Acne vulgaris, simply known as acne is a widespread chronic inflammatory and the widely prevalent human skin condition of the pilosebaceous unit that affects millions of people worldwide (Hareedy et al., 2021; Shah et al., 2021; Kaur et al., 2021 & Suva et al., 2014). It is externally visible one of the most expe-rienced skin diseases in dermatology (Franik et al., 2018). It accounts for the roughly 20% of all appoint-ments of the dermatologists practice (Federman & Kirsner, 2000). It is estimated that 85% of individuals between the age of the 12 and 24 experience acne (Alsulaimani et al., 2020 & Franik et al., 2018). It frequently persists throughout adulthood (Franik et al., 2018) and frequently makes its first appearance during this time (Kamangar & Shinkai, 2012). Acne is widely considered as a self-limited disorder that the resolves naturally (Rahman et al., 2012; Vergou et al., 2011). Acne lesions are typically restricted to skin regions with a high density of the well-developed sebaceous follicles (Utami et al., 2019; Hassan et al., 2015). It predominantly affects face. Neck, upper trunk and back can be involved to a lesser extent (Utami et al., 2019; Rahman et al., 2012; Shahen et al., 2019).

About 9.4% of the worlds population are affected by acne vulgaris (AV), making it the eighth most common disease globally (Nada et al., 2021). Acne is consist-ently estimated as the third most prevalent skin disease in the world (Lynn et al., 2016). Globally, epidmio-logical studies demonstrates that acne can take place at any age. But it usually appears all round puberty and provokes during adolescence (Endres et al., 2021). Significant acne lesions persist in 12% of women and in 3% of men by the time they reach their 40s (Bogino et al., 2014). Recent epidemiological research has revealed that post adolescent acne is the increasing (Skroza et al., 2018; Vergou et al., 2011). This con-dition lasts longer & treatment is necessary (Vergou et al., 2011). Acne vulgaris is identified by areas of the comedones, greasy skin (seborrhea), nodules, pustules, papules and scarring in some circumstances (Kaur et al., 2021; Shah & Parmar, 2015; Adityan et al., 2009). The causes of acne vulgaris development is multi-factorial (Islami et al., 2021; Shah et al., 2021). Both experimental data and clinical observation support the significance of hormones in the etiology of the acne (Zouboulis, 2004). The development of acne requires functional sebaceous glands (Khondker et al., 2012). Acne vulgaris results from the overproduction of sebum, inflammation, hyper keratinization of the follicle and bacterial proliferation of hair follicles by Propionibacterium acnes (Sobhan et al., 2020).

The epidermal homeostasis is significantly regulated by thyroid hormone (Kasumagic-Halilovic & Begovic, 2012). On skin, the thyroid hormone receptor (TR) attributes direct thyroid hormone action (Safer, 2011). The general population frequently experiences thyroid problems (Ogbonna and Ezeani, 2019). It has been calculated that about 1.5 billion people worldwide are at risk for thyroid problems (Mounika et al., 2013). In patients with thyroid dysfunction, acne accounts for 5% of skin abnormalities (Shrestha, 2018). Thyroid hormones cause acne by affecting the sebaceous gland. Thyroxine has been demonstrated to promote lipid production & decrease mitotic activity. TSH increases the activity of sebaceous gland cells (Vergou et al., 2011). Evidence suggests that the role of T4 and TSH have similar effects on secretion of sebum. But they appeared to act in opposite ways (Ebling et al., 1970). It is more likely that TSH stimulates the thyroid gland directly than indirectly by increasing the sebaceous gland response (Ebling et al., 1970). 

Study place

The study was carried out at the Department of Physio-logy, Dhaka medical college, Dhaka, Bangladesh from January 2022 to December 2022. 

Ethical approval of the study protocol

The study protocol was approved by Research Review Committee and Ethical Review Committee of Dhaka Medical College, Dhaka, Bangladesh.

Selection criteria of subjects

Inclusion criteria for case

The inclusion criteria of case were clinically diagnosed case of the acne vulgaris (Seborrhea i.e., greasy skin, pustules, papules, nodules, comedones and scarring) with age range between 15 to 45 years and normal BMI of the both genders.

Inclusion criteria for control 

Age, gender and BMI matched healthy persons were in inclusion criteria for control.

Exclusion criteria 

Patients not willing to participate, pregnant women, lactating women, patients with systemic diseases like diabetes, malignancy, chronic liver disease, chronic renal disease, diagnosed case of the thyroid disorders, patients with any other autoimmune disorders and the patients taking drugs (Lithium, amiodarone, dopamine, levodopa, bromocriptine and oral contraceptive pill) for the last three months that interfere with thyroid functions, alcohol users and smokers were rejected from the study. 

Study population and design

A cross sectional study was conducted in the Depart-ment of Physiology, Dhaka medical college, Dhaka, Bangladesh from January 2022 to December 2022. At the beginning of the study, a total 120 number of the subjects were selected with age ranging from 15 to 45 years including both genders. Among the enrolled subjects, 60 patients with acne vulgaris were included in study group (Group A) and 60 age matched app-arently healthy subjects who were not related to acne or any hormonal conditions with skin manifestations were considered as control group (Group B) for com-parison. Group A was selected based on exclusion & inclusion criteria, from Department of Dermatology & Venerology, Dhaka Medical College Hospital & by personal contact from different areas of Dhaka city. Group B was selected from the personal contact from different areas of Dhaka city based on exclusion & inclusion criteria. Thyroid function results were cate-gorized as normal, hypothyroidism, hyperthyroidism, subclinical hypothyroidism and subclinical hyperthy-roidism. Complete dermatological assessment was performed to ascertain the extent of involvement of acne vulgaris in group A. Again, based on the severity of acne vulgaris, Group A was further divided into three subgroups: mild acne, moderate acne & severe acne. Using clinical criteria based on acne severity, acne was diagnosed dermatologically as follows: Mild acne - determined by the existence of either non-inflammatory lesions, inflammatory lesions (papulo-pustular) or both; Moderate acne - referred to as coin-cidental nodules, inflammatory lesions, mild scarring or combined; Severe acne - characterized by nodules, massive inflammatory lesions or both, together with injuries, moderate acne that still persists after six months of medication and acne determining a serious psychological impact. With all aseptic precautions, venous blood was drawn from antecubital vein for determination of serum free tri-iodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH). Thyroid profile was analyzed in Department of Nuclear Medicine, Dhaka Medical College Hospital, Dhaka in Siemens machine from Germany using an ADVIA Centaur XPT system. 

Statistical analysis

Statistical analysis was performed by using a computer based statistical program SPSS (Statistical Package for Social Science) version 26. All parameters were the expressed as mean ± standard deviation (mean ± SD). Unpaired students t test was performed to compare the mean of hormonal parameters between study group & control group. For comparing the mean of hormonal parameters between two groups in skewed distribution, the Mann-Whitney test was performed. To assess the relationship between two qualitative variables, the chi-square test was performed. The Kruskal-Wallis rank sum test was performed to compare hormonal parameters among three subgroups of patients with acne vulgaris. Spearmans rho correlation coefficient test was performed to assess the relationship between hormonal para-meters & acne vulgaris severity. For all statistical tests, p <0.05 was taken into consideration as statistically significant.

One hundred and twenty participants, aged between 15 to 45 years, who satisfied the inclusion criteria were enrolled in the study. Among the enrolled subjects, 60 patients of acne vulgaris were included in Group A (study group) and 60 age matched apparently healthy subjects who were not related to acne or any hormonal conditions with skin manifestations were considered as Group B (control group) for comparison. The mean age of group A and group B were 29.32±7.60 years and 31.80±7.79 years respectively (Table 1). In group A, there were the 24/60(40%) male and 36/60(60%) female and in group B, there were 25/60(41.7%) male and 35/60(58.3%) female. Male and female ratio in group A and group B were 1:1.5 and 1:1.4 respec-tively. Male and female ratio in both group A and group B was 1:1.4 (Table 1). The mean body mass index (BMI) of group A and group B were 22.14±1.44 kg/m2 and 21.64±1.54 kg/m2 respectively (Table 1). There was no statistical difference observed for age, gender and BMI between the two groups. Therefore, the two groups were matched for age, gender and BMI. 

Results were expressed as mean ± SD for continuous variables and percentage for all categorical variables. Group A = study group and Group B = control group. p–values were based on the unpaired t-test for all continuous variables and chi-square test for categorical variables. The mean FT3 level of group A and group B were 4.56±1.14 p mol/L and the 4.39±0.82 p mol/L respectively. The mean FT3 levels were almost similar in group A and group B. In this study, the difference between the two groups were not the statistically significant (p-0.343) (Table 2). The mean FT4 level of group A and group B were 14.14±7.83 p mol/L and 15.16±3.22 p mol/L respectively. In the current study, statistically significant (p-0.020) difference was observed between the two groups (Table 2). Group A had a significant higher mean TSH level (9.28±8.74 mIU/L) compared with that of group B (4.33±2.44 mIU/L). In this study, TSH levels were observed statistically significantly (p <0.001) increased in Group A compared with that of group B (Table 2).

Results were expressed as mean ± SD for continuous variables. Group A= study group, and the Group B = control group.  ap–value reached from unpaired t-test, bp–value reached from Mann-Whitney test. The mean subclinical hypothyroidism of the group A was 24/60 (40.0%) and group B was 13/60(21.6%) (Table 3 and Fig. 1). The mean hypothyroidism of group A and group B were 18(30.0%) and the 4(6.7%) respectively. Out of the 60 acne vulgaris patients, two-third were observed subclinical hypothyroidism 24(40.0%) and the hypothyroidism 18(30.0%). There was a signifi-cant difference in the prevalence of thyroid disorder between groups A and the B (p- <0.001) (Table 3). 

Results were expressed as frequency, percentage for categorical variables. Group A = study group and the Group B = control group. p–value was based on Chi-square test for categorical variables.

The median value of FT3 level were higher in severe (4.88 p mol/L) and moderate (4.88 p mol/L) type of acne vulgaris followed by mild type (4.25 p mol/L) of acne vulgaris but was not statistically significant (p-0.909) (Table 4). The median value of FT4 level was 

lower in the mild type (11.98 p mol/L) of acne vulgaris followed by the severe (13.86 p mol/L) and moderate (14.37 p mol/L) type of acne vulgaris which was not statistically significant (p-0.424) (Table 4).

The median value of TSH level was higher in the moderate (9.16 m IU/L) type of acne vulgaris followed by severe (8.18 m IU/L) and mild (6.01 m IU/L) type of acne vulgaris but was not statistically significant (p-0.422) (Table 4). 

p-value was based on the Kruskal-Wallis rank sum test for continuous variables FT3, FT4, and the TSH displayed positive correlation with the severity of acne vulgaris 

(r- +0.057, +0.099 and +0.063 respectively) but was statistically not significant (p-0.667, p- 0.451 and p-0.632 respectively) (Table 5 and Fig. 2, 3 and 4). 

In the present study, the mean age of acne and control were 29.32±7.60 years and 31.80±7.79 years respec-tively. The age range of the participants was from 15 to 45 years. In the present study, the most common age group was adolescents which was consistent with the study of the (Skroza et al., 2018); Perkins et al., 2012; Cunliffe & Gould, 1979). The age range varies in different studies because acne vulgaris may appear at any age (Cunliffe & Gould, 1979). During the last 10 years, a growing body of literature suggests that an increasing number of patients suffer from acne after adolescence (Vergou et al., 2011). This might suggest either a genuine increase in the prevalence and severity of the disorder or a rising awareness of skin depart-ments interest in acne (Cunliffe & Gould, 1979). In the current study, among the respondents, frequency of acne vulgaris was more prevalent in female 36/60 (60%) than the male 24/60(40%). The finding was in agreement with the study of many researchers of different countries. Skroza et al. (2018), Srinivasan & Thomas, (2019), Lynn et al. (2016), Suva et al. (2014) & Collier, (2008) demonstrated a female prepond-erance of acne vulgaris. In the present study, regarding the severity of acne vulgaris, more than half of the population 32/60(53.3%) had severe acne. 

The least frequent form was mild acne. The prevalence of acne vulgaris (AV) was close to the prevalence of mild acne 7/60(11.7%). Around 35.0% (n= 21) of the population had moderate acne. In a previous study, Endres et al. (2021) found that significantly more people with severe acne were in the auto-immune thyroiditis (AIT) group (p < 0.001). On the contrary, in previous studies by (Skroza et al., 2018; Vergou et al., 2011) the evaluation of acne severity showed that mild acne was the most frequent form of acne. This difference was might be due to the variation in sample size & method-logy used. Burton et al. (1971) found a peak severity of acne in the teen-age group (Kaur et al., 2021). Perkins et al. (2012) recruited 2895 women aged between 10 - 70 from the general population. Among them, 28% had mild acne and the 27% had clinically severe acne. 

The present study demonstrated the mean FT3 was almost similar in acne patients and control. Difference in FT3 between the two groups was not statistically significant (p-0.343). The finding was in agreement with the study of many researchers of the different countries. In a previous cross-sectional study, the Srinivasan & Thomas, (2019) in India, displayed that all the enrolled 50 acne vulgaris patients exhibited normal FT3. Stewart & Bazergy, (2017) in a case-control study evaluated that 116/130 (89%) cases and 60/65 (92%) controls revealed normal thyroid function tests. On the contrary, Vergou et al. (2011) in Greece, reported that acne patients seemed to have signifi-cantly lower levels of FT3 (P-0.02). This difference was might be due to the variation in sample size, ethnicity and methodology used. In tissue culture studies, using surrogates for DNA expression, triiodothyronine (T3) has been displayed to enhance the proliferation of both dermal fibroblasts and epidermal keratinocytes (Kasu-magic-Halilovic & Begovic, 2012). In this study, the mean FT4 of group A and group B were 14.14±7.83 p mol/L and 15.16±3.22 p mol/L respect-tively. There was a statistically significant (p-0.020) difference observed in FT4 between the two groups. This is may be caused by the increased lipid synthesis and decreased mitotic activity of FT4 (Vergou et al., 2011). In a previous cross-sectional study, (Srinivasan & Thomas, 2019; Vergou et al., 2011) displayed that reporting values for FT4 did not significantly differ between the two groups. This difference was might be due to the difference in ethnicity, variation in sample size and methodology used. In a case-control study by Stewart & Bazergy, (2017) in Australia, observed statistically no significant difference of FT4 between the two groups. The study was limited by its variation in the sample size and retrospectivity (Stewart & Bazergy, 2017). T4 can influence production of thyroid antibody by either acting on the thyroid gland or directly on the B lymphocytes. The B lymphocytes that create anti-bodies against TSH receptors may be directly affected by T4, T3 or both. In several tissues, T4 is known to alter the activity of enzymes that promote the creation of phospholipids for cell-surface membranes in various tissues. Furthermore, the thyroid gland comprises thyroid hormone nuclear receptor which indicates that it might be a target tissue for thyroid hormones (Rieu et al., 1994). The current study revealed that group A had a significant higher mean TSH level (9.28±8.74 mIU/L) compared with that of the group B (4.33±2.44 mIU/L). Statistically significant difference was obser-ved in TSH level between the two groups (p- <0.001). The difference was may be due to the TSH stimulates activity of sebaceous gland cell (Vergou et al., 2011). In a previous study, in Nepal, Shrestha, (2018) observed that TSH was altered in 15.4% patients (Kaur et al., 2021). Their study concluded with the comments that alteration in TSH levels may be responsible for the pathogenesis of acne. In India, Srinivasan & Thomas, (2019) recorded that one-fifth 9/50 (18%) of the acne vulgaris patients exhibited an elevated TSH level. In the study of some resear-chers of different countries, (Stewart & Bazergy, 2017 & Vergou et al., 2011) the role of TSH in the acne vulgaris has been proven insignificant. This difference in results may be because of variation in sample size and different methods used in the statistical analysis. TSH stimulates activity of sebaceous gland cell (Vergou et al., 2011). Although the role of T4 and TSH are similar in their effects on the secretion of sebum, they appeared to sebaceous mitosis in opposite ways. TSH action in the amplifying the sebaceous gland response is more possibly to be direct rather than indirect concerning with the stimulation of the thyroid gland (Ebling et al., 1970). Thyroid stimulators, such as the thyroid stimulating hormone (TSH) and TSHRAb cause the thyroid cell plasma membrane preparations in vitro to release thyroid cell-surface components, including TSH receptors, which may be proved antigenic (Rieu et al., 1994).

The study revealed significantly higher levels of TSH and significantly lower levels of FT4 in acne vulgaris. Subclinical hypothyroidism was more prevalent in the acne vulgaris which was also statistically significant. Levels of FT3, FT4 and TSH were positively correlated with the severity of the acne but statistically not significant. We recommend the assessment of thyroid auto antibodies and urinary iodine concentration. 

We are grateful to the Department of Physiology, Dhaka Medical College for their kind cooperation. We also thank the study participants (both study group and control group) for their active participation.

The authors declare that there is no conflict of interest.