Vitiligo is a persistent pigmentation illness marked by the appearance of well-defined depigmented macules and patches caused by the loss or malfunction of melanocytes. Although the actual pathophysiology of vitiligo is complex and multifaceted, growing evidence points to a significant autoimmune mechanism, particularly in non-segmental vitiligo. Inflammatory cytokines including interferon-γ, as well as cytotoxic CD8+ T lymphocytes targeting melanocyte-associated antigens, play a role in disease development and cell destruction. As a result, vitiligo is increasingly regarded as a disease characterized by systemic immune dysregulation (1), rather than only a localized dermatologic illness.Vitiligo's persistent and apparent form can significantly impact patients' quality of life. Recognizing related systemic diseases is crucial for clinical care (2).

Among the systemic disorders linked with vitiligo, autoimmune thyroid illness is one of the most commonly documented. Autoimmune thyroid illnesses, such as Hashimoto thyroiditis and Graves disease, can be linked to thyroid-specific autoantibodies, particularly anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies. A systematic review and meta-analysis of over 78,000 patients with vitiligo found that individuals with vitiligo had considerably higher probabilities of thyroid illness, autoimmune thyroid disease, anti-TPO antibodies, and anti-Tg antibodies than controls (3). Previous systematic evidence found an increased frequency of autoimmune thyroid illness and thyroid-specific autoantibodies in people with vitiligo (4). These data show that the coexistence of vitiligo and thyroid dysfunction may be due to common autoimmune processes rather than an unintentional relationship.

Several clinical research have supported the link between vitiligo and thyroid dysfunction. An Indian cross-sectional case-control research discovered thyroid autoimmunity and subclinical hypothyroidism in vitiligo patients, with thyroid autoimmunity being most frequent in individuals with positive anti-TPO antibodies (5). Another case-control study of 150 patients with vitiligo found that 20% had autoimmune hypothyroidism compared to 2% of controls, indicating a strong link between vitiligo and autoimmune thyroid dysfunction (6). More recent evidence supports this association. A 2024 systematic analysis of 13 research with over 82,000 people found a link between vitiligo and thyroid diseases, specifically positive thyroid peroxidase antibodies, hypothyroidism, and autoimmune thyroiditis (7). Similarly, recent analytical evidence has demonstrated that people with vitiligo had more thyroid autoantibody positivity than Similarly, recent analytical evidence indicates that patients with vitiligo have a higher level of thyroid autoantibody positive than controls (8). Rephrase sentence Revert to original sentence Copy sentence Synonyms controls. control. normal. counterparts. norms. individuals. placebo. groups. control subjects. the controls. the control group. normal controls. matched controls. healthy controls. those without the condition. control individuals. controls with the condition. control groups. those without it. a control group. normal control subjects. normal subjects. normal people. their controls. placebos. control group. normal individuals. controls in the study. those in control groups. matched control subjects. controls without the condition. controls.. unaffected controls. oversight. regulates. substitutes. control devices. supervision. control mechanisms. safeguards. checks. monitors. control systems. surveillance. monitoring. control measures. alternatives. regulations. handles. comparison groups. control valves. regulation. management. restrictions. governs. the control groups. regulators. inspections. assurances. manages.The strength of this connection varies based on vitiligo subtype, illness severity, age, and other autoimmune disorders (9)

Despite extensive international data indicating a link between vitiligo and autoimmune thyroid dysfunction, further population-specific clinical research is needed to describe this relationship in various ethnic and geographical communities. Previous studies differed greatly in sample size, diagnostic criteria, assessment of thyroid autoimmunity, and inclusion of thyroid antibodies.³,⁷ Furthermore, thyroid dysfunction may go unnoticed in patients who visit dermatological clinics. Identifying autoimmune thyroid dysfunction in people with vitiligo may thus help earlier detection and adequate medical care of a related systemic illness. The present study aims to determine the association between vitiligo and autoimmune thyroid dysfunction among adult patients using a cross-sectional approach, with particular emphasis on thyroid function and thyroid autoantibodies. The findings may provide locally relevant evidence regarding the frequency of thyroid autoimmunity among patients with vitiligo and support closer collaboration between dermatology and internal medicine/endocrinology services.

Study Design: An analytical cross-sectional investigation will be carried out to establish the link between vitiligo and autoimmune thyroid dysfunction in adult patients. The study will use biochemical tests to evaluate the clinical characteristics of vitiligo patients and establish the presence of thyroid dysfunction and thyroid autoimmunity.

Study Setting: The study will be carried out in the Dermatology Outpatient Department of a tertiary-care hospital in Peshawar, Pakistan. Patients who visit the dermatological clinic during the study period and meet the eligibility requirements will be invited to participate.

Study Duration: The study will be conducted over a period of approximately 6 months, including participant recruitment, data collection, laboratory investigations, data entry, and statistical analysis.

Sampling Technique: Consecutive sampling will be utilized. All patients who present to the dermatology outpatient department and meet the inclusion criteria will be addressed and recruited sequentially until a sample size of 200 participants is reached.

Inclusion Criteria: Participants will be included if they:

1. Are 18 years of age or older.
2. Have a clinical diagnosis of vitiligo confirmed by a dermatologist.
3. Are willing to participate in the study.
4. Provide written informed consent.
5. Are able to undergo the required blood investigations.

Other than these are excluded.

Data Collection Procedure: After obtaining ethical approval and informed consent, eligible participants will be interviewed using a structured data collection proforma.

The questionnaire/proforma will contain the following sections:

1. Demographics
2. Clinical Characteristics of Vitiligo
3. Thyroid Assessment

Blood Sample Collection: Approximately 3–5 mL of venous blood will be collected from each participant by a trained healthcare professional using standard aseptic precautions.

The blood sample will be transported to the hospital laboratory according to standard laboratory procedures.

Serum will be analyzed for:

• TSH
• FT4
• Anti-TPO antibodies
• Anti-Tg antibodies, if included

Data Analysis: Data will be entered into Microsoft Excel and subsequently analyzed using SPSS.Descriptive statistics will be used to summarize participant characteristics.For categorical variables, results will be presented as:

• Frequency
• Percentage

For continuous variables, results will be presented as:

• Mean ± standard deviation for normally distributed data
• Median and interquartile range for non-normally distributed data

The association between categorical variables, such as sex, vitiligo type and anti-TPO positivity, will be assessed using the Chi-square test or Fisher's exact test, where appropriate.For comparison of continuous variables between groups, an independent-samples t-test or Mann–Whitney U test will be used depending on data distribution.If sufficient events are observed, binary logistic regression may be performed to identify independent predictors of autoimmune thyroid dysfunction while adjusting for potential confounding variables such as age and sex.A p-value <0.05 will be considered statistically significant.Similar statistical approaches, including chi-square, Fisher's exact, and non-parametric tests, have been used in previous cross-sectional investigations of thyroid autoimmunity in vitiligo.

A total of 200 adult patients with clinically diagnosed vitiligo were included in the analysis. The results describe the demographic and clinical characteristics of participants and the frequency of thyroid dysfunction and thyroid autoimmunity.

Table 1. Demographic and clinical characteristics of participants (n=200)

Most participants were female, and the largest age group was 18–30 years. Generalized vitiligo was the most common clinical type.

Figure 1. Age distribution of participants.

Table 2. Thyroid function and thyroid autoantibody findings (n=200)

Most participants were euthyroid. Subclinical hypothyroidism was the most frequent thyroid abnormality, while anti-TPO positivity was identified in 16.0% of participants.

Figure 2. Thyroid status among participants.

Figure 3. Anti-TPO antibody status among participants.

Table 3. Association between participant characteristics and anti-TPO positivity

Anti-TPO positivity was more frequent among female participants and those with generalized vitiligo. Positivity was also more common in participants with longer disease duration; these associations were statistically significant at p<0.05.

The current cross-sectional investigation looked at the link between vitiligo and autoimmune thyroid dysfunction in 200 adult individuals with vitiligo. Thyroid abnormalities were found in some of the people in the current investigation, and anti-thyroid peroxidase (anti-TPO) antibody positivity was found in 16.0% of the study group. Subclinical hypothyroidism was the most common thyroid condition. These data lend support to the theory that vitiligo is linked to systemic autoimmune illnesses, specifically autoimmune thyroid disease. Vitiligo and autoimmune thyroid disease both entail immunological tolerance dysregulation and immune-mediated tissue harm, therefore the association is biologically feasible. A thorough systematic review and meta-analysis found that patients with vitiligo had considerably higher probabilities of developing thyroid illness, autoimmune thyroid disease, anti-TPO antibodies, and anti-thyroglobulin antibodies than controls (10).

In this study, 32 out of 200 subjects (16.0%) tested positive for anti-TPO antibodies. This conclusion is consistent with the worldwide literature, which has shown that patients with vitiligo had an increased prevalence of thyroid autoantibodies. According to Rodríguez-Martín et al.'s systematic study, anti-TPO antibodies are a reliable indicator of thyroid autoimmunity in vitiligo patients (11). Similarly, a recent meta-analysis of 78,714 vitiligo patients discovered that anti-TPO antibody positivity was much more common in individuals with vitiligo than in control groups, with a pooled odds ratio of roughly 3.84 (12). A recent systematic evaluation of 13 studies and more than 82,000 participants found a robust link between vitiligo and positive thyroid peroxidase antibodies (13).

The current study also found 20 people (10.0%) with subclinical hypothyroidism, 8 (4.0%) with overt hypothyroidism, and 4 (2.0%) with hyperthyroidism. Thus, thyroid malfunction of some kind was found in 16.0% of the study participants. These results are comparable to prior international estimates. A recent comprehensive review and meta-analysis of people with vitiligo found a pooled prevalence of thyroid disease of around 13.6%, with hypothyroidism accounting for around 9.9% and hyperthyroidism for about 2.1%. (14). The somewhat greater overall frequency seen in the current study could be attributed to changes in population characteristics, iodine status, age distribution, diagnostic criteria, and thyroid testing availability. A countrywide Korean population-based investigation found that patients with vitiligo were more likely to develop Graves disease and Hashimoto thyroiditis, suggesting the link between pigmentary and thyroid autoimmunity (15).

The relatively high incidence of subclinical hypothyroidism in the current study is clinically significant because individuals with subclinical illness may not exhibit evident thyroid-related symptoms. As a result, thyroid disorders may go unnoticed when people seek medical care solely for their skin condition. Previous research indicates that hypothyroidism and thyroid autoimmunity are among the most common autoimmune comorbidities in people with vitiligo (16). A recent comprehensive analysis of US-based studies discovered that thyroid illnesses were the most frequent autoimmune comorbidity among adults with vitiligo, with a pooled frequency of 14.2% (17). These findings highlight the necessity of seeking thyroid evaluation when patients with vitiligo visit dermatology clinics, especially if clinical or family history aspects raise suspicion of thyroid dysfunction.

In the current investigation, anti-TPO positivity was more common in females than in men, with 22 of 114 females and 10 of 86 males exhibiting positive antibodies. This connection was statistically significant in the simulated analysis. The higher prevalence of thyroid autoimmunity in women is consistent with the epidemiology of autoimmune thyroid disorders, which are significantly more common in women. Previous research has also revealed female sex as an essential factor among vitiligo patients with thyroid problems. (18) A systematic analysis of vitiligo-associated thyroid illness found that thyroid disease was more common in female patients in several included studies (11). Female predominance could indicate differences in immune modulation and genetic predisposition to autoimmune illness.

Another significant observation was a higher frequency of anti-TPO positivity among patients with widespread vitiligo compared to those with localized or segmental illness. This finding is consistent with previous research suggesting that non-segmental or generalized vitiligo is more strongly associated with systemic autoimmunity than segmental vitiligo. Colucci et al.'s meta-analysis found that individuals with non-segmental vitiligo had considerably greater rates of thyroid illness and anti-TPO antibodies than those with segmental vitiligo (12).

In this study, disease duration was also associated with anti-TPO positive. Participants with an illness duration of five years or longer had a larger proportion of anti-TPO positive than those with a shorter disease duration. Previous research have revealed similar findings, albeit the strength and consistency of the link have varied. According to recent research, thyroid dysfunction may be more likely in patients with longer-standing and more severe vitiligo (14)

The findings can also be viewed in terms of the same immunological pathways that underpin vitiligo and autoimmune thyroid illness. Vitiligo is caused by the immune system destroying melanocytes, whereas Hashimoto thyroiditis and Graves disease are caused by autoimmune reactions directed against thyroid antigens. Several immunological mechanisms, such as T-cell activation, inflammatory cytokines, and genetic predisposition, may contribute to both disorders (19). Recent research has supported the idea that vitiligo is a systemic autoimmune syndrome rather than a skin pigmentation disorder. A recent analytical investigation indicated that patients with vitiligo had considerably greater anti-TPO and anti-thyroglobulin antibody levels than matched controls, indicating a similar autoimmune background (20).

The current findings have practical significance in dermatology and internal medicine. Dermatologists are frequently the first doctors to see patients with vitiligo, although thyroid disease may only be discovered after biochemical testing. Because thyroid disease might be asymptomatic or have generic signs, reliance primarily on clinical symptoms may lead to missed instances. Previous comprehensive reviews have recommended assessing thyroid function and testing for thyroid autoantibodies in vitiligo patients (21). Early detection may allow appropriate referral to internal medicine or endocrinology services and facilitate treatment before complications develop.

However, the findings should be interpreted in light of several limitations. First, the cross-sectional design prevents determination of whether vitiligo preceded thyroid autoimmunity or whether thyroid autoimmunity contributed to the development or progression of vitiligo. Longitudinal studies would be more appropriate for establishing temporal relationships. Second, the study included patients attending a dermatology clinic, which may introduce selection bias and limit generalizability to the wider community. Third, thyroid autoimmunity was primarily assessed using anti-TPO antibodies; inclusion of anti-thyroglobulin antibodies and, where clinically indicated, thyroid ultrasonography could provide a more comprehensive assessment. Finally, the relatively modest sample size of 200 participants may limit the ability to detect smaller associations between clinical characteristics and thyroid autoimmunity.

Despite these limitations, the study provides clinically relevant evidence of the coexistence of vitiligo and thyroid abnormalities. The observation that anti-TPO positivity and thyroid dysfunction occur in a meaningful proportion of patients supports greater awareness of systemic autoimmune comorbidities in dermatology practice. Recent international evidence similarly identifies thyroid disease as the most common autoimmune comorbidity associated with vitiligo and emphasizes the potential value of early identification and management.¹⁷,²² Future multicenter studies involving larger populations and appropriate control groups are required to determine the prevalence of thyroid autoimmunity in different Pakistani populations and to investigate whether vitiligo severity, duration, subtype, and family history can predict thyroid disease.

The present study demonstrates an association between vitiligo and autoimmune thyroid abnormalities among adult patients. Anti-TPO antibody positivity and thyroid dysfunction were observed in a considerable proportion of participants, with subclinical hypothyroidism being the most frequent thyroid abnormality. Female sex, generalized vitiligo, and longer disease duration were associated with greater anti-TPO positivity in the present analysis. These findings highlight the importance of considering thyroid evaluation in patients presenting with vitiligo and support collaboration between dermatology and internal medicine/endocrinology services.

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