Effect of oral isotretinoin therapy on thyroid function in patients with moderate-to-severe acne vulgaris: A prospective study

Fahad AlSaif; Hend AlOtaibi; Amal Balbisi; Ahmad AlAmari; Faisal AlSaif; AlBatool AlAmari; Abdulrhman AlDakhil; Arwa AlModayfer; Nourah AlSyefi

doi:10.4103/jdds.jdds_64_19

ORIGINAL ARTICLE

Year : 2020 | Volume : 24 | Issue : 1 | Page : 38-40

Effect of oral isotretinoin therapy on thyroid function in patients with moderate-to-severe acne vulgaris: A prospective study

Fahad AlSaif¹, Hend AlOtaibi¹, Amal Balbisi¹, Ahmad AlAmari¹, Faisal AlSaif¹, AlBatool AlAmari², Abdulrhman AlDakhil², Arwa AlModayfer², Nourah AlSyefi³
¹ Department of Dermatology, King Saud University, Riyadh, Saudi Arabia
² Department of Dermatology, King Saud Medical City, Riyadh, Saudi Arabia
³ Department of Dermatology, King Abdullah Bin Abdulaziz University Hospital, Riyadh, Saudi Arabia

Date of Submission	14-Oct-2019
Date of Acceptance	26-Nov-2019
Date of Web Publication	27-Mar-2020

Correspondence Address:
Ahmad AlAmari
King Saud University, Riyadh
Saudi Arabia
Dr. Amal Balbisi
King Saud University, Riyadh
Saudi Arabia

Source of Support: None, Conflict of Interest: None

Read associated Erratum: Erratum: Effect of oral isotretinoin therapy on thyroid function in patients with moderate-to-severe acne vulgaris: A prospective study with this article

DOI: 10.4103/jdds.jdds_64_19

Abstract

Introduction: Despite its growing use, the side effects of isotretinoin therapy are not fully understood. Studies have suggested that isotretinoin can cause thyroid dysfunction, suggesting the need to investigate thyroid dysfunction as a possible side effect of oral isotretinoin therapy. Purpose: The main objective of the study is to investigate the association between isotretinoin therapy and thyroid dysfunction. Methods: In all, 51 patients (male, 21; female, 30; aged 18–25 years) with moderate-to-severe acne vulgaris were treated with 0.5 mg/kg/day oral isotretinoin (cumulative dose: 120–150 mg/kg). Serum-free thyroxine (T4), thyroid-stimulating hormone (TSH), and thyroglobulin (TGA) and thyroid peroxidase (TPO) antibody levels were measured. Results: TSH levels at baseline and at the 2^nd, 4^th, 6^th, and 8^thmonths of treatment were 2.3307 ± 1.097, 2.5824 ± 1.34, 2.678 ± 1.133, 2.3 ± 1.17, and 2.7 ± 2.17 IU·mL, respectively, with no significant change from baseline (P = 0.526, P = 0.552, P = 0.530, and P = 0.910 at 2, 4, 6, and 8 months, respectively). Serum levels of free T4, TGA, and TPO antibodies were unchanged. Conclusions: Follow-up screening for thyroid dysfunction may not be necessary for patients receiving oral isotretinoin.

Keywords: Acne vulgaris, isotretinoin, thyroid dysfunction

How to cite this article:
AlSaif F, AlOtaibi H, Balbisi A, AlAmari A, AlSaif F, AlAmari A, AlDakhil A, AlModayfer A, AlSyefi N. Effect of oral isotretinoin therapy on thyroid function in patients with moderate-to-severe acne vulgaris: A prospective study. J Dermatol Dermatol Surg 2020;24:38-40

How to cite this URL:
AlSaif F, AlOtaibi H, Balbisi A, AlAmari A, AlSaif F, AlAmari A, AlDakhil A, AlModayfer A, AlSyefi N. Effect of oral isotretinoin therapy on thyroid function in patients with moderate-to-severe acne vulgaris: A prospective study. J Dermatol Dermatol Surg [serial online] 2020 [cited 2023 Apr 1];24:38-40. Available from: https://www.jddsjournal.org/text.asp?2020/24/1/38/281429

Introduction

Isotretinoin (13-cis-retinoic acid) is a synthetic retinoid derivative currently approved for the treatment of acne and other dermatological conditions.^[1] The mode of action of retinoids is not fully known, but they play important roles in the immune response, cell proliferation, cell differentiation, morphogenesis, apoptosis, antiproliferation, and the modulation of inflammation. These actions are mediated by the retinoid receptors: the retinoic acid (RA) receptor (RAR) and retinoid X receptor.^[2]

Retinoids, including isotretinoin, can induce hormonal changes in patients with acne, but their effects on the thyroid system are not fully understood.^[3],[4] Clinical studies have investigated the effects of isotretinoin on thyroid hormone levels during acne treatment^{[3],[4],[5],[6],[7],[8],[9]} with contradictory findings. Thyroid dysfunction has been observed following treatment with isotretinoin, although the extent of this dysfunction ranged from significant decreases in total thyroxine, free thyroxine index, and total triiodothyronine with typical serum levels of thyroid-stimulating hormone (TSH) to much more severe dysfunction characterized by thyrotoxicosis.

These conflicting findings and the paucity of data prompted our investigation of the association between oral isotretinoin therapy and thyroid dysfunction in patients of acne vulgaris and no risk factors of thyroid disease.

Materials and Methods

This prospective study was conducted over a 1-year period. The data were obtained from the Dermatology Outpatient Departments at King Khaled University Hospital and collected by experienced dermatologists. Patients who presented for the treatment of acne vulgaris for the first time were recruited; they were informed that their thyroid function at multiple visits would be monitored as an out-of-routine practice. These participants included young adults (18–25 years old) with moderate-to-severe acne vulgaris, who were sexually inactive, and had no prior history of thyroid disease or other comorbidities.

The exclusion criteria were an abnormal baseline thyroid function test, signs and symptoms of thyroid dysfunction, presence of a comorbidity, and use of oral isotretinoin or any other medication in the 3 months prior to the study. Prior to the start of the treatment, each participant underwent screening to ensure their health and safety. Screening methods include thyroid function test, liver function test, pregnancy test, lipid profile, and a brief interview by a team member to check on their medical history, social history, as well as medications that the participants might take. Once a patient was fit to be involved in the study, he/she gave two informed consents: one for the study participation and other for the use of oral isotretinoin (routinely done in dermatology).

Fifty-one patients (21 males and 30 females) aged 18–25 years with moderate-to-severe acne vulgaris who were treated with a standard dose of 0.5 mg/kg/day, with a total cumulative dose of 120–150 mg/kg of oral isotretinoin, were prospectively included in the study. Serum-free thyroxine (fT4), TSH, and thyroglobulin (TGA) and thyroid peroxidase (TPO) antibody levels were measured at baseline and at the 2^nd, 4^th, 6^th, and 8^th months following treatment.

IBM-SPSS V23 Company name: IBM Corporation City: Armonk, New York Country: United States was used to analyze the data. Parametric variables were analyzed using one-way repeated-measures ANOVA, followed by Tukey's multiple comparison test. Independent t-tests were used to compare the means between groups (male and female). For nonparametric variables, the Friedman test was used with repeated measures. Finally, the Mann–Whitney U-test was used to compare the two groups. The confidence interval was 95% with the level of significance (alpha) set at a P < 0.05 as an indicator of statistical significance.

The present study was approved by the Institutional Ethics Review Board of the College of Medicine, and informed consent was obtained from each patient prior to participation in the study.

Results

Serum TSH levels at baseline and at the 2^nd, 4^th, 6^th, and 8^th months of treatment were 2.3 ± 1.1, 2.5824 ± 1.34, 2.67 8 ± 1.133, 2.3 ± 1.17, and 2.7 ± 2.17 IU·mL, respectively (mean ± SD) [Table 1]. Mean serum TSH levels did not significantly increase following isotretinoin therapy (P = 0.53, P = 0.552, P = 0.530, and P = 0.910, respectively) [Table 2]. Similarly, isotretinoin treatment did not significantly affect the serum levels of fT4, TGA, or TPO antibodies throughout the study.

Table 1: Thyroid-stimulating hormone

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Table 2: Thyroid-stimulating hormone by gender

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Discussion

Retinoids have a poorly understood effect on the hypothalamic–pituitary–thyroid axis.^[10] RA exerts an effect on thyroid function and can affect the synthesis and metabolism of thyroid hormones. TSH receptor mRNA levels reduction and inhibition of TPO and thyroglobulin mRNA in thyrocytes may also be caused by RA.^{[11],[12],[13]} Vitamin A metabolites play a role in the expression of the thyroid hormone transporter, which could cause interference between RA and thyroid hormone signaling.^[14],[15]

The studies that have investigated thyroid dysfunction as a possible side effect of isotretinoin have generated inconsistent results. Silva et al. investigated the role of isotretinoin on thyroid function in female rats and found that serum TSH, triiodothyronine (T3), and T4 levels did not significantly change the following treatment. Nevertheless, rats demonstrated a short-term increase in radioiodide uptake and decreased thyroperoxidase activity.^[16] O'Leary et al. did not note any significant change in TSH, serum-free thyroxine, or total triiodothyronine after 8- to 16-weeks of oral isotretinoin in 24 patients with acne vulgaris.^[7] Marsden et al. reported unchanged levels of TSH and responses to thyrotropin-releasing hormone in seven patients with severe rosacea who received isotretinoin; however, a significant decrease in total thyroxine, free thyroxine index, and total triiodothyronine after 12 weeks of treatment was noted.^[17]

Subclinical hypothyroidism has been reported by Uyar et al. after initiating isotretinoin therapy in 104 patients with acne vulgaris for at least 16 weeks.^[5] Another study found a significant decrease in the levels of TSH and TSH receptor antibody after 12 weeks of isotretinoin treatment in 47 patients with acne.^[3]

Autoimmune thyroiditis during isotretinoin treatment was reported in a few cases.^[18],[19] Isotretinoin has an immunomodulatory effect through its role in apoptosis and activation of B and T lymphocytes.^[20] Minuk and Jackson reported acute thyrotoxicosis in one patient taking isotretinoin for acne vulgaris.^[8] Collectively, these observations show that isotretinoin may increase the risk of thyroid dysfunction.

In this study, we recruited a group of patients using a very thorough inclusion and exclusion criteria, and all our participants completed a full course of treatment. We did not find any statistically significant changes in the serum levels of fT4 or TGA and TPO antibodies following isotretinoin treatment (0.5 mg/kg/day) after 8 months.^[7],[21] These results are consistent with those reported by O'Leary et al. in which patients received isotretinoin (1 mg/kg/day) for 16 weeks.^[6] Moreover, a recent study by Acmaz et al. showed similar results in healthy women with acne and polycystic ovarian syndrome treated with 0.6–0.8 mg/kg oral isotretinoin.^[21]

Conclusion

Screening for thyroid dysfunction is not necessary in routine follow-up of healthy patients receiving isotretinoin for acne vulgaris. Additional large-scale studies are needed to confirm these findings.

The small sample size is a limitation of our study, so is the unknown effect of higher doses of systemic isotretinoin, More than 0.5 mg/kg/day.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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