Acta Oto-Laryngologica. 2015; Early Online, 1–4

ORIGINAL ARTICLE

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The relationship between benign paroxysmal positional vertigo and thyroid autoimmunity

KAMRAN SARI1, TEKIN YILDIRIM2, HASAN BOREKCI3, IBRAHIM AKIN1, REHA AYDIN1 & MAHMUT OZKIRIS1 1

Department of Otolaryngology & Head and Neck Surgery, 2Department of Internal Medicine and Department of General Surgery, Medical Faculty, Bozok University, Yozgat, Turkey

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Abstract Conclusion: Although there have been few studies concerning BPPV and thyroid autoimmunity and a positive relation was found between them, this study didn’t find any relation between BPPV and thyroid autoimmunity. IT is thought that further large-scale studies must be done to clarify the relation. Objectives: Benign paroxysmal positional vertigo (BPPV) consists of ~ 20% of vestibular disorders. Self-limited rotatory nystagmus with positional vertigo are the main findings of BPPV. Although canalolithiasis theory was confirmed by demonstrating freely floating debris in the endolymph of the posterior semicircular channel in following studies, currently, the etiology hasn’t be explained totally. This study investigated the relation of BPPV and thyroid autoimmunity evaluated via measurement of serum thyroid autoantibodies. Method: Fifty patients (37 female, 13 male) with BPPV (BPPV group), 52 patients (40 famale, 12 male) with non-BPPV vertigo (non-BPPV group) and 60 otherwise normal control (38 female, 22 male) samples were enrolled in the study. All samples of BPPV, non-BPPV groups and controls had undergone a cochleovestibular test following thorough ENT examination. After blood samples were drawn from each subject, thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPO-Ab) and antithyroglobulin antibody (TG-Ab) levels were measured accordingly. Results: In the study, eight patients of the BPPV group (16%) had a high thyroid antibody level. In the non-BPPV group, six patients (11.5%) had elevated thyroid antibodies. In the control group, 15 patients (25%) had elevated thyroid antibodies. TSH values of all subjects were detected to be within normal range. No statistical difference was found between the groups with respect to TG-Ab and TPO-Ab values (p-values = 0.729 and 0.812, respectively).

Keywords: Positional vertigo, autoimmun thyroidit, immun complex, anti-thyroid peroxidase antbody, anti-thyroglobulin antibody

Introduction Benign paroxysmal positional vertigo (BPPV) is the most commonly encountered cause of dizziness. It consists of ~ 20% of vestibular disorders [1]. BPPV co-exists in 90% of the cases with positional vertigo and nystagmus [2]. In most cases posterior semicircular canals were influenced unilaterally. Occasionally the pathology is in the lateral semicircular canals [3]. A superior semicircular canal is a less common form of BPPV because of its vertical orientation,

making it difficult for debris to resist gravitational forces [4]. There are some characteristic clinical findings related to BPPV. Self-limited rotatory nystagmus provoked with head movements is a characteristic finding of BPPV. However, patients sometimes can have unstable dizziness, postural instability, vomitting and lightheadedness [5]. Although Schucknecht [6] introduced the term of cupulolithiasis to explain BPPV in 1969, it was not enough to meet all aspects of the mechanism related to BPPV. Thus, Hall [7] introduced canalolithiasis in 1979. This theory was

Correspondence: Kamran Sari, MD, Assistant Professor, Bozok University, Medical Faculty, Department of Otolaryngology & Head and Neck Surgery, Adnan Menderes Strett, Number:44, Yozgat, Turkey. Tel: +903542127060. Fax: +903542123739. E-mail: [email protected]

(Received 31 December 2014; accepted 16 February 2015) ISSN 0001-6489 print/ISSN 1651-2251 online  2015 Informa Healthcare DOI: 10.3109/00016489.2015.1021932

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confirmed by demonstrating freely floating debris in the endolymph of the posterior semicircular channel in following studies [7]. Currently, the etiology hasn’t be explained totally. In etiology, head trauma is an important cause of BPPV. It has been demonstrated that multi-canal involvement is more common than single canal involvement in post-traumatic cases [8]. Also, Meniere disease is another cause of BPPV. Some authors have claimed that BPPV is triggered following movement of immune complexes in the inner ear, implying a possible autoimmune mechanism [9]. Tertiary or congenital syphilis acts as an autoimmune disorder and is usually associated with fluctuating vestibular symptoms and can cause BPPV [10]. In a study, it was found that 34% of the patients with BPPV had Hashimoto thyroiditis concurrently [11]. The aim of this study was to investigate the relationship of BPPV and thyroid autoimmunity evaluated via measurement of serum thyroid autoantibodies. Materials and methods The study included 50 patients with BPPV (BPPV group), 52 patients with non-BPPV vertigo (nonBPPV group) and 60 otherwise normal control group who applied to the ENT department between March 2014 and October 2014. BPPV was diagnosed in accordance with criteria set by The American Academy of Otolaryngology-Head and Neck Surgery [12]. The history of episodic vertigo due to head movements and development of characteristic rotatory or horizontal nystagmus following dynamic positional test (Dix-Hallpike test for posterior semicircular channel involvement and lateral head movement for lateral semicircular channel involvement) was accepted for the diagnosis of BPPV accordingly. In patients with non-BPPV group there was not a history of episodic vertigo due to head movements and vertiginous symptoms such as nause and vomiting. At repetitive positional tests, if these characteristic findings of nytagmus were fixed we must evaluate these cases as non-BPPV. These are minimal suppression with visual fixation, no latency and fatigue. Patients who can meet these criteria were classified as non-BPPV vertigo. Age- and sexmatched otherwise normal subjects were included in the control group. All subjects of BPPV, nonBPPV groups and controls underwent a cochleovestibular test following thorough ENT examination. In the pure-tone audiometry test, pure-tone averages at 0.25, 0.50, 1, and 2 KHz were obtained (Maico MA-53). Additionally, impedance audiometry measurement was carried out for each subject (Maico MI-44). The results of the Dix-Hallpike test were

analyzed videonystagmographically (interacoustic visual eye) for nystagmus evaluation. Five-milliliter blood samples were drawn from each subject. Thyroid-stimulating hormone (TSH), antithyroid peroxidase antibody (TPO-Ab) and antithyroglobulin antibody (TG-Ab) levels were analyzed accordingly. The criteria of exclusion were as follows: diabetes mellitus, hearing loss due to noise, use of ototoxic drugs, or traumatic reasons, patients with retrocochlear lesion, acoustic nerve tumor, congenital hearing loss, previous cerebrovascular disease, and major psychiatric disorders. Informed consent of each subject and approval of the local ethical committee was provided before the enrollment. Statistical analyses All statistical analyses were performed using the SPSS software program. Continuous variables are expressed as mean ± SD and categorical variables are presented as frequencies (%). All continuous variables of groups didn’t show a normal distribution according to the Kolmogorov-Smirnov test. Categorical variables were compared using the chi-square test. Spearman simple correlation analyses were performed to determine the association between continuous parameters accordingly, while the Mann-Whitney U-test and Kruskal-Wallis tests were used to compare groups accordingly. A p-value of less than 0.05 was accepted as a statistically significant result. Results In the study, the BPPV group included 50 patients aged 47.1 ± 14.9 years (37 female, 13 male), the nonBPPV group included 52 patients aged 47.1 ± 13.8 years (40 female, 12 male), and the control group had 60 subjects with an average age of 44.6 ± 11.6 years (38 female, 22 male). Average TSH, TPO-Ab, and TG-Ab values of the groups are expressed in Table I. Eight patients of the BPPV group (16%) had a high thyroid antibody level. Two of them had high TPO-Ab, five of them had elevated TG-Ab and TPO-Ab at the same time, and one patient had high TG-Ab alone. In the non-BPPV group, six patients (11.5%) had elevated thyroid antibodies (five with high TPO-Ab and one with elevated TPO-Ab and TG-Ab together). In the control group, 15 patients (25%) had elevated thyroid antibodies (13 with high TPO-Ab and two with elevated TPO-Ab and TG-Ab together) (Table II). TSH values of all subjects were detected to be within normal range. All subjects had normal pure tone audiometry and impedance audiometry values. There was not any statistical difference between the

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Thyroid autoimmunity may cause positional vertigo Table I. Level of TSH, TPO-Ab, and TG-Ab among groups.

Age

TPO-Ab

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TG-Ab

TSH

The Control group

n

Mean

60

44.65

SD 11.625

Minimum 26

Maximum 65

BPPV group

50

47.12

14.946

18

65

Non-BPPV group

52

47.19

13.851

18

65

The Control group

60

64.0603

188.909

17.00

1000.00

BPPV group

50

37.4904

148.380

26.00

1000.00

Non-BPPV group

52

48.7590

147.719

12.01

813.21

The Control group

60

34.1245

137.689

11.00

1000.00

BPPV group

49

45.9331

139.774

20.00

646.90

Non-BPPV group

52

11.8400

45.206

04.00

318.25

The Control group

60

2.1834

1.145

38.61

4.80

BPPV group

50

2.5440

1.159

43.64

4.98

Non-BPPV group

52

2.2745

1.147

45.59

5.00

Table II. The presence of autoantibodies among groups was shown in frequencies. BPPV group (n = 50)

Non-BPPV group (n = 52)

The control group (n = 60)

Ab positivity (%)

8 (16%)

6 (11.5%)

15 (25%)

TPO-Ab positivity alone

2

5

13

TG-Ab positivity alone

1

0

0

Positivity for both TPO-Ab and TG-Ab

5

1

2

Ab, antibody; TG, thyroglobulinr; TPO, thyroid topoisomerase.

groups in respect to TG-Ab and TPO-Ab values (p-values = 0.729 and 0.812, respectively). Discussion In a community-based study, it was found that lifelong prevalence of BPPV was 2.4% and it consisted of 8% of moderate and severe vertigo or dizziness [13]. In a review concerning 10 series of case reports, 3342 patients were evaluated and it was found that 90% of BPPV cases had posterior channel involvement and 8% of BPPV cases had lateral channel involvement. Although they are rare, anterior or multiple channel involvement can also be detected [14]. There are several different explanations for pathophysiology of BPPV. According to cupulolithiasis theory, otolytic debris is attached to the cupula. Due to accumulation of otolytic debris, the cupula become heavier so head movements lead to deflection in the cupula, which results in nystagmus [15]. However, currently the most respected theory in BPPV

pathophysiology is canalolithiasis. Here, otolytic debris moves in the endolymph from the utriculus macula toward semicircular canals, and produce vertigo and nystagmus [16]. Debris floating in the endolymph also set the base for canalith repositioning procedure [17]. Still, the etiology hasn’t been enlightened clearly. Head trauma or ear infections have been accused, but mostly the cause is idiopathic. Sometimes BPPV can be found to be secondary to systemic illness in the absence of otologic disorders [9]. Some studies reported development of BPPV in the case of macroglobulinemia or following blood transfusion [18]. These findings suggest that BPPV can develop due to free movement of immunoglobulines within the endolymph. It was assumed that immune complexes can diffuse toward this inner ear fluid. The hemato-endolymphatic barrier is permeable, especially for big-size proteins. Structural abnormalities in the endolymphatic sac can also develop due to the effect of autoimmune vasculitis or autoimmune antibodies [9]. Papi et al. [11] found that prevalence of Hoshimoto thyroiditis, a variant of chronic thyroiditis, was 34% among patients with BPPV. They compared patients with BPPV to ageand sex-matched healthy subjects without vertigo or previous thyroid pathology. They found that TSH, TPO-Ab, and TG-Ab were higher than the control group. Frequency of hypothyroidism was 21% among patients with BPPV, while it was 2% in the control group. It was found that the correlation between anti-thyroid antibodies and BPPV (Odds ratio = 25.6) was stronger than the corelation between hypthyroidism and BPPV (Odds ratio = 12.9). The study found a relationship between thyroid disorders and BPPV, but couldn’t clarify clearly whether this relation derived from low thyroid functions or thyroid

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autoimmunity. Because of this unclear relation, the same authors carried out another study to search the relationship between BPPV and hypothyroidism patients (HT) in euthyroid state. They compared 200 euthyroid HT to otherwise healthy subjects. Prevalence of BPPV among euthyroid HT patients was 18%, while it was 2% among healthy subjects [19]. According to the results they concluded that the relation between BPPV and thyroid autoimmunity was independent from thyroid hormone levels, and they assumed that it had etiopathologically two reasons as follows: first, mechanical movements of thyroid autoantibodies in the fluid of the inner ear; or, second, development of autoimmune microangiitis in the labyrinth. In our study, all the subjects had TSH levels within normal range and none of the subjects had a diagnosis of hypothyroidism. The groups didn’t reveal any statistical difference in respect to thyroid autoantibodies. Madugno et al. [9] examined the autoantibody level of 70 BPPV patients; 27.1% of the patients had a high level of thyroid antibody without the presence of any other risk factor, and they suggested that immune complexes diffused into the inner ear had the potential to change endolymph composition, and they concluded that this increased mechanical stimulation of receptors provoking positional vertigo. In our study, both BPPV and non-BPPV groups were mostly composed of female subjects. The studies indicate that BPPV was found among female subjects more than male subjects, suggesting involvement of hormonal factors [20]. There have been few studies concerning BPPV and thyroid autoimmunity and a positive relation was found between them. In our study, we found that thyroid autoantibody levels of the subjects with BPPV didn’t differ significantly from the others. Thus, we didn’t find any relationship between BPPV and thyroid autoimmunity. We suggest that further large-scale studies are needed to clarify the relation. Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. References [1] Mizukoshi K, Watanabe Y, Shojaku H, Okubo J, Watanabe I. Epidemiological studies on benign paroxysmal positional vertigo in Japan. Acta Otolaryngol Suppl 1988; 447:67–72.

[2] Bertholon P, Tringali S, Faye MB, Antoine JC, Martin C. Prospective study of positional nystagmus in 100 consecutive patients. Ann Otol Rhinol Laryngol 2006;115:587–94. [3] Varela AS, Izquierdo MS. Perez SS. Benign paroxysmal positional vertigo simultaneously affecting several canals: a 46-patient series. Eur Arch Otorhinolaryngol 2013;270: 817–22. [4] Naples JG, Eisen MD. Surgical management for benign paroxysmal positional vertigo of the superior semicircular canal. Laryngoscope 2015;Epub ahead of print. [5] Giacomini PG, Alessandrini M, Magrini A. Long-term postural abnormalities in benign paroxysmal positional vertigo. ORL J Otorhinolaryngol Relat Spec 2002;64:237–41. [6] Lee SH, Kim JS. Benign paroxysmal positional vertigo. J Clin Neurol 2010;6:51–63. [7] Parnes LS, McClure JA. Free-floating endolymph particles: a new operative finding during posterior semicircular canal occlusion. Laryngoscope 1992;102:988–92. [8] Balatsouras DG. Benign paroxysmal positional vertigo with multiple canal involvement. Am J Otolaryngol 2012;33: 250–8. [9] Modugno G, Pirodda A, Ferri G, Montana T, Rasciti L, Ceroni AR. A relationship between autoimmune thyroiditis and benign paroxysmal positional vertigo? Med Hypotheses 2000;54:614–15. [10] Konrad RH, Bawer CA. Peripheral vestibular disorders. In Bailey BJ, editor. Head & neck surgery - Otolaryngology. Philadelphia, PA: Lippincott Williams & Wilkins. 2001. p 1975. [11] Papi G, Corsello SM, Milite MT, Zanni M, Ciardullo AV, Donato CD, et al. Association between benign paroxysmal positional vertigo and autoimmune chronic thyroiditis. Clin Endocrinol(Oxf) 2009;70:169–70. [12] Bhattacharyya N, Baugh RF, Orvidas L, Barrs D, Bronston LJ, Cass S, et al. Clinical practice guideline: benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg 2008;139:47–81. [13] Von Brevern M, Radtke A, Lezius F, Feldmann M, Ziese T, Lempert T, et al. Epidemiology of benign paroxysmal positional vertigo: a population based study. J Neurol Neurosurg Psychiatry 2007;78:710–15. [14] Cakir BO, Ercan I, Cakir ZA, Civelek S, Sayin I, Turgut S. What is the true incidence of horizontal semicircular canal benign paroxysmal positional vertigo? Otolaryngol Head Neck Surg 2006;134:451–4. [15] Schuknecht HF. Cupulolithiasis. Arch Otolaryngol 1969;90: 765–78. [16] Hall SF, Ruby RR, McClure JA. The mechanics of benign paroxysmal vertigo. J Otolaryngol 1979;8:151–8. [17] Epley JM. The canalith repositioning procedure: for treatment of benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg 1992;107:399–404. [18] Gyo K. Benign paroxysmal positional vertigo as a complication of postoperative bedrest. Laryngoscope 1988; 98:332–3. [19] Papi G, Guidetti G, Corsello SM, Di Donato C, Pontecorvi A. The association between benign paroxysmal positional vertigo and autoimmune chronic thyroiditis is not related to thyroid status. Thyroid 2010;20:237–8. [20] Vibert D, Kompis M, Hausler R. Benign paroxysmal positional vertigo in older women may be related to osteoporosis and osteopenia. Ann Otol Rhinol Laryngol 2003;112:885–9.

The relationship between benign paroxysmal positional vertigo and thyroid autoimmunity.

Although there have been few studies concerning BPPV and thyroid autoimmunity and a positive relation was found between them, this study didn't find a...
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