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Table of Contents
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


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 Submission14-Oct-2019
Date of Acceptance26-Nov-2019
Date of Web Publication27-Mar-2020

Correspondence Address:
Ahmad AlAmari
King Saud University, Riyadh
Saudi Arabia
Dr. Amal Balbisi
King Saud University, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdds.jdds_64_19

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  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 2nd, 4th, 6th, and 8th months 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 2020 Sep 21];24:38-40. Available from: http://www.jddsjournal.org/text.asp?2020/24/1/38/281429




  Introduction Top


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 Top


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 2nd, 4th, 6th, and 8th 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 Top


Serum TSH levels at baseline and at the 2nd, 4th, 6th, and 8th 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 Top


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 Top


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.



 
  References Top

1.
Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al. Management of acne: A report from a global alliance to improve outcomes in acne. J Am Acad Dermatol 2003;49:S1-37.  Back to cited text no. 1
    
2.
Rowe A. Retinoid X receptors. Int J Biochem Cell Biol 1997;29:275-8.  Back to cited text no. 2
    
3.
Karadag AS, Ertugrul DT, Tutal E, Akin KO. Isotretinoin influences pituitary hormone levels in acne patients. Acta Derm Venereol 2011;91:31-4.  Back to cited text no. 3
    
4.
Angioni AR, Lania A, Cattaneo A, Beck-Peccoz P, Spada A. Effects of chronic retinoid administration on pituitary function. J Endocrinol Invest 2005;28:961-4.  Back to cited text no. 4
    
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Uyar B, Solak A, Saklamaz A, Akyildiz M, Genc B, Gökduman A. Effects of isotretinoin on the thyroid gland and thyroid function tests in acne patients: A preliminary study. Indian J Dermatol Venereol Leprol 2016;82:587-8.  Back to cited text no. 5
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6.
Yıldırım N, Doǧan S, Atakan N. Evaluation of thyroid function tests of acne vulgaris patients treated with systemic isotretinoin. J Dermatolog Treat 2017;28:141-4.  Back to cited text no. 6
    
7.
O'Leary TJ, Simo IE, Kanigsberg ND, Ooi TC. Lack of effect of isotretinoin on thyroid-function tests. Clin Chem 1986;32:913-4.  Back to cited text no. 7
    
8.
Minuk E, Jackson R. Thyrotoxicosis developing while on isotretinoin. J Am Acad Dermatol 1986;15:120.  Back to cited text no. 8
    
9.
Guerouaz N, Saint Jean M, Peuvrel L, Dreno B. Autoimmune thyroiditis and isotretinoin: Real association or coincidence? J Eur Acad Dermatol Venereol 2016;30:125-6.  Back to cited text no. 9
    
10.
Sharma V, Hays WR, Wood WM, Pugazhenthi U, St. Germain DL, Bianco AC, et al. Effects of rexinoids on thyrotrope function and the hypothalamic-pituitary-thyroid axis. Endocrinology 2006;147:1438-51.  Back to cited text no. 10
    
11.
Tuncel M, Aydin D, Yaman E, Tazebay UH, Güç D, Doǧan AL, et al. The comparative effects of gene modulators on thyroid-specific genes and radioiodine uptake. Cancer Biother Radiopharm 2007;22:281-8.  Back to cited text no. 11
    
12.
Namba H, Yamashita S, Morita S, Villadolid MC, Kimura H, Yokoyama N, et al. Retinoic acid inhibits human thyroid peroxidase and thyroglobulin gene expression in cultured human thyrocytes. J Endocrinol Invest 1993;16:87-93.  Back to cited text no. 12
    
13.
del Senno L, Rossi R, Franceschetti P, degli Uberti EC. Expression of all-trans-retinoic acid receptor RNA in human thyroid cells. Biochem Mol Biol Int 1994;33:1107-15.  Back to cited text no. 13
    
14.
Kogai T, Liu YY, Richter LL, Mody K, Kagechika H, Brent GA. Retinoic acid induces expression of the thyroid hormone transporter, monocarboxylate transporter 8 (Mct8). J Biol Chem 2010;285:27279-88.  Back to cited text no. 14
    
15.
Bernal J. Thyroid hormone transport in developing brain. Curr Opin Endocrinol Diabetes Obes 2011;18:295-9.  Back to cited text no. 15
    
16.
Silva AC, Marassi MP, Mühlbauer M, Lourenço AL, Carvalho DP, Ferreira AC. Retinoic acid effects on thyroid function of female rats. Life Sci 2009;84:673-7.  Back to cited text no. 16
    
17.
Marsden JR, Trinick TR, Laker MF, Shuster S. Effects of isotretinoin on serum lipids and lipoproteins, liver and thyroid function. Clin Chim Acta 1984;143:243-51.  Back to cited text no. 17
    
18.
Gursoy H, Cakmak I, Yildirim N, Basmak H. Presumed isotretinoin-induced, concomitant autoimmune thyroid disease and ocular myasthenia gravis: A case report. Case Rep Dermatol 2012;4:256-60.  Back to cited text no. 18
    
19.
Nugroho J, Schweiger B. Isotretinoin as a Possible Environmental Trigger to Autoimmunity in Genetically Susceptible Patients. Case Rep Pediatr 2017;2017:4207656.  Back to cited text no. 19
    
20.
Shapiro PE, Edelson RA. Effects of retinoids on the immune system. In: Saturat JH, editor. Retinoids: New Trends in Research and Therapy. Basel, Switzerland: Karger; 1985. p. 225-35.  Back to cited text no. 20
    
21.
Acmaz G, Cınar L, Acmaz B, Aksoy H, Kafadar YT, Madendag Y, et al. The effects of oral isotretinoin in women with acne and polycystic ovary syndrome. Biomed Res Int 2019;2019:2513067.  Back to cited text no. 21
    



 
 
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