Top PDF Foot pathology in patients with Paget’s disease of bone

Foot pathology in patients with Paget’s disease of bone

Foot pathology in patients with Paget’s disease of bone

rated using 100-mm visual analog scales, and higher scores indicate greater pain, disability, and limitation of activity, and thus poorer foot health. To obtain a domain score, the item scores are totaled and then divided by the maximum total possible for all of the domain items that the patient indicated were applica- ble. If a subject indicates that he or she did not per- form an activity such as wearing an orthotic device, then that item is marked as not applicable and is ex- cluded from the total possible. To eliminate the deci- mal point, the score for each domain is multiplied by 100. Therefore, domain scores range from 0 to 100, with higher scores indicating greater impairment. A total foot function score is derived by calculating the average of the three domain scores. Although this tool has been validated for patients with rheumatoid arthritis, the Foot Function Index was used here be- cause no viable alternative specific to Paget’s disease was available.
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Current perspectives on bisphosphonate treatment in Paget’s disease of bone

Current perspectives on bisphosphonate treatment in Paget’s disease of bone

Abstract: Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic hypocalcemia may develop. For those intolerant of bisphosphonates, subcutaneous calcitonin can be used for a limited period due to its associated risk of malignancy.
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<p>Response to Pyrotinib in a Chinese Patient with Bone-Metastatic Scrotal Paget&rsquo;s Disease Harboring Triple Uncommon HER2 Mutation: A Case Report</p>

<p>Response to Pyrotinib in a Chinese Patient with Bone-Metastatic Scrotal Paget&rsquo;s Disease Harboring Triple Uncommon HER2 Mutation: A Case Report</p>

Extensive local excision of the skin and subcutaneous tissue with immediate reconstruction is the main method for the treatment of EMPD. 8 Multidisciplinary comprehensive treatment may be a reasonable choice for invasive Pagets disease. Adjuvant therapy such as radiotherapy or systemic chemotherapy may be necessary. Chemotherapy using 5- fl uorouracil, mitomycin-C and paclitaxel has been proven effective in inadequately excised and advanced EMPD. 5 Except for traditional chemotherapy, previous studies have reported HER2-targeted monoclonal antibody (trastuzumab) could yield signi fi cant clinical bene fi t in lymph node- metastatic penoscrotal EMPD patients with HER2 ampli fi cation. 9 Pyrotinib is an oral irreversible tyrosine kinase inhibitor capable of inhibiting the HER1, HER2, and HER4. Until now, there has been no any report about the effective- ness of pyrotinib in those patients with HER2 gene alteration. Here, we present a case of an advanced penoscrotal EMPD patient harboring triple uncommon HER2 muta- tions, namely, ERBB2 R678Q in exon 17, S310Y in exon 8 and S310F in exon 8, who responds well pyrotinib.
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Immunoreactivity of valosin-containing protein in sporadic amyotrophic lateral sclerosis and in a case of its novel mutant

Immunoreactivity of valosin-containing protein in sporadic amyotrophic lateral sclerosis and in a case of its novel mutant

Valosin-containing protein (VCP) is a ubiquitous member of the AAA-ATPase supergene family. VCP is known to play an important role in cellular activities including ubi- quitin (Ub) -dependent protein degradation [1], chromatin- associated protein degradation [2], messenger ribonucleic acid (mRNA) metabolism [3], autophagy [4], anti-apoptotic function [5], and post-mitotic Golgi apparatus reassembly [6]. Mutations in the VCP gene were first found to cause inclusion-body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD) [7,8]. IBMPFD is an autosomal dominantly inherited disorder with variable penetrance of 3 predominant phenotypic features, i.e., my- opathy, Paget disease of bone, and frontotemporal demen- tia (FTD) [9]. The penetrance of the gene is 82% for myopathy, 49% for Paget’s disease, and 30% for FTD [10]. IBMPFD patients with VCP mutations can develop disor- ders in other organ systems including sphincters [11], car- diac muscles [12], auditory system [13], and liver [14], as well as in visuoconstructive ability [14]. Neurodegenerative diseases associated with a VCP mutation encompass scapu- loperoneal muscular dystrophy and dropped head syn- drome [15], Parkinson’s disease [16-18], hereditary spastic paraplegia [19], and cerebellar ataxia [20]. In addition to mutations in VCP [7,8], mutations in Heterogeneous Nu- clear Ribonucleoprotein A2B1 (HNRNPA2B1) and Heteroge- neous Nuclear Ribonucleoprotein A1 (HNRNPA1) [21] have been identified in families with IBMPFD. Given these ob- servations, the name of multisystem proteinopathy (MSP) has been proposed, using the nomenclature of MSP1 for IBMPFD caused by a VCP mutation, MSP2 for IBMPFD related to an HNRNPA2B1 mutation, MSP3 for IBMPFD related to an HNRNPA1 mutation, and MSP4 for IBMPFD due to some unidentified gene [22]. Clinically, 37.7% pa- tients of IBMPFD with a VCP mutation (MSP1) develop FTD [9]. FTD cases with a VCP mutation (MSP1) present with TAR DNA-binding protein 43 kDa (TDP-43) and ubiquitin-positive short dystrophic neurites and frequently lentiform neuronal intranuclear inclusions in their neocor- tex [23-25]. On the other hand, only rare VCP-positive neuronal intranuclear inclusions are detected, and those that are detected lack the characteristic lentiform morph- ology [23]. This finding suggests that TDP-43 and ubiquitin positive-inclusions do not contain VCP and supports the idea that VCP gene mutations in IBMPFD produce a dominant-negative loss of VCP function [23,25].
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Emerging strategies and therapies for treatment of Paget&rsquo;s disease of bone

Emerging strategies and therapies for treatment of Paget&rsquo;s disease of bone

Abstract: Paget’s disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone disorder after osteoporosis, affecting up to 3% of adults over 55 years of age. One of the most striking and intriguing clinical features is the focal nature of the disorder, in that once the disease is established within a bone, there is only local spread within that bone and no systemic dissemination. Despite many years of intense research, the etiology of PDB has still to be conclusively determined. Based on a detailed review of genetic and viral factors incriminated in PDB, we propose a unifying hypothesis from which we can suggest emerging strategies and therapies. PDB results in weakened bone strength and abnormal bone architecture, leading to pain, deformity or, depending on the bone involved, fracture in the affected bone. The diagnostic assessment includes serum total alkaline phosphatase, total body bone scintigraphy, skull and enlarged view pelvis x-rays, and if needed, additional x-rays. The ideal therapeutic option would eliminate bone pain, normal- ize serum total alkaline phosphatase with prolonged remission, heal radiographic osteolytic lesions, restore normal lamellar bone, and prevent recurrence and complications. With the development of increasingly potent bisphosphonates, culminating in the introduction of a single intravenous infusion of zoledronic acid 5 mg, these goals of treatment are close to being achieved, together with long-term remission in almost all patients. Based on the recent pathophysiological findings, emerging strategies and therapies are reviewed: ie, pulse treatment with zoledronic acid; denosumab, a fully human monoclonal antibody directed against RANK ligand; tocilizumab, an interleukin-6 receptor inhibitor; odanacatib, a cathepsin K inhibitor; and proteasome and Dickkopf-1 inhibitors.
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Dental profile of patients with Gaucher disease

Dental profile of patients with Gaucher disease

The mandible, a long bone, has been noted in anecdotal case reports as a nidus of Gaucher cell infiltration and/or bone crisis [12–17]. In our study of a subset of 28 patients with Gaucher disease (of an initial cohort of 87 patients), 25 patients displayed radiologic evidence of bone involve- ment in the jaw, including widening of the marrow spaces, endosteal scalloping, and cortical thinning [18]. A tendency to bleeding is one of the more common present- ing signs; hence, prolonged or excessive bleeding after tooth extraction or other similar invasive dental proce- dures may induce a patient to seek medical attention. Therefore, we initiated this study to ascertain whether patients with Gaucher disease demonstrate greater dental pathology because of poor underlying bone structure, whether pancytopenia affects gingival health, and whether these features of symptomatic Gaucher disease affect oral health.
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Paget disease of bone

Paget disease of bone

Since the osteoclast is the primary cell affected by PD, treatment has been directed at inhibiting osteoclast formation or osteoclastic bone resorption or inducing osteoclast apoptosis. Table 2 lists agents that are currently used for the treatment of PD. Calcitonin was initially used to treat patients with PD because it inhib- its osteoclastic bone resorption and osteoclast formation (53). Calcitonin can induce remission in patients with PD, but more than 50% of patients treated with salmon calcitonin for more than 6 months develop calcitonin antibodies, and 10–20% become resistant to calcitonin. Bisphosphonates, which block osteoclast formation and induce osteoclast apoptosis (54), have supplant- ed calcitonin as the treatment of choice for PD. First-generation bisphosphonates, such as etidronate, can induce partial or com- plete remissions in PD patients, and with the development of more potent bisphosphonates, patients can experience prolonged remis- sions, lasting months to years. In patients with more extensive PD involving many bones, intravenous bisphosphonates such as pami- dronate or zoledronate may be used. However, neither calcitonin nor bisphosphonates cure PD; they only control the disease pro- cess. Treatment of PD is indicated to control bone pain, prevent fractures, minimize bleeding prior to surgery on a pagetic bone, and decrease local progression in weight-bearing bones or the skull. Etiology of PD
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Evaluation of Charcot Neuroarthropathy in Diabetic Foot Disease Patients at Tertiary Hospital

Evaluation of Charcot Neuroarthropathy in Diabetic Foot Disease Patients at Tertiary Hospital

Co-morbidities had a role in development of Charcot disease Associated co-morbidities were obesity in 10.9%, hypertension in 83.8%, dyslipidemia in 31.3%, hypothyroidism in 14.1%, immunosuppression in 3.1% of cases, arrhythmia in 3.1% and anemia in 84.4%. Most associated co-morbidity was hypertension. Charcot arthropathy was in 28.1% of cases and forefoot was involved in 65.5%, midfoot in 4.7% and hindfoot/ankle in 21.9%. Forefoot involvement was found in majority of our patients. X-rays showed subluxation in 40.6%, dis- location in 54.7%, disorganized foot joints in 42.2%, bone resorption in 23.4%, osteomyelitis in 14.1%, fractures in 50%, joint collapse in s39.15 and destruction of articular surfaces in 37.5%. Common pathology in our pa- tients were subluxation and dislocation in forfoot joints.
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Contribution of blood platelets to vascular pathology in Alzheimer&#39;s disease

Contribution of blood platelets to vascular pathology in Alzheimer&#39;s disease

Abstract: Cerebral amyloid angiopathy (CAA) is a critical factor in the pathogenesis of Alzheimer’s disease (AD). In the clinical setting, nearly 98% AD patients have CAA, and 75% of these patients are rated as severe CAA. It is characterized by the deposition of the β-amyloid peptide (mainly Aβ40) in the walls of cerebral vessels, which induces the degeneration of vessel wall components, reduces cerebral blood flow, and aggravates cognitive decline. Platelets are anuclear cell fragments from bone marrow megakaryocytes and their function in hemostasis and thrombosis has long been recognized. Recently, increasing evidence suggests that platelet activa- tion can also mediate the onset and development of CAA. First, platelet activation and adhesion to a vessel wall is the initial step of vascular injury. Activated platelets contribute to more than 90% circulating Aβ (mainly Aβ1-40), which in turn activates platelets and results in the vicious cycle of Aβ overproduction in damaged vessel. Second, the uncontrolled activation of platelets leads to a chronic inflammatory reaction by secretion of chemokines (eg, platelet factor 4 [PF4], regulated upon activation normal T-cell expressed and presumably secreted [RANTES], and macrophage inflammatory protein [MIP-1α]), interleukins (IL-1β, IL-7, and IL-8), prostaglan- dins, and CD40 ligand (CD40L). The interaction of these biological response modulators with platelets, endothelial cells, and leukocytes establishes a localized inflammatory response that contributes to CAA formation. Finally, activated platelets are the upholder of fibrin clots, which are structurally abnormal and resistant to degradation in the presence of Aβ42. Thus, opinion has emerged that targeting blood platelets may provide a new avenue for anti-AD therapy.
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Current options for the treatment of Paget&rsquo;s disease of the bone

Current options for the treatment of Paget&rsquo;s disease of the bone

who have PDB do not know they have it, since the disease may be so mild that is not symptomatic. Moreover, the symptoms are often confused with arthritis or other skeletal disorders. Sometimes, the physician is alerted to the possibility of PDB when physical deformities appears (ie, enlargement of the skull or bowing of the tibia) or when a blood test reveals an elevated level of bone turnover markers. In most cases, the diagnosis of PDB is made only after complica- tions have developed. These complications mainly include osteoarthritis, fractures, severe bone deformity, neurological syndromes and, rarely, osteosarcoma, which significantly affect the morbidity and reduce the quality of life of patients. Osteoarthritis is common, affecting up to 50% of patients with PDB and can be quite painful. 6,13 A variety of
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The association between foot-care self efficacy beliefs and actual foot-care behaviour in people with peripheral neuropathy: a cross-sectional study

The association between foot-care self efficacy beliefs and actual foot-care behaviour in people with peripheral neuropathy: a cross-sectional study

University and the Human Research Ethics Committee of Bendigo Health. The study was carried out within a multi- disciplinary "Diabetic Foot Clinic" in a regional city of Australia with a population of approximately 90,000 peo- ple, 90% of whom are Australian born [35]. People who had been admitted to the Diabetic Foot Clinic at any time from the years 2001 to 2007 were invited to participate. Key inclusion criteria were a self-reported diagnosis of dia- betes and clinically determined "loss of protective sensa- tion" in the feet. The presence of loss of protective sensation was determined clinically by the principal researcher and defined as an inability to detect the 10 g Semmes Weinstein monofilament (Bailey, UK) on four or more sites on at least one foot, and/or a vibratory percep- tion threshold of >25 V on at least one foot (Biomedical Instrument Co, Newbury, Ohio) [36]. The use of these neuropathy testing instruments in this way has been shown to be 100% sensitive and 77% specific in identify- ing people at risk of future neuropathic foot ulceration [36].
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Factors associated with foot ulceration and amputation in adults on dialysis: a cross-sectional observational study

Factors associated with foot ulceration and amputation in adults on dialysis: a cross-sectional observational study

their medical records prior to the baseline assessment, which provides further impetus for regular foot examin- ation in the dialysis population. Interestingly, more than one third of participants without diabetes were found to have neuropathy (35.3%). Our previous meta-analysis [13] found neuropathy to be a significant risk factor for ulceration; however, in the present study it had border- line significance (p = 0.055). This can be explained by the multivariate analysis combining neuropathy with other stronger factors, such as previous amputation and peripheral arterial disease, which may have confounded the effect of neuropathy. In contrast, previous cross- sectional studies have found neuropathy to be a risk fac- tor [30, 31, 42], which highlights that this factor should not be discounted. Prospective studies are required to address this issue.
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Mandibular bone mineral density in patients with Beh&ccedil;et&rsquo;s disease

Mandibular bone mineral density in patients with Beh&ccedil;et&rsquo;s disease

The etiopathogenesis of BD remains unclear because of its rarity and correspond- ing lack of clinical evidence, but the most credited hypothesis suggests a complex interaction among immune mechanisms, genetic factors (especially, in Turks and Japanese patients, HLA-B51 gene may be responsible for genetic susceptibility), and environmental factors, such as microbial agents (Saccharomyces cerevisiae, Mycobacteria, Borrelia burgdorferi, Helicobacter pylori, Escherichia coli, Staphy- lococcus aureus, Mycoplasma fermentans, Streptococcus sanguinis, herpes simplex virus). 4–6 Chronicity, inflammation, and the drugs used for treatment may lead to bone
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Quantification of small fiber pathology in patients with sarcoidosis and chronic pain using cornea confocal microscopy and skin biopsies

Quantification of small fiber pathology in patients with sarcoidosis and chronic pain using cornea confocal microscopy and skin biopsies

studies have stratified chronic pain patients according to QST and pain questionnaire outcomes and identified homogeneous patient groups comparable to ours. For example, in a rather heterogeneous population of neuropathic pain patients (cen- tral post stroke pain, posttraumatic peripheral pain, painful HIV neuropathy, and painful diabetic peripheral neuropathy), four clusters with distinct pain phenotypes were detected based on QST (cold-evoked pain and touch-evoked pain) and questionnaires (provoked, deep, and pinpoint pain). Despite the different determinants for subgroup identification, the results are in agreement with our findings that homogeneous patterns of symptoms and pathology could be identified irrespective of the underlying disease. 1 Similarly, in a large
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Onset of action of indacaterol in patients with COPD: Comparison with salbutamol and salmeterol-fluticasone

Onset of action of indacaterol in patients with COPD: Comparison with salbutamol and salmeterol-fluticasone

This study was therefore designed to compare the onset of action of single doses of indacaterol 150 and 300 µ g with salbutamol, salmeterol-fluticasone, and placebo. The study was conducted as planned, with 96.6% of random- ized patients completing their assigned treatments. This study achieved all primary and secondary objectives. For the primary efficacy variable (FEV 1 at five minutes post- dose), both indacaterol doses were superior to placebo, with treatment–placebo differences of 100 and 120 mL for the 150 and 300 µ g doses, respectively. Such differences (ie, $100 mL) have been described as ones that patients can perceive, and therefore can be considered clinically relevant. 16 Furthermore, the bronchodilator efficacy of
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Onset of action of indacaterol in patients with COPD: Comparison with salbutamol and salmeterol-fluticasone

Onset of action of indacaterol in patients with COPD: Comparison with salbutamol and salmeterol-fluticasone

Al inicio del estudio, los pacien- tes fueron distribuidos aleatoriamente en proporciones iguales (utilizando un sistema de automatización validado) a una de cinco secuencias de tratamie[r]

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<p>White matter hyperintensities are related to pain intensity in an outpatient memory clinic population: preliminary findings</p>

<p>White matter hyperintensities are related to pain intensity in an outpatient memory clinic population: preliminary findings</p>

A recent study in outpatient memory clinics has shown that older patients with Alzheimer ’ s disease (AD) and mixed dementia (MD; AD and vascular pathology) are less likely to report pain than older individuals without dementia. 7 The self-reported pain intensity may also differ between patients with different types of dementia. Patients with AD report a lower chronic pain intensity than indivi- duals without dementia. 8–11 Patients with VaD report a higher pain intensity than individuals without dementia. 12,13 A loss of awareness of pain has been reported by carers of patients with frontotemporal demen- tia (FTD). 14 Differences in pain sensitivity between differ- ent subtypes of dementia have also been the focus in experimental pain studies. The results of those studies were heterogeneous, reporting, for example, a lower pain sensitivity, 15–17 no difference, 18 or even a higher pain sensitivity 19 in AD compared to individuals without dementia. To date, the only experimental pain study focus- ing on pain in FTD indicates a strong increase in pain tolerance compared to individuals without dementia. 20 No studies have been identi fi ed that examined pain in patients with dementia with Lewy bodies (DLB). Despite the use- fulness of a dementia subtype diagnosis for clinical prac- tice, it may lack speci fi city for research into the association between neuropathology and pain, given that, even within dementia subtypes, a considerable amount of heterogeneity in neuropathology exists. 21,22 When study- ing pain in dementia, it may therefore be more appropriate to group participants on brain atrophy and WMH, rather than on the clinical dementia subtype diagnosis.
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Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia

Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia

Peripheral arterial disease: unmet clinical need Up to 10% of the population in the Western world suffers from PAD and this represents a major health problem [1]. The prevalence of PAD has increased exponentially due to the increase in the prevalence of diabetes mellitus (DM) and an aging population. The increasing prevalence of PAD has resulted in a substantial increase in the consumption of health-care costs [2]. DM is prevalent in patients with PAD. In fact, DM itself increases the risk of lower-extremity PAD by two- to fourfold [3]. Poor glycemic control is associated with an increased risk of PAD independently of other known cardiovascular risk factors [4]. Individuals with poor glycemic control (A1c >7.5%) are five times more likely to develop intermittent claudication and be hospitalized for PAD as compared with those with better glycemic control (A1c <6%) [4]. In fact, 1% increment in hemo globin A1c in patients with Type 2 DM correlates with a 28% increase in the risk of PAD [5].
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Relationship Between Neuropathy with Pressure on Foot in Diabetic Patients

Relationship Between Neuropathy with Pressure on Foot in Diabetic Patients

as calluses, analysis of muscle mass, dry skin, hallux valgus, claw and hammer toe, exact touch sensation scoring using monofilament, position and vibration sensation, deep tendon reflexes, velocity of deep peroneal and tibial nerves, amplitude of deep and superficial peroneal, Tibial and sural nerves, latency of deep and superficial peroneal, Tibial and sural nerves, F wave latency of deep peroneal and tibial nerves, H-reflex latency of Tibial nerves, step length, cadence, walking speed, stride length, total double support, stance phase, swing phase, load response, single support, pre-swing phase, step width/ time, the maximum pressure in different areas of the foot, such as toe, toe metatarsal, small fingers, the front part of the foot, middle part of the foot, internal heel, external heel.
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<p>Burden of diabetes mellitus in patients with acromegaly treated with second-line pharmacotherapy in Spain</p>

<p>Burden of diabetes mellitus in patients with acromegaly treated with second-line pharmacotherapy in Spain</p>

Acromegaly is a disease resulting from excessive production of growth hormone (GH) by the pituitary gland. It is caused in the vast majority of cases by a GH- producing adenoma and, in rare cases, by an ectopic secretion of growth hormone- releasing hormone (GHRH). 1 Treatment goals in acromegaly include managing tumour growth, normalising high levels of GH and insulin-like growth factor 1 (IGF-1), managing disease symptoms, improving quality of life, managing comor- bidities and preventing premature death. 1 At present, there are three treatment modalities for acromegaly: surgery, pharmacological treatment and radiotherapy. Surgery is a fi rst-line treatment in most patients. Pharmacotherapy is the treatment of choice in patients with signi fi cant surgical risk, or a complementary treatment
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