10.14639/0392-100X-N1775
Objective. To investigate the relationship between risk of Benign Paroxysmal Positional Vertigo (BPPV) recurrence and hypothyroidism treated with hormone replacement therapy (HRT). Methods. 797 patients with idiopathic BPPV were divided into two groups: 250 patients with recurrence of BPPV (R-BPPV) and 547 patients without recurrence (NR-BPPV). Regarding patients with thyroid disease on HRT, we collected serum test results of thyroidstimulating hormone (TSH), free triiodothyronine f-T3, free thyroxine f-T4, thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab). Results. Hypothyroidism in long-term HRT was found in 61/250 (24.4%) patients of the RBPPV group vs 79/547 (14.4%) of the NR-BPPV–group (p = 0.0006). Hashimoto thyroiditis (HT) was associated with recurrence (p &lt; 0.0001). A significant correlation was found between recurrence and level of serum TPO-Ab (p = 0.0117) and TG-Ab (p = 0.0025), but not with mean serum TSH, f-T3 and f-T4. Conclusions. We assume that patients with hypothyroidism in HRT have an increased risk of BPPV recurrence, which is particularly strong for patients with HT and positive thyroid antibodies, suggesting an association between autoimmunity and recurrent vertigo.
text/xml
1827-675X
1775
en
Pasqualina Maria Picciotti
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
vertigo comorbidities
Benign paroxysmal positional vertigo: is hypothyroidism a risk factor for recurrence?
Text.Serial.Journal
https://www.actaitalica.it/
42
Vestibology
2022-02-07
2021-07-25
2022-12-13
2022-12-13
465-470
1
Pasqualina Maria Picciotti
2022/02/07
10.14639/0392-100X-N1775
465
Fondazione Policlinico Universitario A. Gemelli IRCSS, Istituto di Otorinolaringoiatria, Roma - Università Cattolica del Sacro Cuore, Rome, Italy
1827-675X
vertigo comorbidities
en
470
Benign paroxysmal positional vertigo: is hypothyroidism a risk factor for recurrence?
https://www.actaitalica.it/article/download/1775/735
42
ACTA OTORHINOLARYNGOLOGICA ITALICA 2022;42:465-470; doi: 10.14639/0392-100X-N1775




Vestibology


Benign paroxysmal positional vertigo:
is hypothyroidism a risk factor for recurrence?
Vertigine parossistica posizionale benigna: l’ipotiroidismo è un fattore di rischio
per la ricorrenza?
Laura Tricarico, Tiziana Di Cesare, Jacopo Galli, Anna Rita Fetoni, Gaetano Paludetti, Pasqualina Maria Picciotti
Fondazione Policlinico Universitario A. Gemelli IRCSS, Istituto di Otorinolaringoiatria, Roma - Università Cattolica del Sacro Cuore,
Rome, Italy


SUMMARY
Objective. To investigate the relationship between risk of Benign Paroxysmal Positional
Vertigo (BPPV) recurrence and hypothyroidism treated with hormone replacement therapy
(HRT).
Methods. 797 patients with idiopathic BPPV were divided into two groups: 250 patients
with recurrence of BPPV (R-BPPV) and 547 patients without recurrence (NR-BPPV). Re-
garding patients with thyroid disease on HRT, we collected serum test results of thyroid-
stimulating hormone (TSH), free triiodothyronine f-T3, free thyroxine f-T4, thyroglobulin
antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab).
Results. Hypothyroidism in long-term HRT was found in 61/250 (24.4%) patients of the R-
BPPV group vs 79/547 (14.4%) of the NR-BPPV–group (p = 0.0006). Hashimoto thyroidi-
tis (HT) was associated with recurrence (p < 0.0001). A significant correlation was found
between recurrence and level of serum TPO-Ab (p = 0.0117) and TG-Ab (p = 0.0025), but
not with mean serum TSH, f-T3 and f-T4.
Conclusions. We assume that patients with hypothyroidism in HRT have an increased risk
of BPPV recurrence, which is particularly strong for patients with HT and positive thyroid
antibodies, suggesting an association between autoimmunity and recurrent vertigo.
                                                                                               Received: July 25, 2021
KEY WORDS: BPPV, recurrence vertigo, hypothyroidism, thyroid autoimmunity, vertigo
                                                                                               Accepted: September 27, 2021
comorbidities                                                                                  Published online: February 7, 2022

RIASSUNTO                                                                                      Correspondence
Obiettivo. Analisi dell’associazione tra la ricorrenza della Vertigine parossistica posizio-   Laura Tricarico
nale benigna (BPPV) e l’ipotiroidismo in corso di terapia ormonale sostitutiva (TOS).          Fondazione Policlinico Universitario A. Gemelli
Metodi. 797 pazienti affetti da BPPV idiopatica sono stati suddivisi in due gruppi: 250 con    IRCSS, Clinica di Otorinolaringoiatria; Università
vertigine ricorrente (R-BPPV) e 547 (NR-BPPV) non ricorrente. Nei pazienti ipotiroidei         Cattolica del Sacro Cuore
                                                                                               largo A. Gemelli 1, 00168 Rome, Italy
sono stati analizzati i valori ematici tiroidei: ormone tireotropo (TSH), frazioni libere di
                                                                                               E-mail: lauratricarico90bis@gmail.com
tetraiodotironina (f-T4) e triiodiotironina (f-T3), anticorpi anti tireoperossidasi (TPO-Ab)
ed anti tireoglobulina (TG-Ab).
Risultati. L’ipotiroidismo è emerso in 61/250 (24,4%) pazienti del gruppo R-BPPV vs              How to cite this article: Tricarico L, Di Cesare
79/547 (14,4%) del gruppo NR - BPPV (p = 0,0006). La ricorrenza è risultata statistica-          T, Galli J, et al. Benign paroxysmal positional
mente associata alla tiroidite di Hashimoto (HT) (p < 0,0001) ed alla positività anticorpale     vertigo: is hypothyroidism a risk factor for recur-
di Ab-TPO (p = 0,0117) e Ab-TG (p = 0,0025); le concentrazioni sieriche medie di TSH,            rence? Acta Otorhinolaryngol Ital 2022;42:465-
                                                                                                 470. https://doi.org/10.14639/0392-100X-N1775
f-T3 e f-T4 non sono risultate statisticamente significative.
Conclusioni. Nei pazienti affetti da ipotiroidismo in TOS è stato dimostrato un aumentato
                                                                                               © Società Italiana di Otorinolaringoiatria
rischio di ricorrenza di BPPV, particolarmente evidente nei pazienti con HT e dosaggio an-     e Chirurgia Cervico-Facciale
ticorpale tiroideo positivo, suggerendo l’associazione tra autoimmunità e ricorrenza della
vertigine.
                                                                                                              OPEN ACCESS
PAROLE CHIAVE: vertigine parossistica posizionale benigna (VPPB), vertigine ricorrente,        This is an open access article distributed in accordance with
ipotiroidismo, autoimmunità tiroidea, comorbidità nella VPPB                                   the CC-BY-NC-ND (Creative Commons Attribution-Non-
                                                                                               Commercial-NoDerivatives 4.0 International) license. The
                                                                                               article can be used by giving appropriate credit and mentio-
                                                                                               ning the license, but only for non-commercial purposes and
                                                                                               only in the original version. For further information: https://
                                                                                               creativecommons.org/licenses/by-nc-nd/4.0/deed.en




                                                                                                                                                       465
L. Tricarico et al.




Introduction                                                     associated diseases further increase the risk of recurrence
                                                                 of idiopathic BPPV. Among the associated pathologies, hy-
Hypothyroidism is one of the most common disorders of            pothyroidism and its autoimmune pathogenesis has gained
the endocrine system. It can refer to insufficient synthesis     increasing emphasis, but there are still few studies investi-
of thyroxine (T4) and triiodothyronine (T3), released into       gating the relationship between thyroid function or pathol-
the bloodstream in response to stimulation by pituitary thy-     ogy and BPPV pathogenesis or recurrence. Moreover, not
roid stimulating hormone (TSH), or to the dysfunction of         all studies on the topic have consistent results and large-
hormone-free biologically active forms (f-T3, f-T4) related      scale clinical trials to clarify the associations are needed 16.
to peripheral receptors 1. The prevalence of hypothyroidism      The aim of this study was to investigate the relationship
is approximately 1-3% in Western general population 2. In        between hypothyroidism, thyroid autoimmunity and BPPV
iodine sufficient areas of the world, the most frequent cause    recurrence by measurement of thyroid hormones and se-
of hypothyroidism is chronic autoimmune thyroiditis, also        rum thyroid autoantibodies.
known as Hashimoto’s thyroiditis (HT). Hypothyroidism
is also common following radioiodine treatment, hemithy-
roidectomy or total thyroidectomy, and neck radiation or         Materials and methods
surgery for cancer therapy. Furthermore, suboptimal iodine       Patients consecutively referred to the Vestibular Service, in
status can result in goitre, thyroid nodules and hypothyroid-    the day clinic, reporting vertigo and diagnosed with idi-
ism 1. Thyroid hormone replacement with levothyroxine is         opathic BPPV, were recruited for the study. We collected
the standard treatment for patients with hypothyroidism 3.       data on 797 patients aged from 12 to 87 years (mean 62.5 ±
The most typical clinical manifestations of hypothyroidism       14.3 years): 506 females (63.5%) and 291 males (36.5%).
include fatigue, lethargy, bradycardia, weight gain and cold     We retrospectively divided all patients in two groups: non-
intolerance, but it has also been recently associated with       recurrent BPPV (NR-BPPV), reporting first occurrence of
ENT disorders, such as hearing loss 4, tinnitus 5 and vestibu-   vertigo, and recurrent (R-BPPV) defined as the reappearance
lar disorders 6. Among the different vestibular pathologies,     of positional nystagmus after at least 2 weeks from its reso-
the association between hypothyroidism and benign parox-         lution 12. We excluded patients with previous head trauma,
ysmal positional vertigo (BPPV) has recently been inves-         whiplash injuries, or “persistent” BPPV, namely no remis-
tigated 7. BPPV is the most common peripheral vestibular         sion of symptoms or nystagmus after 2 weeks or 5 reposi-
disease accounting for approximately 17-42% of diagnoses         tioning manoeuvres. We excluded patients with hyperthy-
of dizziness in specialised clinics. It can be described as a    roidism and/or thyroid eye-related disease from the study.
sudden and abnormal sensation of motion and/or rotational        All patients were evaluated based on accurate clinical his-
vertigo, lasting less than one minute, accompanied by char-      tory and bedside-examination by an experienced examiner.
acteristic nystagmus. In this disorder, otoliths detach from     Posterior canal (PC)-BPPV was diagnosed in case of geo-
the utricle and enter in the semicircular canals to cause        tropic torsional nystagmus with specific latency, frequen-
vertigo 8. Symptoms are triggered by positional changes of       cy, duration and “reduction effect” (nystagmus reduction
the head and can range from mild dizziness to debilitating       after repetition of the manoeuvre) by the Dix-Hallpike or
episodes that may induce nausea or vomiting.                     Semont manoeuvre. On the other hand, horizontal canal
BPPV can be classified as primary or idiopathic (50-70%)         (HC)-BPPV diagnosis was based on the observation of
and secondary to trauma or viral infections, Meniere’s dis-      horizontal direction-changing positional nystagmus with
ease, migraine, otologic and non-otologic surgery, and pro-      the McClure-Pagnini manoeuvre. We treated patients with
longed bed rest 9. In idiopathic cases, no apparent cause of     specific repositioning manoeuvres and reassessed them af-
BPPV is identiﬁed in the patient’s history. Most episodes        ter 7 days, until the resolution of symptoms and nystagmus
of BPPV, even if untreated, recover spontaneously in 2 to        disappeared. In case of recurrence of symptoms, patients
6 weeks 10. However, clinical resolution is more often ob-       were re-evaluated in the day clinic and treated again.
tained by executing one of more manoeuvres in 50-70%             Previous histories of hypothyroidism on hormone replace-
of cases 11. Later recurrences of BPPV are common. Choi          ment therapy (HRT), such as autoimmune thyroiditis, goi-
et al. defined recurrent BPPV as the reappearance of posi-       tre and thyroidectomy, were investigated in both the R -BP-
tional nystagmus after at least 2 weeks from the execution       PV and NR-BPPV groups. We collected laboratory data on
of repositioning manoeuvres 12.                                  TSH (normal values: 0·35-2.80 μIU/mL), f-T3 (n.v. 2.3-4.2
Previous papers by our group 13,14 and other authors 15          pg/ml), f-T4 (n.v. 8.5-15.5 pg/ml), Thyroglobulin antibod-
showed that risk of recurrence increases for patients with       ies TG-Ab (n.v. < 4.1 IU/ml) and thyroid peroxidase anti-
a comorbidity compared to healthy patients, and multiple         bodies TPO-Ab (n.v. < 5.6 IU/ml).



466
                                                                                                                                       Recurrence vertigo and hypothyroidism




In accordance with AACE/ATA guidelines 17, we consid-                                        Results
ered mild or subclinical hypothyroidism patients with TSH
                                                                                             The group of non-recurrent (NR-BPPV) consisted of
concentrations above the reference range with f-T3 and
                                                                                             547/797 (68.6%) patients, whereas 250/797 (31.4%) had
f-T4 concentrations within normal range; overt or clinical
                                                                                             recurrent vertigo (R-BPPV) (Tab. I).
hypothyroidism high TSH with f-T4 and/or f-T3 concentra-
                                                                                             140/797 (17.6%) patients suffered from hypothyroidism
tions below the reference range. Autoimmunity pattern was
                                                                                             treated with HRT. In detail, 61/250 (24.4%) patients with
defined in the presence of serum antibody titres (TG-Ab
                                                                                             R-BPPV vs 79/547 (14.4%) with NR-BPPV reporting a his-
and/or TPO-Ab) above the reference range.
                                                                                             tory of thyroid dysfunction. Thyroid disease requiring HRT,
We analysed the clinical characteristics of BPPV (number                                     regardless of aetiology, can be considered a risk factor for
of recurrences, canal involved, number and type of ma-                                       recurrence vertigo (p = 0.0006, OR = 1.92) (Tab. I).
noeuvres, duration of therapy) to establish possible differ-                                 Laboratory evaluation of thyroid gland functional activ-
ences in patients with thyroid disease compared to other                                     ity showed that in the R-BPPV group, 22/250 (8.8%) pa-
idiopathic BPPV patients. Moreover, data were evaluated                                      tients had hypothyroidism: 10/22 with a subclinical pattern
statistically in order to establish the relationship between                                 and 12/22 with overt hypothyroidism. In the NR-BPPV
BPPV recurrence and thyroid disease in patients taking                                       group, 21/549 (3.8%) subjects showed hypothyroidism,
hormone replacement therapy, and the risk of recurrence in                                   of whom 6/21 had subclinical and 15/21 overt. Statistical
both subclinical/overt hypothyroidism related to different                                   analysis showed that hypothyroidism was more frequently
etiopathogeneses.                                                                            encountered in the group of recurrent BPPV (p = 0.0039,
Statistical analysis was performed using commercially                                        OR = 3.01), although a significant association was pre-
available software (Excel–Microsoft Corporation, Red-                                        sent only with subclinical hypothyroidism (p = 0.0067,
mond, Washington, USA). Continuously distributed data                                        OR = 3.76) and not with overt hypothyroidism (p > 0.05)
were summarised as the mean and median, and categorical                                      (Tab. I). Mean serum TSH, free-T3 and free-T4 concen-
variables with frequencies and percentages. The χ² test and                                  trations, on the other hand, were not significantly different
odds ratios (OR) with 95% confidence intervals were used                                     between the two groups (p > 0.05) (Tab. II).
for non-parametric variables; Student t-test was performed                                   Previous history of thyroid disorders such as goitre, hypo-
for parametric variables. A p value less than 0.05 was con-                                  thyroidism and autoimmune thyroiditis was investigated in
sidered as significant.                                                                      both the R-BPPV and NR-BPPV groups. In relation to the


Table I. Thyroid functional pattern.
                                                                                        R-BPPV                  NR-BPPV                   p value                     OR
                                                                                        n = 250                 n = 547
 History of thyroid dysfunction in HRT                                                61 (24.4%)               79 (14.4%)                 0.0006                     1.92
 Patients with altered thyroid hormones                                                22 (8.8%)               21 (3.8%)                  0.0039                     3.01
 Subclinical hypothyroidism                                                             10 (4%)                  6 (1%)                   0.0067                     3.76
 Overt hypothyroidism                                                                 12 (4.8%)                15 (2.7%)                  > 0.05
 Autoimmunity                                                                         49 (19.6%)               35 (6.4%)                 < 0.0001                    3.57
Comparison between recurrent benign paroxysmal positional vertigo (R -BPPV) and non-recurrent (NR-BPPV). Statistical significance was set at p < 0.05. HRT: hormone replacement
therapy. BPPV: benign paroxysmal positional vertigo.


Table II. Laboratory testing in thyroid disorders.
 Laboratory                                                                              R-BPPV                              NR-BPPV                             p value
                                                                                         n = 61                               n = 79
 TSH (n.v. 0·35-2.80 mIU/ml)                                                            1.8 ± 0.9                           1.4 ± 0.9                            > 0.05
 f-T3 (n.v. 2.3-4.2 pg/ml)                                                              2.9 ± 0.6                           2.5 ± 0.4                            > 0.05
 f-T4 (n.v. 8.5-15.5 pg/ml)                                                            10.8 ± 4.3                           8.8 ± 2.6                            > 0.05
 TPO-Ab (n.v. < 5.6 IU/ml)                                                            249.6 ± 393                         107.1 ± 213.8                          0.0117
 TG-Ab (n.v. < 4.1 IU/ml)                                                             132.1 ± 162                          22.3 ± 54.3                           0.0025
Hormonal dosages and thyroid autoantibodies: comparison between the two groups of BPPV patients suffering from thyroid diseases. Statistical significance was set at p < 0.05. TSH:
thyroid stimulating hormone; f-T3: triiodothyronine; f-T4: free thyroxine; TG-Ab: Thyroglobulin antibodies; TPO-Ab: thyroid peroxidase antibodies; BPPV: benign paroxysmal positional
vertigo; R-BPPV: recurrent BPPV; NR-BPPV: non-recurrent BPPV.




                                                                                                                                                                              467
L. Tricarico et al.




different causes of hypothyroidism, an autoimmune patho-                 resolution rate after one manoeuvre and multicanalar in-
genesis was detected in 84/140 (60%) patients: 49/250                    volvement (Tab. III).
(19.6%) R-BPPV vs 35/547 (6.4%) NR-BPPV (Tab. I).
The association between autoimmune chronic thyroiditis                   Discussion
pattern and BPPV recurrence was significant (p < 0.0001,
OR = 3.57). In particular, the presence of high antibody                 This retrospective analysis, performed on a large sample
serum titres increased the risk of recurrence by 3.57 times              of idiopathic BPPV patients, showed that 17.6% (140/797)
(Table I), and mean TPO-Ab and TG-Ab levels were signif-                 had hypothyroidism and were undergoing long-term treat-
icantly higher in the R-BPPV group (p = 0.0117) (Tab. II).               ment with HRT. Papi et al. described a similar prevalence
Multinodular goitre was the cause of HRT in 22.4%                        result in a multicentre case-control study with a percentage
(31/140) of cases: 6/250 (2.4%) with R-BPPV and 25/574                   of 21% in the BPPV group 18. In literature, the relation-
(4.3%) with NR-BPPV, with no significant difference (p>                  ship between thyroid disease and inner ear dysfunction has
0.05). In all, 17.8% (25/140) of patients were taking HRT                been attributed to abnormal thyroid functioning resulting in
following total thyroidectomy: 9/250 (3.6%) in the group                 changes of the endolymphatic ionic composition of the lab-
of R-BPPV and 16/574 (2.7%) in NR-BPPV, with no sig-                     yrinth, through altered expression of ion transporters such
nificant difference (p > 0.05) (Fig. 1).                                 as sodium iodide symporter (NIS) and pendrin 19, identified
Clinical characteristics of BPPV in patients with thyroid                both in the inner ear and thyroid. It has been suggested that
dysfunction are reported in Table III: the affected ear was              the volume or compositional changes of the endolymph
the right one in 76/140 (54.3%) patients and the left in                 of the vestibular labyrinth can induce BPPV 20. Therefore,
60/140 (42.8%); 4/140 patients (2.8%) had bilateral dis-                 reduced levels of thyroid hormones were also related to
ease. The canal involved was posterior in 127/140 (90.7%)                cardiovascular compromise, endothelial dysfunction and
and horizontal in 13/140 (9.3%): 69.2% had the apogeo-                   changes in blood pressure, thus reducing blood flow in the
                                                                         inner ear 21. The combination of the aforementioned patho-
tropic type and 30.8% the geotropic type. Multicanalar in-
                                                                         genic mechanisms can bring about the absorption or pre-
volvement occurred in 9/140 patients (6.4%) with a double
                                                                         cipitation of otoconial debris, inducing BPPV 7.
involvement of horizontal and posterior canals, in one or
                                                                         Similarly, we can hypothesise that altered thyroid func-
both inner ears. The analysis of clinical management of T-
                                                                         tion may be somewhat related to the recurrence of BPPV.
BPPV patients showed that this group required a mean of
                                                                         From our results, clinical history for hypothyroidism on
1.9 ± 1.5 manoeuvres. In 86/140 (61.5%) patients, resolu-
                                                                         treatment with HRT was significantly (p = 0.0006) more
tion was achieved with a single manoeuvre, while 54/140
                                                                         frequent in patients with R-BPPV (61/250; 24.4%) than in
(38%) needed more than one manoeuvre. Comparison be-
                                                                         NR-BPPV (79/547; 14.4%). This result underscores that a
tween thyroid dysfunctional BPPV and other idiopathic
                                                                         history of hypothyroidism, on its own, represents a risk fac-
BPPV patients showed that the posterior semicircular canal
                                                                         tor for development of the recurrence of BPPV, regardless
was more involved in the first group with a significant dif-
                                                                         of its aetiopathogenesis.
ference (p = 0.0087). There was no difference as to side
                                                                         Nevertheless, considering laboratory examination for thy-
involved and prognosis, or mean number of manoeuvres,
                                                                         roid function, no certain association was found between
                                                                         TSH, f-T4 and/or f-T3 levels and recurrence, since only
                                                                         subclinical hypothyroidism showed an increased risk of R-
                                                                         BPPV (OR = 3.76). Conversely, we did not find a signifi-
                                                                         cantly positive association between recurrence and overt
                                                                         hypothyroidism. Furthermore, the mean values of f-T3,
                                                                         f-T4 and TSH were not significantly different between the
                                                                         two groups (R-BPPV and NR-BPPV), showing that re-
                                                                         duced levels of hormones in the bloodstream alone does not
                                                                         influence the clinical course of benign positional vertigo. In
                                                                         line with these results, Chiarella et al. showed a significant
                                                                         correlation between vestibular disease and serum TPO-Ab
                                                                         but not with TSH 22, hypothesising that the association be-
                                                                         tween vestibular lesions and HT was not influenced by the
Figure 1. Percentage distribution of NR-BPPV and R-BPPV patients based   thyroid functional status.
on different causes of hypothyroidism. *: statistical significance.      Among different causes of hypothyroidism, chronic au-



468
                                                                                                                                     Recurrence vertigo and hypothyroidism




Table III. Clinical characteristics of study patients.
 BPPV tot.                                                                   Thyroid dysfunctional BPPV                           Other BPPV                       P value
 N = 797                                                                               N =140                                     N = 657
 Bilateral                                                                             4 (2.8%)                                   8 (1.2%)                          > 0.05
 Side affected                                                                    Right: 76 (54.3%)                          Right: 363 (55.2%)                     > 0.05
                                                                                  Left: 60 (42.8%)                           Left: 286 (43.5%)
 Posterior canal                                                                    127 (90.7%)                                 536 (81.6%)                         0.0087
 Horizontal canal                                                                     13 (9.3%)                                 121 (18.4%)                         0.0087
                                                                              Apogeotropic: 9/13(69.2%)                 Apogeotropic: 66/121 (54.5%)
                                                                               Geotropic: 4/13 (30.8%)                   Geotropic: 55/121 (45.4%)
 No. manoeuvres                                                                       1.9 ± 1.5                                  1.8 ± 1.3                          > 0.05
 Single episode resolution after 1 manoeuvre                                         86 (61.5%)                                  401 (61%)                          > 0.05
 Multicanalar Involvement                                                             9 (6.4%)                                   39 (5.9%)                          > 0.05
Comparison between patients with thyroid dysfunctional BPPV and patients with other type of idiopathic BPPV. Statistical significance was set at p < 0.05. BPPV: benign paroxysmal
positional vertigo.



toimmune thyroiditis or HT was reported as the most fre-                                   suggesting that autoimmune pathogenesis can overload the
quent thyroid disease in our sample, and its prevalence                                    clinical course of vertigo. In contrast with our results, Sari
was higher among R–BVVP (49/250; 19.6%) patients                                           et al. 16 found that thyroid autoantibody levels in subjects
compared to NR-BVVP (35/547; 6.4%) with a significant                                      with BPPV did not significantly differ from those in pa-
difference between the two groups. TPO-Ab and TG-Ab                                        tients with other vestibular diseases and in normal subjects,
are the most common HT autoantibodies identified and are                                   taking into account that further large-scale studies should
associated with complement-mediated cytotoxicity against                                   be done to clarify the relation.
thyrocytes 23.                                                                             Regarding the clinical characteristics of BPPV in patients
Further interesting data emerged concerning the antibody                                   with thyroid dysfunction, the posterior semicircular canal
dosage of the recruited patients with a diagnosis of HT.                                   was most frequently involved compared to other idiopathic
Both antibody titres were increased in patients with recur-                                patients (p = 0.0087). We can hypothesise that the posterior
rence compared to the NR-BVVP group: mean TPO-Ab                                           canal can be more easily damaged by a terminal vasculari-
titre was 249.6 vs 107 IU/ml, while mean TG-Ab titre was                                   sation ensured by the posterior vestibular artery, since there
132.1 IU/ml vs 22.3 IU/ml. This result confirms the evi-                                   is a longer distance from the main internal auditory artery
dence of a positive linkage between thyroid antibodies and                                 without collateral pathway, compared to the horizontal ca-
vestibular disease as previously demonstrated by Papi et                                   nal. In case of cardiovascular impairment due to hypothy-
al. 18: these authors showed that the association of BPPV                                  roidism, this mechanism could be exacerbated.
with elevated anti-thyroid antibodies (OR 25.6) was strong-
er than the association of BPPV with hypothyroidism (OR
                                                                                           Conclusions
12.9). Moreover, the same group of authors found BPPV in
18% of patients affected by HT and normal thyroid hormo-                                   The present study revealed an increased risk of recurrence
nal pattern, compared to 2% of healthy control subjects 24.                                of BPPV in patients with a history of hypothyroidism on
Modugno et al. 25 also hypothesised autoimmune altera-                                     HRT; the association is particularly strong for patients
tions in patients with BPPV: they discovered autoimmune                                    with positive thyroid antibodies dosage. TPO-Ab and TG-
alterations in 48.5%, with a major level of anti-thyroid an-                               Ab levels were significantly higher in the R-BPPV group,
tibodies in 27.1%, without other ‘risk factors’. The authors                               demonstrating an association between autoimmunity and
postulated a link between HT and vestibular disease, possi-                                recurrence. Therefore, in complete evaluation of recurrent
bly related to mechanical stimulation by immune complex-                                   BPPV, we suggest investigating thyroid dysfunction by
es and possible co-existence of microangioitis in the inner                                studying not only TSH, fT3 and fT4, but also the autoanti-
ear. Our experience on recurrent BPPV and thyroid autoim-                                  body thyroid pattern. Finally, a multidisciplinary approach
munity could be related to this hypothesis, with a tendency                                and collaboration between the ENT and endocrinologist
of vertigo not to heal quickly, compared with other types                                  specialists is desirable.
of idiopathic BPPV. On the other hand, patients with non-
autoimmune hypothyroidism, such as post-thyroidectomy                                      Conflict of interest statement
or multinodular goitre, had no increased risk of recurrence,                               The authors declare no conflict of interest.



                                                                                                                                                                            469
L. Tricarico et al.




Funding                                                                       10
                                                                                   Zucca G, Valli S, Valli P, et al. Why do benign paroxysmal positional
This research did not receive any specific grant from fund-                        vertigo episodes recover spontaneously? J Vestib Res 1998;8:325-329.
ing agencies in the public, commercial, or not-for-profit
                                                                              11
                                                                                   Brandt T, Huppert D, Hecht J, et al. Benign paroxysmal positioning ver-
                                                                                   tigo: a long-term follow-up (6-17 years) of 125 patients. Acta Otolaryn-
sectors.                                                                           gol 2006;126:160-163. https://doi.org/10.1080/00016480500280140
                                                                              12
                                                                                   Choi SJ, Lee JB, Lim HJ, et al. Clinical features of recurrent or per-
Authors’ contributions                                                             sistent benign paroxysmal positional vertigo. Otolaryngol Head Neck
All authors contributed to the study conception and design.                        Surg 2012;147:919-924. https://doi.org/10.1177/0194599812454642.
                                                                                   Corrigendum. Otolaryngol Head Neck Surg 2013;149:798. https://
Material preparation, data collection and analysis were per-
                                                                                   doi.org/10.1177/0194599813505840
formed by LT, TDC, MPP. LT wrote the first draft of the                       13
                                                                                   Picciotti PM, Lucidi D, De Corso E, et al. Comorbidities and recur-
manuscript and others authors commented on previous ver-                           rence of benign paroxysmal positional vertigo: personal experience.
sions of the manuscript.                                                           Int J Audiol 2016;55:279-284. https://doi.org/10.3109/14992027.201
                                                                                   6.1143981
Ethical consideration                                                         14
                                                                                   Picciotti PM, Di Cesare T, Tricarico L, et al. Is drug consumption
                                                                                   correlated with benign paroxysmal positional vertigo (BPPV) recur-
The study protocol was approved by the local Ethics Com-                           rence? Eur Arch Otorhinolaryngol 2020;277:1609-1616. https://doi.
mittee (44075/2018).                                                               org/10.1007/s00405-020-05855-6
The research was conducted ethically, with all study pro-                     15
                                                                                   Messina A, Casani AP, Manfrin M, et al. Italian survey on benign par-
cedures being performed in accordance with the require-                            oxysmal positional vertigo. Survey italiana sulla vertigine parossistica
ments of the World Medical Association’s Declaration of                            posizionale. Acta Otorhinolaryngol Ital 2017;37:328-335. https://doi.
                                                                                   org/10.14639/0392-100X-1121
Helsinki.                                                                     16
                                                                                   Sari K, Yildirim T, Borekci H, et al. The relationship between benign
Written informed consent was obtained from all partici-                            paroxysmal positional vertigo and thyroid autoimmunity. Acta Oto-
pants included in the study.                                                       laryngol 2015;135:754-757. https://doi.org/10.3109/00016489.2015.
                                                                                   1021932
                                                                                   Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for
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