The Relationship between Triiodothyronine and Thyroid Stimulating Hormone Serum Level into Melasma Severity

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Author(s): Frien Refla Syarif*, Sri Lestari and Satya Wydya Yenny

Abstract

Melasma is a chronic acquired hypermelanosis of the skin and relatively common skin disorder that primarily affects sunlight-exposed areas in women. While etiology of melasma is not yet well understood, a possible factor is thyroid hormones. Few studies have been conducted in order to find the relationship between melasma and thyroid disorders with varying results. This study is conducted to investigate the association between thyroid parameters (triiodothyronine and thyroid stimulating hormone) and melasma severity.

Introduction

Melasma is an acquired hipermelanosis with irregular lesion, colored from light to dark brown, on sun-exposed areas. The lesion could appear either on the upper lip, nose, cheeks, chin, forehead, sometimes on the neck, chest and the dorsal arm. Melasma is usually shaped irregularly, often demarcated, with bright to brownblack pigmentation.

Melasma is epidemiologically found in all races. Based on available data, it is found more often on women rather than men. As much as 90% of the cases are found in people with an age range of 30 to 50 years old, but the exact number is unknown. Melasma is often found in tropical countries, including Indonesia, with a varying incidence rate in different spectrums of population. Melasma prevalence in Southeast Asia reaches 40% in female and 20% in male. Incidence rate of melasma in women during 2012-2014 at the Dermato-Venereology Outpatient Clinic of Dr. M. Djamil Hospital Padang is 129 (0.095%) out of 1,355 patient visits to the Division of Cosmetic Dermatology (non-publication). The etiology of melasma is not yet known for certain, but there are several factors that play a role in melasma pathogenesis such as exposure to ultraviolet radiation, genetic predisposition, pregnancy, oral contraceptives, hormone replacement therapy, cosmetics, phototoxic medications, anticonvulsant drugs and endocrine factors associated with thyroid disorders. Thyroid disorder is known to involve the entire organ system of the body and the skin is no exception. Both hyperthyroidism and hypothyroidism cause changes to structure and function of the skin.

Assessment levels of T3 and TSH serum is a useful indicator to determine the status of clinical hypothyroidism as TSH serum concentration is a sensitive indicator of thyroid dysfunction. If the thyroid function is abnormal, TSH serum level will change even under subclinical conditions. Thyroid stimulating hormone serum levels that exceed 2.5 μIU/mL is referred as subclinical hypothyroidism. Hypothyroidism is clinically defined as endocrine status with a value of TSH> 4.0 μIU/L; T3<1.2 nmol/L. The relationship between thyroid hormone and the incidence rate of melasma has long been studied, but the relationship between them is very complex and there is only limited research.

Subjects and Methods

This study is an observational analytic study with a cross-sectional design. It is conducted at the Division of Cosmetic Dermatology of Outpatient Clinic of Dr. M. Djamil Hospital Padang and the Regional Health Laboratory Padang. Subjects of research are patients with a diagnosis of melasma who come to the Division of Cosmetic Dermatology of Outpatient Clinic and worked at Dr. M. Djamil Hospital Padang. The study is approved by the the Faculty of Medicine Ethics Committee, Andalas University Padang.

The number of samples are determined by a sampling quota method based on a specified number. The specified number of samples in this study are 36 people who has been verified through the inclusion and exclusion criteria. The study is conducted from January to May 2016.

Inclusion and exclusion criteria

Inclusion criteria: women with melasma aged >18 years old, working indoor between 9am to 3pm local time and willing to participate in the study by signing an informed consent after being given an explanation of the study. Exclusion criteria: pregnant and nursing women, taking oral contraceptives, received hormonal therapy, taking systemic antifungal (griseofulvin) or photosensitiser medication (amiodarone, tetracycline, minocycline, chloroquine, cytostatics such as cyclophosphamide, 5-flourouracil, doxorubicin, daunorubicin and bleomycin, heavy metals, inorganic arsenic), treated by anticonvulsants (hydantoin, dilantin, phenytoin, phenothiazines, chlorpromazine, levodopa and barbiturates) and in treatment of melasma (topical and/or systemic).

Informed consent

All patients are required to provide a written informed consent for participation in the study.

Study Assessments

All patients are assessed for demographics including age, clinical distribution of melasma, melasma severeity degree and MASI score. Patients are examined to identify their distribution of melasma which is divided into three regions: centrofacial (cheeks, forehead, upper lip, nose and chin), malar (cheeks and nose) and mandibular (ramus of the mandible). All the patients are examined by a certified dermatologist.

Data collection

The data of all patients are collected in study protocol report forms and are saved to computer using Microsoft Excel for review.

Statistical Analysis

The mean age of all patients is calculated using observational analytic statistics. One-way analysis of variance (ANOVA) is performed to determine statistical difference in T3 and TSH mean value. The mean value of T3 and TSH to melasma severeity (for each degree of melasma) is obtained and evaluated for statistical significance using one-way ANOVA. A p<0.05 is considered as statistically significant.

A total of 36 female patients (ranged from 27 to 56 years old) with mean age of 47.52±8.11 years old suffering from melasma are included in the study. Observation at pattern of clinical features mostly found malar type in 22 (61.1%) while no mandibular type found on research subjects. Based on the severity of melasma, mild degree is mostly found in 19 people (52.8%). The mean value MASI scores in this study is 21.46±10.40 (table 1).

Table 1

Characteristic	f (n = 36)	p (%)
Age
15 - 19 year-old	0	0
20 - 24 year-old	0	0
25 - 29 year-old	1	2,7
30 - 34 year-old	4	11,1
35 - 39 year-old	1	2,7
40 - 44 year-old	3	8,3
45 - 49 year-old	9	25
> 50 year-old	18	50
Mean ± standard deviation	47,52 ± 8,11 year-old
Pattern of clinical features
Malar	22	61,1
Centrofacial	14	38,9
Mandibular	0	0
Severity
Mild	19	52,8
Moderate	12	33,3
Severe	5	13,9
MASI Score	Mean Value
Mild	13,15
Moderate	27,54
Severe	38,42
Mean ± standard deviation	21,46 ± 10,40

The mean value levels of T3 and TSH in severe degree of melasma is higher (1.605±0.309 and 2,4±1,158) compared to mild and moderate degree. As seen in each degree, there is an increasing mean value of T3 and TSH (table 2).

Table 2

Melasma Severity	Mean value of T3 serum level (nmol/l	Mean value of TSH serum level (μIU/L)
Mild	1,572 ± 0,340	1,607 ± 1,723
Moderate	1,574 ± 0,169	1,776 ± 1,089
Severe	1,605 ± 0,309	2,4 ± 1,158

Relationship between T3 and TSH serum level to the severeity of melasma as analysed using ANOVA statistical test does not find a significant association between mean value of T3 and TSH serum levels to the severeity of melasma (1.578±0.282 nmol/L and 1.773±1.457 μIU/L; p>0.05) (table 3).

Table 3

Melasma Severity	Mean value of T3 serum level (nmol/l)	p value	Mean value of TSH serum level (μIU/L)	p value
Mild	1,572	1,000	1,607	1,000
Moderate	1,574	1,000	1,776	1,000
Severe	1,605	0,085	2,400	0,879
Mean ± standard deviation	1,578 ± 0,282	0,975	1,773 ± 1,457	0,571

Discussion

Mean age of patients suffering from melasma the study is 47.52±8.11 years old. Epidemiologically, mean age of patients suffering from melasma in women is aged between 30 and 50 years old. Mean age of patients in this study therefore corresponds to the epidemiology of melasma.

Based on age, T3 hormone levels is reduced at an older age due to secretion of thyroid hormone T3. Although TSH level is relatively stable between 40 and 50 years old, it can be decreased or increased through iodine intake. In case of decreasing level of TSH, it is caused by the increasing sensitivity of pituitary gland to decrease circulating thyroid hormones and TSH secretion. As the secretion of hormones T3 and TSH are influenced by age, in normal circumstances despite T3 hormone declines with increasing age, TSH can either decrease or increase. In this study, mean age of patients suffering from melasma is in the range of epidemiological age (between 30 and 50 years old). Therefore, it can be concluded that in this study, age does not affect the level of hormones T3 and TSH.

The pattern of clinical feature malar type is found in 22 patients (61.1%). There is no mandibular type in this study because of mandibular type is rarely found (16%). Melasma is more commonly found on sun-exposed areas such as forehead, nose, cheeks, chin and upper lip, whereas the mandible area is rarely exposed to sun.

Indonesia is a tropical country, where it is exposed to the sun with strong enough intensity almost all year long. In countries with 4 seasons, people with melasma are more prevalent in the summer and appear to be less in winter. This shows the magnitude of relationship between the severeity of melasma and sun exposure. Based on theories and research results that are previously discussed where T3 and TSH hormone levels are lower in the summe and Indonesia is a tropical country with strong intensity of exposure to the sun, it can be concluded that the patttern of clinical feature of melasma is greatly influenced by the ultraviolet where the malar and centrofacial type are found in this study. However, since the whole subject of research is worked indoor and not exposed to sunlight at peak time (between 10am and 2pm), it can be concluded that exposure to sunlight does not affect thyroid hormone level on the subjects of this study.

Results of melasma severeity mostly found to be mild in 19 (52.8%) out of 36 people. According to the reviews mentioned by Handel AC, et al. (2014) patients who have melasma are often more motivated to go to a dermatologist. Cestari T, et al. (2006) examine 300 patients suffering from melasma with a result of 65% patients report feeling discomfort because of patches on their face, 55% feeling frustrated and 57% feeling ashamed of the disease. This is because melasma appears mainly on the face, although mild, do often cause cosmetic and psychological problems. Women, especially, in turn will quicky go to a dermatologist.

The mean value of MASI score is 21.46±10.40. Validity testing shows that the MASI score is able to provide precise estimation of on melasma severeity. Total MASI score on mild degree is <24, moderate is if the total score is between 25 and 36, whilst severe is if the total score is between 37 and 48. Triiodothyronine hormone level affects the degradation of melanosomes at the time of melanin transfer to keratinocytes and their resillience in kreatinocytes, whereas TSH affects the amount of melanin in melanogenesis. The mean proportion of the number of samples in each degree of melasma is not equal where mild degree has the most subjects (19 people/52.8%).

The distribution of mean value of T3 and TSH serum level is in the normal range (1.605±0.309 and 2.4±1.158). The mean value result of the two hormones are relatively normal. It might be caused by the compensation of endocrine hormones’ negative feedback loop in the thyroid gland pituitary. Table 2 shows an increase in T3 and TSH serum levels due to the severeity of melasma.

TSH serum level that exceed 2.5 μIU/L is referred as subclinical hypothyroidism. Hypothyroidism is clinically defined as endocrine status with a value of TSH > 4.0 μIU/L and T3 < 1.2 nmol/L. Normal TSH value is ranged from 0.5 to 4.0 μIU/L and T3 from 1.2 to 1.8 nmol/L. T3 and TSH serum levels are useful indicators for determining the status of hypothyroidism. Clinical concentration of TSH serum is a sensitive indicator of dysfunction tiroid.

Melasma is the result of hyperactivity of local dermal-epidermal melanin unit resulting in hypermalanisation. Epidermal hypermalamisation is influenced by thyroid hormones. Hypothyroidism occurs in the case where melanogenesis and intact of melanosomes epidermis increase. In case of hypothyroidism, the levels of T3 and T4 are decreasing and a negative feedback loop on the hypothalamus and the pituitary gland of the brain activate and stimulate the formation of TRH. TSH level then increases and produces pro-hormones T4 and the active from T3.

Research on the relationship between melasma and thyroid hormone has been carried out for years. Perez M, et al. (1983) found a link between hormone in the incidence of melasma, but the data obtains many conflicting views possibly due to various genetic backgrounds on study populations. On the other hand, the relation between thyroid hormone abnormalities and the incidence of melasma has not yet been reported much. Handel AC, et al. (2014) states there is no strong evidence to support a connection between thyroid abnormalities to melasma and melasma or thyroid disease even though it is very common in women.

Statistic analysis result using ANOVA test in this study found no significant relationship between the mean value of T3 and TSH hromone levels to the severeity of melasma. Even so, mean value of both hormones in each of the severeity degree of melasma is associated with an increase to the severeity of melasma (graphic 1).

Aetiopathogenesis melasma that has not been evaluated by the researcher is the emotional stress factors. There have been case reports of melasma that is obtained onset after an episode of emotional stress and affective disorders (e.g. depression). Level of stress on a person can be desribed as interference or may cause physiological and psychological malfunctioning to someone. Stressor can come from outside the human body (external stressor) and internal stressor (associated with genetic factors, development and growth). External stressors can be measured using a scale, the one that is used is the Holmes scale. The scale that is used to measure the level of an external stressor which the questions are given is a general perception that could potentially cause stress on the subjects.

Several studies that prove stress affects the skin through nerupeptidergic peripheral nerve fibers and exacerbates beurogenic aspect because melanocytes is derived from the neural crest. This explains why the melanocytes in human skin has been linked with neural fibers. Some hormones that activate the melanocortin receptor that induces melanogenesis which are propiomelanocortin, adrenocorticotropin hormone (ACTH) and melanocyte stimulating hormone (MSH), of which are related to stress. Besides affecting melanogenesis, hormone level changes in response to stress, one of the hormones that are affected by stress conditions is thyroid hormone. Thyroid function usually is down-regulated during stressful conditions. Triiodothyronine and tyroxine levels is decreased in a state of stress. Stress inhibits the secretion of TSH as the action of glucocorticoids on the central nerveous system. Verma K, et al. (2016) in their study shows 40.9% of the total 66 study subjects had a history of stress and emotional factors before contracts melasma.

We did not assess the emotional stress factors on the subject of research. The status of hypothyroidism in this study subjects to melasma studied is not homogeneous. It is expected for further research to get the subject of research number equally to each degree of melasma severeity, homogeneous status of hypothyroidism in melasma patients and assess the emotional stress factors to get significant relationship between T3 and TSH serum level to melasma severeity

Conclusion

The result of this study shows that mean levels of both T3 and TSH serum in melasma patients are relatively normal, nevertheless increasing level of both hormones are in accordance with an increase in the severeity of melasma. Further study can be done to larger subjects by adding the inclusion criteria of melasma patients with hypothyroidism and comparing them to control patients without hypothyroidism using cross-sectional comparative sampling and assess the stress factors using a scale to get more significant results [1-127].

Conflict of interest

I declare that there are no conflict of interrests regarding the publication of this paper.

References

1. Lapeere H, Boone B, Schepper SD, Verhaeghe E, Gele MV, Ongenae K, (2012) et al. Hypomelanoses and hypermelanoses. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffel DJ, Wolff K, eds. Fitzpatrick’s dermatology in general medicine, New York: Mc Graw Hill 1: 804-826.
2. Trout CR, Levine N, Chang MW (2004) Disorders of pigmentation. In: Bolognia JL, Jorizzo JL, Rapini R, editor. Dermatology 1: 975-1004.
3. Soepardiman L, Kelainan pigmen (2007) In: Djuanda A, Hamzah M, Aisah S, editors. Ilmu penyakit kulit dan kelamin. 5th ed. Jakarta: FKUI 289-299.
4. Rizal Y, Lestari S (2008) Insidens melasma di Poli Kulit dan Kelamin RSUP Dr. M.Djamil Padang tahun 2001-2006. Media Dermato-Venereologica Indonesiana 35: 56-59.
5. James WD, Berger TG, Elston DM (2011) Disturbances of pigmentation. In: James WD, Berger TG, Elston DM, eds. Andrews’ disease of the skin clinical dermatology. 11th ed. New York: WB Saunders Comp 843-862.
6. Rendon M, Berneburg M, Arellano I, Picardo M (2006) Treatment of melasma. Journal of the American Academy Dermatology 54: S272-281.
7. Pinto JM, Borges MDFM, Magalhaes GM (2006) A review of melasma, part 1: Ethiopathogenic factors, clinical and histopathologic evaluations. Cosmetic Dermatology 19: 683- 687.
8. Jimbow K, Jimbow M (1989) Pigmentary disorders in oriental skin. Clinico Dermatology 7: 11-27.
9. Taylor SC (2003) Epidemiology of skin diseases in people of color. Highlighting Skin of Color 71: 271-275.
10. Sheth VM, Pandya AG (2011) Melasma: A comprehensive update part I. Journal of the American Academy Dermatology 65: 689-697.
11. Shankar KDSR, Somani VK, Kohli M, Sharad J, Ganjoo A, (2014) et al. A cross-sectional, multicentric clinicoepidemiological study of melasma in India. Dermatologic Therapy 3: 71-81.
12. Goh CL, Dlova CN (1999) A retrospective study on the clinical presentation and treatment outcome of melasma in a tertiary dermatological referral center in Singapore. Singapore Medical Journal 40: 455-458.
13. Almosuly IM, Butros RO (2010) Clinical assessment of melasma in patients attending the Department of Dermatology and Venereology at Rizgary Teaching Hospital in Erbil City. Zanco Journal of Medical Sciences 14: 55-60.
14. Parsad D, Kumarasinge PW (2006) Psycho-social implications of pigmentary disorders in Asia. Journal of Investigative Dermatology 1-8.
15. Walker C (2005) Skin disease and psychology: A multitude of links. In: Walker C dan Papadopoulos L, editors. Pshychodermatology the psychological impact of skin disorders. New York: Cambridge University Press, Cambridge 1-14.
16. Doward LC, McKenna SP (1998) Evolution of quality assessment. In: Rajagopalan R, Sheretz EF, Anderson TR, editors. Care management of skin disease. New York: Marcell-Dekker 9-94.
17. Ali R, Aman S, Nadeem M, Kazmi AH (2013) Quality of life in patients of melasma. Journal Pakistan of Dermatologists 23: 143-148.
18. Pawaskar MD, Parikh P, Markowsky T, McMichael AJ, Feldman SR, et al. (2007) Melasma and its impact on health-related quality of life in Hispanic women. Journal of Dermatology Treatment 18: 5-9.
19. Balkrishnan R, McMichael AJ, Camacho FT, Saltzberg F, Housman TS, et al. (2003) Development and validation of a health-related quality of life instrument for women with melasma. British Journal of Dermatology149: 572-577.
20. . Steiner D, Feola C, Bialeski N, Silva FAM (2009) Treatment of melasma: Systematic review. Surgical & Cosmetic Dermatology 1: 87-94.
21. Shweta K, Khozema S, Meenu R, Anupama S, Singh SK, et al. (2011) A systemic review on melasma: A review. International Journal of Current Bio Medical Sciences 1: 63-68.
22. Cranenburgh OD, Prinsen CAC, Sprangers MAG, Spuls P, Korte JD. (2012) Health-related quality of life assessment in dermatologic practice: Relevance and application. Dermatologic Clinics 30: 323-332.
23. . Yazdanfar A, Hashemi B (2010) Association of melasma with thyroid autoimmunity: A case-control study. Iranian Journal of Dermatology13: 51-53.
24. Odom RB, James WD, Berger TG (2011) Disturbances of pigmentation. In: James WD, Berger TG, Elston DM, eds. Andrew’s diseases of the skin, 11th ed. Philadelphia: WB Saunders-Elsevier Company 846-862.
25. Achar A, Rathi SK (2011) Melasma: A clinico-epidemiological study of 312 cases. Indian Journal of Dermatology 56: 380- 382.
26. Dogra A, Dua A, Singh P (2006) Thyroid and skin. Indian Journal of Dermatology 51: 96-99.
27. Dogra A, Dua A (2006) Cutaneous changes in hypotiroidism. Thyroid Research and Practice 3: 45-49.
28. . Haritha S, Sampath K (2013) Skin manifestation of hypothyroidism - a clinical study. Journal of Dental and Medical Sciences 7: 58-60.
29. Malek ZAA, Kadekaro AL (2010) Human cutaneous pigmentation. Physiological Regulation of Human Cutaneous Pigmentation 11: 81-100.
30. Solano F (2014) Melanins: Skin pigments and much more types, structural models, biological functions, and formation routes. New Journal of Science 6: 1-28.
31. Dentice M, Salvatore D (2011) Deiodinase: The balance of thyroid hormone: Local impact of thyroid hormone inactivation. Journal of Endocrinology 209: 273-282.
32. Safer JD (2011) Thyroid hormone action on skin. DermatoEndocrinology 3: 211-215.
33. Paus R (2010) Exploring the “thyroid-skin connection”: Concepts, questions, and clinical relevance. Journal of Investigative Dermatology 130: 7-10.
34. Bodo E, Kany B, Gaspar E, Knuver J, Kromminga A, et al. (2010) Thyroid-stimulating hormone, a novel, locally produced modulator of human epidermal functions, is regulated by thyrotropin-releasing hormone and thyroid hormones. Endocrinology 151: 1633-1642.
35. Zouboulis CC (2004) The human skin as a hormone target and an endocrine gland. Hormones 3: 9-26.
36. Jurado CC, Serrano LG, Ferreria MG, Costa C, Paramio JM, et al. (2011) The thyroid hormone receptors as modulators of skin proliferation and inflammation. Journal of Biological Chemistry 286: 24079-24088.
37. Kasraee B (2002) Depigmentation of brown Guinea pig skin by topical application of methimazole. The Journal of Investigative Dermatology 1: 205-207.
38. Mullin GE, Eastern JS (1986) Cutaneous consequences of accelerated thyroid function. Cutis 37: 109-114.
39. Kasumagic HE (2014) Thyroid disease and the skin. Annals of Thyroid Research 1: 27-31.
40. Park KC, Huh SY, Choi HR, Kim DS (2010) Biology of melanogenesis and the search for hypopigmenting agents. Dermatologica Sinica 28: 53-58.
41. . Choi HI, Sohn KC, Hong DK, Lee Y, Kim CD, et al (2014) Melanosom uptake is associated with the proliferation and differentiation of keratinocytes. Archives of Dermatological Research 306: 59-66.
42. Videira IFS, Magina S, Moura DFL (2013) Mechanism regulating melanogenesis. Anais Brasileiros de Dermatologia 88: 76-83.
43. Ebanks JP, Koshoffer A, Wickett RR, Schwemberger S, Babcock G, et al. (2011) Epidermal keratinocytes from light vs. dark skin exhibit differential degradation of melanosomes. Journal of Investigative Dermatology 131: 1226-1233.
44. Ebanks JP, Wickett RR, Boissy RE (2009) Mechanism regulating skin pigmentation: The rise and fall of complexion coloration. International Journal of Molecular Sciences 10: 4066-4087
45. Grando SA (1993) Physiology of endocrine skin interrelations. Journal of the American Academy of Dermatology 28: 981- 992.
46. Kasraee B, Hugin A, Tran C, Sorg O, Saurat JH (2004) Methimazole is an inhibitor of melanin synthesis in cultured B16 melanocytes. The Journal of Investigative Dermatology. 12: 1338-1341.
47. Barrett EJ (2003) The thyroid gland. In: Boron WF, Boulpaep EL, eds. Medical physiology. A cellular and mollecular approach. 1st ed. Philadelphia: Saunders 1035-1048.
48. Chiamolera MI, Wondisford FE (2009) Minireview: Thyrotropin-releasing hormone and the thyroid hormone feedback mechanism. Endocrinology 150: 1091-1096.
49. Gaspar E, Nguyen-Thi KT, Hardenbicker C, Tiede S, Plate C, et al. (2011) Thyrotropin-releasing hormone selectively stimulates human hair follicle pigmentation. Journal of Investigative Dermatolology 131: 2368-2377.
50. Slominski A (2009) Neuroendocrine activity of melanocyte. Experimental Dermatology 18: 760-763.
51. Tsygankova OM, Saavedra A, Rebhun JF, Quilliam LA, Meinkoth JL (2001) Coordinated regulation of Rap1 and thyroid differentiation by cyclic AMP and protein kinase A. Molecular and Cellular Biology 21: 1921-1929.
52. Zanni MSG, Campana R, Papa M, Ragazzini L, Monetti E, et al. (2008) Cutaneous manifestation in hypothyroid patients. Clinica Universitaria Reina Fabiola 2:1-4.
53. Antonini D, Sibilio A, Dentice M, Missero C (2013) An intimate relationship between thyroid hormone and skin: Regulation of gene expression. Frontiers in Endocrinology 4: 1-9.
54. Sugimoto K, Mori K (2012) Thyroid-stimulating hormone regulation and transcription in hypothyroidism. Influences and Treatments Intechopen 15: 255-276.
55. Guarneri F (2014) Ethiopathogenesis of melasma. Pigmentary Disorders S1: 1-5.
56. Talaee R, Ghafarpasand I, Masror H (2015) The relationship between melasma and disturbances in the serum level of thyroid hormones and indices. Medicine Journal 2: 19-23.
57. Luthfi RJ, Fridmanis M, Misiunas AL, Pafume O, Gonzales EA, et al. (1985) Association of melasma with thyroid autoimmunity and other thyroidal abnormalities and their relationship to the origin of the melasma. Journal of Clinical Endocrinology & Metabolism 61: 28-31.
58. Kiani A, Ahmari M, Rezvan FMR (2006) Association of melasma with thyroid disorders: A case-control study. Iranian Journal of Dermatology 9: 154-158.
59. Niepomniszcze H, Amad H (2001) Skin disorders and thyroid diseases. Journal of Endocrinological Investigation 24: 628- 638.
60. Kavya M (2014) Melasma: A clinico-epidemiological study. International Journal of Basic and Applied Medical Sciences 4: 388-391.
61. Mogaddam MR, Alamdari MI, Maleki N, Ardabili NS, Abedkouhi S (2015) Evaluation of autoimmune thyroid disease in melasma. Journal of Cosmetic Dermatology 0: 1-5.
62. Taylor SC (2007) Objective and subjective measures of melasma. Cosmetic Dermatology. 2007 20: 93-95.
63. Taylor S, Westerhof W, Im S, Lim J (2006) Noninvasive techniques for the evaluation of skin color. Journal of theAmerican Academy Dermatology 54: S282-290.
64. Pandya AG, Hynan LS, Bhore R, Riley FC, Guevara IL, et al. (2011) Reliability assessment and validation of the melasma area and severity index (MASI) and a new modified MASI scoring method. Journal of the American Academy Dermatology 64:78-83.
65. . Treesirichod A, Chansakulporn S, Wattanapan P (2014) Correlation between skin color evaluation by skin color scale chart and narrowband reflectance spectrophotometer. Indian Journal of Dermatology 59: 339-342.
66. Damevska K (2014) New aspects of melasma. Serbian Journal of Dermatology and Venereology 6: 5-18.
67. Handel AC, Miot LDB, Miot HA (2014) Melasma: A clinical and epidemiological review. Anais Brasileiros de Dermatologia 89: 771-782
68. Werlinger KD, Guevara IL, Gonzales CM, Rincon ET, Caetano R, et al. (2007) Prevalence of self-diagnosed melasma among pre-menopausal Latino women in Dallas and Forth Worth Tex. Archives of Dermatology 143: 424-425.
69. Sanchez MR (2003) cutaneous disease in Latinos. Dermatological Clinics 21: 689-697.
70. Ishiy PS, Silva LR, Penha MA, Handel AC, Miot HA (2014) Skin diseases reported by workers from the campus UNESP Rubiao Jr, Botucatu-SP (Brazil). Anais Brasileiros de Dermatologia 89: 529-531.
71. Tomb RR, Nassar JS (2000) Profile of skin diseases observed in a department of dermatology (1995-2000). Journal Medical Libanais 48: 302-309.
72. Shenoi SD, Davis SV, Rao S, Rao G, Nair S (2005) Dermatoses among paddy field workers - A descriptive, cross-sectional pilot study. Indian Journal of Dermatology Venereology and Leprology 71: 254-258.
73. El-Essawi D, Musial JL, Hammad A, Lim HW (2007) A survey of skin disease and skin-related issues in Arab Americans. Journal of the American Academy Dermatology 56: 933-8.
74. Sivayathorn A (1995) Melasma in orientals. Clinical Drug Investigation 10: 34-40
75. Febrianti T, Sudharmono A, Rata IGAK, Bernadette I (2004) Epidemiologi melasma di Poliklinik Departemen Ilmu Kesehatan Kulit dan Kelamin RS dr. Cipto Mangunkusumo Jakarta tahun 2004. Perdoski [Internet]. Tersedia di: perdoski. org/index.php/public/information/mdvi-detai-content/86.
76. Park HY, Yaar M (2012) Biology of melanocytes. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffel DJ, Wolff K, eds. Fitzpatrick’s dermatology in general medicine, 8th ed, vol 1. New York: Mc Graw Hill 765-781.
77. Seiberg M (2001) Keratinocyte-melanocyte interactions during melanosome transfer. European Society for Pigment Cell Research and the International Pigment Cell Society14: 236-242.
78. Eberle AN (1988) Proopiomelanocortin and the melanocortin peptides. In: Eberle AN, Cone RD, eds. The melanotropins: chemistry, physiology and mechanism of actions. Basel: Karger Verlag 3-67.
79. Mastore M, Kohler L, Nappi AJ (2005) Production and utilization of hydrogen peroxide associated with melanogenesis and tyrosinase-mediated oxidation of DOPA and dopamine. Federation of European Biochemical Societies Journal. 272: 2407-2415.
80. Boissy RE (2003) Melanosome transfer to and translocation in the keratinocyte. Experimental Dermatology 12: 5-12.
81. Lee ES, Kom JH, Im S, Lee KB, Sohn S, et al. (2001) Application of computerized image analysis in pigmentary skin disease. International Journal of Dermatology 40: 45-49.
82. Hamed SH, Asaf SA, Amro B (2011) Innovative non-invasive technique in skin pharmaceutics vs valid complements in cosmetic dermatology practice. Jordan Journal of Pharmaceuticals Sciences 4: 174-180.
83. Devpura S, Pattamadilok B, Syed ZU, Vemulapalli P, Henderson M, et al. (2011) Critical comparison of diffuse reflectance spectroscopy and colorimetry as dermatological diagnostic tools for acanthosis nigricans: A chemometric approach. Biomedical Optics Express 2: 1664-1673.
84. Jacques SL (2015) Quick analysis of optical spectra to quantify epidermal melanin and papillary dermal blood content skin. J Biophotonics 8: 309-316.
85. Chatterjee M, Vasudevan B (2014) Recent advances in melasma. Pigment International1: 70-80.
86. Galeano J, Jolivot R, Marzani F, Benezeth Y (2012) Unmixing of human skin optical reflectance maps by non-negative matrix factorization algorithm. National Electronics and Computer Technology Center 10: 1-13.
87. Hindritiani R (2015) Melasma. In: Wasitaatmadja SM, editor. Pigmentasi kulit. Jakarta: Badan Penerbit FKUI 114-126.
88. Nikolaou V, Stratigos AJ, Katsambas AD (2006) Established treatments of skin hypermelanoses. Journal of Cosmetic Dermatology 5: 303-308.
89. Ortonne JP, Bose SK (2005) Pigmentation: dyschromia. In: Baran R, Maibach HI, editor. Textbook of cosmetic dermatology. 3rd ed. London: Taylor&Francis 393-410.
90. Ortonne JP (2006) Retinoid therapy of pigmentary disorders. Dermatologic Therapy 19: 280-288.
91. Olumide YM, Akinkugbe AO, Altraide D, Mohammed T, Ahamefule M, et al. (2008) Complications of chronic use of skin lightening cosmetics. International Journal of Dermatology 47: 344-353.
92. Lynde CB, Kraft JN, Lynde CW (2007) Topical treatment of melasma and postinflammatory hyperpigmentation. Skin Therapy Letter 1-12.
93. Fisher AA (1982) Leukoderma from bleaching creams containing 2% hydroquinone. Contact Dermatitis 8: 272-273.
94. Mann RJ, Harman RRM (1983) Nail staining due to hydroquinone skin-lightening creams. British Journal of Dermatology 108: 363-365.
95. BPOM RI (2003) Kosmetik mengandung bahan berbahaya dan zat warna yang dilarang. Jakarta: BPOM RI.
96. Rendon M, Cardona LM, Bussear EW, Benitez AL, Colon LE, et al. (2008) Successful treatment of moderate to severe melasma with triple-combination cream and glycolic acid peels: A pilot study. Cutis 28: 372-378.
97. Szkudlinski MW, Fremont V, Bonin C, Weintraub BD (2002)Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships. Pysiological Review 82: 473-502.
98. . Brownstein D (2010) 59 diseases now linked to thyroid imbalance, millions affected. Newsmax Media 3: 1-8.
99. Slominski A (2005) Neuroendocrine system of the skin. Dermatology 211: 199-208
100. Slominski A, Wortsman J, Kohn L, Ain KB, Venkataraman GM, et al. (2002) Expression of hypothalamic-pituitarythyroid axis related genes in the human skin. Journal of Investigative Dermatology 119: 1449-1455.
101. .Burman KD, McKinley GL (2006) Dermatologic aspects of thyroid disease. Clinical Dermatology 24: 247-55.
102. Slominski A, Wortsman J (2000) Neuroendocrinology of the skin. Endocrine Reviews 21: 457-87.
103. .Lee AY, Noh M (2013) The regulation of epidermal melanogenesis via cAMP and/or PKC signaling pathways: Insight for the development of hypopigmenting agents.Archive of Pharmacal Research 36: 792-801.
104. .Braverman L, Wartofsky L (2010) Thyroid function tests. In: National Endocrine and Metabolic Disease Information Service. U.S Department of Health and Human Services NIH Publication No. 10-6284.
105. Tijn DA, Vijder JJM, Vulsma T (2008) Role of throtropinreleasing hormone stimulation test in diagnosis of congenital central hypotiroidism in infants. Journal of Clinical Endocrinology & Metabolism 93: 410-419.
106. .Shankar K, Godse K, Aurangbadkar S, Lahiri K, Mysore V, et al. (2014) Evidence-based treatment for melasma: Expert opinion and a review. Dermatologic Therapy 4: 165-186.
107. Moncada B, Sanchez LKS, Alvarez BT, Cazares JPC, Ramirez JDM, et al. (2009) Molecular structure and concentration of melanin in the stratum corneum of patients with melasma. Photodermatology, Photoimmunology & Photomedicine 25: 159-160.
108. .Malek J, Chedraoui A, Nikolic D, Baroutt N, Ghosn S, et al. (2013) Successful treatment of hydroquinone-resistant melasma using topical methimazole. Dermatologic Therapy 26: 69-72.
109. Kim H, Choi HR, Kim DS, Park KC (2012) Topical hypopigmenting agents for pigmentary disorders and their mechanisms of action. Annals of Dermatology 24: 1-6.
110. Roy G, Mugesh G (2006) Bioinorganic chemistry in thyroid gland: Effect of antithyroid drugs on peroxidase-catalyzed oxidation and iodination reactions. Bioinorganic Chemistry and Applications 0: 1-9.
111. Taieb A, Andre MC, Briganti S, Picardo M (2011) Inhibitors and enhancers of melanogenesis. In: Riley PA, Borovansky J, editors. Melanin and melanosomes biosynthesis, biogenesis, physiological, and pathological function. Germany: WileyBlackwell 117-165.
112. Kasraee B, Ardekani GHS, Parhizgar A, Handjani F, Omrani GR, et al. (2008) Safety topical methimazole for the treatment of melasma. Skin Pharmacology & Physiology 21: 300-305.
113. Khani C, Hoffman C, Gropper C, Desai S (2014) Topical methimazole for the treatment of moderate to severe melasma. American Osteopathic College of Dermatology Fall Meeting 0: 96-101.
114. Madiyono B, Moeslichan S, Sastroasmoro S, Budiman I, Purwanto SH (2010) Perkiraan besar sampel. In: Sastroasmoro S, Ismael S, editors. Dasar-dasar metodologi penelitian klinis. 3rd ed. Jakarta: Sagung Seto 302-331.
115. Kumari T, Prasad A, Sinha KK, Bharti MLG, Satyam K (2015) Age and specific thyroid hormone profile in euthyroid subjects. Journal of Biochemical Technology 6: 1008-1012.
116. Watanabe S (2014) Facial dermal melanocytosis. Austin Journal of Dermatology 1: 1-6.
117. Tranggono RIS, Adityarini (2010) Cosmeceuticals for Asian who are living in the tropics. Journal of Applied Cosmetology 28: 71-86
118. Umborowati MA, Rahmadewi (2014) Studi Retrospektif: Diagnosis dan Terapi Pasien Melasma. Berkala Ilmu Kesehatan Kulit dan Kelamin 26: 56-63.
119. .Cestari TF, Hexsel D, Viegas ML, Azulay L, Hassun K, et al. (2006) Validation of a melasma quality of life questionnaire for Brazillian Portuguese language: The MelasQol-BP study and improvement of QoL of melasma patients after triple combination therapy. British Journal of Dermatology 156: 13-20
120. Verma K, Kumre K, Sharma H, Singh U (2015) A study of various etiological factors in the causation of melasma. International Journal of Comparative Education and Development 1: 28-32.
121. Damevska K (2014) New aspects of melasma. Serbian Journal of Dermatology & Venereology 6: 5-18
122. .Tamega AA, Miot LD, Bonfietti C, Gige TC, Marques ME, et al. (2013) Clinical patterns and epidemiological characteristics of facial melasma in Brazilian women. Journal of European Academy Dermatology & Venereology 27: 151- 156.
123. .Kaplan LA, Evans L, Monk C (2007) Effects of mothers’ prenatal psychiatric status and postnatal caregiving on infant biobehavioral regulation: Can prenatal programming be modified?. Early Human Development 84:249-256.
124. .Mimura C, Griffiths P (2004) A Japanese version of the perceived stress scale: Translation and preliminary test. International Joournal of Neuronal System 41: 379-385.
125. Cui S, Li Y, Lu H, Gao XH, Wei H, et al. (2016) Morphological relationship between nerve fibers and melanocytes in the epidermis of melasma. Clinical Pediatric Dermatology 2: 1-4.
126. .Parsad D, Kumarasinge PW (2006) Psycho-social implications of pigmentary disorders in Asia. Journal of Investagative Dermatology 1-8.
127. Walker C (2005) Skin disease and psychology: a multitude of links. In: Walker C dan Papadopoulos L, editors. Pshychodermatology the psychological impact of skin disorders. New York: Cambridge University Press, Cambridge 1-14.

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