Status of Thyroid Function in Indian Adults: Two Decades After Universal Salt Iodization
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32 © JAPI • april 2012 • VOL. 60
Original Article
Status of Thyroid Function in Indian Adults: Two
Decades After Universal Salt Iodization
Raman Kumar Marwaha†, Nikhil Tandon#, Mohd Ashraf Ganie**, Ratnesh Kanwar‡,
Aparna Sastry***, MK Garg*, Kuntal Bhadra****, Satveer Singh*****
Abstract
Objectives: The aim was to find impact of two decades of universal salt iodization on the prevalence of goiter,
thyroid autoimmunity and thyroid dysfunction in Indian adults.
Methods: This was a cross sectional study from Delhi, India. The subject population included 4409 adult members
of resident welfare associations of 5 residential colonies, from 18-90 years of age, who participated in general
health check-up camps. The subjects underwent a detailed evaluation including history, anthropometry, goiter
grading, USG thyroid, thyroid auto-antibodies and thyroid function tests. All these subjects were regularly
consuming iodized salt.
Results: Overall, 9.6 % of subjects had clinical goiter (13.3% women and 3.3% in men). Prevalence of nodules
on palpation was found to be in 1.6% which was lower in men. The nodule prevalence increased to 4.6% in men
and 5.6 % in women on ultrasonography. Thyroid hypoechogenicity was seen in 30.6% of subjects with severe
hypoechogenicity higher in women (5.7% men and 15.5 % women). TPO antibody was positive in 13.3% adults
and it showed a positive correlation with age, female sex and hypothyroidism. Subclinical hypothyroidism
was the commonest abnormality encountered and affected 19.3 % subjects (15.9% men; 21.4% women). Thyroid
dysfunction showed a rising trend with age in both genders.
Conclusions: Normal UIE and low goiter prevalence, especially in males, suggest success of the universal salt
iodization program in the region under review. High prevalence of subclinical hypothyroidism was not correlated
with either thyroid autoimmunity or iodine intake, as reflected in urinary iodine excretion.
Introduction Subjects and Methods
I odine deficiency disorders (IDD) encompass a broad spectrum
including goiter, reduced cognitive function and work
efficiency, delay in physical and mental milestones in childhood,
Study participants
This cross sectional study was conducted between Dec
2007- Jan 2010 in 18-90 year old men and women recruited from
and in the extreme, cretinism.1 Though supplementation of various regions of Delhi. The subject population was taken from
iodine is associated with large scale benefits, concerns have general health camps established in residential colonies (one
been raised regarding side effects related to varying levels of each from 5 different geographical zones of Delhi). These camps
iodine intake.2,3 Evidence from literature indicates that iodine were conducted in association with the Residential Welfare
intake up to 1 mg/day is tolerated by normal adults.4 However, Associations of these colonies. All adults residing in these
reports suggest that continued exposure to iodine may result in colonies were invited to participate. All subjects were asked to
clinical conditions like goiter, thyroid dysfunction (both hypo- sign an informed consent and the study was approved by the
and hyper-thyroidism), and thyroid autoimmunity.3-5 In India, Institutional Ethics committee of the Army Referral and Research
Universal Salt Iodization (USI) has been in force since 1984. The Hospital, New Delhi.
impact of this programme on thyroid status has been reported by
Methods
us and other Indian workers in school age children.3,5,6 However,
there are limited data evaluating the impact of salt iodization on All adults (n=4409) were evaluated by taking a detailed
thyroid function in Indian adults. clinical history and general physical examination, including
anthropometry. After excluding 107 adults with history of
In view of this, the present study was undertaken to evaluate
receiving thyroid medication, the study population comprised
thyroid functional status of adults after more than two decades
of 4302 subjects (1600 males; 2702 females). Thyroid palpation
of salt iodization.
was carried out independently by two endocrinologists with
experience in thyroid epidemiology. The concordance of grading
was recorded and in case there was disagreement between
the observers, a higher grade was chosen. Goiter was graded
according to WHO/UNICEF/ICCIDD recommendations and
†
Additional Director and Head, #Professor, **Associate Professor, any evidence of nodularity and characteristics of consistency
‡
Scientist D, ***Scientist C, *Adviser Medicine, ****Senior Technical was also recorded.6 Body weight was measured to the nearest
Assistant (B), *****Technical Officer (B), Department of Endocrinology 0.1 kg using a beam balance-weighing scale. The adults were
and Thyroid Research Centre, Institute of Nuclear Medicine and
weighed wearing the light clothing but without shoes, belts or
Allied Sciences, Timarpur, *Army Referral and Research Hospital,
#Department of Endocrinology and Metabolism, All India Institute
any other items found on them. Height was measured to the
of Medical Sciences New Delhi 110054, INDIA and Department of nearest 0.1 cm using the height scale. Body mass index (BMI) was
**
Endocrinology Sher-i-Kashmir Institute of Medical Sciences Srinagar, calculated as weight in kgs /(height in meters)2. Family history
Jammu and Kashmir. of known thyroid dysfunction in first degree relatives of study
Received: 10.08.2011; Revised: 02.11.2011; Re-revised: 26.12.2011; subjects was noted.
Accepted: 27.12.2011© JAPI • april 2012 • VOL. 60 33
Thyroid ultrasonography thyroid echogenecity was considered suggestive of autoimmune
USG thyroid gland was performed with subjects in supine thyroid disease as described in literature.7 The presence and size
position with neck hyper-extended by a single sonologist who of any nodules was noted.
was blinded to the results of thyroid palpation, using a portable Assays
ultrasound machine (Sonosite Titan, Germany) with a 7.5 MHz All adults were subjected to blood sampling for estimation of
transducer. The gain settings of the ultrasound scanner were thyroid function status (free T4, free T3 and TSH), and thyroid
adjusted so that the lumina of the carotid artery and internal peroxidase autoantibody (TPO Ab). FT3, FT4 and TSH were
jugular vein were free of echoes. Hypoechogenicity was analysed by electrochemiluminescence assay (Cobas-Roche
diagnosed if echogenecity of the thyroid was uniformly less than Elecys 1010 analyzer). Normal range for FT4, FT3 and TSH
that of the connective tissue and similar to or less than that of were 12.0-22.0 pmol/L, 2.8–7.1 pmol /L and 0.28–4.2 mIU/L
the neck muscles. Mild hypoechogenicity was defined when the respectively, with intra assay and inter assay coefficient of
echogenecity was less than that of connective tissue but more variation (CV) being less than 7 % for all three parameters. The
than that of strap muscles of the neck. This USG reduction in presence of either subclinical or overt, hypo- or hyperthyroidism
Table 1 : Description of clinical parameters in the study was used to define thyroid dysfunction. The definition of
population subclinical hypothyroidism/ hyperthyroidism was defined as
normal FT3, FT4 and elevated TSH (between 4.2 to 10.0 mIU/L)
Parameter Overall Men Women /suppressed TSH ((less than 0.28 mIU/L) respectively. TPO Ab
n=4302 n=1600 n=2702
were analyzed by electrochemiluminescence assay (Cobas-Roche
Mean ±SD Mean ±SD Mean ±SD
(Range (Range) (Range) Elecys 1010 analyser) with an analytical sensitivity of 102 IU/mL as strongly TPO Ab positive.
Height (cm) The intra assay CV for TPO Ab was34 © JAPI • april 2012 • VOL. 60
Table 3 : Association of thyroid dysfunction with thyroid autoimmunity, as represented by TPO Ab positivity and ultrasound
hypoechogenecity
Sub Clinical Overt Subclinical
Euthyroid Hypothyroidism Overt Hypothyroidism Hyperthyroidism Hyperthyroidism
Men Women Men Women Men Women Men Women Men Women
N(%) N(%) N(%) N(%) N(%) N(%) N(%) N(%) N(%) N(%)
TPO Ab Positivity
Normal
TPO Ab negative 1178 1767 213 423 16 24 5 8 3 14
subjects (102) (4.7) (7.4) (10.7) (19.1) (36.0) (46.0) (16.7) (25.0) (20.0) (38.5)
Thyroid echogenecity on ultrasound
Normal 1073 1364 172 322 10 22 6 6 4 11
echogenecity (81.9) (67.0) (67.7) (55.7) (40.0) (44.0) (100.) (50.0) (80.0) (42.3)
Mild 179 398 59 142 5 8 0 3 1 7
Hypoechogenicity (13.7) (19.5) (23.2) (24.6) (20.0) (16.0) (0.0) (25.0) (20.0) (26.9)
Moderate 58 274 23 114 10 20 0 3 0 8
Hypoechogenicity (4.4) (13.5) (9.1) (19.7) (40.0) (40.0) (0.0) (25.0) (0.0) (30.8)
Logistic regression was used in the analysis of the influence and hypothyroidism (r= 0.078, p=0.01;r=0.74, p=0.01 and r=0.168,
of urinary iodine excretion and TPO Ab levels on thyroid p= 0.001 respectively). Serum TSH levels and TPO Ab were
nodules and thyroid enlargement. A p value of 300 µg/L. There was no significant difference in TPO,
decreased as age advanced e.g. it was 5.8 % in 3rd decade as echogenecity and thyroid function status between the subjects
compared to 2.0% in 7th decade in men while it was 18.5 % in 3rd with UIE more than 300 µg/L or those below this.
decade as compared to 3.8 % in 7th decade in women (Table 2). Thyroid dysfunction
Family history of thyroid dysfunction was noted in 176 (4.1%) The prevalence of thyroid dysfunction was high and was
of subjects and it was similar in men (4%) and women (4.1%). commoner in women than men (24.7% % vs. 18.2%). Subclinical
Thyroid nodularity and echogenecity hypothyroidism (SCH) was the commonest abnormality
On palpation, thyroid nodules were found in 68 (1.6%) encountered and affected 19.3% subjects (15.9% men, 21.4%
subjects, (0.9% in men; 2.0% in women). On ultrasonography, the women). The prevalence of SCH in men and women with TPO
prevalence of thyroid nodules increased to 4.6% in men and 5.6 Ab was 15.8% and 25.9% respectively. Overt hypothyroidism was
% in women. The nodule prevalence decreased with advancing the second commonest abnormality and affected a total of 181
age in both men and women. Hypoechoic pattern on ultrasound subjects (4.2%), which included 75 (1.7%) subjects with newly
was noted in 1315 (30.6%) subjects, of which mild and severe diagnosed disease and 106 subjects with previously diagnosed
hypoechogenicity was observed in 805 (18.7%) and 510 (11.9 %) hypothyroidism on therapy. Hyperthyroidism, both overt and
subjects respectively. Sex-wise segregation indicated that 5.7% sub-clinical was found in 49 (1.13%) subjects and affected 0.7 %
men had severe hypoechogenicity as compared to 15.5% women men and 1.4 % women. Thyroid dysfunction showed a rising
(p=102). TPO
this in an adult population.
Ab positivity showed positive correlation with age, female sex
Since conventionally, goiter prevalence in school age children© JAPI • april 2012 • VOL. 60 35
is estimated to assess response to iodine supplementation, there either in transition from iodine deficient to replete states (9-17.8
are limited data on adult goiter prevalence from community %)11,21 or with long-term iodine sufficiency (11.3 %-18.5%).8,28
based studies.6 We report an overall goiter prevalence of 9.6% in Higher prevalence of TPO Ab positivity in these populations
adults (3.3% males; 13.3% females), which suggests persistence can be explained by unmasking of underlying autoimmunity
of mild endemicity of goiter despite two decades of successful or cytopathic effect of supra-physiological doses of iodine.
USI. A small study from coastal Kerala of India, reported similar However, the prevalence of the positive antibodies reported by
goiter prevalence in adults (12.2%), in a region where median different groups is difficult to compare given the variability in
UIE was consistent with iodine sufficiency (8), while as in contrast assay methods, lack of international standards, varying cut off
a study performed in rural North India, in a population with values and use of one or both antibodies in different studies. In
persistent iodine deficiency (UIE < 100 µg/L in 47.8% subjects) an Italian adult population with similar iodine status as ours
reported a much higher goiter prevalence in adults – 16.7% in 2.3% men and 10.2% women had TPO Ab positivity as was
men; and 33.6% in women.9 shown in another Italian study from three regions (4.1% in men
There are several reports of adult goiter prevalence after and 10% in women).29
iodine supplementation programs from across the world. While Our observation of a high prevalence of thyroid dysfunction, in
some suggest an impressive decline in goiter prevalence to as low women more than men, especially sub-clinical hypothyroidism,
as 1.3-5.6%,10,11 others report a post iodization goiter prevalence is consistent with earlier reports from iodine sufficient
similar to that in the present study.11-13 In contrast, two studies regions.13,30 The prevalence of SCH in the present study is 19.3%,
conducted at least 15 years post salt iodization, from Iran and but a cross-sectional population survey from Kerala, India,
Taiwan, continue to show significantly higher goiter prevalence showed a relatively lower prevalence (9.4%) of SCH. This study
rates ranging from 19-25%.14,15 was conducted in a coastal region, where due to consumption
Prevalence of clinical nodules reported in the present study of sea-food the population has always been iodine sufficient
(1.6% subjects; 0.9 % men; 2.0% women) was lower than that (median UIE 220 micro gm/l).8 The studies from areas with
observed in other recent studies, though most of these were in borderline to moderate iodine deficiency, including a report
iodine deficient regions.16,17 The prevalence of thyroid nodules from the Indian state of Gujarat, show a lower prevalence of
by USG in our study was 4.6% in men and 5.6 % in women. SCH ranging from 1.8% to 7%.11,30,32 The prevalence of sub-clinical
Reports from regions which have recently become iodine hypothyroidism from areas transitioning to an iodine sufficient
sufficient demonstrate nodule prevalence from a low of 1.3- state, have been shown to vary between 4.9 and 10.4%.12,27,30,31
3.6%15,17 to a high of between 13-33%.17,18 The precise reason The data from populations with iodine sufficiency show variable
for such a wide range of ultrasound diagnosed nodules could prevalence of subclinical hypothyroidism, e.g 2.7% in Denmark,
include the duration and severity of iodine deficiency, age of 2.4%27 Zhangwu region of China, 10 4.3% in NHANES data
population studied (younger ages showing lower prevalence), on US population,285.8 % from Isfahan, Iran,14 and 9.5% from
pre-supplementation prevalence of nodules, and efficacy of the Colorado health fair study.33 Overt hypothyroidism was
supplementation program. Further, different studies have used the second commonest abnormality (1.6% men and 1.9 % of
ultrasound transducers which vary from the commonly used 7.5 women) which was comparable to some of the data published
MHz transducer, as used by us, to highly sensitive transducers worldwide from iodine sufficient areas13,34 but higher than that
ranging from 10-13 MHz. The impact of different transducers reported by Menon et al from Kerala, India.8 However, studies
on estimation of nodules becomes apparent from a nation-wide from iodine rich areas of Japan show a higher prevalence of overt
study from an area of borderline iodine deficiency in Germany, hypothyroidism than in the present study.34 Hyperthyroidism,
where nodule prevalence rose from 33% (7.5MHz transducer) both overt and subclinical was found in 0.7 % of men and 1.4
to 68% (13 MHz transducer).19,20 Even iodine sufficient regions % of women. These values are not significantly different from
show varying prevalence of nodules, with studies from China10 other population based studies reported in literature,10,34 except
and Hungary12 reporting a prevalence of 2.4-3.3%, while that for a study from Germany which reported a significantly lower
from HongKong demonstrating 12.1% nodule prevalence.21 prevalence (0.12%).35
Reduced thyroid echogenecity on USG is considered to The mean urinary iodine excretion (UIE) was adequate
be characteristic of autoimmune thyroiditis.22 The degree of 230.34±113.08 µg/L (15-664; median 221) suggesting iodine
hypoechogenicity has not only been shown to correlate with the sufficiency, similar to that reported from Kerala.8 No correlation
levels of circulating thyroid antibodies and thyroid dysfunction was seen between UIE and thyroid autoimmunity and thyroid
but also to predict the evolution towards hypothyroidism in dysfunction. Similar observation was seen earlier by our group in
euthyroid subjects.22-24 The present study also confirmed the studies conducted in children.5 The mean UIE (SE) was 203 µg/L
positive correlation between thyroid hypoechogenicity and and 201 (137) µg/ L for euthyroid and hypothyroid individuals
TPO Ab positivity reported by other investigators and by us in respectively, in the Isfahan study.14
children.23-25
Thyroid TPO Ab was mildly positive (>34 but < 102 IU/mL) in
Conclusion
13.3% adults and strongly positive (i.e. >102 IU/mL) in 6.1% men In conclusion, after two decades of USI, this is the first Indian
and 10.8% women. The only other Indian study describing adults study on adults assessing their thyroid functional status. The
with long term iodine sufficiency (Median UIE 220 micro gm/l) in normal UIE and low goiter prevalence in adults, especially in
the South Indian state of Kerala showed a prevalence of 16.7%.8 males, indicates the success of the program. The high prevalence
While some reports suggest a lower TPO Ab positivity in iodine of subclinical hypothyroidism did not correlate with TPO Ab
deficient regions (4.3-9.5%),25 studies from iodine deficient areas positivity or UIE. These results may represent the pattern of
of Brazil and Denmark report high TPO Ab positivity prevalence thyroid dysfunction during the transition period of iodine
(13-16.9%).26,27 The prevalence of TPO Ab positivity was higher deficiency to sufficiency.
than that in the present study, in several reports from areas36 © JAPI • april 2012 • VOL. 60
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