Journal of Rawalpindi Medical College (JRMC); 2013;17(2):284-287
Original Article
Iodized Salt: A Risk Factor for Hyperthyroidism.
Samia Sarwar*, Muhammmad Aslam**, Muhammad Amin Waqar***,
Mazhar Hussain**, Idrees Farooq Butt**
*Department of Physiology Rawalpindi Medical College, Rawalpindi **Department of Physiology,Army
Medical College, Rawalpindi. ***Armed Forces Institute of Pathology, Rawalpindi.
Abstract
suffered from IDD in 118 countries.4The incidence is
high in mountainous and flood-prone areas where
iodine deficient soils exist. Pakistan established Goiter
Council Cell in 1986 and in 1987, Lugols iodine oil
capsules and injections were introduced. In 1989, the
strategy was shifted to salt iodinization.5The ratio of
salt to iodine depends upon the average amount of salt
consumed per capita of target population. The daily
recommended body requirement of iodine is 150
µg.6This amount is based on: the calculated daily
thyroid hormone turnover in euthyroid, the iodine
intake producing the lowest values for serum TSH and
for serum thyroglobulin. The amount of thyroid
hormone
replacement
necessary
to
restore
euthyroidism to athyreotic subjects,iodine intake
associated with the smallest thyroid volumes in
populations and the lowest incidence of transient
hypothyroidism in neonatal screening with blood spot
TSH also helps in determining daily iodine
uptake.7The appropriate fortification level is about one
part iodine per 20000 – 40000 parts salt or 25-50 gm
iodine per metric ton salt.5
It has been observed that one of the most
undesirable effects of salt iodization is Iodine Induced
Hyperthyroidism (IIH), which has been reported from
many countries of the world specifically in iodine
deficient areas.8 In Pakistan, the development of
hyperthyroidism after iodine fortification to the table
salt poses a great challenge.
Background: To evaluate dietary use of iodized
salt as a risk factor for hyperthyroidism in people
living in iodine deficient areas of Pakistan.
Methods: In this case control study, patients
(n=150), 50 male and 100 female, aged 35-75 years,
from Northern region of Pakistan, with goiter and
hyperthyroidism; and healthy control group (n=100),
32 males and 68 females aged 35-75 years from same
region, were selected by probability convenience
sampling. The patient and control group were
interviewed regarding use of iodized salt. History
and physical examination of patient group was done
for assessment of symptoms and goiter. Thyroid
stimulating hormone (TSH) and free thyroxin (FT4)
were analyzed in Patient and Control group both.
Results: The study revealed 67% prevalence of
goiter between 46-55 years in patient group with
female predominance. Grade two multinodular
goiters were followed by Solitary nodules and
diffuse goiter in patient group. The residents of
Azad Jammu and Kashmir region were more affected
in patient group. Mean FT 4 was 46.5+/-22 pmol/L in
patients and 16.036+/-8 in controls. Mean TSH was
0.099+/-0.03 and 1.44061+/-0.39 in patients and
controls respectively. The family history for thyroid
disease was positive in 72% of patients and 56% in
controls. The relative risk in iodized salt exposed vs.
non exposed individuals showed Odd ratio of 5.2.
Conclusion: Iodized salt is a risk factor for
development of hyperthyroidism in iodized salt
users living in iodine deficient areas of Pakistan.
Key Words: Iodized salt, Hyperthyroidism,
Thyroid stimulating hormone, Free Thyroxine (FT 4 )
Patients and Methods
The study was carried out by Department of
Physiology, Army Medical College – Rawalpindi and
Armed Forces Institute of Pathology- Rawalpindi, in
2007. Through non probability convenience sampling,
a total of 250 individuals were selected, 150 cases of
hyperthyroidism, and 100 healthy controls. The
criteria for selection of cases included hyperthyroid
patients who were residents of northern region of
Pakistan, male or female, and having goiter and
clinical symptoms of hyperthyroidism. The Control
group was symptom free. The exclusion criteria was,
thyroxin intake, medicine/applicants having iodine
Introduction
Iodine,a nonmetallic element, is nutritionally an
essential element, especially for thyroid gland. In
solutions, it is used as anti infective, in contrast media
and in certain medicines.1-3 The Iodine Deficiency
Disorder (IDD) is a major nutritional problem in the
world as estimated in 1990, about 1572000000 people
284
Journal of Rawalpindi Medical College (JRMC); 2013;17(2):284-287
(systemic medicine, skin, vaginal, dental and contrast
media), history of renal disease, thyroid surgery and
thyroid radiotherapy. The goiter was assessed by
palpation method using WHO Grade system. All the
individuals were examined by 3 independent medical
specialists, to clinically establish hyperthyroidism and
also to record the prominent symptoms in these
patients. For the assessment of TSH and FT 4 , venous
blood sample was drawn between 7:00 –9:00 am, after
+/- 6 hrs fasting. The blood samples were stored at 20OC till analysis. Chemiluminescent technique on
fully automated 2000 Analyzer, was used to analyze
samples.
individuals showed Odd ratio of 5.2 {(significant >2)
(Table-3).
Area
Peshawar
Taxila
Hassan
Abdal
Total
Results
35-45
46-55
56-65
66-75
Controls (n=100)
No (%)
Gender
Male/Female
24(16)
100(67)
23(15)
3(2)
14(14)
70(70)
11(11)
5(5)
8/16
33/67
8/15
1/2
Controls
Patients (n = 150)
(n = 100) Users of Non-users
iodized of iodized
salt
salt
Hilly area
68 (61.2%)
40
59
9
35
18
28
7
8
5
3
5
111
63
90
21
(74%)
(63%) (81.0%))
(18.9%))
Non Hilly Area
14
12
10
4
12
14
6
6
13
11
7
6
39
(26%)
37
(37%)
23
(58.9%)
16
(41.0%)
Controls(n = 100)
Users of Non-users
iodized of iodized
salt
salt
31
11
3
45
(71.4%)
9
7
2
18
(28.5%)
7
6
6
5
8
5
19
(51.3%))
18
(48.6%)
Table-3:Dietary use of iodized salt in
Patient and Control group
Use of iodized
salt
Users
Patients
(n=150)
113(75.3%)
Controls
(n=100)
37(37%)
Non users
37(24.6%)
63(63%)
Odds
ratio
5.2
Odds ratio > 2 is significant.
Table-4: Duration (in years) of iodized salt
intake in Patient group (n=150)
Years
One year
Two years
More than two years
Table 1:Age groups and gender of Patients and
Controls
Patients (n=150)
No(%)
Gender
Male/Female
Patients
(n = 150)
AJ&K
Murree
Harripur
Total
In patient group (n=150), 67% were between 46-55
years, with male/female ratio 1:2 (Table-1). Out of 74%
from hilly area, 81 % were iodized salt user and 19 %
were non user and out of 26 % from non hilly areas,
58.9% were user and 41% were non user. In control
group (n=100), 63 % belonged to hilly areas, with
71.4% user and 28.5% were non user. Azad Jammu
and Kashmir people were more affected, 61.2% (Table2). Overall in patient and control group 75.3% and
63%,respectively, were users(Table-3). The duration of
iodized salt intake in patients was over 2 years in
66.6% (n=103) of patients (Table-4). Heat intolerance
(36%0 and palpitation (36%) were commonest
presentations (Table 5). Goiter grading exhibited 26%
Grade one and 74% Grade two goiters in patient group
(Table-6). Multinodular goiter (72%) was commonest
(Table 7). The mean concentration of FT4 was 46.5 +/22 pmol/L in patients and 16.036 +/- 8 pmol/L in
control group (normal 8-24 pmol/L) (Table-8). The
Age
group
(Years)
Table-2:Place of residence of Patients and
Controls in hilly and non-hilly areas
Patients
Frequency
3
7
140
(%)
2
4.66
93..33
Table-5: Frequency distribution of presenting
complaints in Patient group (n=150)
Presenting complaint
Heat Intolerance
Palpitations
Dyspnoea
Fatigue
Fine Tremors
Eye Symptoms
5/9
22/48
4/7
2/3
TSH was 0.099 +/-0.03 and 1.44061 +/-0.39 µIU/L in
patients and in control group respectively (normal 0.44 µIU/L) (Table-8). The family history of thyroid
diseases was positive in 72% of patients and 56 % of
control group (Table-9).The relative risk calculated to
compare iodized salt exposed vs. non exposed
Frequency
(%)
57
54
25
7
5
2
38
36
17
5
3
1
Table-6:Grading of goitre in Patient group (n=150)
285
Grade of goitre
Number of Patients
Percentage
Grade zero
Grade one
Grade two
0
39
111
0%
26%
74%
Journal of Rawalpindi Medical College (JRMC); 2013;17(2):284-287
outbreak of IIH, in Tasmania in late 1960s following
iodine supplementation which occurred most
frequently in individuals over 40 years of age with
multinodular goitre.20
The reason for IIH in patients of multinodular
goiter, living in long standing iodine deficiency
conditions seems to be the iodine intake, which is an
important up or downregulator of the activity of the
follicular cells of the normal thyroid gland. Changes in
iodine intake may modify the risk for or modulate
thyroid diseases. The follicular cells of the thyroid
often
undergo
transformation
to
develop
monoclonal(benign) nodules or polyclonal multifocal
nodularity,a process modulated by iodine intake.
Studies of patients with thyroid disorders have
demonstrated that the abnormal thyroid gland is often
unable to handle a sudden iodine load appropriately.21
In our study the frequency of history of Iodized salt
use for more than 2 years by patients (n=150) was
found 68.6%. Similar kind of results were obtained in
Zaire.22 The introduction of iodized salt in Zimbabwe
was associated with a sharp increase over 18 months
in the incidence of IIH, from 2.8 in 100,000 to 7.4 in
100,000 inhabitants.11 In another study carried out in
seven countries, it was reported that IIH occurred only
when the introduction of iodized salt had been of
recent onset (<2 years).It seems that the risk of IIH
after correction of iodine deficiency is closely related
to a recent excessive increment of iodine supply.23 In
Brazil, Argentina, and Chile, from 1969 to 1989, a
marked increase in thyrotoxicosis was observed, three
years after introduction of iodized salt.23-26 These
diverse findings must be interpreted carefully because
they are subject to amount of iodized salt imported or
produced in an affected country. The iodized salt
quality from the site of production to household level
is not necessarily accurate. For example, in South
Africa, only 62.4% of salt at household level was
adequately iodized (contains more than 15 mg iodine
per kilogram).27 A study from Germany in borderline
iodine
deficiency
region,
disclosed
iodine
contamination from various sources in 21.3% of 395
subjects, who had thyrotoxicosis.8
Available evidence clearly confirms that the
benefits of correcting iodine deficiency far outweigh
the risks of iodine supplementation.37 Some studies
regarding Quality Control of iodized salt have already
been done in our country, but we still need extensive
salt quality control and monitoring of population
iodine status to avoid over or under iodization of
salt.28-30
Use of iodized salt for 2 years is found more
frequent among patients of hyperthyroidism in this
study. Study also confirms that nodular goiter is the
most frequent type of goiter found in hilly areas. In
Table-7: Type of goitre in Patient group (n=150)
Type of Goitre
Diffuse goitre
Solitary nodule
Multinodular goitre
Number of Patients
19
23
108
Percentage
13
15
72
Table-8:Serum Free T4 and TSH concentration
in Patient and Control group
Concentration of Hormones
Serum Free T4 (pmol/L)
Serum TSH (mIU/L)
Mean ± SD
Patients
Controls
46.5±22
16.036±8
0.099±0.03
1.44061±0.39
Total number of patients = 150, Total number of controls = 100
Table-9: Family history of thyroid disease in
Patient and Control group
Family history
Positive
Negative
Patients (n=150)
108 (72%)
42 (28%)
Controls(n=100)
56 (56%)
44 (44%)
Discussion
Iodine Deficiency Disorders (IDD) constitute major
nutrition problem in the world.9 Iodine deficiency is
known to exist in northern region of Pakistan
including Azad Jamu and Kashmir. Certain
consequences of iodine deficiency are not reversible
once they occur, but all can be prevented by easily
available techniques of iodine supplementation. The
Pakistan Government in the mid 1960’s promoted the
use of iodized salt as the cost effective way of getting
iodine to the affected population.10 The occurrences of
hyperthyroidism after administration of iodized salt
has been reported by many countries.11-16
At the age of fifty years or older the incidence is 3.8
times more than that occurring before, compared to 1.6
times for persons less than 40 years old.16 In a
comparative study, 68 year old subjects were
investigated
and
found
hyperthyroid
after
implementation of iodine supplementation program.17
Female predominance as reported in our study, has
also been documented in many other countries.18 The
reason for female predominance seems genetic factors,
since there is an increased frequency haplotypes HLAB8 and -DRw3 in Caucasian, HLA-Bw36 in Japanese,
and HLA-Bw46 in Chinese patients with the disease.19
In present study multinodular goitre was the most
frequent one (72 %).Our findings regarding type of
goiter are supported by another study in which
hyperthyroidism was found most frequent in people
suffering from multinodular goiter followed by
solitary toxic adenomas.18 Our findings also match
with the results of the most extensively investigated
286
Journal of Rawalpindi Medical College (JRMC); 2013;17(2):284-287
our study positive family history of goiter is also more
common among patients of hyperthyroidism and
symptom of heat intolerance is the most frequently
reported symptom.
14. Joseph K, Mahlstedt J, Gonnermann R. Early recognition of
the risk of hyperthyroidism in thyroid autonomy in an
endemic goitre area. J Mol Med 1980; 4:21-37
15. Khan A, Akhtar S, Siddique M M, Nawab G. Continuous use
of iodized salt may cause thyrotoxicosis in plain areas of
North West Frontier Province (NWFP) of Pakistan. J Med Sci
2003; 3(5-6):423-28
16. Koutras D A. Clinical aspects of excess iodine in iodine
deficiency. J Mol Med 1980; 4:139-49
17. Laurberg P, Pedersen KM, Vestergaard H. Hyperfunctioning
thyroid nodules. Thyroidology 1991; 3:1-6
18. Laurberg P, Pedersen KM, Vestergaard H, Sigurdsson G.
High incidence of multinodular toxic goiter in the elderly
population in a low iodine intake area vs. high incidence of
Grave’s disease in the young in a high iodine intake area. J
Intern Med 1991; 229:415-20
19. IDD Newsletter, World Health Organization. IDD in the
Middle East, 2001;17(3):5-13
20. .Watson PF, Pickerill AP, Davies R. Analysis of cytokine gene
expression in Graves’ disease and multinodular goitre. J Clin
Endocrinol Metab 1994; 79: 355-60
21. Connolly RJ, Vidor GI, Stewart JC. Increase in thyrotoxicosis
in endemic goiter area after iodation of bread. Lancet 1970;
500-02
22. Laurberg P, Nohr S.B, Pedersen K.M, Hreidarsson A.B.
Thyroid Disorders in Mild Iodine . Thyroid 2000;10 (11):
951-63.
23. Roti E, Uberti E. Iodine excess and hyperthyroidism. Thyroid
2001; 11:493-500.
24. Delange F, de Benoist B, Alnwick D. Risk of iodine Induced
hyperthyroidism after correction of iodine deficiency by
iodized salt. Thyroid 1999; 9:545-56.
25. Lima N and Medeiros-Neto G. Transient thyrotoxicosis in
endemic goiter patients following exposure to a normal
iodine intake. Clin Endocrinol 1984; 21:631-34.
26. Wanatabe T, Moran D, Tamera El. Iodized oil in the
prophylaxis of endemic goiter in Argentina In: Dunn JT,
Medeiros G (eds). Endemic goitre and cretinism continuing
threats to world health. PAHO Scientific publication No.
292, PAHO, Washington DC 1974;231.
27. Montecinos LA, Arias D, Larenas G. Epidemia de
hipertiroideimo en la 1X Region 2nd Congreso Chilereo de
endocrinologia, Diabetes & Metabolism, Santiago 1980;P.30.
28. Hegedu SL, Bonnema SJ, Bennedbaek FN Management of
simple nodular goiter: current status and future
perspectives. Endocr Rev 2003 24:102–32.
29. Delange F and Lecomte P. Iodine supplementation: benefits
outweigh risks. Drug Saf 2000; 22(2):89-95.
30. \Ali A, Khan MM, Malik ZU, Charania BA, Bhojani FA, Baig
SM. Impact of the long term supply of iodized salt to the
endemic goitre area. J Pak Med Assoc 1992 ;42(6):138-40.
31. Khan G N, Hussain I, Soofi S B, Rizvi A,Bhutta Z A. A Study
on the Household Use of Iodised Salt in Sindh and Punjab
Provinces, Pakistan: Implications for Policy Makers. J.
Pharm. Nutr. Sci 2012, 2 (2), 148-154.
Conclusion
1.Iodine-induced hyperthyroidism and other adverse
effects can be avoided by adequate and sustained
quality
control
and
monitoring
of
iodine
supplementation.
2.It is required to identify people at risk of developing
hyperthyroidism so that indiscriminate use of iodized
salt can be avoided in these people.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Reference
Cavalieri RR. Iodine metabolism and thyroid physiology:
current concepts. Thyroid 1997; 7:177-81.
Vorherr H, Vorherr UF, Mehta P. Vaginal absorption of
povidone – iodine. JAMA 1980; 12(23): 2628-30.
Alexander NM, Nishimoto M. Protein – linked iodotyrosines
in serum after topical application of povidone iodine. J Clin
Endocrinol Metab 1981; 53(1):105-08.
Delange F, Benoist BD,Alnmick D. Risk of iodine induced
hyperthyroidism after correction of iodine deficiency by
iodized salt. Thyroid 1999; 9(6):545-50.
Istiaq A. Khan, Rana T. Ahmed, Rizwan N. Iodine deficiency
– A national problem. The Medical Spectrum 1995; 16: 1314.
Roti E and Uberti E. Iodine Excess and hyperthyroidism.
Thyroid 2001; 11(5):493-95.
John T Dunn. What is happening to our iodine? J Clin
Endocrinol Metab 1998; 8(10):3398-402
Stanbury JB, Ermans AM, Bourdoux P, Todd C, Oken E.
Iodine-Induced
Hyperthyroidism:
Occurrence
and
Epidemiology. Thyroid 1998; 8:83-100.
Hetzel BS.Iodine deficiency disorders (IDD) and their
eradication. Lancet 1983; ii: 1126-29.
Sirajul Haq M. Goitre in Pakistan. Planning and
Development Division (Nutrition Cell), Govt of Pakistan
1978: 4-5
Todd CH, Allain T, Gomo ZAR. Increase in thyrotoxicosis
associated with iodine supplements in Zimbabwe. Lancet
1995; 346:1563-65
Bourrdoux P, Eramans AM, Mukalay AMW. Iodine induced
thyrotoxicosis in Kivn Zaire. Lancet 1996; 347:552-54
Baltisberger BL, Minde CE, Burgi H. Decrease of incidence of
toxic nodular goiter after full correction of mild iodine
deficiency. Eur J Endocrinol 1995; 132:546-49
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