Illness-related burden, personal resources and need for support in patients with acromegaly: Results of a focus group analysis.

OBJECTIVE: It was the aim of this study to evaluate illness-related burdens and support needs of patients with acromegaly to identify hitherto unadressed research questions and to open up avenues for improvements in patient care. This was done by using the focus group approach as a qualitative research method. DESIGN: Seven patients with acromegaly took part in a focus group moderated by an external medical communication specialist. The discourse focused on topics such as impact of the illness on everyday life, support needs and personal resources. The discussion was recorded and transcribed and analyzed by qualitative content analysis. RESULTS: Participants reported a huge impact of acromegaly on daily life, ranging from time expenditure for managing their illness, to bodily and mental sequelae and strain caused by physical disfigurement. Patients' coping strategies included family support, physical activities and humor. The participants wished for a sound patient-doctor relationship, more interdisciplinary and holistic treatment, medical rehabilitation services with special knowledge on acromegaly-related morbidity, a stable contact person in the medical process and reliable information material for themselves and their relatives. CONCLUSIONS: The results provide multi-facetted impressions of the overwhelming impact of acromegaly and unmet support needs of the afflicted patients. Further quantitative research is necessary to examine the generalisibility of the present results in order to implement tailored support measures. We suggest to develop standardized questionnaires to explore the prevalence and severity of the addressed problems in a large patient sample and to establish screening instruments to monitor disease burden in clinical practice.

Disease Control and Gender Predict the Socioeconomic Effects of Acromegaly: A Nationwide Cohort Study.

CONTEXT: Acromegaly is an insidious disease associated with severe somatic morbidity but data on socioeconomic status are scarce. OBJECTIVE: To study the socioeconomic status in acromegaly in a population-based follow-up study. METHODS: All incident cases of acromegaly (n = 576) during the period 1977-2010 were included. For every patient, 100 persons were sampled from the general population matched for date of birth and gender (comparison cohort). Cox regression and hazard ratios (HR), conditional logistic regression and linear regression with 95% confidence intervals (CI) were used. OUTCOME MEASURES: Retirement, social security benefit, annual income, cohabitation, separation, parenthood and educational level. RESULTS: The proportion of retired individuals was significantly higher in patients with acromegaly after the time of diagnosis (HR, 1.43; 95% CI, 1.26-1.62) and also during the 5-year pre-diagnostic period (HR, 1.15; 95% CI, 1.03-1.28). More individuals with acromegaly received social security benefit compared with the comparison cohort during the initial period after the time of diagnosis. Among patients who maintained a job, the annual income was similar to the comparison cohort. Compared with the background population, cohabitation was lower (HR, 0.69; 95% CI, 0.50-0.95) as was parenthood (HR, 0.56; 95% CI, 0.39-0.80), whereas neither educational level (HR, 0.61; 95% CI, 0.35-1.06) nor separation (HR, 1.13; 95% CI, 0.86-1.47) were different. Female gender and insufficient disease control were associated with a significantly worse socioeconomic status. CONCLUSIONS: 1) Socioeconomic status is impaired in patients with acromegaly even before a diagnosis of acromegaly. 2) Females and patients without disease remission have worse outcomes. 3) Early diagnosis and effective treatment of acromegaly could be important factors in mitigating the negative impact on socioeconomic factors.

Daily life, needs and expectations of patients with acromegaly in France: An on-line survey.

Acromegaly can impair quality of life, but impact on patients' daily life, needs and expectations have been poorly explored. OBJECTIVES: To better understand the impact of acromegaly on patients' daily life, and evaluate their needs and expectations. PATIENTS AND METHODS: An on-line questionnaire survey of acromegaly patient and relative community members was conducted on the Carenity website. RESULTS: Twenty-five patients and 3 relatives, with a mean age of 48.9 years, responded. Diagnosis of acromegaly was recent (60% within 10 years). Signs at diagnosis were mainly clinical (fatigue, headache) and physical changes (acral enlargement). Reported complications comprised morphological changes (93%), bone and joint symptoms (75%) and metabolic disorders (75%). Pain and fatigue impacted the daily life of 61% and 54% patients, respectively. Acromegaly had strong impact on mood (79%), leisure (75%) and social life (71%). Patients mostly got information from specialized websites (71%), their endocrinologist (61%) and patient associations (54%). The information sought was patient testimony (82%), practical advice (64%), and information on clinical trials (61%) and treatments (50%). Patients wished to have patient-physician discussion groups (25%), and better knowledge of acromegaly on the part of those they were in contact with (25%). CONCLUSION: Acromegaly has a major impact on patients' daily life and mood. Patients wished their disease to be better known, and advocated setting up discussion groups. This study should encourage acromegaly education programs to adapt the services and information that are needed by acromegalic patients.

Comorbidities, treatment patterns and cost-of-illness of acromegaly in Sweden: a register-linkage population-based study.

OBJECTIVE: Acromegaly is a complex endocrine disease with multiple comorbidities. Treatment to obtain biochemical remission includes surgery, medical therapy and radiation. We aimed to describe comorbidities, treatment patterns and cost-of-illness in patients with acromegaly in Sweden. DESIGN: A nationwide population-based study. METHODS: Patients with acromegaly were identified and followed in national registers in Sweden. Longitudinal treatment patterns were assessed in patients diagnosed between July 2005 and December 2013. The cost-of-illness during 2013 was estimated from a societal perspective among patients diagnosed between 1987 and 2013. RESULTS: Among 358 patients with acromegaly (48% men, mean age at diagnosis 50.0 (s.d. 15.3) years) at least one comorbidity was reported in 81% (n = 290). The most common comorbidities were hypertension (40%, n = 142), neoplasms outside the pituitary (30%, n = 109), hypopituitarism (22%, n = 80) and diabetes mellitus (17%, n = 61). Acromegaly treatment was initiated on average 3.7 (s.d. 6.9) months after diagnosis. Among the 301 treated patients, the most common first-line treatments were surgery (60%, n = 180), somatostatin analogues (21%, n = 64) and dopamine agonists (14%, n = 41). After primary surgery, 24% (n = 44) received somatostatin analogues. The annual per-patient cost was €12 000; this was €8700 and €16 000 if diagnosed before or after July 2005, respectively. The cost-of-illness for acromegaly and its comorbidities was 77% from direct costs and 23% from production loss. CONCLUSIONS: The prevalence of comorbidity is high in patients with acromegaly. The most common first-line treatment in acromegalic patients was surgery followed by somatostatin analogues. The annual per-patient cost of acromegaly and its comorbidities was €12 000.

Cephalometric assessment of soft tissue morphology of patients with acromegaly.

AIM: To assess the sagittal soft tissue morphology of patients with acromegaly in comparison with a healthy control group. METHODS: Twenty-seven patients with acromegaly (11 male, 16 female; mean age 47.3 ± 11.5 years) and 30 healthy subjects (15 male, 15 female; mean age 42.2 ± 17.4 years) were included in the study. Linear and angular measurements were made on lateral cephalograms to evaluate soft tissue and skeletal characteristics. The intergroup comparisons were analysed with the Student's t-test. RESULTS: Facial convexity (p < 0.01) and the nasolabial angle (p < 0.001) were reduced in patients with acromegaly, whereas nose prominence (p < 0.01), upper lip sulcus depth (p < 0.01), upper lip thickness (p < 0.01), basic upper lip thickness (p < 0.01), lower lip protrusion (p < 0.05), mentolabial sulcus depth (p < 0.05) and soft tissue chin thickness (p < 0.001) were increased. Anterior cranial base length (p < 0.05), the supraorbital ridge (p < 0.01), the length of the maxilla and mandible (p < 0.001, p < 0.01, respectively) were significantly increased, and mandibular prognathism was an acromegalic feature (p < 0.05). CONCLUSION: Acromegalic coarsening and thickening of the craniofacial soft tissues was identified from lateral cephalograms, which may therefore contribute to early diagnosis when evaluated together with other changes caused by the disease.

Structural tendon changes in patients with acromegaly: assessment of Achilles tendon with sonoelastography.

AIMS: To describe the sonoelastographic appearance of the Achilles tendon in acromegalic patients and to determine whether the blood concentrations of growth hormone (GH) and insulin-like growth factor (IGF-1) are associated with the various sonographic elasticity types of Achilles tendons. MATERIAL AND METHODS: Eighty-four Achilles tendons of 42 acromegaly patients and 84 Achilles tendons of 42 healthy volunteers were assessed with sonoelastography. The tendons were classified into two main types according to the elasticity features: type 1 blue/green (hard tissue) and type 2 yellow/red within green (intermediate-soft tissue). Two subtypes of these types were also defined. According to the definition, the elasticity of the tissue was in a spectrum ranging from hard to soft as the type progressed from 1a to 2b. RESULTS: The mean thickness of Achilles tendons in patients with acromegaly was significantly higher compared with healthy Achilles tendons (5.1+/-0.7 mm vs. 4.4+/-0.5, p<0.001), and patients with active disease had thicker Achilles tendons (5.5+/-0.8 mm vs. 4.8+/-0.5 mm in inactive disease, p=0.003). A significantly higher proportion of acromegaly patients had type 2 sonoelastographic appearance of the Achilles tendon (124/252 third; 49.2% vs. 81/252 third; 32.1%, p=0.0001). Activity status of acromegaly and GH/IGF-I levels were similar in patients with different types of elasticity (p>0.05). CONCLUSIONS: Sonoelastography revealed structural changes in the tendinous tissue of patients with acromegaly, but it was not sensitive enough to reflect changes in the serum levels of GH/IGF-1.

Aggressive tumors and difficult choices in acromegaly.

PURPOSE: The current article looks at some of the factors associated with pituitary adenomas displaying unusually aggressive biological and clinical behaviour in patients with acromegaly. METHODS: This was a retrospective, narrative review of previously published evidence chosen at the authors' discretion and presented from the perspective of a Latin American case study. FINDINGS AND CONCLUSIONS: Although most pituitary tumors in acromegalic patients are benign and non-aggressive many can behave more aggressively, compromising local surrounding structures. These lesions tend to respond poorly to somatostatin analogs, have a higher risk of recurrence after surgery and, thus, a worse prognosis. Patients with more aggressive tumors constitute a particular challenge, as they often require several therapeutic approaches and may be difficult to manage, especially when options are restricted due to limited resources.

Biochemical diagnosis and assessment of disease activity in acromegaly: a two-decade experience.

The objective of this study is to assess the secretory pattern of GH after Oral Glucose Tolerance Test (OGTT) or day-curve (DC), in relation with IGF-I and to evaluate the influence of therapy on OGTT. A retrospective analysis in 279 OGTTs performed in 93 acromegalic patients in our unit from January 1988 to December 2005, in 77 patients also DC data were retrived. GH concentration was evaluated by 3 different systems (RIA, IRMA and chemiluminescence assays), and IGF-I by two RIAs. About 12% of OGTT samples were discordant with the baseline, while discordance between nadir and 120th minute was much lower (5%), with all discordant values, except one, near the cut-off lines. Correlation between DC and OGTT data was around 0.99 among all values, discordance rate between nadir and minimum DC was much lower than that with mean DC. In almost 80% of cases there was a complete concordance between OGTT and DC results, and in about 30% IGF-I was discordant with GH. Correlation analysis between IGF-I and GH was highest with DC data and lowest with OGTT baseline (T0). Considering different treatments discrepancy rates between GH and IGF-I were comparable. The best GH parameter is the minimum GH DC, although in the clinical practice the evaluation of OGTT GH in association with IGF-I is the most practical approach. In this case, the basal and T120 GH values can replace multiple sampling. Different treatment modalities do not influence the discordance rate between GH and IGF-I.

Electrophysiological assessment of the autonomic nervous system in male patients with acromegaly.

BACKGROUND/AIMS: We aimed to electrophysiologically evaluate the autonomic function in acromegalic patients using sympathetic skin response (SSR) as a reflection of the sympathetic sudomotor activity and RR interval variation (RRIV) as an indicator of the cardiovagal autonomic function. METHODS: The study group consisted of 18 male acromegalics, and the control group was composed of 18 age- and sex-matched healthy subjects. Participants underwent SSR and RRIV tests. Beginning latencies and amplitudes of the median and tibial SSRs were compared among the groups. The RRIV values recorded at rest and during hyperventilation were compared among the patients and controls. RESULTS: Latencies of SSRs recorded from the palms (median) and soles (tibial) of acromegalics were significantly longer than in healthy subjects (p = 0.004, p < 0.001). The amplitude of SSR recorded from the sole (tibial) was significantly decreased (p = 0.028). The RRIVs obtained from acromegalics at rest and during hyperventilation were significantly decreased compared with those of controls (p < 0.001). The RRIVs obtained from controls prolonged significantly during hyperventilation (p < 0.001); however, in the acromegaly group, hyperventilation did not cause a significant change in RRIV (p = 0.983). CONCLUSIONS: The present study suggests that an autonomic dysfunction exists in patients with acromegaly. Dysautonomia in acromegalics may be documented by means of SSR and RRIV.

Increased mammographic breast density in acromegaly: quantitative and qualitative assessment.

CONTEXT: Mammographic density is a strong independent risk factor for breast cancer, whose prevalence in acromegaly is still controversial. OBJECTIVE: To compare breast density in premenopausal acromegalic patients and controls and to determine whether density correlated with disease duration, GH, and IGF1 levels. DESIGN, SETTING AND PARTICIPANTS: A prospective study involving 30 patients and 60 controls matched for age and body mass index. INTERVENTIONS: A quantitative computer-aided mammographic density estimation (MDEST) and a qualitative blind evaluation by two experienced radiologists using the breast imaging reporting and data system (BI-RADS) was performed. Totally, 60 (acromegaly) and 120 (controls) craniocaudal and mediolateral oblique mammograms were evaluated in both patients and controls. MAIN OUTCOME MEASURES: Breast density. RESULTS: Patients showed a significantly (P<0.01) increased mammographic breast density with both methods (MDEST: 0.33 ± 0.21% and BI-RADS category: 2.81 ± 0.78) in comparison with controls (MDEST: 0.26 ± 0.19% and BI-RADS category: 2.35 ± 0.61). The agreement between the two methods and inter-observer agreement between the two radiologists were excellent (k=0.63 and k=0.85). In patients grouped according to disease activity (17 controlled and 13 uncontrolled) and medical therapy (15 treated and 15 untreated), no differences were found. All these groups had significantly increased mammographic breast density compared with controls (P<0.01). A positive correlation was found between mammographic breast density, IGF1 values and disease duration (r=0.29 and r=0.39), whereas it was not found with GH (r=-0.02). CONCLUSIONS: Mammographic breast density in premenopausal acromegalic patients is significantly higher than controls and positively correlated with IGF1 and disease duration.

Intraoperative conversion from endoscopic to microscopic approach for the management of sellar pathology: incidence and rationale in a contemporary series.

BACKGROUND: The endoscopic transsphenoidal approach has become widely used for pituitary and extended skull base operations. Intraoperative conversion to a microscopic approach may be an important option in selected cases. We aim to characterize the operative situations in which such conversion occurred and facilitated the procedure. METHODS: From April 2008 through August 2009, 148 planned endoscopic transsphenoidal approaches were performed. All cases were retrospectively reviewed to identify those patients converted to a microscopic approach. Clinical and operative characteristics, reasons for conversion, and patient outcomes were reviewed. RESULTS: Of the 148 endoscopic cases, conversion was undertaken in 27 (18%). Ten patients (37%) had undergone previous transsphenoidal surgery. Reasons for conversion in nonreoperation cases were atypical nasal anatomy (6 patients), acromegaly with distorted anatomy (5 patients), desire for binocular vision (3 patients), complex sphenoid sinus anatomy and difficulty visualizing sella/midline (2 patients), and obstructive mucosal bleeding (1 patient). Of the 10 reoperation procedures, conversions occurred in 3 patients with Cushing's disease and 2 with acromegaly. The primary reasons for conversion in reoperations were scarring with loss of anatomic landmarks (4 patients), mucosal bleeding (2 patients), acromegaly with distorted anatomy (2 patients), technical problem with visualization (1 patient), and desire for binocular surgery (1 patient). CONCLUSIONS: Although endoscopic transsphenoidal surgery provides superior visualization in most patients, conversion to a microscopic or endoscopic-assisted approach may provide essential visualization in selected patients. This may be especially true in patients undergoing reoperation and patients with acromegaly or Cushing's disease. Trainees learning the endoscopic transsphenoidal approach should become familiar with the benefits and limitations of the various transsphenoidal approaches.

An assessment of the predictors of difficult intubation in patients with acromegaly.

Various clinical signs have been used for assessing difficult intubation in patients with acromegaly. These signs include the modified Mallampati classification, measurement of thyromental distance and head and neck movements. Some authors have also tried to establish a relationship between growth hormone levels and difficult intubation. We hypothesized that duration of symptoms in patients with acromegaly may have an association with difficult airway and difficult laryngoscopy. In this prospective study we evaluated tests of airway assessment such as: (i) the Mallampati grade; (ii) the thyromental distance; and (iii) the laryngoscopic grade (Cormack-Lehane). The growth hormone levels and the duration of disease symptoms were also examined. Significant correlation was observed between the Cormack-Lehane and Mallampati gradings (p = 0.05; rho = 19.3%), and between the thyromental distance and the duration of the symptoms (p = 0.03; rho = 26.9%). The incidence of Mallampati III and IV grades was higher in patients with acromegaly. Increased thyromental distance was noted in patients with a long duration of disease. However, increased thyromental distance was not associated with difficult laryngoscopy.

Cephalometric assessment of cranial abnormalities in patients with acromegaly.

OBJECTIVE AND PATIENTS: Patients with acromegaly (12 women, 26 men) and a control group (36 women, 50 men) were chosen for cephalometry to assess the size, shape and positional characteristics of the craniofacial bones and the upper airways. RESULTS: When compared with the controls, patients of both sexes with acromegaly were found to have significant anomalies in the orofacial skeleton: increased facial height, elongated ascending ramus mandibulae and greater basion-supramentale distance, a negative difference between maxillary and mandibular protrusions, enlarged lower part of the gonion angle and of the angle of inclination of the maxilla, as well as alterations in the neurocranium: enlargement of sella turcica and of sinus frontalis and protrusion of the supraorbital ridges. As for the soft tissues, patients with acromegaly exhibited an elongated soft palate and a diminished angle between the uvular axis and the palatal plane. A comparison between the cephalometric parameters of patients with active acromegaly and those without active disease revealed no significant differences in either sex. CONCLUSION: Patients with acromegaly exhibited an enlargement of all parts of the neurocranium and orofacial bones except the maxilla. The greatest anomaly was seen in the mandible, with greater enlargement of the ascending ramus than of the body of the mandible. The shape of this bone was also altered.

A simple method for assessment of glomerular size and its use in the study of kidneys in acromegaly and compensatory renal enlargement.

As measurement of absolute glomerular size is difficult we developed a method of assessing glomerular size that was simple and practical and could be used to compare the kidneys in different groups of patients. Using a semi-automatic image analyser, the cross-sectional area of 100 randomly-selected glomeruli, outlined by Bowman's capsule, was measured on sections of kidneys taken at necropsy. The mean of the logarithms of the largest 25 areas was calculated. The method was applied to compare control kidneys (53) with the kidneys in acromegalics (20), in patients with one kidney (10) and in patients with asymmetrical kidneys (12). Kidneys were heavier in the three test groups than in controls. Glomerular sizes were similar in controls and in acromegalics but were larger in single and disparate kidneys. There was a relationship between glomerular size and kidney weight within the control group and across the four groups taken together. This only partly accounted for the observed differences in glomerular size between the groups. Histological comparison of the acromegalic and single kidneys showed more global glomerulosclerosis in single kidneys and also segmental lesions, mainly at the glomerular hilum, only in the single kidneys. These findings show that renal enlargement occurs in acromegaly and in single and disparate kidneys but is accompanied by markedly different glomerular features. This implies different mechanisms for the renal enlargement. The method of assessing glomerular size is useful in the study of these and other conditions affecting the kidney.

Echocardiographic assessment of cardiac anatomy and function in acromegalic patients.

Echocardiography was used to evaluate cardiac anatomy and function in 25 patients with accromegaly. Eighty per cent of the patients (20 of 25) had abnormal echocardiograms including 13 patients without other signs or symptoms of cardiac involvement. The most common abnormality was increased left ventricular mass with concentric left ventricular wall thickening, which was found in 64 per cent (16 of 25) of the patients. Increased left ventricular transverse dimension at end diastole was found in 36 per cent (nine of 25) of the patients. Other echocardiographic abnormalities found included left atrial or aortic root enlargement (three patients), disproportionate septal thickening (one patient) and depressed left ventricular ejection fraction (three patients). Since five of the patients with increased left ventricular mass had no history of hypertension or hyperthyroidism, the increased mass cannot be ascribed solely to these conditions commonly associated with acromegaly. Furthermore, the degree of cardiac hypertrophy showed no significant correlation with pre- or post-treatment growth hormone levels, or with known duration of acromegaly prior to treatment. Thus, although the pathophysiology and significance of cardiac abnormalities in acromegalic patients is not yeat fully understood, echocardiography does provide a sensitive tool for detecting such abnormalities before they are otherwise apparent.