European Journal of Cardiovascular Medicine

Gallstone disease, one of the most prevalent gastrointestinal disorders, affects millions worldwide, manifesting a significant burden on healthcare systems. Characterized by the formation of stones in the gallbladder or bile ducts, this condition can lead to a range of clinical presentations, from asymptomatic gallstones to acute cholecystitis.

The pathophysiology of gallstone formation is multifactorial, involving genetic predisposition, environmental factors, and metabolic abnormalities. Among these, the role of metabolic endocrine disorders, particularly thyroid dysfunction, has garnered research interest due to the intricate interplay between thyroid hormones and lipid metabolism.

Subclinical hypothyroidism (SCH), a condition defined by elevated serum thyroid-stimulating hormone (TSH) levels with normal free thyroxine (T4) concentrations, has been increasingly recognized for its potential impact on various metabolic processes, including those involved in cholesterol and bile acid metabolism. Given the central role of cholesterol supersaturation in gallstone pathogenesis, SCH could theoretically contribute to gallstone disease by altering lipid profiles and promoting cholesterol crystal formation in bile [1-3].

Recent epidemiological studies have suggested a potential association between SCH and an increased risk of gallstone disease, positing thyroid dysfunction as a modifiable risk factor for gallstone formation [4,5]. These findings underscore the importance of exploring the underlying mechanisms linking SCH to gallstone disease, which could have significant implications for the prevention and management of this common gastrointestinal disorder.

The relationship between thyroid function and lipid metabolism offers a plausible biological basis for this association. Thyroid hormones are known to influence hepatic cholesterol synthesis and secretion, as well as the expression of enzymes critical for bile acid synthesis. In SCH, the subtle decrease in thyroid hormone activity could lead to dysregulated cholesterol homeostasis, enhancing the risk of cholesterol gallstone formation [6,7]. Furthermore, thyroid hormones affect gastrointestinal motility, and alterations in gut motility associated with SCH may further predispose individuals to gallstone formation by affecting gallbladder emptying and bile stasis [8,9].

Despite these theoretical associations, the literature presents a heterogeneous picture, with studies yielding conflicting results regarding the strength and significance of the relationship between SCH and gallstone disease. This variability may be attributed to differences in study design, population characteristics, diagnostic criteria for SCH, and the methods used to assess gallstone disease [10,11].

This study aims to systematically examine the association between subclinical hypothyroidism and gallstone disease. By synthesizing findings, we seek to clarify the nature of this relationship, explore the potential biological mechanisms involved, and discuss the clinical implications of these findings. Understanding the link between SCH and gallstone disease could not only shed light on the pathophysiology of gallstone formation but also inform strategies for risk assessment, prevention, and management of gallstone disease in individuals with thyroid dysfunction.

Aims and Objectives

The study aimed to investigate the association between subclinical hypothyroidism and gallstone disease among patients admitted to Victoria Hospital and Bowring and Lady Curzon Hospital, both attached to Bangalore Medical College and Research Institute, Bengaluru. The objective was to elucidate any potential correlation between subclinical hypothyroidism and the prevalence of gallstone diseases, contributing to the understanding of the metabolic interplays affecting gallstone pathogenesis. This research was pivotal in identifying novel diagnostic and therapeutic strategies for managing patients with gallstone disease, potentially highlighting subclinical hypothyroidism as a modifiable risk factor.

The methodology employed in this research was meticulously designed to ensure the collection of relevant and accurate data. The study was conducted as a prospective observational study, with the duration spanning from October 2018 to May 2020. The setting for this investigation was the department of general surgery in both Victoria Hospital and Bowring and Lady Curzon Hospital, under the aegis of the Bangalore Medical College and Research Institute, Bengaluru. A total of 120 patients constituted the sample size for this study. This figure was derived using a sample size estimation formula, which considered an estimated proportion of 13% based on previous studies, with an alpha error of 5% and an absolute error of 6%. The calculation utilized a Z-score of 1.96 to achieve a 95% confidence interval, ultimately determining that 120 subjects would be adequate for the study.

The inclusion criteria specified that only patients presenting with cholelithiasis and aged above 18 years were eligible for participation, provided they consented to be part of the study. Conversely, the study excluded patients with a prior history of hypothyroidism or hyperthyroidism who were receiving treatment for these conditions. This delineation ensured the research focused on patients whose thyroid status could be accurately categorized into subclinical hypothyroidism, clinical hypothyroidism, or euthyroid groups, without the confounding effects of ongoing thyroid disease management.

Upon securing clearance from the institutional ethics committee and obtaining written informed consent from participants, the study commenced. Patients attending the department of general surgery who met the inclusion and exclusion criteria were enrolled. The research protocol entailed recording medical history, clinical and physical examination findings, vital signs, and other investigatory results from the baseline visit in the case record form. The categorization of thyroid function status into subclinical hypothyroidism, clinical hypothyroidism, and euthyroid groups was based on serum TSH concentration levels and the presence or absence of symptoms, alongside T3 and T4 levels.

Data collected throughout the study period were subjected to rigorous analysis using descriptive statistics. The chi-square test was employed to ascertain the association between categorical variables. Tools such as Microsoft Excel and Epi-info facilitated the data analysis process, enabling the presentation of findings in various formats, including tables, graphs, and diagrams, to comprehensively convey the research outcomes.

Ethical considerations were paramount throughout the research. Institutional ethical committee approval was obtained before the study's initiation, ensuring adherence to ethical standards and respect for patient rights and welfare. Informed consent was a prerequisite for all study participants, guaranteeing that they were fully aware of the study's nature and their role within it. Additionally, the standard of care provided to patients during their participation in the study and subsequent follow-up was maintained at the highest level, ensuring that the research's conduct did not compromise patient care.

In the detailed investigation conducted at the Department of General Surgery in Bangalore Medical College and Research Institute, Bangalore, a comprehensive analysis of 120 patients diagnosed with gallstone disease was performed over an 11-month period from October 2018 to May 2020. The study meticulously evaluated the age distribution, presence of comorbidities, thyroid status, and cholesterol levels among the patients, yielding insightful observations into the demographics and clinical characteristics of individuals with gallstone disease.

The age distribution of the patients indicated a predominance of the disease in older age groups, with the largest cohort being those over 50 years of age (44 patients), followed by the 41-50 age group (36 patients), the 31-40 age group (29 patients), and the 21-30 age group (11 patients). The mean age of presentation was 46.64 years, suggesting a higher susceptibility to gallstone disease with advancing age. The study also noted a significant gender disparity, with a male to female ratio of 1:2.1, highlighting a greater prevalence of gallstone disease among females.

Comorbidity analysis revealed that 59.1% of the patients had no comorbid conditions, while diabetes mellitus (DM) and hypertension (HTN) were the most common comorbidities, present in 15.8% and 14% of the patients, respectively. Furthermore, a combination of both DM and HTN was observed in 10.8% of the study population. These findings underscore the importance of managing metabolic and cardiovascular risk factors in patients with gallstone disease.

Thyroid function tests played a crucial role in the study, revealing that 75% of the patients were euthyroid. Subclinical hypothyroidism was identified in 17.5% of the patients (21 individuals), and overt hypothyroidism was found in 6.7% (8 individuals). A solitary case of hyperthyroidism was observed, accounting for 0.8% of the study cohort. Notably, subclinical hypothyroidism and hypothyroidism were more prevalent among female patients, with 21% of females showing subclinical hypothyroidism compared to 10% of males. The statistical analysis yielded a p-value of less than 0.05, indicating a significant association between thyroid dysfunction, specifically subclinical hypothyroidism, and gallstone disease, with a pronounced gender disparity favoring females.

Cholesterol levels were evaluated, with results indicating that 64.2% of patients (77 individuals) had elevated total cholesterol levels (>160 mg/dL). The analysis of cholesterol levels in relation to age revealed that elevated cholesterol was more common in patients above 40 years of age, correlating with the increased prevalence of gallstone disease in this age group. This observation suggests a potential link between lipid metabolism abnormalities and gallstone pathogenesis, especially in the context of aging and thyroid dysfunction.

In summary, the study highlights the complex interplay between age, gender, comorbid conditions, thyroid status, and cholesterol levels in the context of gallstone disease. The significant association between subclinical hypothyroidism and gallstone disease, especially among females and older individuals, emphasizes the need for a multidisciplinary approach in the management and prevention strategies for gallstone disease. The findings underscore the importance of screening for thyroid dysfunction and managing comorbid conditions to mitigate the risk and impact of gallstone disease.

The association between thyroid dysfunction, particularly subclinical hypothyroidism, and gallstone disease has been a subject of interest within the medical community. The present study, conducted at the Department of General Surgery in Bangalore Medical College and Research Institute, Bangalore, contributes valuable insights into this association, emphasizing the prevalence of subclinical hypothyroidism in patients with gallstone disease, especially among females and individuals above the age of 40. This section discusses the findings of the current study in the context of existing literature, highlighting similarities, differences, and the implications of these results.

The observed male to female ratio of 1:2.1 in gallstone prevalence in our study is consistent with existing research, which has documented a higher incidence of gallbladder diseases among females [12]. The hormonal and metabolic factors have been suggested as possible explanations for this gender disparity, with estrogen being a known contributor to cholesterol gallstone formation due to its role in increasing biliary cholesterol secretion [13].

Our study's identification of subclinical hypothyroidism in 17.5% of gallstone patients further underscores the potential endocrine influence on gallstone pathogenesis. This finding is in line with previous studies that have reported an association between thyroid dysfunction and altered gallbladder motility and bile composition [14]. Notably, a study by Duntas LH and Biondi B [15] highlighted the impact of thyroid hormones on lipid metabolism, suggesting a mechanism through which thyroid dysfunction could contribute to gallstone formation. However, our study extends these findings by demonstrating a significant gender-related difference in the prevalence of subclinical hypothyroidism among gallstone patients, with a higher incidence in females. This gender-specific association warrants further investigation to elucidate the underlying biological mechanisms.

The significant association between elevated total cholesterol levels and gallstone disease observed in our study, particularly among individuals above the age of 40, aligns with the well-established link between cholesterol metabolism and gallstone formation [16]. Cholesterol supersaturation of bile is a primary factor in cholesterol gallstone pathogenesis, and our findings suggest that subclinical hypothyroidism may exacerbate this process, especially in the presence of other risk factors such as age and gender.

Contrasting with our findings, some studies have not found a significant association between subclinical hypothyroidism and gallstone disease [17]. These discrepancies could be attributed to differences in study populations, diagnostic criteria for subclinical hypothyroidism, and the methods used to detect gallstones. It highlights the need for standardized diagnostic criteria and methodologies in future research to clarify the relationship between thyroid dysfunction and gallstone disease.

The statistical significance of our findings, indicated by a p-value of less than 0.05, adds to the growing body of evidence suggesting that subclinical hypothyroidism is a modifiable risk factor for gallstone disease. It underscores the importance of screening for and managing thyroid dysfunction as part of a comprehensive approach to preventing and treating gallstone disease, particularly in high-risk populations.

Our study contributes to the understanding of the complex interplay between thyroid function, cholesterol metabolism, and gallstone disease. It highlights the need for heightened clinical awareness of the risk factors for gallstone disease, including subclinical hypothyroidism, especially among females and older adults. Future research should focus on longitudinal studies to explore the causative relationship between thyroid dysfunction and gallstone disease and to evaluate the impact of managing thyroid dysfunction on the incidence and progression of gallstone disease.

The present study elucidated the significant association between subclinical hypothyroidism and gallstone disease, highlighting a notable gender disparity with a higher prevalence in females. Conducted at Bangalore Medical College and Research Institute, this research meticulously analyzed 120 patients, revealing that subclinical hypothyroidism was present in 17.5% of individuals with gallstone disease. The findings underscored an increased susceptibility in females, with 21% of female patients affected by subclinical hypothyroidism compared to 10% of males, a difference that was statistically significant (p < 0.05). Furthermore, the study illuminated the role of comorbidities, demonstrating that hypertension and diabetes mellitus were prevalent in 14% and 15.8% of the gallstone population, respectively. Additionally, a notable correlation was observed between elevated total cholesterol levels, particularly in patients above 40 years of age, and the incidence of gallstone disease. This correlation further validates the intricate link between lipid metabolism and gallstone pathogenesis, especially in the context of thyroid dysfunction.

These insights not only contribute to the broader understanding of the metabolic and endocrine underpinnings of gallstone disease but also highlight the importance of considering thyroid function status in the clinical evaluation and management of gallstone patients. The gender-specific findings call for a tailored approach in the screening and treatment of gallstone disease, emphasizing the need for heightened awareness among clinicians regarding the risk factors, especially in female patients and those with comorbid metabolic conditions.

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