|Year : 2019 | Volume
| Issue : 1 | Page : 12-19
Guwahati thyroid epidemiology study: High prevalence of primary hypothyroidism among the adult population of Guwahati city
Manash P Baruah1, Sarojini Duttachoudhury2, Mihir Saikia3, Uma K Saikia4, Sonali B Bhuyan5, Ananya Bhowmick1, Anup K Barman6, Abha R Bora7, Murchana Barkakoti8
1 Department of Endocrinology, Excelcare Hospitals, Guwahati, India
2 NL Medicare and Research Centre, Guwahati, India
3 Senior Consultant Endocrinologist, Guwahati, India
4 Department of Endocrinology, Gauhati Medical College, Guwahati, Assam, India
5 Department of Accident and Emergency, Excelcare Hospitals, Guwahati, India
6 Director of Medical Education, Assam, India
7 Department of Laboratory Medicine, Excelcare Hospitals, Guwahati, India
8 Dr. Shroff's Charity Eye Hospital, New Delhi, India
|Date of Web Publication||1-Apr-2019|
Dr. Manash P Baruah
Excelcare Hospitals, Guwahati - 781 033, Assam
Source of Support: None, Conflict of Interest: None
Background: Thyroid disorders have emerged as a common disease in India. Hence, it is pertinent to search the real reasons behind the high prevalence of thyroid disease in India, post salt iodization phase.
Objective: This study was executed to unravel the nature of thyroid disorders and there associations with thyroid autoimmunity in the unexplored North east Indian region.
Methods: This community based Cross sectional (pilot) survey involved 8 wards of Guwahati city, implementing the “cluster sampling technique”. Abnormal thyroid parameters were classified as Hypothyroid: serum T4 < 4.6 μg/dL and Thyroid stimulating hormone (TSH) > 4.2) μIU/mL; Subclinical hypothyroidism (SCH): normal serum T4 (4.6-12 μg/dL) and TSH > 4.2 IU/mL, and Anti-TPO antibody positive: titre of ≥ 34 IU/ml.
Results: Out of the 209 subjects enrolled, incidence of newly detected SCH, self reported hypothyroidism, and cumulative figure of the hypothyroidism cohort were higher amongst female population (27.84%, 14.43%, and 42.27% respectively). Significant association was found between female sex and hypothyroidism [Relative risk (RR) 1.73 (1.16-2.56), P < 0.01]. Significant association was found between family history of thyroid disease and SCH (RR 2.59), elucidating a direct influence of heredity on pre-disposition towards thyroid disorder.
Conclusion: A considerable percentage (33.01%) of the adult population in Guwahati city has some form of thyroid disorder. There is lack of evidence pointing out auto immunity being the major driver for primary hypothyroidism; hence we are left to reflect upon whether dietary iodine deficiency or being geographically located near to the sub-Himalayan goitrogenic belt, or frequent consumption of cyanogenic food stuffs, is cumulatively involved in thyroid disorder development.
Keywords: Antithyroid peroxidase antibody, hypothyroidism, subclinical hypothyroidism, thyroid autoimmunity
|How to cite this article:|
Baruah MP, Duttachoudhury S, Saikia M, Saikia UK, Bhuyan SB, Bhowmick A, Barman AK, Bora AR, Barkakoti M. Guwahati thyroid epidemiology study: High prevalence of primary hypothyroidism among the adult population of Guwahati city. Thyroid Res Pract 2019;16:12-9
|How to cite this URL:|
Baruah MP, Duttachoudhury S, Saikia M, Saikia UK, Bhuyan SB, Bhowmick A, Barman AK, Bora AR, Barkakoti M. Guwahati thyroid epidemiology study: High prevalence of primary hypothyroidism among the adult population of Guwahati city. Thyroid Res Pract [serial online] 2019 [cited 2021 Oct 17];16:12-9. Available from: https://www.thetrp.net/text.asp?2019/16/1/12/255303
| Introduction|| |
Hypothyroidism is a condition where the thyroid gland does not produce enough thyroid hormones which lead to poor metabolic functions. Common symptoms of hypothyroidism are fatigue, feeling cold, weight gain, hoarse voice, irregular menstrual period, etc., Hypothyroidism is treated with manufactured levothyroxine available commercially; dosage needs adjustment according to thyroid-stimulating hormone (TSH) and thyroxine (T4) level. Overt hypothyroidism is biochemically defined as an elevated serum TSH and serum-free T4 concentration that is below the population reference range. Subclinical hypothyroidism (SCH) is a milder form of hypothyroidism where TSH is elevated in which the free thyroxine level is normal.,
Measurement of antithyroid antibody helps to confirm the diagnosis of lymphocytic thyroiditis and aids in the prediction of which patient with mild decompensation will progress to overt hypothyroidism. Progression from subclinical to overt hypothyroidism has been reported to occur in 5%–18% of patients per year. Individuals most likely to undergo progression are those with higher initial serum TSH levels, positive antithyroid antibodies, and a prior history of radioiodine or external beam radiation therapy.
The prevalence of hypothyroidism is variable because existing studies have differed significantly with regard to population age range, geographic location, ethnicity, environmental factors (dietary iodine and goitrogen intake), genetic characteristics of study population, and criteria used to define presence and degree of thyroid failure. At present, the overall global prevalence of hypothyroidism is 4.6% while in India, it is reported to be around 10.95%. The Colorado Thyroid Disease Prevalence Study of 25,862 state residents reported an elevated serum TSH concentration in 9.5% of all individuals and in 8.9% of those who were not already taking thyroid hormone. The National Health and Nutritional Examination survey III screened 17,353 adults and children in the United States and found the prevalence of hypothyroidism to be 4.6% (0.3% clinical and 4.3% subclinical). The distribution of antithyroid peroxidase (anti-TPO) antibody-positive population ranged from 11.3% ±0.4% and were more prevalent in women, elderly people and whites (12.3% ±0.5%) when compared to African-Americans (4.5% ±0.3%).
In India, a population-based study done in Cochin estimated the prevalence of hypothyroidism to be 3.9% and that of SCH to be 9.4%. In women, the prevalence was higher (11.4%), whereas it was 6.2% in men. About 53% of the individuals with SCH were positive for anti-TPO antibodies. The median value of urinary Iodine 211 μg/L suggested that this population was iodine sufficient. Unnikrishnan et al. conducted an epidemiological study in eight cities across India where 8.02% of the entire study population was found to have SCH. Among all cities, Kolkata in Eastern India recorded the highest prevalence of hypothyroidism (21.67%). Hence, it is pertinent to search the real reasons behind the high prevalence of thyroid disease in India, postsalt iodization phase.,
In India, a nation-wide goiter survey spanning 29 states and 4 union territories indicated the presence of endemic goiter in 235 districts. A study undertaken in Imphal West District indicated that goiter was prevalent at endemic level in all study areas even many years after salt iodization program among children, evidenced by total goiter rate of 34.96%. Interestingly, the mean urinary thiocyanate value obtained was 0.839 ± 0.33 mg/dl. As the indigenous populations of Manipur are regular consumers of common cyanogenic vegetables and bamboo shoot pickles containing huge concentrations of thiocyanate precursors such as cyanogenic glucosides and thioglucosides, it could be interpreted that consumption of cyanogenic plants was a crucial reason of goiter persistence in North East India, inspite of recommended iodine intake by 95% of the households.
The review of recent epidemiology of thyroid disorders in India reveals few interesting facets. On one hand, part of the country is yet to become iodine sufficient, whereas on the other hand, the emergence of SCH has emerged as a new endemic. Although clinic-based study reports are available, it is essential to penetrate newer population and newer geographic areas of the country which have hitherto remain uncovered in such epidemiological surveys to comprehend the nature of thyroid disorders and their associations with thyroid autoimmunity and other common comorbidities. Such understandings underscore the rationale behind the execution of a study like ours.
| Materials and Methods|| |
Study design and enrollment criteria
The principal outcome of this community-based Cross-sectional (pilot) study was the prevalence of primary hypothyroidism, assessed by measurement of blood level thyroid hormones. The secondary outcome to be measured was the prevalence of (i) self-reported and undetected hypothyroidism, (ii) subclinical hypothyroidism (SCH) and (iii) anti-TPO antibody positivity in the selected population.
Guwahati is the main hub of northeastern India and comprises of a mixed population. In this study, adult individuals (18 years and above) of both the sexes were eligible for participation on fulfilling the inclusion criteria and were willing to sign a written informed consent form and provide blood sample for prespecified laboratory investigations. Pediatric and adolescent individuals, pregnant participants, participants having any acute or chronic systemic illnesses as judged by investigator, or if receiving drugs that could interfere with thyroid function test results were excluded from the study.
The study was conducted following the “cluster sampling technique.” Guwahati city is divided into 31 municipal wards over 4 zones. 8 wards were randomly selected (2 from each zone) and each ward was considered as a cluster. A minimum of 200 individuals was included in the study which was selected from 8 clusters, i.e., 25 individuals from each selected cluster. In the selected cluster, sampling was started from the center and was progressed in one direction till the desired sample size of 25 was met. If the required number was not met in one direction, then sampling was done in another direction restarting from the center of the cluster. The study was approved by an independent human research ethics committee and executed in accordance with the approved protocol, principles of Declaration of Helsinki, and good clinical practices.
Demographic and clinical data were collected from each individual only after obtaining written consent form. Individuals were interviewed by study personnel using pretested and predesigned pro forma for the sociodemographic profile regarding their age, education, marital status, occupation, diet, and duration of stay in Guwahati. Participants underwent thorough medical history assessment before enrollment by a general physical examination (including anthropometry and thyroid gland examination). A detailed medical history was collected including that of existing thyroid disorder on or off treatment. Clinical examinations were done especially looking for height, weight, pulse rate, blood pressure (BP), pallor, and edema. Thyroid palpation was performed by experienced medical persons.
Following all aseptic and antiseptic measures, 5 mL of blood sample from each individual was collected by trained phlebotomists before 11 AM. The individuals were preinformed to remain in fasting or only allowed to have light snacks without significant fat content. Blood and serum samples, after proper labeling, were stored at −20°. Blood samples were then analyzed periodically (within a maximum of 15 days duration) for T4, TSH, anti-TPO antibody, and low-density lipoprotein (LDL) estimation.
Assays for T4, TSH, and anti-TPO antibody were performed by the electrochemiluminescence method using Elecsys E411-automated immunoassay analyzer (Roche Diagnostic GmbH, Sandhofer Strasse 116, Germany). The limit of detection of TSH assay was 0.005–100 uIU/ml, T4 was 0.420–24.86 μg/dL, and anti-TPO antibody was 5–600 IU/ml. Estimation of LDL was performed by homogeneous enzymatic colorimetric assay with a lower limit of detection at 3.87 mg/dl.
Based on previous medical history of thyroid and current thyroid function test results, participants were classified using the following definitions: hypothyroid: serum T4 <4.6 μg/dL and TSH >4.2 μIU/mL; hyperthyroid: serum T4 >12.0 μg/dL and TSH <0.27 IU/mL; SCH: normal serum T4 (4.6–12 μg/dL) and TSH >4.2 IU/mL; subclinical hyperthyroidism: normal serum T4 (4.6–12 μg/dL) and TSH <0.27 IU/ml; self-reported hypothyroidism: individuals with a history of hypothyroidism and/or taking levothyroxine therapy; and newly detected hypothyroidism: individuals without a history of hypothyroidism and detected newly to have hypothyroidism during this study. Anti-TPO antibody was considered to be positive when the titer of anti-TPO antibodies was ≥34 IU/ml.
Statistical hypothyroidism prevalence was estimated as counts and percentages and presented as bar diagrams, histogram, and Pie diagrams wherever applicable. Chi-square test was used to evaluate the trends in the prevalence of hypothyroidism, among different age groups and gender categories. Similar analyses were performed for SCH and anti-TPO antibody positivity. Statistical analysis was performed using GraphPad Prism Ver 6. To study the characteristics of persons with high or low TSH and/or the presence of antibodies, we calculated prevalence, prevalence differences, prevalence ratios, and odds ratios. Logistic regression was used to determine the association of high or low TSH values with other variables including sex, age, smoking habits, food habits, the presence of thyroid antibodies, LDL, and other ailments including diabetes and hypertension.
| Results|| |
A total 209 individuals were enrolled in this cross-sectional study, of which 112 (53.59%) were male and 97 (46.41%) were female [Table 1] giving a male: female (M:F) ratio (1.15:1) The mean age of the study individuals was 48.39 ± 10.85, with a range of 30–80 years [Table 2]. While 138 (66.02%) studied individuals were euthyroid, the numbers of individuals in each of the newly detected subclinical hypothyroid and preexisting self-reported hypothyroid groups on thyroxin supplement were 48 and 21, respectively. The prevalence of any type of hypothyroidism in the studied population was 33.01%. The overall incidence rate of newly detected hypothyroidism among the entire population was 22.97%, with all the individuals qualifying a diagnosis of SCH. No new case of overt primary hypothyroidism or central hypothyroidism was found in the studied population. In this study, the incidence of SCH or any newly detected hypothyroidism, and the prevalence of self-reported hypothyroidism, and the cumulative figure of the entire cohort of hypothyroidism was higher among female population (27.84%, 14.43%, and 42.27%, respectively) compared to the male counterparts (18.75%, 6.25%, and 25%, respectively) [Table 1]. Two individuals, both females, qualified for a diagnosis of subclinical thyrotoxicosis (0.01% prevalence), and none of them were on any antithyroid drugs. Both had palpable goiters but tested negative for thyroid autoimmunity (AbTPO <34 IU/mL), suggesting colloid multinodular goiter as possible etiology. No new case of overt thyrotoxicosis was found. The prevalence rate of goiter by manual palpation was 10.05% (N = 21/209) in this study.
|Table 1: Relationship between gender and thyroid status of the study population|
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|Table 2: Thyroid status, family history of thyroid disease, and thyroid autoimmunity|
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Prevalence of subclinical hypothyroidism and self-reported hypothyroidism
Significant association was found between female sex and prevalence of hypothyroidism when all hypothyroid patients were considered (relative risk [RR] 1.73 (1.16–2.56), P < 0.010) and also incidence of new cases of SCH (RR 1.67 [1.02–2.72], P < 0.05) [Table 1]. Significant association was found between family history of thyroid disease and incidence of SCH (RR 2.59 [1.43–4.70], P < 0.05), and prevalence of self-reported hypothyroidism (RR 4.25 [1.71–10.56], P < 0.05), and cumulative prevalence of hypothyroidism of any type (RR 2.34 [1.54–3.55], P < 0.01), in comparison to euthyroid cohort. This data indicated that family history of thyroid disorder predisposes a person toward the development of thyroid and SCH [Table 2]. No association was detected between the occurrence of hypothyroidism/SCH and consumption of soy products, tobacco, or nonvegetarian dietary habits.
Anthropometric parameters' comorbidities
Anthropometric parameters such as BMI, waist circumference, systolic, and diastolic BP between study groups are described in [Table 3]; significant association was found between the presence of hypertension and SCH when compared to euthyroid individuals (43.75% vs. 27.54%; RR 1.67 [1.04–2.70], P < 0.05). Such association was not seen with the self-reported group (28.57% vs. 27.54%; RR 1.40 [0.956–2.06], P = 0.09). Prevalence of diabetes mellitus did not differ significantly among the groups [Table 3].
|Table 3: Mean values for demography and vitals in different thyroid status|
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Thyroid function tests
As anticipated, mean (± standard deviation) serum TSH levels (μIU/mL) were significantly higher in both subclinical hypothyroid (7.68 ± 2.95) and self-reported hypothyroid (7.13 ± 4.99) groups when compared to euthyroid individuals (2.24 ± 1.12) (P < 0.001 for all comparisons) [Table 4]. No significant differences were observed between T4 levels and either of the treatment groups [Table 4].
In this study, 14.49% of euthyroid population were AbTPO positive, compared to 23.19% in the hypothyroid group (old and new cases). There was no significant difference in AbTPO positivity among euthyroid individuals when compared to either SCH patients (RR 1.49 [0.86–2.58], P = 0.18) or self-reported hypothyroidism (RR 1.68 [0.67–4.16], P = 0.33) and all hypothyroidism (RR 1.43 [0.93–2.20], P = 0.12) groups [Table 2]. Through this analysis, we could not draw a conclusion about the direct role of anti-TPO antibody in the progression toward hypothyroidism in our population.
| Discussion|| |
In this study, hypothyroidism including both SCH and self-reported was found to be highly prevalent affecting 33.01% of the population, much higher than 10.95% prevalence reported by Unnikrishnan et al. The incidence of SCH (22.97%) was also high in our population compared to earlier reports by Unnikrishnan et al., 2013 (8.02%) and Deshmukh et al. 2013 (11.3%). High percentage of the SCH population indicated that a significant proportion of study individuals may remain undetected and untreated for hypothyroidism. Self-reported hypothyroidism was found to be 10.14%. Interestingly, Kolkata from eastern India reported highest prevalence of any type of hypothyroidism (21.63%) and preexisting self-reported hypothyroidism (18.03%) compared to seven others cities in India in a nationwide survey by Unnikrishnan et al., in 2013. During that survey, the incidence of SCH (11.8%) was also higher than the nationwide average (8.02%) in Kolkata. The emergence of Kolkata as the most highly affected area was beyond expectation, as the city was declared iodine sufficient two decades ago., This indicated a higher prevalence in the Indo-Gangetic plains compared to western and southern India. A similar study was reported by researchers from Bangladesh where residual levels of dichlorodiphenyltrichloroethane (DDT) (1, 1, 1-trichloro-2,2-bis (4-chlorophenyl) ethane) and its metabolites were evidently found in three large size fish samples, Labeo rohita (rui), Katla katla (katla), and Pangasius pangasius (pangus)., The residents of the Indo-Gangetic plain are regular fish and poultry consumers -mainly procure fish available from the Bay of Bengal region, where illegally, industrial wastes are discarded causing chronic toxic effects. Contrastingly, in our study, no significant association was detected between the occurrence of hypothyroidism/SCH and consumption of soy products, tobacco, or nonvegetarian dietary habits.
Individuals who self-reported hypothyroidism, also presented considerably high TSH values (7.13 ± 4.99), almost similar to the SCH group (7.58 ± 2.93). This observation poses a question on the adequacy of the recent thyroid medications in the management of thyroid disorders and calls for improved management of the disorder by religiously monitoring TSH levels and adjusting medicine doses effectively. Although WHO assessment of global iodine status affirmed India to have optimal iodine nutrition in 2004 (WHO, 2004), the WHO survey conducted in the year 2003 showed up high prevalence percentage of urinary iodine (μg/L) levels of up to 44% among the northeastern regions. Hence, India falls under the postiodization phase now; but still, a significant percentage (33.01%) of the adult population in Guwahati city have some form of thyroid disorder. As no reference data is available to compare the prevalence results with the preiodization phase, we are thus left to contemplate whether iodine deficiency in the diet or intake of goitrogenic/cyanogenic foods or being located closer geographically to the sub-Himalayan goitrogenic belt, is leading to thyroid disease development in this region. An autoimmune etiology behind such high prevalence of SCH is difficult to establish as insignificantly higher prevalence in anti-TPO antibody positivity among hypothyroid cohort and their euthyroid counterparts (please see below).
In recent times, there has been a steady rise in the predominance of anti-TPO antibody, an established marker of autoimmune thyroid disorder. Earlier, the 20-year spanning follow-up Whickham Survey was conducted to deduce the incidence and natural history of thyroid disease in this cohort. The odds ratios (with 95% confidence intervals) of developing hypothyroidism with both high serum TSH and positive anti-thyroid antibodies were 38 (22–65) for women and 173 (81–370) for men. Individuals with first TSH levels higher than 2 mIU/L were predisposed to developing hypothyroidism within the following 20 years, primarily ones with elevated thyroid antibodies. In the year 2010, a Delhi-based study reported the percentage of adult patients testing TPO antibody positive to be 13.3%. Similarly, Unnikrishnan et al. reported 22.01% prevalence of anti-TPO antibody in Delhi. A study from Kerala demonstrated 16.7% prevalence of anti-TPO positivity in adults. The prevalence of high levels of the anti-TPO antibody in our study population was 23.81% and 22.92% in the case of self-reported hypothyroidism and SCH group, respectively. Therefore, the prevalence percentage was in line and hence comparable to the earlier study findings. Nevertheless, no statistically significant association was found between hypothyroidism of any category such as self-reported/subclinical/all hypothyroidism and the presence of high titers of anti-TPO antibodies. The presence of anti-thyroglobulin antibody or TSH receptor autoantibodies (TSH-R) which were not estimated in this study could also influence the clinical profile of the thyroid patients.
Statistically significant association was found between family history of thyroid disease and all the study groups: SCH (RR 2.59), self-reported hypothyroidism (RR 4.25), and all hypothyroidism group (RR 2.34). This finding points out a direct influence of heredity on predisposition toward thyroid disorder, and growing needs to strategize the screening process for early detection of cases. The prevalence rate of goiter by manual palpation was 10.05% and was almost in line with previous study data reporting 13% prevalence in a clinic-based study from Guwahati and 12% prevalence found in a recent Indian population-based study., The prevalence of thyrotoxicosis in India was around 2% in a nationwide epidemiological study, including both subclinical and overt cases. However, in our study, only two individuals, both females, qualified for a diagnosis of subclinical thyrotoxicosis (0.01% prevalence), which may either be a geographical variation or due to changing pattern of thyroid epidemiology.
Significant association was observed between SCH and hypertension in our study population and thus could validate findings from a previous global study by Luboshitzky and Herer, 2004. The same study also reported that mean values of LDL cholesterol were not significantly different in patients with SCH compared to the controls, which was similar to our study findings. However, some other Indian and global studies reported significant association (P < 0.05) between LDL levels and SCH., No significant association was observed between thyroid and diabetes in our study population. The worldwide data in this regard still remain inconclusive, with some studies showing significant positive correlation while others showing the opposite.,, There was a significant predominance of thyroid disorder among women in our study population, and this was consistent with worldwide reports.,,,
In conclusion, two things became apparent from our study: first, the higher prevalence of hypothyroidism in general and SCH in particular and second, the lack of evidence for autoimmunity being the major driver for such prevalence. Our population included individuals only from the urban area; autoimmune hypothyroidism scenario in rural population remains unexplored. Furthermore, we assumed that the study population was iodine sufficient, without testing for reliable markers such as iodine content in salt samples or urinary iodine excretion amounts. The consumption of soya rich foods or nonvegetarian food where content of organochlorine pesticides like (1, 1, 1-trichloro-2,2-bis (4-chlorophenyl) ethane) DDT could be high and did not significantly influence the TSH levels of the study individuals. Thus, other environmental/hereditary/racial factors and frequent consumption of cyanogenic foodstuffs may be cumulatively involved in the development of primary hypothyroidism in our population. In view of the findings from the present study and the need to explore the prevalence of autoimmune thyroid disorders in the extended sub-Himalayan goiter belt, an extensive long-term study involving more number of individuals needs to be conducted in the northeastern region of India.
The authors extend their heartfelt gratitude to Saptarshi Bose for statistical analysis of the study data.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]