The Spectrum of Thyroid Disorders in an Iodine-
Deficient Community: The Pescopagano Survey*
FABRIZIO AGHINI-LOMBARDI, LUCIA ANTONANGELI, ENIO MARTINO,
PAOLO VITTI, DORETTA MACCHERINI, FRANCESCO LEOLI, TERESA RAGO,
LUCIA GRASSO, ROCCO VALERIANO, ANGELO BALESTRIERI, AND
Department of Endocrinology (F.A.-L., L.A., E.M., P.V., D.M., F.L., T.R., L.G., R.V., A.P.), University
of Pisa, Pisa; and the Department of Internal Medical Sciences, University of Cagliari (A.B.), Cagliari,
We carefully assessed thyroid status and goiter by ultrasound in
1411 subjects virtually representing the entire resident population of
Pescopagano, an iodine-deficient village of Southern Italy. Median
urinary iodine excretion was 55 ?g/L. The prevalence of goiter was
16.0% in children and 59.8% in adults. Thyroid nodularity was 0.5%
in children and progressively increased with age to 28.5% in the 56-
to 65-yr-old group. The prevalence of present or past hyperthyroidism
was 2.9%, including 9 cases with toxic diffuse goiter and 20 with toxic
nodular goiter. Functional autonomy was rare in children, progres-
sively increased with age up to 15.4% in the elderly, and was related
to nodular goiter. The prevalences of overt and subclinical hypothy-
roidism in the adults were 0.2% and 3.8%, respectively. Serum au-
toantibodies to thyroglobulin and thyroperoxidase were detected in
12.6% of the entire population. The prevalence of diffuse autoimmune
thyroiditis was 3.5%, being very low in children. Thyroid cancer was
found in only 1 case. In conclusion, in the present survey of an iodine-
deficient community, a progressive increase with age of goiter prev-
alence, thyroid nodularity, and functional autonomy was observed.
Hyperthyroidism was twice as high as that reported in iodine-suffi-
cient areas, mainly due to an increased frequency of toxic nodular
goiter. Although low titer serum thyroid antibodies were relatively
frequent, the prevalences of both overt and subclinical autoimmune
hypothyroidism were not different from those observed in iodine-
sufficient areas. (J Clin Endocrinol Metab 84: 561–566, 1999)
iodine-sufficient environment were well documented in the
classic Whickham survey carried out by Tunbridge et al. in
a mixed urban and rural region in Northeastern England (1).
Studies of other iodine-sufficient areas confirmed the find-
ings of this survey (2, 3). The spectrum and the prevalence
of thyroid disorders are known to be influenced by envi-
ronmental factors, especially by iodine intake (4). Indeed,
iodine deficiency is regarded as the most common cause of
thyroid disorders worldwide (4–6). Epidemiological studies
in iodine-deficient areas have mainly focused on the prev-
alence of goiter and cretinism (6–9). To our knowledge there
are no recent cross-sectional studies using modern technol-
ogies on the spectrum of thyroid disorders occurring in com-
munities with mild or moderate iodine deficiency.
In the present study, the prevalence of thyroid disorders
has been investigated in virtually the entire child population
HE SPECTRUM and the natural history of thyroid dis-
orders occurring in the adult population living in an
and in a high and representative proportion of the adult
population living in Pescopagano, a southern Italian village
with mild to moderate iodine deficiency.
Subjects and Methods
The survey was conducted in Pescopagano, a southern Italian village
located in the Lucan Apennines at 954 meters above the sea level. The
nearest town is 70 km away. Pescopagano was selected for its long term
exposure to iodine deficiency with no previous iodine prophylaxis. The
economy of this area is progressively converting from agriculture to
service activities. The usual diet consists mainly of local products. At the
time of the survey, the registered population of Pescopagano was 2348
people. Daily commuters with neighboring towns accounted for 620
people. They were excluded from the survey because of their exposure
to higher iodine dietary intake. A total of 317 people of the 1728 per-
manently residing in the village failed to respond to 2 consecutive calls
to participate in the survey. Thus, 1411 residents were actually exam-
ined: 419 (215 males and 204 females) 1- to 14-yr-old children, repre-
senting 94.1% of this age group, and 992 (573 females and 419 males) of
the 1368 subjects aged 15 yr or more, representing 72.5% of this age
group and referred to as the adult population. General practitioners of
the village actively took part in each step of the survey. Civil and health
authorities strongly supported the project, and informed consent was
obtained from parents of the minors and from adult subjects. A ques-
tionnaire sheet was completed for each subject and included personal
and family histories of thyroid disease with details of treatment and
special attention being paid to l-T4and any other medication affecting
thyroid function. Alimentary habits and coexistent autoimmune disor-
ders were also taken into account. In the schoolchildren, population
height and weight were measured.
A randomized sample of 75 adult subjects, drawn from the group of
317 subjects who failed to respond to the first and second calls, was
personally approached by family physicians and invited to participate
Received February 4, 1998. Revision received September 30, 1998.
Accepted November 12, 1998.
Address all correspondence and requests for reprints to: Fabrizio
Aghini-Lombardi, M.D., Department of Endocrinology, University of
Pisa, via Paradisa 2, I-56124 Pisa, Italy.
dell’Universita ` e della Ricerca Scientifica e Tecnologica (MURST 40%),
the National Research Council (National Research Center, Rome, Italy);
Target Project Biotechnology and Bioinstrumentation (Grant 91.01219,
PF70), Target Project Aging (Grant 91.00418, PF40), Target Project Pre-
vention and Control of Disease Factors (FATMA, Grant 9300689 PF41),
by grantsfrom theMinistero
Journal of Clinical Endocrinology and Metabolism
Copyright © 1999 by The Endocrine Society
Vol. 84, No. 2
Printed in U.S.A.
in the survey again. In 64 subjects complying with such personalized
invitation, urinary iodine excretion (UIE) measurements and goiter as-
sessments were performed. The data were compared with those ob-
tained in the general survey.
Casual urinary samples were collected for measurement of iodine
of iodine per L urine and are expressed as a median.
Thyroid ultrasound examination was performed by a portable real-
time instrument (Esaote, Biomedica, Firenze, Italy) using a 7.5-MHz
linear transducer. Subjects were examined in the supine position with
the neck hyperextended. Thyroid volume was calculated according to
the formula of the ellipsoid model: width ? length ? thickness ? 0.52
for each lobe (11). As previously described, goiter as assessed by ultra-
sound was defined when the thyroid volume was more than 2 sd above
the mean thyroid volume of age-matched controls in children and of
sex-matched controls in adults. The normal thyroid volume in children
was obtained from 2709 children residing in urban nonendemic areas
(12). The normal thyroid volume in adults residing in nonendemic areas
6.8 mL (mean ? 2 sd) in males (n ? 125) and 8.6 ? 4.4 mL in females
and 13 mL in females were considered to indicate goiter. The repro-
ducibility of thyroid volume measurement by ultrasound was assessed
and 30 adults.
Thyroid function tests
Serum free T4(FT4) and serum free T3(FT3) were measured by RIA
Serum TSH was measured by a sensitive immunoradiometric assay
(Gamma Coat125I, Incstar Corp., Stillwater, MN). The functional sen-
sitivity of the TSH assay was 0.03 mU/L. The normal range, determined
in 123 15- to 75-yr-old subjects, was 0.4–3.7 mU/L. Serum autoantibod-
ies to thyroglobulin (TgAb) and thyroperoxidase (TPOAb) were mea-
sured by agglutination (Serodia-ATG and Serodia-AMC, Fujirebio, Inc.,
Fine needle aspiration
goiter and was performed in 132 of 171 (77.2%) subjects who gave their
consents. FNA was performed in 119 solid and mixed nodules larger
clinical findings or the echographic pattern suggested the opportunity
of excluding malignancy.
Statistical evaluation was performed by the ?2test and t test using the
Statxact Program of Cytel Software Corp. (Cambridge, MA).
At the time of the survey, no subject was receiving treat-
ment. Previous treatment with methimazole was docu-
mented in 9 patients with a past history of toxic nodular
goiter. Six of 10 patients who were previously subjected to
partial thyroidectomy and 11 subjects with nontoxic nodular
had normal serum concentrations of FT4, FT3, and TSH. No
subject reported the use of iodized salt or iodine-containing
lower than 100 ?g/L were found in 81% of subjects, and
values greater than 200 ?g/L were documented in less than
1.0% of subjects (Fig. 1).
Prevalence of goiter
As reported in Table 1, the overall prevalence of goiter
progressively increased with age. Thyroid enlargement was
found in 67 of 419 children (16.0%). The prevalence of goiter
progressively increased from 10.1% in 6- to 8-yr-old children
to 17.0% and 37.6% in 9- to 11-yr-old and 12- to 14-yr-old
groups, respectively. No thyroid abnormality was docu-
mented in children under 6 yr of age. All goitrous children
had a diffuse goiter less than twice the thyroid volume of
age-matched controls, with the exception of one 14-yr-old
girl and one 13-yr-old boy who had nodular goiter. No sig-
nificant difference was found in the prevalence of goiter
between females and males [39 of 204 (19.1%) and 28 of 215
In the adult population (?15 yr-old), goiter, regardless of
Ten patients were previously subjected to partial thyroidec-
tomy for nontoxic goiter. Thus, the overall prevalence of
goiter in the adult population was 59.8%. The prevalence of
nodular goiter was negligible in the 15–25 yr age class, in-
creased up to 28.5% in the 56–65 yr age class, and declined
in older subjects. The prevalence of goiter was not different
between females (59.5%) and males (58.0%). Among subjects
with enlarged thyroid (excluding patients previously sub-
jected to thyroidectomy), moderate goiter (?30 mL) was
found in 62.3% of subjects, large goiter (30–60 mL) was
found in 30.2% of subjects, and very large goiter (?60 mL)
was found in 7.5% of subjects. Symptoms and/or signs in-
dicating a compression of adjacent structures of the neck
were present in 142 goitrous subjects (14.3% of the adults).
FIG. 1. Frequency of distribution of median values of UIE (micro-
grams per L) in the study population.
562AGHINI-LOMBARDI ET AL.
JCE & M • 1999
Vol 84 • No 2
The frequency of symptoms was related to thyroid size,
being present in 5.2% of subjects with moderate goiter, in
46.6% of subjects with large goiter, and in 93.2% of subjects
with very large goiter. Seventy-three subjects were consid-
ered possible candidates for surgery. Surgical removal of the
goiter because of severe pressure symptoms was advised in
27 and has been performed in 6 subjects to date.
Nontoxic goiter accounted for virtually all cases of goiter
in children (64 of 67) and for the large majority of adults (490
of 593, 82.6%). Thyroid disorders associated with thyroid
enlargement in the remaining subjects are described below.
For the purpose of the present study, thyroid functional
autonomy was defined by the finding of normal serum con-
centrations of FT4and FT3and subnormal serum TSH con-
centrations (?0.4 mU/L). Thyroid hormone medication and
other conditions leading to TSH suppression were excluded.
As reported in Table 2, thyroid functional autonomy was
found in 67 of 1411 (4.7%) subjects, with no difference be-
tween females (5.2%) and males (4.1%). Its frequency pro-
gressively increased with age from 0.7% in children to 15.4%
in elderly subjects (?75 yr old); the overall prevalence in the
adult population was 6.4%. Thyroid functional autonomy
was unrelated to goiter size and occurred in both nodular
(n ? 36) and diffuse goiter (n ? 31), but its relative frequency
P ? 0.0001).
Nine patients had a history of toxic nodular goiter. Active
hyperthyroidism was documented in 20 adults and in none
of the 419 children. The overall prevalence of hyperthyroid-
ism was 29 of 992 (2.9%) adults (Table 3), with no difference
between females (17 of 573, 2.96%) and males (12 of 419,
2.86%). Nine patients (0.9%) had toxic diffuse goiter, and 20
(2.0%) had toxic nodular goiter, including 1 male with active
toxic adenoma in whom the diagnosis was confirmed by
scintiscan and all 9 patients with a past history of hyperthy-
roidism. Thus, the nonautoimmune/autoimmune hyperthy-
roidism ratio was 2.2:1. Toxic diffuse goiter was equally
distributed in each class of adult age, whereas toxic nodular
goiter increased from 1.0% in 26–35 yr age class to 7.7% in
the 56–65 yr age class. No cases of toxic nodular goiter were
found beyond the age of 75 yr.
Overt and subclinical hypothyroidism
No subject had previously been diagnosed and treated for
hypothyroidism. Spontaneous overt hypothyroidism was
newly diagnosed in 2 of 992 (0.2%) adults and in none of the
419 children. Both hypothyroid subjects were females (2 of
of them had a reduced thyroid volume and diffuse hypo-
echogenicity at ultrasound, indicative of atrophic autoim-
mune thyroiditis, whereas the other had a diffuse goiter.
Subclinical hypothyroidism, as defined by serum TSH
greater than 3.7 mU/L with serum levels of free thyroid
hormones within the normal range, was found in 38 of 992
(3.8%) adults with no difference between females (25 of 573,
4.4%) and males (13 of 419, 3.1%). Ten of 38 subjects had
humoral evidence (TPOAb and/or TgAb, ?1:100) of thyroid
Serum thyroid antibodies and diffuse
Figure 2 shows the prevalence of thyroid autoantibody-
positive tests (?1:100 for both TPOAb and TgAb) in each age
class regardless of other thyroid abnormalities. The overall
prevalence was 12.6% (females, 17.3%; males, 7.0%) and pro-
gressively increased from 2.4% in children to 21.9% in the
46–55 yr age class, with little change in older subjects. Thy-
TABLE 1. Prevalence and age distribution of diffuse and nodular
goiter regardless of thyroid function
[n (m, f)]
135 (66, 69)
79 (43, 36)
88 (46, 42)
117 (60, 57)
419 (215, 204)
193 (88, 105)
194 (78, 116)
204 (94, 110)
140 (65, 75)
130 (50, 80)
79 (22, 57)
52 (22, 30)
992 (419, 573)
m, males; f, females.
TABLE 2. Prevalence and age distribution of thyroid functional
TABLE 3. Prevalence and age distribution of toxic diffuse goiter
and toxic nodular goiter in the adult population
Age (yr)Subjects (n)
2 ? 1a
3 ? 7a
4 ? 1a
11 ? 9a
aPatients with past history of hyperthyroidism.
THYROID DISORDERS IN AN IODINE DEFICIENT COMMUNITY563
roid autoantibodies were more frequently found in goitrous
(95 of 651, 14.6%) than in nongoitrous (45 of 760, 5.9%) sub-
jects (P ? 0.0001).
Circulating TgAb and TPOAb (?1:400) and thyroid echo-
graphic pattern of diffuse hypoechogenicity indicative of
diffuse autoimmune thyroiditis (13) were found in 50 of 1411
(3.5%) subjects (Table 4): 44 were euthyroid, 5 were subclin-
ically hypothyroid, and 1 had overt hypothyroidism. Goiter
was present in 26 of these 50 subjects.
Serum TSH distribution
As shown in Fig. 3, median TSH values progressively
decreased from 2.2 mU/L in children to 0.9 mU/L in 56- to
65-yr-old subjects, with no further changes in the older age
classes. No significant difference between males and females
was found in any age class. The mean serum TSH concen-
tration in the adult population was significantly lower (P ?
0.0001) in goitrous (1.4 ? 1.1 mU/L) than in nongoitrous
(2.0 ? 2.4 mU/L) subjects.
cancer confirmed by histology. Thus, the prevalence of as-
certained thyroid cancer in the study population was 1 of
1411. A follicular adenoma was documented by histology in
an additional subject with a microfollicular pattern with nu-
clear atypias by cytology. Benign thyroid lesions at cytology
were found in 116 (87.9%) subjects, whereas the FNA spec-
imens were nondiagnostic in 14 (10.6%) subjects.
Other thyroid disorders
In a 53-yr-old male, clinical features of panhypopituita-
rism associated with low serum FT4, FT3, and TSH concen-
trations were documented, indicating the diagnosis of cen-
tral hypothyroidism. Two cases of thyroid hemiagenesis
with normal thyroid function were also identified.
In the randomized sample, the median UIE was 51 ?g/L,
and the overall frequency of goiter was 54.7%, with no sig-
nificant difference with respect to the study population.
The prevalence and the spectrum of thyroid disorders in
an iodine-deficient community were assessed in the present
survey. The study was conducted in Pescopagano, a south-
ern Italian village located in an area of iodine deficiency that
has never been submitted to any iodine prophylaxis pro-
gram. Virtually all the children and the large majority of the
adults were examined. The results obtained by examining a
randomized sample of the adult residents who failed to re-
spond to the initial recruitment showed that the data are
representative of the entire population.
The prevalence of goiter progressively increased with age,
being 16.0% in children and 59.8% in adults. Age and sex
FIG. 2. Prevalence of thyroid autoantibody-positive tests (TPOAb
and TgAb, ?1:100) in each age class regardless of other thyroid ab-
FIG. 3. Median TSH (milliunits per L) values in each age class.
TABLE 4. Prevalence, age and sex distribution of diffuse
Age (yr) Subjects (n) Cases (n)
m, Males; f, females.
564 AGHINI-LOMBARDI ET AL.
JCE & M • 1999
Vol 84 • No 2
goiter distributions were similar to those observed in other
iodine-deficient areas (5–9, 14–16), but differed from those
observed in iodine-sufficient areas in which the goiter prev-
alence is higher in young adults than in middle-aged and
elderly people and is much more frequent in females than in
males (2). Thus, it would appear that iodine deficiency not
only overcomes the increased female susceptibility to de-
velop goiter, but also influences the natural history of goiter
by counteracting its declining prevalence with age. Rather
than an increase, we observed a fall in goiter prevalence in
very old subjects (?75 yr old), as reported in other iodine-
deficient areas (5–9). The question of whether and to what
extent this decline is due to the selection of people reaching
of the UIE of 55 ?g/L, Pescopagano could be classified as an
area with mild to moderate iodine deficiency. Compared
with areas with similar degrees of iodine deficiency, the
prevalence of goiter observed in the present study appears
to be much higher than expected, especially in the adults.
This may be related to a prolonged exposure of this area to
a more severe iodine deficiency in the past. As previously
reported from other areas of Italy, silent prophylaxis due to
improved socioeconomic and nutritional conditions most
likely occurred in recent years, resulting in an improved
iodine intake. This prevented the development of new goi-
ters in younger subjects, but was not accompanied by a
In the present survey, thyroid nodularity was exceptional
in children and was rare in 15- to 25-yr-old subjects, pro-
gressively increased with age up to 65 yr and tended to
decline thereafter. Clinically significant pressure symptoms
were not rare in the adults; 73 patients required medical
attention for pressure symptoms, and surgery was advised
in 27 subjects. These findings underscore the role of pro-
longed exposure to iodine deficiency in the growth of goiter
and the progression of nodularity. The prevalence of thyroid
nodularity in the adults living in Pescopagano was appar-
ently lower than that recently reported from some iodine-
sufficient areas using thyroid ultrasound (18, 19). The use of
different criteria for the definition of nodularity largely ac-
counts for this discrepancy. Although only lesions greater
than 10 mm were considered in the present survey, lesions
as small as 3–10 mm were included in the above reports.
The overall prevalence of overt hyperthyroidism was
twice as high as that found in the Whickham survey (1, 3).
At variance with iodine-sufficient areas, in which hyperthy-
roidism is mainly due to toxic diffuse goiter (4, 20–24), toxic
nodular goiter accounted for the majority of thyrotoxic sub-
jects living in Pescopagano, being twice as frequent as toxic
and was more prevalent in males than in females. On the
contrary, toxic diffuse goiter was equally distributed in dif-
ferent age classes of adults, with a pronounced preponder-
ance of female subjects. The prevalence of thyroid functional
autonomy progressively increased from 0.7% in children to
15.4% in subjects more than 75 yr old and was more frequent
in subjects with nodular goiter. The prevalence of functional
autonomy observed in the adults (6.4%) was much higher
than that reported in iodine-sufficient areas, where this con-
dition is rare (25–28). When data from the survey carried out
in the iodine-sufficient Whickham community were recal-
culated (3) using the same criteria adopted in this study, a
frequency of 0.6% for functional autonomy was found.
Overt hypothyroidism was only found in two adult fe-
males and in none of the males, with a prevalence of 0.2% of
the adult population. Subclinical hypothyroidism was found
in 3.8% of the adults. Thus, the overall prevalence of both
overt and subclinical hypothyroidism was slightly, but not
significantly, lower than that recalculated from the Whick-
ham survey (0.5% and 5.3%, respectively) (1–3).
Humoral and echographic evidence of diffuse autoim-
mune thyroiditis was found in 3.5% of the entire population;
women over the age of 45 yr were more frequently affected.
Most of these subjects were clinically and biochemically eu-
thyroid, and about half of them had an enlarged thyroid
gland. To our knowledge, no epidemiological study using
thyroid antibody tests combined with ultrasound for the
assessment of thyroid autoimmunity has been performed as
deficient areas (29, 30), the detection of serum thyroid anti-
bodies was relatively frequent, especially in goitrous fe-
males. Antibody titers were low in most cases and were not
associated with thyroid functional alterations or with diffuse
autoimmune thyroiditis, as assessed by ultrasound. This
finding is in keeping with the concept that the development
of goiter due to iodine deficiency may overexpose the im-
mune system to thyroid antigens, leading to humoral and
cell-mediated immune reactions (29–32).
The question of whether iodine intake influences the de-
velopment of thyroid cancer remains controversial (33). In
the present survey only a single case of papillary thyroid
carcinoma was found. Although a number of surgical and
autopic (34–37) data on the relationship between iodine in-
take and thyroid cancer are available, to our knowledge no
comparable epidemiological studies have been performed in
iodine-deficient areas. The size of the iodine-deficient com-
munity examined by us is not sufficient to draw any con-
clusion. Clearly, more extensive studies are required to ad-
dress this problem.
In conclusion, the present survey performed in virtually
the entire population of a village with mild to moderate
iodine deficiency shows a cross-sectional picture of the spec-
trum of thyroid disorders occurring in iodine deficiency and
provides relevant information on the natural history of
iodine-deficient goiter. In the present survey of an iodine-
deficient community, a progressive increase with age in goi-
ter prevalence, thyroid nodularity, and functional autonomy
was observed. Hyperthyroidism was twice as high as that
reported in iodine-sufficient areas, mainly due to an in-
creased frequency of toxic nodular goiter. Although low titer
serum thyroid antibodies were relatively frequent, the prev-
alence of both overt and subclinical autoimmune hypothy-
roidism was not different from that observed in iodine-suf-
The authors thank the following people for their contributions: Luigi
Bartalena, M.D., Agostino Gigliotti, M.D., and Franco Golia, M.D., De-
partment of Endocrinology, University of Pisa (Pisa, Italy); Andrea Lo-
viselli, M.D., Department of Internal Medical Sciences, University of
THYROID DISORDERS IN AN IODINE DEFICIENT COMMUNITY565
Cagliari (Cagliari, Italy); Daniela Balzi, M.D., Unita ` Operativa di Epi-
demiologia, Servizio Multizonale di Prevenzione Oncologica, USL 10
(Firenze, Italy); Giuseppe Araneo, M.D., Assessore Sanita `, Comune di
Pescopagano (Potenza, Italy); and Lidia Gallucci, M.D., and Carmela
Silvestri, M.D., general practitioners of Pescopagano, Italy.
1. Tunbridge WMG, Evered DC, Hall R, et al. 1977 The spectrum of thyroid
disease in a community: the Whickham Survey. Clin Endocrinol (Oxf).
2. Vanderpump MPJ, Tunbridge WMG, French JM, et al. 1995 The incidence of
Survey. Clin Endocrinol (Oxf). 43:55–68.
3. Wang C, Crapo LM. 1997 The epidemiology of thyroid disease and implica-
tions for screening. Endocrinol Metab Clin North Am. 26:189–218.
4. Vanderpump MPJ, Tunbridge WMG. 1996 The epidemiology of thyroid
diseases. In: Braverman LE, Utiger RD, eds. Werner and Ingbar’s the thyroid.
Philadelphia: Lippincott-Raven; 474–482.
5. Dunn JT, Pretell EA, Daza CH, Viteri FE. 1986 Towards the eradication of
endemic goiter, cretinism and iodine deficiency. Pan American Health Orga-
nization. Washington: WHO; Scientific publication. 502:215–370.
6. Delange F. 1994 The disorders induced by iodine deficiency. Thyroid.
7. Delange F. 1974 Endemic goitre and thyroid function in Central Africa. In:
Monographs in pediatrics. Basel: Karger; vol 2:1–171.
8. Gutekunst R, Scriba PC. 1989 Goiter and iodine deficiency in Europe. The
European Thyroid Association report as updated in 1988. J Endocrinol Invest.
9. Gaitan E, Dunn JT. 1992 Epidemiology of iodine deficiency. Trends Endo-
crinol Metab. 3:170–175.
for measuring iodine in urine. Thyroid. 3:119–123.
11. Brunn J, Blocjk U, Ruf J, Bos I, Kunze WP, Scriba PC. 1993 Volumetrie der
12. Vitti P, Martino E, Aghini-Lombardi F, et al. 1994 Thyroid volume measure-
ment by ultrasound in children as a tool for the assessment of mild iodine
deficiency. J Clin Endocrinol Metab. 79:600–603.
13. Marcocci C, Vitti P, Cetani F, et al. 1991 Thyroid ultrasonography helps to
identify patients with diffuse lymphocytic thyroiditis who are prone to de-
velop hypothyroidism. J Clin Endocrinol Metab. 72:209–213.
14. Delange F, Burgi H. 1989 Iodine deficiency disorders in Europe. Bull WHO.
15. Aghini-Lombardi F, Antonangeli L, Vitti P, Pinchera A. 1993 Status of iodine
nutrition in Italy. In: Delange F, Dunn JT, Glinoer D, eds. Iodine deficiency in
Europe. A continuing concern. New York: Plenum Press; 403–408.
16. Martino E, Loviselli A, Velluzzi F, et al. 1994 Endemic goiter and thyroid
function in Central-Southern Sardinia: report on an extensive epidemiological
survey. J Endocrinol Invest. 17:653–657.
17. Aghini-Lombardi F, Antonangeli L, Vitti P, Pinchera A. 1993 Iodized salt
prophylaxis of endemic goiter: an experience in Tuscany (Italy). Acta Endo-
crinol (Copenh). 129:497–500.
18. Woestyn J, Afschrift M, Schelstrete K, Vermeulen A. 1985 Demonstration of
nodules in the normal thyroid by echography. Br J Radiol. 58:1179–1182.
19. Brander A, Viikinkoski P, Nickels J, Kivisaari L. 1991 Thyroid gland: US
screening in a random adult population. Radiology. 181:683–687.
20. Barker DJP, Phillips DIW. 1984 Current incidence of thyrotoxicosis and prev-
alence of goiter in 12 British towns. Lancet. 2:567–570.
21. Reinwein D, Benker G, Konig MP, Pinchera A, Shatz H, Schleuener H. 1988
The different types of hyperthyroidism in Europe. Results of a prospective
survey of 924 cases. J Endocrinol Invest. 11:193–200.
disease. Endocr Rev. 8:439–450.
23. Laurberg P, Pedersen KM, Vestergard D, Sigurdson G. 1991 High incidence
of multinodular toxic goitre in the elderly population in a low iodine intake
area vs. high incidence of Graves’ disease in the young in a high iodine intake
mark and Iceland. J Intern Med. 229:415–420.
24. Hay ID, Morris JC. 1996 Toxic adenoma and toxic multinodular goiter. In:
Braverman LE, Utiger RD, eds. Werner and Ingbar’s the thyroid. Philadelphia:
25. Baltisberger BL, Minder CE, Burgi H. 1995 Decrease of incidence of toxic
nodular goitre in a region of Switzerland after full correction of mild iodine
deficiency. Eur J Endocrinol. 132:546–569.
26. Belfiore A, Sava L, Runelli F, Tomaselli L, Vigneri R. 1983 Solitary auton-
omously functioning thyroid nodules in iodine deficiency. J Clin Endocrinol
hyperfunctioning thyroid nodule. Ann Intern Med. 67:539–541.
28. Hamburger JI. 1980 Evolution of toxicity in solitary nontoxic autonomously
functioning thyroid nodules. J Clin Endocrinol Metab. 50:1089–1092.
29. Fenzi GF, Giani C, Ceccarelli P, et al. 1986 Role of autoimmune and familial
factors in goiter prevalence. Studies performed in a moderately endemic area.
J Endocrinol Invest. 9:161–164.
30. Mariotti S, Sansoni P, Barbesino G, et al. 1992 Thyroid and other organ-
specific autoantibodies in healthy centenerians. Lancet. 339:1506–1508.
31. Laurberg P, Pedersen KM, Hreidarsson A, Sigfusson N, Iversen E, Knudsen
PR. 1998 Iodine intake and the pattern of thyroid disorders: a comparative
epidemiological study of thyroid abnormalities in the elderly in Iceland and
in Jutland, Denmark. J Clin Endocrinol Metab. 83:765–769.
32. Costa A, De Filippis V, Balsamo A, et al. 1984 Serum autoantibodies and
thyroid lymphocytic infiltration in endemic goiter. Clin Exp Immunol.
33. Williams ED. 1994 Thyroid tumorigenesis. Horm Res. 42:31–34.
and 161 autopsy cases observed over a thirty-year period. Cancer.
35. Williams ED, Doniach I, Bjarnason O, Michie W. 1977 Thyroid cancer in an
iodide rich area. Cancer. 39:215–222.
36. Hofstadter F. 1980 Frequency and morphology of malignant tumours of the
A Pathol Anat Histol. 385:263–270.
37. Harach HR, Williams ED. 1995 Thyroid cancer and thyroiditis in the goitrous
566 AGHINI-LOMBARDI ET AL.
JCE & M • 1999
Vol 84 • No 2