperthyroidism
Subclinical hyperthyroidism is defined as a low serum
TSH concentration and normal serum T4 and T3 con-
centrations, in the absence of hypothalamic or pituitary
disease, non-thyroidal illness, or ingestion of drugs that
inhibit TSH secretion such as glucocorticoids or dopa-
mine. The available studies differ in the definition of a
low serum TSH concentration and whether the subjects
included were receiving thyroxine therapy. The third
generation assays have rarely been used in epidemiologi-
cal studies.1
The reported overall prevalence ranges from 0.5% to
6.3%, with men and women over 65 years having the
highest prevalence; approximately half of them are tak-
8 Thyroid International 2 2009
ing thyroxine.1,9 Among these studies, the serum TSH
cut-off value ranged from less than 0.1mU/L to less than
0.5mU/L and it is not clear how this difference affected
the reported prevalence rates. Among subjects with sub-
clinical hyperthyroidism, those with low but detectable
serum TSH values may recover spontaneously when re-
tested. In the Colorado study of 25,862 subjects (of whom
88% were white), and in which the serum TSH cut-off
value was 0.3mU/L, the overall prevalence of subclinical
hyperthyroidism was 2.1%.4 In contrast, the NHANES III
study, defining subclinical hyperthyroidism using a more
stringent 0.1mU/L as the serum TSH cut-off, reported an
overall prevalence of 0.7% in the total population and
0.2% in the thyroid disease-free population (n=13,344).
The rates were highest in those subjects aged 20 to 39
years and those more than age 79 years. In this study the
percentage of subjects with serum TSH concentrations
less than 0.4mU/L was significantly higher in women
than men, and black subjects had significantly lower
mean serum TSH concentrations, and therefore a higher
prevalence of subclinical hyperthyroidism (0.4%) than
whites (0.1%) or Mexican Americans (0.3%). In the US
study of subjects aged 71 to 79 years the prevalence
was 1.1% in women and 0.7% in men and there was no
difference between black and white residents.14 In the
Leiden study of subjects aged over 85 years, the preva-
lence was 3%.12
The prevalence of subnormal serum TSH concentrations
(detection limit 0.01mU/L and excluding those subjects
taking thyroxine) was higher in the iodine-deficient
population of Pescopagano (6%), due to functional
autonomy from nodular goitres.10 In Jutland, an area
of mild iodine deficiency in Denmark, 10% of a random
sample of 423 subjects had low serum TSH concentra-
tions, as compared with 1% of 100 subjects of similar age
in iodine-rich Iceland. Subclinical hyperthyroidism was
not detected in a group of elderly nursing home residents
in an iodine-rich region of Hungary.3
3.3 Incidence of hyperthyroidism
The incidence data available for overt hyperthyroidism in
men and women from large population studies are com-
parable, at 0.4 per 1000 women and 0.1 per 1000 men,
but the age-specific incidence varies considerably (Table
3 and [1] for references). The peak age-specific incidence
of Graves disease was between 20 and 49 years in two
studies, but increased with age in Iceland and peaked at
60 to 69 years in Malm, Sweden. The peak age-specific
incidence of hyperthyroidism caused by toxic nodular
goitre and autonomously functioning thyroid adenomas
in the Malm study was over 80 years. The only available
data in a black population, from Johannesburg, South
Africa, also suggest a tenfold lower annual incidence of
hyperthyroidism (0.09 per 1000 women and 0.007 per
1000 men) than in whites.
In the survivors of the Whickham survey cohort, 11
women had been diagnosed and treated for hyperthy-
roidism after the first survey and five women were
diagnosed at the second survey.15 The aetiology in these
16 new cases was Graves' disease in 10 subjects, multi-
nodular goitre in three subjects, an autonomously func-
tioning thyroid adenoma in one, chronic autoimmune
thyroiditis in one and unknown in one. The mean annual
incidence of hyperthyroidism in women was 0.8 per 1000
survivors (95% confidence interval [CI] 0.5 to 1.4).9 The
incidence rate was similar in the deceased women. No
new cases were detected in men. Other cohort studies
provide comparable incidence data, which suggests that
many cases of hyperthyroidism remain undiagnosed in
the community unless routine testing is undertaken.1
In the large population study in Tayside, Scotland, 620
incident cases of hyperthyroidism were identified with an
incidence rate of 0.77/1000 per year (95% CI 0.70 to 0.84)
in women and 0.14/1000 per year (95% CI 0.12 to 0.18)
in men.16 The incidence increased with age, and women
were affected two to eight times more than men across
the age range. Recent further analysis suggested that the
incidence of thyrotoxicosis was increasing in women but
not in men between 1997 and 2001.17
Data on the risk of progression of subclinical hyper-
thyroidism to overt hyperthyroidism are limited. In the
majority of subjects a detectable below normal serum
TSH will eventually rise towards normal. In those sub-
jects with an undetectable serum TSH and a confirmed
aetiology due to Graves disease or nodular disease, it
has been calculated from short follow-up studies that the
annual incidence is approximately 5%.1,9
 Iodine Deficiency Disorders: Silent Pandemic 9

Table 3. Prevalence of previously undiagnosed overt hyperthyroidism and incidence of overt hyperthyroidism in selected
epidemiological surveys of thyroid dysfunction
(*TRAB = TSH receptor antibody, PBI =Protein-bound iodine, FT4I = Free thyroxine index).
(See reference 1 unless stated)
Study Name N Age (Years) Test Prevalence n/1000 Incidence n/1000/year
Men Women Follow-up Men Women
Whickham, UK8,15 2779 18+ T4, FT4I 0 4.7 20 years <0.1 0.8
(0.61.4)
Colorado, USA4 25,862 18+ TSH 1.0
NHANES III, USA5 16,533 12+ TSH, TT4 2.0
Pescopagano, Italy10 922 15+ TSH, FT4 20.0
Sapporo, Japan 4110 25+ TSH, TRAB* 2.7 5.1
Copenhagen, Denmark11 2656 4171 TSH, FT4 0 12.0
Memphis/Pittsburgh, USA14 2797 7079 TSH, FT4 0.7 2.8
Leiden, Netherlands12 599 8589 TSH, FT4 4.0
Tayside, UK (1993-1997)16 390,000 0+ Treatment 4 years 0.14 0.77
for hyper- (0.11-0.22) (0.70-0.84)
thyroidism
Tayside, UK (1997-2001)17 390,000 0+ As above 4 years 0.15 0.91
(0.10-0.22) (0.78-1.05)
Johannesburg, South Africa ? 0+ T4 1 year 0.007 0.09
Birmingham, UK 1210 60+ TSH 0.9 1 year 0 1.5
Gothenburg, Sweden 1148 70+ TSH 10 years 1.0
Funen, Denmark 450000 0+ PBI, T4, T4 3 years 0.1 0.5
Iceland 230000 0+ T4, T4 3 years 0.1 0.4
Malm, Sweden 257764 0+ PBI 5 years 0.1 0.4

4. Screening for thyroid disorders

Controversy exists as to whether healthy adults living
in an area of iodine sufficiency benefit from screening
for thyroid disease. It is desirable to detect any disease
in its early stage, particularly when treatment is avail-
able that will benefit the affected person and forestall
or improve the natural history of the condition. The
benefit from a screening programme must outweigh
the physical and psychological harm caused by the test,
diagnostic procedures and treatment. Thyroid disorders
secondary to autoimmune thyroid disease are amongst
the most prevalent of medical conditions, and their
symptoms and signs may be subtle and non-specific
and they can be mistakenly attributed to other illnesses,
particularly in the elderly. The prevalence of unsus-
pected overt thyroid disease is low, but a substantial
proportion of subjects tested will have evidence of
thyroid dysfunction, with approximately 10% with
subclinical hypothyroidism and 1% with subclinical
hyperthyroidism. In the absence of the confounding
effects of non-thyroidal illness or drugs, a normal
serum TSH concentration has a high predictive value
in ruling out thyroid disease in healthy subjects. In
unselected populations, measurement of serum TSH
has a sensitivity of 89 to 95% and specificity of 90
to 96% for overt thyroid dysfunction, as compared
to cases confirmed by history, examination and addi-
tional testing. Normal serum TSH concentrations are
found in some patients with hypothyroidism caused
by pituitary or hypothalamic disease, but both these
situations are rare. In nearly all populations screened,
a serum TSH value greater than 5 or 6 mU/L is accepted
as being raised.18
Different recommendations and position papers have
been reported by various physician organisations as
to whether subclinical thyroid disease is of sufficient
clinical importance to warrant screening and therapy.
In subclinical hypothyroidism, there is still debate
10 Thyroid International 2 2009
as to what constitutes a normal TSH, particularly in
older subjects. Although some subjects will progress
to overt hypothyroidism, recent data suggest a sig-
nificant proportion revert to normal without treatment.
Adopting a wait and see policy rather than interven-
tion will avoid unnecessary treatment or the potential
for harm. Cardiovascular risk may be more significant
in younger adults, approximately 1.5 versus 1.0 for
populations with mean ages younger or older than 65
years respectively.19 Treatment in subjects less than
65 years and those older subjects with evidence of
heart failure may now be justified.20 No appropriately
powered prospective, randomised, controlled, double-
blinded interventional trial of thyroxine therapy for
subclinical hypothyroidism exists. No consensus exists
regarding the treatment of subclinical hyperthyroidism
and any potential benefits of therapy must be weighed
against the substantial morbidity associated with the
treatment of hyperthyroidism. There is an urgent need
for long-term studies of the effects of identification
and treatment of both subclinical hypothyroidism and
subclinical hyperthyroidism, to determine if there is
indeed benefit from screening for thyroid dysfunction
in adults.21

References
1.Vanderpump MPJ. The epidemiology of thyroid diseases.
In: Braverman LE, Utiger RD, eds. Werner and Ingbar's
The Thyroid: A Fundamental and Clinical Text. 2005,
9th edn, pp 398-406. JB Lippincott-Raven, Philadelphia.
2.Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency
disorders. Lancet 2008; 372:1251-1262.
3.Laurberg P, Bulow Pedersen I, Knudsen N, Ovesen L,
Andersen S. Environmental iodine intake affects the type of
non-malignant thyroid disease. Thyroid 2001; 11:457-469.
4.Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The
Colorado Thyroid Disease Prevalence Study. Arch Intern
Med 2000; 160:526-534.
5.Hollowell JG, Staehling NW, Flanders WD, Hannon WH,
Gunter EW, Spencer CA, Braverman LE. Serum TSH,
T4, and thyroid antibodies in the United States popu-
lation (1988 to 1994): National Health and Nutrition
Examination Survey (NHANES III). J Clin Endocrinol
Metab 2002; 87:489-499.
6.Vanderpump MPJ, Tunbridge WMG. Epidemiology and
prevention of clinical and subclinical hypothyroidism.
Thyroid 2002; 12:839-847.
7.McGrogan A, Seaman HE, Wright JW, de Vries CS. The
incidence of autoimmune thyroid disease: a systematic
review of the literature. Clin Endocrinol 2008; 69:687-696.
8.Tunbridge WMG, Evered DC, Hall R, Appleton D, Brewis
M, Clark F, Evans JG, Young E, Bird T, Smith PA.
The spectrum of thyroid disease in the community: the
Whickham survey. Clin Endocrinol 1977; 7:481-493.
9.Biondi B, Cooper DC. The clinical significance of subclini-
cal thyroid dysfunction. Endocr Rev 2008; 29:76-131
10.Aghini-Lombardi F, Antonangeli L, Martino E, Vitti P,
Macherini D, Leoli F, Rago T, Grasse L, Valeriano R,
Balestrieri A, Pinchera A. The spectrum of thyroid disor-
ders in an iodine-deficient community: The Pescopagano
Survey. J Clin Endocrinol Metab 1999; 84:561-566.
11.Knudsen N, Jrgensen T, Rasmussen S, Christiansen,
Perrild H. The prevalence of thyroid dysfunction in a pop-
ulation with borderline iodine deficiency. Clin Endocrinol
1999; 51:361-367.
12.Gussekloo J, van Exel E, de Craen AJM, Frlich M,
Westendorp RGJ. Thyroid status, disability and cogni-
tive function, and survival in old age. JAMA 2004;
292:2591-2599.
Iodine Deficiency Disorders: Silent Pandemic 11
13.Surks MI, Hollowell JG. Age-specific distribution of
serum thyrotrophin and anti-thyroid antibodies in the
US population: implications for the prevalence of sub-
clinical hypothyroidism. J Clin Endocrinol Metab 2007;
92:4575-4582.
14.Kanaya AM, Harris F, Volpato S, Prez-Stable EJ, Harris
T, Bauer D. Association between thyroid dysfunction and
total cholesterol level in an older biracial population. The
Health, Aging and Body Composition Study. Arch Intern
Med 2002; 162:773-779.
15.Vanderpump MPJ, Tunbridge WMG, French JM, Appleton
D, Bates D, Clark F, Grimley Evans J, Hasan DM, Rodgers
H, Tunbridge F, Young ET. The incidence of thyroid dis-
orders in the community: a twenty-year follow-up of the
Whickham survey. Clin Endocrinol 1995; 43:55-69.
16.Flynn RV, MacDonald TM, Morris AD, Jung RT, Leese GP.
The Thyroid Epidemiology, Audit and Research Study;
thyroid dysfunction in the general population. J Clin
Endocrinol Metab 2004; 89:3879-3884.
17.Leese GP, Flynn RV, Jung RT, MacDonald TM, Murphy
MJ, Morris AD. Increasing prevalence and incidence
of thyroid disease in Tayside, Scotland: The Thyroid
Epidemiology, Audit and Research Study (TEARS). Clin
Endocrinol 2008; 68:311-316.
18.Tunbridge WMG, Vanderpump MPJ. Population screen-
ing for autoimmune thyroid disease. Endocrinol Metab
Clin North Am 2000; 29:239-253.
19.Razvi S, Shakoor A, Vanderpump M, Weaver J, Pearce S.
The influence of age on the relationship between subclini-
cal hypothyroidism and ischemic heart disease: A meta-
analysis. J Clin Endocrinol Metab 2008; 93:2998-3007.
20.Rodondi N, Bauer DC, Cappola AR, Cornuz J, Robbins
J, Fried LP, Ladenson PW, Vittinghoff E, Gottdiener JS,
Newman AB. Subclinical thyroid dysfunction, cardiac
function, and the risk of heart failure. The Cardiovascular
Health Study. J Am Coll Cardiol 2008; 52:1152-1159.
21.Surks MI, Ortiz E, Daniels GH et al. Subclinical thyroid
disease: scientific review and guidelines for diagnosis and
management. JAMA 2004; 291:228-238.
12 Thyroid International 2 2009

Former Editions of Thyroid International

No 1-2009 R
 eport on the 33rd Annual Meeting
of the European Thyroid Association
(L.H. Duntas, P.P.A. Smyth)
No 4-2008 T hyroid autoimmunity and female infertility
(Kris Poppe, Daniel Glinoer, Brigitte Velkeniers)
No 3-2008 N
 ew reference range for TSH?
(Georg Brabant)
No 2-2008 A
 merican Thyroid Association: Highlights of the
78th Annual Meeting (Stephen W Spaulding, Peter
PA Smyth)
No 1-2008 R
 eport of the 32th Annual Meeting of the European
Thyroid Association (GJ Kahaly, P.P.A. Smyth)
No 4-2007 T he Thyroid and Twins (Pia Skov Hansen, Thomas
Heiberg Brix, Laszlo Hegeds)
No 3-2007 C
 linical Aspects of Thyroid Disorders in the
Elderly (Valentin Fadeyev)
No 2-2007 R
 eport of the 31th Annual Meeting
of the European Thyroid Association
(John H Lazarus, Peter PA Smyth)
No 1-2007 T he story of the ThyroMobil (F. Delange,
C.J. Eastman, U. Hostalek, S. Butz, P.P.A. Smyth)
No 3-2006 T hyroid Peroxidase Enzyme and Antigen
(Barbara Czarnocka)
No 2-2006 G
 enetics of benign and malignant thyroid tumours
(Dagmar Fhrer)
No 1-2006 H
 ighlights of the 13th ITC
(Sheue-yann Cheng, Peter PA Smyth)
No 4-2005 Thyroid
 Eye Disease:
Current Concepts and the EUGOGOPerspective
(Gerasimos E Krassas, Wilmar M Wiersinga)
No 3-2005 Clinical
 Expression of Mutations in the TSH
Receptor: TSH-R Disorders
(Davide Calebiro, Luca Persani, Paolo Beck-Peccoz)
No 2-2005 Transient
 Hypothyroxinaemia and
Preterm Infant Brain Development
(Robert Hume, Fiona LRWilliams, Theo JVisser)
No 1-2005 The
 Spectrum of Autoimmunity in Thyroid Disease
(Anthony P. Weetman)
No 5-2004 Postpartum
 Thyroiditis:An Update
(Kuvera E. Premawardhana, John H. Lazarus)
No 4-2004 Report
 of the 29th Annual Meeting of the
European Thyroid Association (G. Hennemann)
No 3-2004 A
 utoimmune Thyroiditis And Pregnancy
(Alex F. Muller, Arie Berghout)
No 2-2004 R
 eport of the 75th Annual Meeting of the
American Thyroid Association (G. Hennemann)
No 1-2004 T hyroid and Lipids: a Reappraisal
(Leonidas H. Duntas)
No 5-2003 U
 se of Recombinant TSH in Thyroid Disease:
An Evidence-Based Review (Sara Tolaney M.D.,
Paul W. Ladenson M.D.)
No 4-2003 New
 Insights for Using Serum Thyroglobulin
(Tg) Measurement for Managing Patients with
Differentiated Thyroid Carcinomas (C.A. Spencer)
No 3-2003 The
 Significance of Thyroid Antibody Measurement
in Clinical Practice (A. Pinchera, M. Marin, E. Fiore)
No 2-2003 Etiology,
 diagnosis and treatment of Graves disease
(A.P. Weetman)
No 1-2003 Report
 of the 74th Annual Meeting of the
American Thyroid Association (G. Hennemann)
No 6-2002 Report
 of the 28th Annual Meeting of the
European Thyroid Association (G. Hennemann)
No 5-200 2 Iodine Deficiency in Europe anno 2002
(Franois M. Delange, MD, PhD)
No 4-200 2 Thyroid Imaging in Nuclear Medicine
(Dik J. Kwekkeboom, Eric P. Krenning)
No 3-200 2 Congenital Hypothyroidism (Delbert A. Fisher)
No 2-200 2 T he Use of Fine Needle Aspiration Biopsy (FNAB) in
Thyroid Disease (Antonino Belfiore)
No 1-200 2 R
 eport of the 73rd Annual Meeting of the
American Thyroid Association (G. Hennemann)
No 6-2001 R
 eport of the 27th Annual Meeting of the
European Thyroid Association (G. Hennemann)
No 5-2001 S ubclinical Hyperthyroidism
(E.N. Pearce, L.E. Braverman)
No 4-2001 T hyroid hormone treatment how and when?
(A.D. Toft)
No 3-2001 R
 esistance to thyroid hormone
(O. Bakker, W.M. Wiersinga)
No 1/2-200 1 Report of the 12th International
Thyroid Congress (G. Hennemann)
No 5-2000 Percutaneous
 ethanol injection therapy for thyroid
diseases (Enio Martino)
No 4-2000 Inheritable
 forms of thyroid carcinoma
(Martin Schlumberger)
No 3-2000 Multinodular goitre (Peter Laurberg)
No 2-2000 Drug effects on thyroid function (Jan R. Stockigt)
No 1-2000 T hyroid disease, menstrual function and fertility
(Gerasimos E. Krassas)
No 6-1999 R
 eport of the 27th Annual Meeting of the
American Thyroid Association (G. Hennemann)
No 5-1999 R
 eport of the 26th Annual Meeting of the
European Thyroid Association (G. Hennemann)
No 4-1999 R
 eport of the 8th Biannual Meeting of the
Latin American Thyroid Society (LATS)
(Geraldo Medeiros-Neto)

Thyroid International is also published on the website ThyroLink: www.thyrolink.com (Literature)

 When the thyroid
secretly steals life.
Taking the offensive against hypothyroidism. With Euthyrox.
multiple dosage strengths for precise dose titration Euthyrox
galenic formulation with reliable unit conformity Offensive against hypothyroidism.
first levothyroxine preparation with a European and FDA approval

Other registered tradenames: Eutirox, Supratirox, Lvothyrox

Active substance: Levothyroxine sodium. Prescription only medicine. Composition: Each tablet (round with cross score) of Euthyrox 25/50/75/88/100/112/125/137/150/175/200 g contains 25/50/75/88/100/112/125/137/150/175/200 g of levothyro
xine sodium. Other ingredients: Corn starch, croscarmellose sodium, gelatin, lactose monohydrate, magnesium stearate. Indications: Euthyrox 25 - 200 g: Euthyroid goitre, prophylaxis of relapse goitre after goitre resection, hypothyroidism,
suppression therapy in thyroid cancer. Additional indication for Euthyrox 25 - 100 g: Concomitant therapy in antithyroid drug therapy of hyperthyroidism after having achieved a euthyroid function. Additional indication for Euthyrox
100/150/200 g: Thyroid suppression test. Contraindications: Intolerance to the active substance or any of the excipients. Untreated adrenocortical insufficiency, untreated pituitary insufficiency, untreated hyperthyroidism. Do not
initiate therapy in acute myocardial infarction, acute myocarditis, acute pancarditis. Adverse reactions: Adverse reactions are not to be expected under adequate therapy. In (individual) intolerance of the chosen dosage or overdosage
(particularly if the dose is increased too quickly at the start of treatment): tachycardia, palpitations, cardiac arrhythmias, angina pectoris, headache, muscle weakness and cramps, sensation of heat, fever, vomiting, menstrual disorders,
pseudotumor cerebri, tremor, restlessness, insomnia, hyperhidrosis, weight loss, and diarrhoea. In such cases reduce the daily dosage or interrupt treatment for several days. Allergic reactions may occur in the case of hypersensitivity. Other
notes: Treatment with thyroid hormones should be continued consistently during pregnancy in particular. The thyroid hormone quantity secreted into breast milk during lactation is not sufficient to cause development of hyperthyroidism
or suppression of TSH secretion in the infant. During pregnancy contraindicated as concomitant treatment to antithyroid drug therapy. Exclude or treat coronary insufficiency, angina pectoris, arteriosclerosis, hypertension, pituitary or
adrenocortical insufficiency, and thyroid autonomy before initiating therapy with thyroid hormones. Prevent drug-induced hyperthyroidism in coronary insufficiency, heart failure, and achycardiac arrhythmias. Clarify cause of secondary
hypothyroidism before initiating replacement therapy. In compensated adrenocortical insufficiency start adequate replacement therapy where necessary. When hypothyroid, postmenopausal women at increased risk of developing oste-
oporosis are treated, their thyroid function should be checked more frequently in order to prevent supraphysiologic levothyroxine blood levels. Do not use in: patients with galactose intolerance, lactase deficiency or glucose-galactose-
malabsorption. Presentation and pack sizes: depending on the local registration state. For more detailed information please refer to the data sheet or package leaflet. Issued: August 2007. Merck KGaA, D-64271 Darmstadt, Germany.