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1. Acromegaly: clinical features at diagnosis
Lucio Vilar1 • Clarice Freitas Vilar2 • Ruy Lyra1 • Raissa Lyra2 •
Luciana A. Naves3
Ó Springer Science+Business Media New York 2016
Abstract
Background Acromegaly is a rare and underdiagnosed
disorder caused, in more than 95% of cases, by a growth
hormone (GH)-secreting pituitary adenoma. The GH hyper-
secretion leads to overproduction of insulin-like growth
factor 1 (IGF-1) which results in a multisystem disease
characterized by somatic overgrowth, multiple comorbidities,
physical disfigurement, and increased mortality.
Objective This article aims to review the clinical features
of acromegaly at diagnosis.
Discussion/Conclusion Acromegaly affects both males
and females equally and the average age at diagnosis ran-
ges from 40 to 50 years (up to 5% of cases the age 20).
Due to insidious onset and slow progression, acromegaly is
often diagnosed five to more than ten years after its onset.
The typical coarsening of facial features include furrowing
of fronthead, pronounced brow protrusion, enlargement of
the nose and the ears, thickening of the lips, skin wrinkles
and nasolabial folds, as well as mandibular prognathism that
leads to dental malocclusion and increased interdental
spacing. Excessive growth of hands and feet (predominantly
due to soft tissue swelling) is present in the vast majority of
acromegalic patients. Gigantism accounts for up to 5% of
cases and occurs when the excess of GH becomes manifest
in the young, before the epiphyseal fusion. The disease also
has rheumatologic, cardiovascular, respiratory, neoplastic,
neurological, and metabolic manifestations which negatively
impact its prognosis and patients quality of life. Less than
15% of acromegalic patients actively seek medical attention
for change in appearance or enlargement of the extremities.
The presentation of acromegaly is more often related to its
systemic comorbidities or to local tumor effects.
Keywords Acromegaly Gigantism Somatotropinoma
Clinical features
Introduction
Acromegaly is a rare and underdiagnosed disease that
results from the overproduction of growth hormone (GH)
and insulin-like growth factor 1 (IGF-1) [1]. More than
95% of patients with acromegaly harbor a GH-secreting
pituitary adenoma (somatotropinoma) arising from soma-
totroph cells, leading to GH and IGF-1 hypersecretion [2].
In less than 5% of cases, excess growth hormone releasing
hormone (GHRH) secretion from a hypothalamic tumor or
a neuroendocrine tumor (usually from lung or pancreas
origin) may lead to somatotroph hyperplasia and acrome-
galy [3]. Acromegaly due to peripheral GH-secretion
tumors rare exceedingly rare, with no more than two cases
reported in the literature so far [4, 5].
Over 90–95% of GH-secreting pituitary adenomas are
sporadic and occur as an isolated disorder [1]. However,
acromegaly can also occur in a familial setting, either
associated with other endocrine abnormalities (in multiple
endocrine neoplasia syndromes type 1 and type 4, and
Carney complex) or as an isolated disorder [6, 7]. This last
condition is called familial isolated pituitary adenoma
(FIPA); 15–20% of these cases harbor germline mutations
Lucio Vilar
lvilarf@gmail.com
1
Division of Endocrinology, Hospital das Clı́nicas, Federal
University of Pernambuco, Rua Heitor Maia Filho, 100/502,
Madalena, Recife CEP 50.720-525, Brazil
2
Endocrine Research Center of Pernambuco, Recife, Brazil
3
Division of Endocrinology, Brasilia University Hospital,
Brasilia, Brazil
123
Pituitary
DOI 10.1007/s11102-016-0772-8

2. of the AIP gene (encoding the aryl-hydrocarbon receptor
interacting protein), but the responsible gene mutation is
still unknown in most cases [6, 7]. X-linked acrogigantism
(XLAG) is a newly described syndrome of pituitary
gigantism, caused by microduplications on chromosome
Xq26.3, encompassing the gene GPR101, which is highly
upregulated in pituitary tumors [8]. Somatic mosaicism
was described in some cases [11]. Acromegaly also affects
around 20% of patients with the McCune-Albright syn-
drome (MAS) which includes the triad of poly/monostotic
fibrous dysplasia, café-au-lait spots, and hyperfunctioning
endocrinopathies [12]. MAS is caused by mosaic mutations
of GNAS that cause constitutive activity of the alpha-sub-
unit of the stimulatory G protein (Gsa) [13].
Clinical features and comorbidities
Acromegaly affects both males and females equally and the
average age at diagnosis ranges from 40 to 50 years. Patients
under the age 20 account for up to 5% of cases [14, 15]. The
clinical features of acromegaly are due to local effects of an
expanding pituitary mass, as well as to the direct and indi-
rect effects of excessive secretion of GH and IGF-1, which
can lead to systemic complications and impaired quality of
life (QoL) [1, 16]. These clinical manifestations range from
subtle signs of acral overgrowth, soft-tissue swelling,
arthralgias, jaw prognathism, mild hyperglycemia, men-
strual disturbances, erectile dysfunction and hyperhidrosis to
facial and skeletal disfigurement, florid osteoarthritis, severe
headache, sleep apnea, severe hypertension, diabetic
ketoacidosis, and respiratory and cardiac failure (Tables 1,
2) [1, 16] The appearance of a somatotropinoma in young
patients before the closure of epiphyseal bone results in
accelerated growth and gigantism [1, 6, 7, 16, 17].
Although typical facial and acral changes in acromegaly
are quite characteristicand fairly straightforward, they usually
develop insidiously and are not readily noticed bythe patients,
their families nor their doctors [1, 16, 18, 19]. Therefore, there
isusually a delay between the time offirstsymptoms are noted
and when the diagnosis is made [14, 18, 19]. Reviewing the
available literature, Holdaway and Rajasoorya estimated that
thisdelayrangedfrom6.6to10.2 years,withanaverage delay
of 8 years [14]. In the study by Reid et al. [19], involving 324
patients, the diagnostic delay (*6 years) and the features at
diagnosis did not change from 1981 to 2006.
Local tumor effects
Headache
Headache is found in about 60% of patients and may be
severe and disproportionate to the size of the tumor. It
likely reflects tumor growth with stretching of the dura
mater, cavernous sinus invasion with trigeminal nerve
irritation, or GH hypersecretion itself [2, 20, 21].
Visual disorders
The growth of the adenoma upwards can compress the
optic chiasm, leading to visual field disturbances, which
begin in the mid-periphery of the superior temporal sectors,
then progress to bitemporal hemianopsia. Persistent com-
pression can result in blindness [20].
Other manifestations
Further neurological features may appear in case of huge
pituitary adenomas, such as hydrocephaly, unilateral
exophthalmos (due to orbital invasion) and seizures
[20, 22–25].
As *80% of GH-producing adenomas are macroade-
nomas, some degree of hypopituitarism is present in up to
three-quarters of the patients at diagnosis [7, 24]. Hyper-
prolactinemia is found in about one-third of cases of
acromegaly, as a consequence of pituitary stalk compres-
sion or prolactin co-secretion by the tumor [24, 26]. Pro-
lactin (PRL) levels are usually mild (100 ng/mL
[2100 mIU/L]) [26, 27] but very seldom they may be as
high as 5000 ng/dL (*105,000 mIU/L) or more in cases of
GH/PRL co-secreting adenomas [28, 29].
Systemic manifestations
Acral growth
Excessive growth of hands and feet is present in the
overwhelming majority of acromegalic patients in large
series [16]. Acral growth is predominantly due to soft tis-
sue swelling, which increases the width of the fingers,
hands (spade-like hands) and feet, leading do successive
changes in shoe, glove and ring size [1, 16, 24, 30].
Osteoarthritis and joint hyperlaxity can also contribute to
hands deformities [30].
Orofacial changes
The typical coarsening of facial features include pro-
nounced brow protrusion, furrowing of fronthead,
enlargement of the nose and the ears, thickening of the lips,
skin wrinkles and nasolabial folds, as well as mandibular
prognathism that leads to dental malocclusion and
increased interdental spacing (Fig. 1) [16, 18, 22, 24].
Macroglossia is a frequent finding and contributes to the
appearance of obstructive sleep apnea (Fig. 2) [22, 30].
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3. Sonorous voice deepening often occurs due to laryngeal
hypertrophy and enlarged paranasal sinuses [22].
Skin and appendices changes
Profound skin changes are characteristic of acromegaly and
contribute to facial and acral deformities. Skin puffiness is
most prominent in the face, hands and feet. Facial skin
wrinkles, nasolabial folds and heel pads thicken. Thickened
skin, especially on palms of hands or soles of feet, is often
found in patients with longstanding acromegaly. All these
changes are attributed to glycosaminoglycan deposition,
increased connective tissue collagen production, and
edema [22, 24, 30, 31].
Enlargement of sebaceous glands leads to hyperhidrosis
and malodorous oily skin that are common early signs,
occurring in up to 70% of patients [22, 30, 31]. Skin tags are
common and may be markers for the adenomatous colonic
polyps [22, 30–32]. Acanthosis nigricans, due to insulin
resistance, and psoriasis are also encountered [31]. As
alteration in skin capillaries produce increased vasocon-
striction, Raynaud’s phenomenon is reported in up to one-
third of patients [20, 31]. Hirsutism and hypertrichosis may
also be found, and body hair may become coarsened [31–33].
Table 1 Clinical features of acromegaly
Local tumor effects Headache; visual impairment; seazures; hyperprolactinemia; hypopituitarism; diabetes insipidus (very rarely)
Systemic effects of GH/IGF-1 excess
Face and oral cavity Prominence of the brow; furrowing of the fronthead; enlargement of the nose and the ears; thickening of the lips, facial
skin wrinkles, and nasolabial fold; prognathism, dental malocclusion and increased interdental spacing (due to
mandibular overgrowth); macroglossia
Skin and appendices Acral enlargment (excessive growth of hands and feet); increased skin thickness; thickening of the heel pads;
hyperhidrosis; oily texture; skin tags; acanthosis nigricans; hirsutism; hypertrichosis; Raynaud́s phenomenon
Cardiovascular system Hypertension; left ventricular hypertrophy; cardiomiopathy; congestive heart failure; arrhythmias
Musculoskeletal
system
Gigantism; increased articular cartilage thickness; arthralgias and arthritis; carpal tunnel syndrome; acroparesthesia;
proximal myopathy
Visceromegalies Increased volume of the tongue (macroglossia), thyroid (goiter), liver, spleen, salivary glands, kidneys, and prostate
Gastrintestinal system Colonic polyps; dolichomegacolon; slow colonic transit
Neuropsychiatric
features
Impaired self-esteem; body image distortion; disruption in interpersonal relations; social withdrawal; impaired
cognition; anxiety; depression
Respiratory
complications
Upper airway obstruction; excessive snoring; sleep apnea (obstructive and central); narcolepsy; dyspnea (due to
ventilatory dysfunction)
Metabolic
complications
Insulin resistance; impaired glucose tolerance; diabetes mellitus; dyslipidemia
Neoplastic
complications
Increased risk for some malignancies, particularly colon cancer and thyroid cancer
Neurological
complications
Intracranial aneurysms; herniation of cerebellar tonsils; pituitary apoplexy
Adapted from Melmed [1], Molich [16], Vilar et al. [24], and Abreu et al. [43]
Table 2 Prevalence of signs
and symptoms of acromegaly in
a series of 500 patients
30% 30–60% [60%
Depression Headache Acral growth
Reduce libido Erectyle dysfunction Deformity of facial features
Carpal tunnel syndrome Arthritis Soft tissue swelling
Daytime somnolence Asthenia/fatigue Increased sweating
Myopathy Peripheral neuropathy
Increased hair growth Parestesia
Dyspnea/breathlessness
Galactorrhea
Adapted from Ezzat et al. [21]
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4. Musculoskeletal features
Acromegalic arthropathy can affect up to 84% of the cases,
especially older patients or females, and any joint may be
involved [34, 35]. Most of patients exhibit joint swelling,
hypermobility, and cartilaginous thickening. Up to half
may experience joint symptoms severe enough to limit
their daily activities [22, 36]. Acromegaly may also be
associated with an increased risk of vertebral compression
fractures despite normal bone density, and fracture risk
may be accelerated by hypogonadism [2, 37, 38]. Periph-
eral neuropathies with sensory disturbances in hands and
feet are frequently present, with carpal tunnel syndrome
being found in 20–64% of patients due to neural enlarge-
ment and wrist tissue swelling [20, 39, 40]. Debilitating
osteoarthritis may result in bone remodeling, osteophyte
formation, subchondral cysts, narrowed joint spaces, and
periarticular ligament laxity [22, 36]. Musculoskeletal pain
is extremely prevalent and negatively impacts the quality
of life [41, 42].
Respiratory comorbidities
Upper airway obstruction (due to macroglossia, prog-
nathism, thick lips, and hypertrophy of the laryngeal
mucosa and cartilage) can result in snoring and sleep
apnea, as well as in difficult intubation at the time of sur-
gery [7, 39, 43]. Sleep apnea (manifested as snoring, dis-
turbed night sleep with somnolence during the day) affects
20 to 87% of patients [39, 44], more frequently in diabetic
or hypertensive cases [44]. Most cases have obstructive
sleep apnea (mediated by the GH-related soft tissue growth
around the upper airways), whereas a minority of cases
have either pure central apnea or mixed apnea [7, 39, 45].
Hypoventilation and hypoxemia may also occur because of
central respiratory depression and kyphoscoliosis [42, 45].
Metabolic complications
GH excess is associated with insulin resistance (in the liver
and in periphery), increased gluconeogenesis and lipolysis,
and decreased peripheral glucose uptake [7, 39, 46].
Acromegaly is therefore often associated with impaired
glucose tolerance (in up to 40–52% of cases), diabetes
mellitus (up to 28–46% of cases) and dyslipidemia (par-
ticularly hypertriglyceridemia, elevated lipoprotein-a and
an excess of small dense LDL particles) [7, 47–49].
Fig. 1 Increased interdental spacing and dental malocclusion due to
mandibular prognathism
Fig. 2 Typical coarse facial features and macroglossia in two acromegalic patients whose presenting chief complaints were loud snoring and
excessive daytime sleepiness due to obstructive sleep apnea
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5. Cardiovascular complications
Acromegaly is associated with a high prevalence of
hypertension [20, 39]. In a meta-analysis, the mean
prevalence of hypertension was 35% (ranging from 18 to
60%) in 18 series with 2562 patients [50]. Valvulopathies
(especially aortic or mitral regurgitation), arrhythmias, and
conduction disorders are also frequent [2]. Moreover, GH
and IGF-1 excess may induce a specific cardiomyopathy
characterized by concentric hypertrophy (predominantly
affecting the left ventricle), diastolic dysfunction and pro-
gressive systolic impairment eventually leading to heart
failure [7, 39, 51]. Left ventricular hypertrophy (LVH) had
a mean frequency of 60% among 200 acromegalic patients
when analyzed by echocardiography [39]. However, the
rate of LVH was recently shown to be significantly lower
with cardiac magnetic resonance imaging, the gold-stan-
dard method, as compared to echocardiography (5 vs. 31%)
[52]. If heart disease is present at diagnosis there is a
mortality rate of 100% within 15 years [39]. In one study,
the 1- and 5-year mortality rates for patients with heart
failure were 25 and 37.5%, respectively [53].
Other cardiovascular risk factors are also present in
acromegaly, such as increased levels of triglycerides,
lipoprotein-a, fibrinogen and plasminogen activator inhi-
bitor, as well as an excess of small dense LDL particles
[39, 48]. Interestingly, the prevalence of coronary artery
disease is not clearly increased in acromegalic patients
[2, 39]. However, aggressive management of all cardio-
vascular risk factors is indicated, in order to reduce the
cardiovascular morbidity and mortality [2].
Neuropsychological changes
As a consequence of the multiple comorbidities and the
somatic changes, acromegalic patients have severely
impaired QoL [41]. Moreover, a wide range of emotional
and psychological changes have been reported in these
subjects, including alterations in personality due to
impaired self-esteem, body image distortion, disruption in
interpersonal relations, and social withdrawal, as well as
impaired cognition, anxiety and depression [2, 54, 55].
Neurological disorders
Some studies have reported increased risk for some neu-
rological conditions in acromegalic patients, besides
headaches and visual impairment, such as intracranial
aneurysms [56], herniation of cerebellar tonsils [57],
hearing loss [58], and pituitary apoplexy [59, 60]. The
latter may result in spontaneous remission of acromegaly
due to complete destruction of the tumor [60].
Neoplastic complications
Presumably due to the stimulatory effect of the IGF-1 on
tumorigenesis, acromegaly has been associated with an
increased risk of certain tumors [7, 39]. The best-docu-
mented data are those regarding colorectal neoplasia. The
pooled odds ratio (OR) are increased for both benign
tumors (2.48 for adenomas and 3.557 for hyperplastic
polyps) and colon cancer (2.04–4.351) [7, 61, 62]. The
standardized mortality ratio (SMR) for colon cancer was
also shown to be higher in active acromegaly (2.47) as
compared to the general population [63].
The risk of thyroid nodular disease and thyroid cancer is
also increased in acromegaly with OR of 6.9 and 7.5
respectively [7, 64]. In multicenter studies, 54% of subjects
had thyroid nodules (approximately 25% with toxic nod-
ules), 18–20% with diffuse goiter, and 1.2–7.2% with
thyroid cancer (particularly, papillary carcinomas)
[2, 63–68]. Over the past few years, thyroid cancer has
been one of the more commonly detected cancers in
acromegaly [2, 66–69]. However, it is still controversial
whether this reflects a specific effect of the GH/IGF-1
excess or the increased worldwide availability and use of
precise diagnostic techniques [7, 69].
The mortality rate in acromegaly can be successfully
reduced, provided patients are treated using a multimodal
approach with careful management of comorbidities [70].
Cardiovascular complications have often been considered
the leading cause of death in acromegaly [1, 2, 14, 39, 48].
Nevertheless, in two recent studies, the most common
cause were malignancies [70, 71].
Gigantism
Gigantism is a rare condition that occurs in 5% of soma-
totropinomas. The clinical features appears when GH
hypersecretion occurs before the closure of epiphyseal
cartilages and results in excessive linear growth in children,
more than three standard deviations above the mean for age
and height or more than two standard deviations apart from
the height adjusted to the parents’ height [1, 17, 24, 72].
AIP gene mutations are found in 29–50% of gigantism
cases [6, 72, 73], causing a low-penetrance disease typi-
cally manifesting clinically in the second decade of life,
either sporadically or in the setting of FIPA. Soma-
totropinomas account for 30% of FIPA cases [74].
Recently, a new syndrome named X-linked acrogigan-
tism (XLAG) was described. This infant-onset gigantism
syndrome has a severe clinical phenotype, where increase
in growth velocity starts as early as 2–3 months of age
(median 12 months) [8–10]. Acral enlargement and facial
coarsening are also found. More than a third of patients
have increased appetite [8].
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6. Fig. 3 Radiological presentation of pituitary tumors with inherited non syndromic gigantism: a XLAg syndrome; b AIP mutation (AIP fs174X)
and c AIP mutation (AIP A195V)
Table 3 Clinical features of inherited non syndromic pediatric-onset gigantism
AIP mutations XLAG
Genetic background Mutations on chromosome 11q13 Microduplication Xq26.3, GPR101 gene; somatic mosaicism (in
some cases)
Frequency 29–50% of cases 5% of cases
Age of first
manifestation
20 years 12–36 months of life
Clinical presentation Familial isolated pituitary adenomas (FIPA) or
sporadic
Mostly sporadic
Hormonal Secretion GH and/or Prolactin Severe GH and prolactin hypersecretion
Pathological Features Invasive macroadenomas Somatoprolactin hyperplasia and/or invasive macroadenomas
Therapeutic response Resistance to somatostatin analogs Resistance to somatostatin analogs
Adapted from Naves et al. [9]; Naves et al. [24]; Naves et al. [75]; and Naves et al. [76]
Coronary artery disease
Galactorrhea
Sleep apnea
Visual field defects
Hypertension
ED and/or ↓ libido
Diabetes or IGT
Carpal tunnel syndrome
Arthritis
Headache
Menstrual disturbances
Hyperhydrosis
Acral growth and/or Coarse features
52–91
55–100
32–87
37–87
30–45
25–51
10–68
12–46
17–51
4–62
5–48
7–30
11–13
0 20 40 60 80 100
% with complication
Fig. 4 Prevalence of clinical features of acromegaly at diagnosis, averaged from reported series (IGT, impaired glucose tolerance; ED, erectile
dysfunction; ;, decreased). Adapted from Clemmons et al. [78]
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7. Somatotropinomas found in patients with AIP mutations
or XLAG are usually invasive macroadenomas and resis-
tant to somatostatin analogs therapy (Fig. 3) [9, 74–76].
The main clinical features associated to inherited gigantism
are shown in Table 3.
Presentation of acromegaly
About 40% of acromegalic patients cases are initially
diagnosed by an internist, and the remaining cases are
diagnosed when they are seen by ophthalmologists for
visual disturbances, by dental surgeons for bite disorders,
by gynecologists for menstrual dysfunction and infertility,
by rheumatologists for osteoarthritis, or by sleep-disorder
specialists for obstructive sleep apnea [1, 22].
Despite the acral and facial manifestations of acrome-
galy being so characteristic, they usually develop insidi-
ously and progress slowly [1, 20, 22]. Thus, in large series,
only 10 to 15% of acromegalic patients actively seek
medical attention for change in appearance or enlargement
of the extremities, underscoring the elusiveness of the
symptoms [16, 20, 21, 43]. More often the presentation of
acromegaly is related to its systemic complications or local
tumor effects (Fig. 4) [16, 21, 24, 77]. The disease may
Table 4 Presentation of
acromegaly among 310 patients
Presenting chief complaint Frequency (%)
Menstrual disturbances 13
Change in appearance or acral growth 11
Headaches 8
Paresthesias/carpal tunnel syndrome 6
Diabetes mellitus or impaired glucose tolerance 5
Heart disease 3
Visual impairment 3
Decreased libido or erectile dysfunction 3
Arthropathy 3
Thyroid disorder 2
Hypertension 1
Gigantism 1
Fatigue 0,3
Hyperhydrosis 0,3
Somnolence 0,3
Others 5
By chance (detected by unrelated physical or dental examination or radiograph) 40
Total 100
Adapted from Molich [16]
Fig. 5 Acromegaly in a 25-year old woman with subtle facial
changes and a 2.5 cm pituitary adenoma which compressed the optic
chiasm. The patient was initially misdiagnosed as having a
prolactinoma due to amenorrhea as the present key complaint and
PRL levels of 226 ng/mL (4760 mIU/L). High levels of serum IGF-1
subsequently confirmed the diagnosis of acromegaly
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123

8. also be detected incidentally while examining the patient
for an unrelated complaint or during imaging procedures
[2, 20, 78]. A review of 310 patients revealed that 40% had
their diagnosis established during unrelated physical or
dental examination or radiographs (Table 4) [16]. In our
cohort of 64 patients, the most prevalent presenting chief
complaints in females were menstrual disorders (21.2%)
(Fig. 5), change in appearance and/or acral growth
(15.2%), visual impairment (12.2%), headaches (12.2%),
diabetes mellitus (9.1%), and acroparesthesias/carpal tun-
nel syndrome (9.1%) symptoms [24]. In males, the main
presenting symptoms were erectile dysfunction and/or
decreased libido (19.4%), headaches (12.9%), visual
impairment (9.7%), diabetes mellitus (9.7%), change in
appearance and/or acral growth (9.7%), gigantism (9.7%),
and sleep apnea or excessive snoring (9.7%) (Table 5) [24].
Further presenting symptoms of acromegaly may be heart
failure [79], pituitary apoplexy [59], hyperhydrosis
[16, 18], diabetes mellitus [16, 24], arthropathy [16, 21] or
hypertension [16]. Rare or atypical clinical presentations
include coronary artery disease [78], seizures [21], diabetes
insipidus [23], bilateral vocal cord immobility [80], hir-
sutism [33], cutis verticis gyrata [81], and diabetic
ketoacidosis [82]. Because GH behaves as an agonist for
breast prolactin binding sites, galactorrhea may occur in
the presence of normal PRL levels [22].
It is worth commenting that typical features of acro-
megaly may be missing despite the presence of a large
somatotropinoma [83]. Therefore, measurement of serum
IGF-1 to rule out acromegaly has been recommended in
any patient harboring a pituitary adenoma, even in cases of
incidentally detected tumors [2, 26, 77, 84, 85].
Compliance with ethical standards
Conflict of interest For this review article, the authors have no
conflicts of interest and they do not receive any kind of funding. This
review article was mostly based on previous articles published in
indexed journals of the english literature on acromegaly and pituitary
tumors, including some where the authors were coworkers or the first
authors.
Human and animals rights This article does not contain results
from interventional studies with human participants or animals per-
formed by any of the authors.
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Table 5 Presentation of acromegaly in a cohort of 64 patients
Presenting chief complaint Frequency in men (n = 31) (%) Frequency in women (n = 33) (%)
Menstrual disturbances – 21.2
Decreased libido and/or erectile dysfunction 19.4 –
Visual impairment 9.7 12.2
Change in appearance or acral growth 9.7 15.2
Headaches 12.9 12.2
Diabetes mellitus 9.7 9.1
Cardiomyopathy/heart failure 6.4 6.0
Acroparesthesias/carpal tunnel syndrome 6.4 9.1
Sleep apnea or loud snoring 9.7 6.0
Arthropathy 0.0 6.0
Gigantism 9.7 0.0
Hyperhydrosis 0.0 3.0
By chance 6.4 0.0
Total 100.0 100.0
Adapted from Naves et al. [24]
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