**2.3. Results**

300 Thyroid Hormone

**2.1. Introduction** 

with AA.

**2.2. Patients and methods** 

responsive genes have been identified in skin.

connective tissue diseases and palmoplantar pustulosis.

alopecia areata, which have especially autoimmune etiology.

**2. Thyroid autoimmunity in patients with alopecia areata** 

thyroid hormone binding isoforms of TR have been identified in skin tissues [14, 21]. TRs have been detected in epidermal keratinocytes, skin fibroblasts, hair arrector pili muscle cells, sebaceous gland cells, vascular endothelial cells, and a number of cells types that make up the hair follicle [9]. The demonstration of TR expression in hair follicle cells indicates that thyroid hormone can affect hair growth directly, rather than through an intermediate mechanism such as a general metabolic status [22]. In addition, several thyroid hormone

When thyroid disease is of autoimmune etiology, additional skin findings may be evident which reflect associated autoimmune disease [9]. Patients with autoimmune thyroid disease are at increased risk for other autoimmune diseases, both tissue-specific and generalized. In autoimmune disease such as Graves' disease and Hashimoto's thyroiditis the skin manifestations may be related to either thyroid hormone levels themselves or to associated T and/or B cell abnormalities [23]. A list of autoimmune conditions apparent when examining the skin includes alopecia areata, vitiligo, chronic urticaria, bullous disorders,

There is convincing evidence of a significant association between thyroid autoimmunity and skin disorders. Most commonly reported cutaneous disorder related with thyroid diseases is

Alopecia areata (AA) is a clinical condition characterized by well circumscribed, round, or oval patches of hair loss on the scalp or other parts of the body. Sometimes, alopecia totalis (AT), loss of all scalp hair, or alopacia universalis (AU), loss of all body hair, may develop. This disorder affects both sexes equally and occurs at all ages, although children and young adults are affected most often. The etiopathogenesis of AA is still unclear, but there is evidence that autoimmunity and endocrine dysfunction may be involved [24-26]. The autoimmune etiology has been proposed on the basis of its association with various autoimmune diseases, the presence of autoantibodies and various underlying immune abnormalities in the affected sites of these patients [27, 28]. One of the main associations is with thyroid abnormalities. This association was further supported by an increased incidence of abnormal thyroid structure,

function tests and/or presence of thyroid autoantibodies found in many studies [29-32].

The aim of this study was to determine the prevalence of thyroid autoimmunity in patients

The study included 70 patients with AA (40 female and 30 male). A detailed history and examination were taken in all study subjects, including patients age, age at onset, duration of disease, associated diseases, history of thyroid disorders and the extent and severity of We performed a cross-sectional study in 70 consecutive patients with alopecia areata and 70 age- and sex-matched controls. Demographic data of patients and controls are shown in Table 1. The mean (SD) age of the patient and control groups was 40.39 (±14.39) and 40.71 (±15.30), respectively (P = 0.896). The onset of AA occurred in 14 (20%) of the patients before 16 years of age, 3 (4.28%) patients had AA more than 10 years. The duration of alopecia areata ranged from 1 to 150 months. A family history of the same disease was present in 7 (10%) patients. According to the clinical type of AA, 13 patients had unilocular lesion, 37 patients had multilocular lesions, 12 alopecia totalis and 8 alopecia universalis (Table 2).

Thyroid functional abnormalities were found in 8 (11,43%) patients. In the control group only one patient had abnormalities in hormonal status.

Hypoechogenic thyroid tissue was seen in 7 (10%) patients who all had elevated levels of thyroid autoatibodies. The thyroid gland was enlarged in 5 (7.14%) patients. Goitre was diagnosed in 4 (5.71%) cases. The ultrasound examination of the thyroid gland in control group was interpreted as normal in 64 (91.42%), and 6 (5.45%) volunteers had small simple goiter. Thyroid volume did not differ significantly between the study patients and the controls (p>0.05).

In patients with alopecia areata anti-Tg titers were ranging from 11.10 to 915.30 IU/mL and anti-TPO antibody titers from 5.10 to 714.40 IU/mL. In control group anti-Tg titers were

ranging from 10.00 to 153.00 IU/mL, and anti-TPO antibody titers from 4.40 to 129.00 IU/mL. Anti-Tg antibody in 16 (23%) patients, anti-TPO antibody in 21 (30%) and both anti-Tg and anti-TPO antibodies in 13 (19%) were higher than the normal antibody titres. In the control group, one subject (1%) had positive anti-Tg and one volunteer (1%) had positive anti-TPO. The frequency of thyroid autoantibodies was significantly higher in alopecia areata patients than in control group (Table 3).

Thyroid Autoimmunity in Patients with Skin Disorders 303

Negative

Positive

Negative Positive

**Scheme 1.** Differences of frequencies positive/negative values of anti-Tg (threshold value115 IU/ml)

**Differences of frequencies positive/negative values of anti-TPO (threshold value 34 IU/ml) between groups**

69

Alopecia areata Control

**Differences of frequencies positive/negative values of anti-Tg (threshold value115 IU/ml) between groups**

69

1

1

**Scheme 2.** Differences of frequencies positive/negative values of anti-TPO (threshold value 34 IU/ml)

Alopecia areata Control

between groups

0

10

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30

40

50

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70

80

54

49

21

16

between groups

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80

A Chi-square test for independence (with Yates Continuity Correction) indicated significant association between higher values of anti-Tg (values more than 115 IU/ml) and alopecia areata, χ2 (1, n=140)= 13.123, P=0.0003.

A Chi-square test for independence (with Yates Continuity Correction) indicated significant association between higher values of anti-TPO (values more than 34 IU/ml) and alopecia areata, χ2 (1, n=140)=19.468, P<0.0001.



**Table 1.** Demographic data of patients (Alopecia areata group) and volunteers (Control group)

**Table 2.** Clinical characteristics of alopecia areata patients


**Table 3.** The frequencies of positive detectable thyroid autoantibody (anti-Tg and anti-TPO)

than in control group (Table 3).

areata, χ2 (1, n=140)= 13.123, P=0.0003.

areata, χ2 (1, n=140)=19.468, P<0.0001.

Type of alopecia areata n, (%)

Multiloculares 37 (53)

Unilocularis 13 (19)

Universalis 8 (11) Totalis 12 (17)

**Table 2.** Clinical characteristics of alopecia areata patients

(%)

ranging from 10.00 to 153.00 IU/mL, and anti-TPO antibody titers from 4.40 to 129.00 IU/mL. Anti-Tg antibody in 16 (23%) patients, anti-TPO antibody in 21 (30%) and both anti-Tg and anti-TPO antibodies in 13 (19%) were higher than the normal antibody titres. In the control group, one subject (1%) had positive anti-Tg and one volunteer (1%) had positive anti-TPO. The frequency of thyroid autoantibodies was significantly higher in alopecia areata patients

A Chi-square test for independence (with Yates Continuity Correction) indicated significant association between higher values of anti-Tg (values more than 115 IU/ml) and alopecia

A Chi-square test for independence (with Yates Continuity Correction) indicated significant association between higher values of anti-TPO (values more than 34 IU/ml) and alopecia

Age, mean years (SD) 40.39 (14.39) 40.71 (15.30) 0.896

**Table 1.** Demographic data of patients (Alopecia areata group) and volunteers (Control group)

Control group n

P

(%)

anti-Tg (threshold value115 IU/ml) anti-TPO (threshold value 34 IU/ml)

Group Negative n(%) Positive n(%) Negative n(%) Positive n(%) Alopecia areata 54 (77) 16 (23) 49 (70) 21(30) Control 69 (99) 1 (1) 69 (99) 1 (1) Total 123 (88) 17 (12) 118 (84) 22 (16)

Difference n (%) 15 (22) 20 (29) χ2, P χ2=13.123, P=0.0003 χ2=19.468, P<0.0001 **Table 3.** The frequencies of positive detectable thyroid autoantibody (anti-Tg and anti-TPO)

Alopecia areata group n

Men, n (%) 30 (43) 30 (43) Women, n (%) 40 (57) 40 (57) Age range, years 17-66 16-66

Mean age of onset (SD) (year) 38.14 (14.61)

Mean duration (SD) (month) 21.93 (30.69)

Age of onset range (year) 14-65

Duration Range (month) 1-150

**Scheme 1.** Differences of frequencies positive/negative values of anti-Tg (threshold value115 IU/ml) between groups

**Scheme 2.** Differences of frequencies positive/negative values of anti-TPO (threshold value 34 IU/ml) between groups


Thyroid Autoimmunity in Patients with Skin Disorders 305

(threshold value 34 IU/ml) Types of alopecia areata (P)

alopecia areata Negative n Positive n Total Multiloculares Totalis Universalis Unilocularis 13 0 13 0.092788 0.005217**\*** 0.000069**\*** Multiloculares 29 8 37 N/A 0.075803 0.000925**\*** Totalis 6 6 12 N/A N/A 0.157688 Universalis 1 7 8 N/A N/A N/A

**Table 5.** The frequencies of positive detectable thyroid autoantibody (anti-TPO) and differences

**Types of alopecia areata and frequencies positive/negative values of anti-TPO (threshold value 34 IU/ml)** 

**Scheme 4.** Types of alopecia areata and frequencies positive/negative values of anti-TPO (threshold

<sup>1</sup> <sup>0</sup>

Unilocularis Multiloculares Totalis Universalis

8

6

<sup>6</sup> <sup>7</sup>

Negative Positive

Alopecia areata is an ancient disease that was known to Egyptians even in the pre-Christian time [33]. Despite its long history, our knowledge is actually limited. Today, AA is hypothezed to be an autoimmune, organ specific T-cell mediated reaction directed against an unknown autoantigen of the hair follicle. T lymphocytes that have been shown to be oligoclonal and autoreactive are predominantly present in the peribulbous inflammatory infiltrate [34]. Although the skin is the primary location of the clinical phenotype, the determination of disease expression involves a complex interplay between different

anti-TPO

between types of alopecia areata

13

value 34 IU/ml)

0

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25

30

35

**2.4. Discusion** 

Total 49 21 70

29

Type of

**Table 4.** The frequencies of positive detectable thyroid autoantibody (anti-Tg) and differences between types of alopecia areata

A Fisher's exact indicated significant association between higher values of anti-Tg (values more than 115 IU/ml) and some types of alopecia areata, Universalis vs Unilocularis (P=0.047472) (Table 4.)

**Scheme 3.** Types of alopecia areata and frequencies positive/negative values of anti-Tg (threshold value115 IU/ml)

A Fisher's exact indicated significant association between higher values of anti-TPO (values more than 34 IU/ml) and some types of alopecia areata: Unilocularis vs Totalis (P=0.005217), Unilocularis vs Universalis (P=0.000069) and Multiloculares vs Universalis (P=0.000925) (Table 5).


**Table 5.** The frequencies of positive detectable thyroid autoantibody (anti-TPO) and differences between types of alopecia areata

**Scheme 4.** Types of alopecia areata and frequencies positive/negative values of anti-TPO (threshold value 34 IU/ml)
