Keywords
deafness - acromegaly - hearing loss
Introduction
Acromegaly is a chronic disease caused by growth hormone (GH) excess due to a GH-secreting
pituitary adenoma in most cases.[1] It is associated with an increase in mortality and morbidity, especially due to
cardiovascular complications.[2] Among other consequences, it is characterized by the overgrowth of bone, including
the skull and soft tissues.
Although usually presenting an indolent, slow evolution, diagnosed 5 years after the
first signs of acromegaly, cardiovascular and metabolic comorbidities are accompanied
with an increased mortality in untreated patients. Without an appropriate therapy,
the life of patients with acromegaly can be shortened by ten years. Before the current
therapies became available, the standard mortality rate for these patients was reported
to be of 2–3 years. However, in some studies there are meta-analyses reporting mortality rates similar
to those of the general population in patients with normal GH after successful therapy,
and even normal insulin-like growth factor 1 (IGF-1). Using sensitive assays, the
cut-off level for “safe” GH is still a matter of debate, but a recent consensus suggested
it could be of 1 ng/mL.[3]
[4]
Pituitary adenomas are common benign monoclonal neoplasms accounting for ∼ 15% of
intracranial neoplasms. Some pituitary adenomas (mainly microadenomas that have a
diameter of less than 1 cm) are exceedingly common, and are incidentally diagnosed
on magnetic resonance imaging (MRI) performed for an unrelated reason (headache, vertigo,
head trauma). Most microadenomas remain clinically occult and stable in size, without
an increase in tumor cells, and without local mass effects. However, some pituitary
adenomas grow slowly, enlarged by expansion, and become demarcated on the normal pituitary
gland (macroadenomas have a diameter greater than 1 cm). They may be clinically silent
or secrete anterior pituitary hormones in excess, such as prolactin, GH, or adrenocorticotropic
hormone (ACTH), causing diseases like prolactinoma, acromegaly, Cushing's disease,
or rarely, diseases involving the thyroid-stimulating hormone (TSH) or gonadotropins
(luteinizing hormone [LH], follicle-stimulating hormone [FSH]).[5]
There is reasonable data to presume the possible influence of chronic GH and IGF-1
hyperproduction on the anatomical structures involved in normal sound perception,
and on its conductive and/or sensorineural part.[3] Additionally, there is a possibility of inferior pituitary tumor invasion of the
epipharynx with impact on the Eustachian tubes. Although it received some attention
in the past, this problem has not been investigated frequently.
Deafness, in all of its forms, affects 1 in every 1,000 newborns in the United States,
and progressively afflicts larger numbers of individuals with advancing age. Some
studies have described that by the age of 60, 1 out of every 3 individuals in the
United States experiences communication difficulties as a consequence of hearing loss, and by 85 years of age, half of the population has some degree of hearing disability.
Significantly, most peripheral auditory diseases involve some form of cochlear abnormality
that disrupts sensory transduction. The variety of conditions that produce such disabilities
include genetic abnormalities, trauma (acoustic and mechanical), ototoxic agents,
bacterial and viral infections, and disturbances in other organ systems that influence
cochlear physiology indirectly.[4]
[5]
Acromegaly-related soft tissue expansion and bone hypertrophy are thought to cause
ear problems; however, such an association has yet to be confirmed. Graham and Brackmann
observed hypertrophy of the mastoid cortical bone and posterior bony wall in three
patients with acromegaly during middle ear surgery.[6]
Little is known about hearing loss in patients with acromegaly. As it is a scarcely
studied subject, it is important to start investigating it. The best way to do it
would be to go over everything on the subject, in order to get ideas about it.
Due to the impact of deafness in society, and to the supposed pathophysiological relationship
that can exist between acromegaly and hearing loss, we performed a review of the literature
on this subject.
Review of Literature
The search strategy employed in this literature review was guided by the combination
of two descriptors indexed in the Medical Subject Headings (MeSH): acromegaly and hearing loss. Therefore, we performed a systematic review using the same descriptors in the PubMed
library, and analyzed all articles published. The last manual search conducted in
electronic databases occurred in July 2016.
The entire search process, the selection of articles, and data extraction were conducted
in pairs. After the search, the articles were selected based on their titles and abstracts.
Subsequently, the texts of all selected articles were obtained in full.
A systematic literature search was performed using MEDLINE database, including hand-searching
reference lists from original articles. We identified five studies.
Each study was reviewed by two separate authors (L.S.T and I.B.O), who independently screened abstracts and titles using the following inclusion criteria: 1) the articles
had to be written in English; and 2) they had to be studies on acromegaly and hearing
loss. The exclusion criteria were: 1) articles not written in English; and 2) studies
that did not correlate hearing loss with acromegaly.
The relevant data for each article found are listed in [Table 1]. The evaluated items included author and origin, number of patients (N), journal,
study design, and subject. [Table 2] shows the type of hearing loss (conductive, sensorineural or mixed) found in the
articles, and the percentage of each one. A complete analysis of the articles was
performed, and encountered computed tomography (CT) findings in only two of them,
as shown in [Table 3].
Table 1
Characterization of the Studies
|
Author and origin
|
N
|
Journal
|
Study design
|
Subject
|
|
Doig and Gatehouse
[7]
USA
|
56
|
The Journal of Laryngology & Otology, v. 98, 1984
|
Transversal
|
Comparison of the audiometry and clinic examinations of an acromegaly group and a
control one
|
|
Carvalho et al
[8]
Brazil
|
34
|
Brazilian Journal of Otorhinolaryngology, v. 78, 2012
|
Cross-sectional
|
A metabolic evaluation, tonal audiometry and brainstem auditory evoked potential study
in acromegalic patients.
|
|
Aydin et al
[6]
Turkey
|
44
|
Clinical Endocrinology, v. 76, 2012
|
Transversal
|
Pure tone audiometry, speech audiometry, tympanometry, otoacoustic emissions testing,
computed tomography of the temporal bone and magnetic resonance imaging of the ear
performed in acromegalic and healthy patients.
|
|
Graham and Brackmann
[9]
USA
|
3
|
The Journal of Laryngology & Otology, v. 92, 1978
|
Series of cases
|
Review of the cases of three patients with acromegaly
|
|
Babic et al
[10]
Serbia
|
30
|
Otology & Neurotology, v. 27, 2006
|
Prospective
|
A prospective study in a tertiary referral center, because of rare conflicting results
reported concerning a possible higher frequency of hearing loss in acromegalic patients.
|
Table 2
Hearing loss characterization in acromegalic patients
|
Author
|
Type of Hearing Loss
|
Percentage of Hearing Loss
|
|
Doig and Gatehouse
[7]
|
Conductive hearing loss
|
There is no significant
difference between the air-bone gaps in the acromegalic patients and those of the
controls
|
|
Carvalho et al
[8]
|
Sensorineural hearing loss: 8 bilateral and 4 unilateral.
|
38.9%
|
|
Aydin et al
[6]
|
Conductive, sensorineural and mixed hearing losses in at least one ear
|
9%; 30%, 18%
|
|
Graham and Brackmann
[9]
|
Case 1: findings typical of Meniere's disease
Case 2: cholesteatoma with a 40 dB conductive hearing loss
Case 3: recurrent episodes of purulent drainage
|
33%, 33%, 33%
|
|
Babic et al
[10]
|
Conductive hearing loss; middle ear ventilation problem
|
23%
|
Table 3
Computed Tomography Findings
|
Author
|
Computed tomography findings
|
|
Doig and Gatehouse
[7]
|
No CT results
|
|
Carvalho et al
[8]
|
No CT results
|
|
Aydin et al
[6]
|
Auditory imaging showed that 50% of the patients had temporomandibular joint degeneration.
The most common abnormality in the patients with acromegaly was mastoid sclerosis.
|
|
Graham and Brackmann
[9]
|
In all three patients, considerable difficulty was encountered in clearly demonstrating
the radiographic features of the temporal bone due to marked bone hypertrophy. However,
in all patients, the internal auditory canal, the cochlea and the vestibule appeared
normal.
|
|
Babic et al
[10]
|
No CT results
|
Discussion
Doig and Gatehouse (1978)
[7] evaluated 56 patients with acromegaly through audiometry and clinical examinations.
Those patients were compared with a healthy control group. In this study, there were
no significant differences between the case and control groups in terms of the audiometric
evaluation.
Carvalho et al (2012)
[8] conducted the first study in acromegalic patients in which the evaluation was performed
with auditory brainstem response besides audiometry. This exam is more objective,
and, therefore, allows for a more reliable analysis. In this study, only sensorineural
hearing loss (SNHL) was found (35.3%), and it was most prevalent in higher frequencies
and bilaterally. The researchers noticed that lower levels of GH and IGF-1 were found
in higher prevalence in patients with hearing loss, but there was no significant association
between these variables, or between hearing loss and the clinical parameters.
The present study may have been the first to make the comparison model of the brainstem
auditory evoked potential among acromegalic patients with and without SNHL.
Aydin et al (2012)
[6] conducted a study to profile the audiological and structural function in patients
with acromegaly. The evaluated group was composed of 44 patients with acromegaly and
36 healthy patients. All of the patients underwent a CT of the mastoids, an MRI of
the inner ear, tonal and vocal audiometries and impedancemetry. A clinical research focused on auditory symptoms was also conducted. The patients
with acromegaly were divided into 3 groups: those who had controlled the disease,
those who had partially controlled it, and those with uncontrolled diseases. From
the viewpoint of the structure, the significant finding was the presence of degeneration
of the temporomandibular joint. In this study, three types of hearing loss were found:
conductive, sensorineural and mixed. The elevated hearing thresholds in the patients
with acromegaly were not correlated with disease activity in this study, suggesting
that acromegaly – whether or not controlled – caused hearing loss.
This study shows that acromegaly is commonly associated with heterogeneous ear problems.[6]
Graham and Brackmann (1978)
[9] reviewed 3 patients with acromegaly and clinical characteristics. In all patients,
the gross clinical features of acromegaly were present, and considerable difficulty
was encountered in clearly demonstrating the radiographic features of the temporal
bone due to marked bone hypertrophy. However, the internal auditory canal, the cochlea
and the vestibule appeared normal. Prior to the surgical intervention, whether or
not the facial nerve would be in the normal position due to excessive bone overgrowth
was initially a considerable concern. However, in spite of a massive mastoid cortex
bone and generally heavy posterior bony canal wall with secondary lengthening of the
bony external auditory canal, the structures of the otic capsule, horizontal semicircular
canal, oval window, round window, and facial nerve were in perfectly normal relationships.
Surgery performed on two patients confirmed these findings. Despite the small number
of patients in the study, it was very important to evaluate the temporal bone alterations
that may occur in patients with acromegaly.
Babic et al (2006)
[10] performed a prospective study in a tertiary referral center because of rare conflicting
results reported concerning a possible higher frequency of hearing loss in acromegalic
patients. The goal was to determine whether there is a higher frequency of conductive
hearing loss in acromegalic patients. Thirty previously untreated patients with acromegaly
were compared with 20 age- and sex-matched healthy control subjects. The interventions
in all subjects included: otomicroscopy, tuning fork tests, audiometry, tympanometry,
cochleostapedial reflex, and otoacoustic emissions. In the acromegalic patients, endocrinological
assessments, MRIs, and, if necessary, epipharyngoscopies were performed. The only
statistically significant difference between the untreated acromegalic patients and
the healthy subjects was the presence of middle ear ventilation problem: it occurred
in 7/30 acromegalic patients (23%), and in none of the 20 healthy controls (0%), p = 0.033. The acromegalic patients with middle ear ventilation problem were significantly
older, with diseases of longer duration, and with lower mean growth hormone (GH) levels
in comparison with the acromegalic patients without this problem.
Opinions concerning the presence of conductive hearing loss in acromegaly in the literature
are contradictory. Therefore, this study has the goal of investigating possible conductive
hearing disturbances in acromegalic patients.
Issues as to the real cause-and-effect relationship between acromegaly and hearing
loss require longitudinal studies. However, because of the rarity of this disease,
we cannot expect to have studies with larger groups of individuals.
Final Comments
According to the literature discussed, we can infer that there are no consistent results,
and that they lead to different conclusions. This probably occurred due to the significant
prevalence of hearing loss in the world, which would require a larger amount of acromegaly
patients to be studied.
We conclude that a study with a greater number of patients with acromegaly is needed
to achieve more confident results.
