Navigating Thyroid Dysfunction and Comorbidities Among University Students in Abbottabad, Pakistan – A Cross-Sectional Evaluation of Screening Tool for Thyroid Dysfunction

Introduction

Screening of certain medical diseases through risk factors is a scientifically accepted method of finding diseases in their early stages and identifying high-risk populations.^1,2 One of the most effective methods of diagnosis in the early stages of disease is preliminary screening.^1,2 Screening can be performed by pharmacists as they have acknowledged their role in interdisciplinary clinical practice settings and are an integral and vital part of health care teams.^1,2 Thyroid is one of the endocrine diseases whose prevalence is increasing day by day.¹ According to a recent epidemiological study, the prevalence of hypothyroidism is between 1% and 2%, and it is more common in older women and ten times more common in women than in men.³ In addition, it was believed that females are more prone to have alternation in thyroid function than males.^3,4

The overall prevalence of hypothyroidism and hyperthyroidism in Pakistan is 4.1% and 5.1%, respectively. According to another recent study, 1.6% had a newly diagnosed subclinical hypothyroidism. While 1.2% of women had hyperthyroidism, 6% had known hypothyroidism, and 1% had overt hypothyroidism.⁵ A recent systematic review and meta-analysis on the global prevalence of thyroid revealed that the prevalence of Hashimoto’s thyroiditis was 7.5%, while in the low-middle-income group, the prevalence was 11.4%. Similarly, the prevalence was 5.6 in the upper-middle-income group, and in the high-income group, the prevalence was 8.4. The prevalence of thyroid was 14.2% in Africa, while in Oceania it was 11.0% in South America and Europe it was 8.0, and 7.8%. On the other hand, in North America, and Asia it was 5.8%.⁶ The American Thyroid Association revealed that approximately 20 million Americans have some form of thyroid disease; interestingly, the majority of the thyroids were unaware of their disease status.^7,8

The most common early signs of thyroid diseases were a lump in the neck or swelling, followed by pain in the neck or difficulty in swallowing.^7,8 The risk factors identified were gender, more particularly being a female, elderly aged above 60 years, recent pregnancy, posing autoimmune disease, presence of hypertension, and obesity are positively related to thyroid disease development.^9,10 Other studies revealed that radiation is one of the most common predisposing factors especially irradiation of the head and neck in early childhood, which is found to link to thyroid carcinomas.^9,10 Some earlier research showed a link that a high level of thyroid-stimulating hormone (TSH) is linked with thyroid various carcinoma.^11,12

Thyroid diseases mainly constitute abnormal levels of TSH, triiodothyronine (T3), or thyroxine (T4).^13,14 TSH is the major chemical marker to identify thyroid function.⁶ When the level of TSH is low, it results in hyperthyroidism while if the value increases it indicates hypothyroidism. Overall people who are suffering from thyroid dysfunction have 2% hyperthyroidism people, while 98% of people suffer from hypothyroidism.^13,14 The most common cause of hyperthyroidism in Pakistan in the majority of cases is Grave’s disease, or multinodular goiter or adenoma^5,15,16 and is characterized by multi-nodular goiter in the middle age and elderly population.^5,15,16 Hypothyroidism is more common and involves increased TSH, slow metabolic rate, growth retardation, and impaired physical and mental development. The most common cause of hypothyroidism is iodine deficiency.^16,17 Hypothyroidism can also be drug-induced, drugs like interferon alpha, thalidomide, and lithium can also precipitate or cause hypothyroidism.¹⁸

The lack of knowledge about this illness, as well as the ignorance of key risk factors like food, genetic predisposition, and environmental risk factors, is one of the causes for this increased frequency of thyroid disease among people. Due to a lack of data generated in various regional and geographical strategic points, it is currently impossible to determine the area-wise distribution of thyroid dysfunction and thyroid carcinoma in Pakistan; however, if this data is obtained, it will be useful for comparisons with the rest of Asia and the rest of the world. Screening camps are typically useful in identifying secondary or asymptomatic diseases that go unnoticed by the general populace. The goal of this medical camp is to test university students for thyroid dysfunctional symptoms and risk factors to diagnose thyroid issues early, treat them, and lower their risk of developing thyroid cancer. As a result, a questionnaire was created to assess thyroid dysfunction in various age and sex categories among Comsats University Abbottabad, Pakistan, students through medical camps.

Methodology

Study Design

A cross-sectional study design was used for the assessment of thyroid-related signs and symptoms in university students. This camp was organized in collaboration with Agha Khan University Hospital Karachi (AKUH), Al-Rasheed Cancer Cure Trust Abbottabad and was organized from 29 to 30th August 2016 in Comsats Abbottabad campus during the Thyroid Cancer Awareness Month, which is listed in the American Hospital Association’s Calendar of Health Observances & Recognition Days. The students who participated in this study were enrolled in different undergraduate and graduate academic programs at the university. The ethical committee of Comsats University Abbottabad campus, Islamabad, reviewed and approved the study protocol before data collection (Approval No. 6734-CUIATD). Furthermore, written informed consent was obtained from students before data collection, and the study followed the guidelines outlined in the Helsinki Declaration. Students were informed that the data would be used solely for research purposes, that the submitted information would be kept confidential, and that they had the opportunity to withdraw from the study at any time throughout the study period.

Sample Size

Out of the total departments who participated in this medical camp, 1396 students visited the medical camp out of which 1032 were willing for the Thyroid problem assessment program, which corresponds to a response rate to 73.92%.

Study Tool

The questionnaire was designed using guidelines from the Thyroid Foundation of Canada, hyperthyroidism from Wayne’s Index 10, and the Billewicz score for hypothyroidism.¹⁹ The overall score was calculated as a sign and symptom score less than 3 was graded as low risk of thyroid dysfunction, a score between 3 and 8 was interpreted as a moderate risk of thyroid dysfunction and a score of 9 or above showed a high risk of thyroid dysfunction.

Implementation and Data Analysis

Before data collection, the data collection instrument was pilot-tested on a group of 30 university students who were randomly selected on campus to determine the validity and reliability of the tool. The value of Cronbach’s α was found to be 0.85 which indicates good reliability of the tool. A total of 1032 students visited the medical camp and were assessed by a direct interview as well as physical assessment and the data was recorded in the questionnaire (paper format). The questionnaire provided information about the assessment of thyroid-related signs and symptoms and screening of pre-disposing risk factors for thyroid dysfunction in all Comsats University Abbottabad campus students. The medical camp included a team of 08 volunteer members including doctors and pharmacists and examined each person individually for approximately 15 minutes. Volunteers collected demographic data including the age of the student, gender, area of residence, number of household members, and monthly income. The second portion of the assessment consisted of direct close-ended questions focusing on persistent symptoms for more than 05 weeks to detect any signs and symptoms linked to thyroid dysfunction. The students explained all conditions in a non-medical language (Urdu – A common language) so that they could understand properly. The third portion of data entry was focused on the assessment of thyroid personal and family history; the medical history of the student (presence of thyroid or not), and their family members including any diagnosed thyroid disorders current or past, current or past medication thyroid medicine use history, and any herbal dietary supplement for thyroid-related signs and symptoms. The last portion of the assessment included any co-morbid conditions like hypertension, diabetes ellitus, heart disease or angina, high cholesterolemia, and any form of malignancy.

Data Analysis

The data were analyzed using Statistical Package for Social Sciences version 26.0 (SPSS Inc., Chicago, IL, USA). A descriptive statistic was used to assess students’ responses, frequencies(n) and percentages (%) were used to describe categorical data, and the Chi-square/Fisher exact test was used to perform comparisons between variables. The dependent variables (means core of risk levels of thyroid) were considered numeric variables, and independent variables (age, gender residential status) were categorical, so we used multiple linear regression analysis to compute the association. A P-value of <0.05 was considered a statistically significant difference.

Results

Out of a total of 1396 students who participated in the medical assessment camp, there was a diverse age group which included 474 (45.3%) in 15–20 years of age, 523 (50.7%) in 21–25 years, 32 (3.1%) in 26–30 years and 03 (0.3%) in 31–35 years. Out of a total of 1032 students, 707 (68.5%) were males and 323 (31.5%) were females. In this study, 670 (64.9%) were from urban areas and 362 (35.1%) belonged to rural areas. Students come from different families and have different economic backgrounds. Those students whose family income was less than 25,000 Pakistani rupees (PKR) (average) were 156 (15.1%), whose income was 25,000–50,000 (high) PKR were 521 (50.5%) and those whose family income exceeded 50,000 (low income) PKR were 355 (34.4%) as shown in Table 1.

Table 1 Students’ Demographics (n=1032)

Of those students who had no co-morbid disease were 810 (78.5%). Among all 63 (6.1%) students were suffering from high BP, 33 (3.2%) students had high cholesterolemia levels, 35 (3.4%) students had angina, 9 (0.9%) students had diabetes mellitus (DM), 5 (0.5%) students had cancer (Table 2). Comorbidities with regard to gender, high BP was reported higher among females 20 (6.2%) than male 43 (6.1%), while cholesterol, angina, and diabetes were reported higher among male 24 (3.4%), 25 (3.5%),8 (1.1%) students than female 9 (2.8%), 10 (3.1%),1 (0.3%). Figure 1.

Table 2 Comorbidities of Students (n=1032)

Figure 1 Comorbidities among respondents according to gender.

Furthermore, out of all, 42 students were suffering from a combination of diseases, such as BP and cholesterol, 17 (1.6%), followed by BP and angina, 6 (0.6%), diabetes and high cholesterolemia, 4 (0.4%) BP, cholesterol and cancer, 2 (0.2%) has BP, cholesterol and cancer, 1 (0.1) student had BP and DM, 1 (0.1) student had high cholesterolemia and DM, 1 (0.1) student had DM and heart disease and 1 (0.1) student had DM, angina and cancer as indicated in Table 2. Similarly, the combination of the comorbidities was significantly different among genders, where a combination of BP and cholesterol, was higher among male students 37 (5.2%) than female 5 (1. 5%). Similarly, the BP and angina were higher in males 14 (2%) than females 3 (0.9%) as shown in Figure 2, indicating a statistically significant difference.

Figure 2 Combination of comorbidities according to gender.

Out of total 1032 students 435 (42.2%) felt the need for excessive sleep, 364 (35.3%) felt fatigued, 311 (30.1%) were experiencing palpitations, 380 (36.8%) had poor concentration, 335 (32.5%) experienced memory loss, 334 (32.4%) had difficulty sleeping, 318 (30.8%) had weak muscles, 248 (24%) had sore muscles, 337 (32.7%) were experiencing anxiety, 347 (33.6%) felt depressed, 323 (31.3%) students experienced dry skin, while 235 (22.8%) were experiencing itchy skin, 442 (42.8%) had cracked, 143 (13.9%) were experiencing infrequent bowel movements, 157 (15.2%) had frequent bowel movements, 199 (19.3%) experienced weight gain, while 157 (15.2%) lost weight, 134 (13%) experienced persistent pain at the front of the neck, 120 (11.6%) had hoarseness of voice, lump in throat was by 171 (16.6%), 171 (16.6%) reported diplopia, swelling or protrusion of eyes was felt by 167 (16.2%), 220 (21.3%) reported facial changes, sweating was experienced by 351 (34%), 265 (25.7%) reported difficulty tolerating cold, while 208 (20.2%) reported difficulty tolerating heat, hand tremors were felt by 157 (15.2%) as indicated in Table 3.

Table 3 Signs and Symptoms Persist for More Than 05 Weeks in Students (n=1032)

Students who had family members suffering from diagnosed thyroid disease were 91 (8.8%), and students who themselves were suffering from a thyroid disease were 78 (7.6%) out of 1032 students. Among those majority of them found to have under active thyroid (Figure 3). Those who were currently on treatment for any thyroid disease were 28 (2.7%), while those students who had taken treatment in the past medical history for thyroid disease were 39 (3.8%). All those students who themselves or their family members were diagnosed with a thyroid problem and who were taking/had taken any herbal remedy or any dietary supplement to benefit their thyroid disease constituted 3.2% (33) of all students as indicated in Table 4.

Table 4 Thyroid Personal and Family History (n=1032)

Figure 3 Types of thyroid disease among students.

Those students who had no or low risk of thyroid dysfunction were 406 (39.3%), those students who were at moderate risk were 379 (36.7%), while 247 (23.9%) had a high score and were at high risk of thyroid dysfunction (Table 5). All high-risk students were advised to visit a primary or secondary clinic with a physician to undergo further investigations for assessment of any underlying thyroid disease.

Table 5 Estimation of Thyroid Dysfunction Risk Based on Physical Assessment

Table 6 details the association between thyroid risk levels and students’ gender and age. As shown in the table, there was a significant association between the age of the student and thyroid risk levels, where high risk was observed mostly among students aged between 15 and 20 years (31.2% n=148), compared to other age groups (p<0.001). Similarly, the thyroid risk levels were significantly associated with gender, where 26.5% of the females were associated with a high risk of thyroid, compared to males (22.8%) indicating significant association (p <0.001).

Table 6 Association Between Students ‘Age and Gender in Relation to Thyroid Risk Levels

The risk levels of the thyroid among students were significantly associated with the presence of comorbidities, high BP was higher among low-risk students, compared to moderate and high-risk students (p<0.001). The comorbidity of high BP was found to be higher among all the three risk levels of the students as shown in Figure 4. Similarly, the cholesterol levels were found to be high among moderate risk levels of the students compared to low-risk and high-risk students, indicating significant association (p<0.001) (Figure 4). As shown in Figure 5 herbal medicine consumption was significantly associated with risk levels of thyroid, indicating a significant association (p<0.001).

Figure 4 Association between comorbidities and thyroid risk levels.

Figure 5 Association between consumption of herbal medicine versus risk levels of thyroid.

To find out the relationship between the mean risk levels of thyroid, and student demographics, a multiple linear regression model was utilized in which gender, age, area of residence, monthly income, presence of comorbidities, family member diagnosed with thyroid, currently and ever treatment status for thyroid and consumption status of herbal medicine status were considered as explanatory variables and mean score of risk levels of thyroid the dependent variable. There was a significant association between age, gender, residential status, and the presence of family members diagnosed with thyroid with risk levels mean score of thyroid risk. The results of the regression model demonstrated that there was a significant relationship between the mean score of risk levels of thyroid and gender (p<0.001), age (p<0.001), and residential status (p<0.001) as shown in Table 7.

Table 7 Regression Results of Thyroid Risk with Some Demographic Features of Students

Discussion

The thyroid gland performs important functions like regulation of metabolism, growth of organs and body tissues as well as hemostatic functions. Although the risk of thyroid and its cancer is not fully understood²⁰ certain predisposing risk factors have a major contribution like genetics, being female gender and living with chronic diseases, such as diabetes and graves diseases, and another factor.²¹ In this cross-sectional study of 1032, students were medically assessed for thyroid dysfunction. Many studies have shown the association of thyroid dysfunction with thyroid carcinoma as well as other cancer risks.^22–24 Although previous studies like a cohort study showed a link between subclinical hypothyroidism with an increased risk of thyroid cancer incidence.²⁵ On the other hand, previous results also revealed that untreated subclinical hypothyroidism may be associated with an increased risk of colorectal cancer.²⁵ Similarly, another study showed a high incidence of thyroid cancer after being treated with radioactive iodine therapy.²⁶ In addition, hyperthyroid patients receiving radioactive iodine treatment may have a little higher chance of developing cancer in the future. However, results regarding cancer mortality are more erratic, showing either no increased risk or a very slight absolute increase in risk.²⁷

Thyroid dysfunction serious risk and was seen in about 7.6% of students, this finding is consistent with other studies where thyroid dysfunction was found in college students.^28–30 For instance, Mohammed et al reported that 8.1% (n=395) of the students treated for hypothyroidism.²⁸ Similarly, another previous study revealed that 41 (24.7%) subjects had positive results on thyroid disease screening, 24 (70.6%) students had solitary nodules, and 10 (29.4%) had multiple nodules.²⁹ Likewise, another study among college students reported that 12.5% (n=1292) of the students had abnormal TSH. The overall prevalence of elevated TSH was 11% out of which 9.7% had mild TSH elevation. A low TSH was seen in 1.3% of the study population. These findings suggested that thyroid dysfunction is common among university students, and more particularly in females, since thyroid dysfunction is associated with difficulty in concentration, memory loss, fatigue, and other complications, which may raise the challenge for students in their education. Therefore, the findings suggest early detection and appropriate treatment can prevent the complications associated with it.

The risk of hypothyroidism poses a threat of infertility, loss of reproductive functions, and abnormalities in developing fetuses in the young population, especially females, and screening for thyroid disorders should be made a routine as a medical checkup. In this study, there are many female students, who are also listed as high-risk students for thyroid dysfunction. Thyroid function is an important parameter in pregnant women where it causes premature births and miscarriages. If this is left untreated, it causes mental and behavioral impairment in 60% of babies and congenital malformations in 20% of babies. It is also responsible for perinatal death.³¹ Our study shows that 23.9% of students were at high risk of thyroid dysfunction, which can lead to hypothyroidism or hyperthyroidism. In one of the studies conducted hypothyroidism can help in reducing the overall risk of breast cancer as well as improving the prognosis of breast cancer,²² but in another study, the results were inconsistent with the aforementioned study, and thyroid antibodies were found indicating autoimmune hypothyroidism contributed towards breast cancer risk.²² Thus, students having a high risk of thyroid dysfunction, especially the female population are at not only a risk for thyroid carcinoma but also other common malignancies.

In this study, the majority of students who participated in the medical camp were young, healthy, and active but still, some of the students reported having high cholesterolemia, hypertension, and angina. Some of them even had a combination of two or more of these serious medical problems. Thyroid dysfunction is found to raise the levels of total cholesterol, low-density lipoproteins (LDL), and triglycerides, hence leading to heart disease and increasing the risk of hypertension and cardiovascular events. Students presented with heart disease (angina), high cholesterolemia, and hypertension along with a high score of thyroid dysfunction may eventually lead to diagnosing thyroid-related signs and symptoms, which may lead them to develop serious medical conditions and mortality. The thyroid gland helps regulate the metabolism of the body and the disorder of the thyroid gland is a crucial health issue. Thyroid dysfunction leads to an increased level of lipids in the body.³² The direct link of hypothyroidism with hypertension is controversial, but the majority of them reported an increased prevalence of high BP in patients with diagnosed hypothyroidism³³ but hypothyroidism is directly linked with hyperlipidemia.^33,34 In this study, some of the students were suffering from DM which has an established link with thyroid disorder.³⁵ Furthermore, obesity, hypertension, diabetes, and dyslipidemia have been associated with cancer incidence or mortality.^35,36 In this study, the co-morbidities were recorded and included in the analysis, which is not found in other similar studies.³⁰ Additionally, in the current findings, many students reported memory loss and depression which is consistent with other studies where thyroid dysfunction is linked with depression and dementia.³⁷

The sample size was as large as possible, however, 30% of the sample did not finish the survey and was thus eliminated from the study, which is one of the study’s drawbacks. Second, because just one university in Abbottabad, Pakistan, participated in the study, the findings might not truly represent the risks that other undergraduates in Pakistan or other nations face. Third, due to a lack of funding for lab testing, blood TSH, T3, and T4 levels were not measured when individuals were physically evaluated in the medical camp. Lipid profile testing was also excluded. Even after adjusting for demographic, clinical symptom manifestation, socioeconomic, and lifestyle characteristics as in our analysis, there may still be residual confounding factors because this is an observational cross-sectional study. Despite these limitations, current findings have several benefits to get started, this study examines the value of individual’s health status in early thyroid illness screening to avoid issues related to thyroid. Additionally, there is a dearth of such research in the sector, particularly among students. However, utilizing the results of this kind of assessment, policymakers may be able to quickly examine societal issues and offer recommendations.

Conclusion

In conclusion, 7.6% of the students, had thyroid disease, and 23.9% of the students were found to have had a high risk of thyroid dysfunction. This study serves as a baseline for motivating people to get a medical checkup if their score is high without putting a cost burden on individuals. This study is specifically important for low-income populations and people from developing countries where thyroid blood testing, a costly process can be done secondary to this questionnaire medical assessment if the candidate’s score is high and is at potential risk of thyroid dysfunction. People from developing countries are not medically insured. It will eventually result in more people getting checked earlier, early diagnosis of thyroid dysfunction, early detection of thyroid gland malignancies, and overall decreased morbidity and mortality associated with thyroid carcinoma.