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Purpose: The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis (i.e., higher BSI indicates a lower bone's resistance to loads with consequent higher risk of fractures). We aimed to investigate the association between lumbar BSI and vertebral fractures (VFs) in acromegaly., Methods: Twenty-three patients with acromegaly (13 males, mean age 58 years; three with active disease) were evaluated for morphometric VFs, trabecular bone score (TBS), bone mineral density (BMD) and BSI at lumbar spine, the latter being corrected for the kyphosis as measured by low-dose X-ray imaging system (EOS®-2D/3D)., Results: Lumbar BSI was significantly higher in patients with VFs as compared to those without fractures (2.90 ± 1.46 vs. 1.78 ± 0.33, p = 0.041). BSI was inversely associated with TBS (rho -0.44; p = 0.034), without significant associations with BMD (p = 0.151), age (p = 0.500), BMI (p = 0.957), serum IGF-I (p = 0.889), duration of active disease (p = 0.434) and sex (p = 0.563)., Conclusions: Lumbar BSI corrected for kyphosis could be proposed as integrated parameter of spine arthropathy and osteopathy in acromegaly helping the clinicians in identifying patients with skeletal fragility possibly predisposed to VFs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the incidence of malignancies in acromegaly and to identify risk factors for newly-diagnostic cancers, especially the excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1)., Methods: A retrospective cohort including 1738 consecutive hospitalized patients with acromegaly in a single referral center between 2012 and 2020 (mean follow-up 4.3 years). A gender- and age-matched case-control study (280 patients from the cohort) was performed for risk factor analysis., Results: One hundred thirteen malignancies (67 diagnosed after acromegaly) were observed. The overall newly-diagnostic cancer risk of acromegaly was higher than the general population (standardized incidence ratio (SIR) 2.81; 95% CI 2.18-3.57). The risk of thyroid cancer (n = 33, SIR 21.42; 95% CI 13.74-30.08) and colorectal cancer (n = 8, SIR 3.17; 95% CI 1.37-6.25) was elevated. In the overall cohort, IGF-1 (ULN: 1.27 vs. 0.94, p = 0.057), GH (1.30 vs. 1.00 ng/ml, p = 0.12), and disease-controlled rate (34.9% vs. 45.9%, p = 0.203) at the last visit did not reach significance between patients with and without post-diagnostic cancer. In the case-control study, GH (1.80 vs. 0.90 ng/ml, p = 0.018) and IGF-1 (ULN: 1.27 vs. 0.91, p = 0.003) at the last visit were higher in patients with post-diagnostic cancers, with a lower disease-controlled rate. Elder age was a risk factor for cancer. Other metabolic comorbidities and the size of pituitary tumors were similar., Conclusion: The risk of malignancies, especially thyroid cancer, was increased in patients with acromegaly in our center. More cancer screening should be considered when managing acromegaly, especially in patients with higher posttreatment GH and IGF-1., (© 2023. The Author(s).)

Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher in cohorts of patients with type 2 DM (T2DM). The presence of secondary DM depends primarily on acromegaly status and is associated with increased cardiovascular morbidity, malignancy rate and overall mortality. The principal pathophysiologic mechanism is increased insulin resistance due to excessive lipolysis and altered fat distribution, reflected at the presence of intermuscular fat and attenuated, dysfunctional adipose tissue. Insulin resistance is ascribed to the direct, diabetogenic effects of growth hormone (GH), which prevail over the insulin-sensitizing effects of insulin-like growth factor 1 (IGF-1), probably due to higher glucometabolic potency of GH, IGF-1 resistance, or both. Inversely, GH and IGF-1 act synergistically in increasing insulin secretion. Hyperinsulinemia in portal vein leads to enhanced responsiveness of liver GH receptors and IGF-1 production, pointing towards a mutually amplifying loop between GH-IGF-1 axis and insulin. Secondary DM occurs upon beta cell exhaustion, principally due to gluco-lipo-toxicity. Somatostatin analogues inhibit insulin secretion; especially pasireotide (PASI) impairs glycaemic profile in up to 75% of cases, establishing a separate pathophysiologic entity, PASI-induced DM. In contrast, pegvisomant and dopamine agonizts improve insulin sensitivity. In turn, metformin, pioglitazone and sodium-glucose transporters 2 inhibitors might be disease-modifying by counteracting hyperinsulinemia or acting pleiotropically. Large, prospective cohort studies are needed to validate the above notions and define optimal DM management in acromegaly., (© 2023. The Author(s).)

Background and Aim: The risk of second primary tumors is increased in general cancer population, however, there is no data on acromegalic cancer patients in this regard. The aim of this study is to determine the prevalence of patients with two primary tumors among acromegalic cancer patients and to evaluate if patients with two primaries have distinct clinical characteristics or risk factors compared to those with one., Methods: This is a single-center retrospective cohort study. The study included 63 patients with at least one malignant tumor out of a total number of 394 acromegaly patients. Patients with multiple primary neoplasms were evaluated in detail., Results: This study revealed a 16% cancer prevalence in acromegaly patients, with 14% (9/63) having two primary neoplasms. Papillary thyroid carcinoma was the most prevalent tumor in the entire cancer cohort (41%, 26/63), and in the group of patients with two primaries (44%, 4/9). Patients with two primary tumors were older than those with one when diagnosed with acromegaly (48.3 ± 16.6 vs. 43.3 ± 10.7 years), which might be attributed to a longer diagnostic delay (median of 4.5 vs. 2 years). The period between the onset of acromegaly symptoms and diagnosis was not associated with earlier cancer diagnosis. No relationship between circulating GH or IGF-I levels and the number of neoplasms was found., Conclusion: The development of second primary tumors in acromegalic patients with cancer diagnosis is not rare. Acromegalic cancer patients should be closely monitored for new symptoms or signs that could be associated with second primary tumors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Acromegaly is a rare but potentially life-threatening disease, if not promptly managed, for the systemic complications due to the GH/IGF-I hypersecretion. According to the increased population life span, the number of older acromegaly patients is growing. We aim to investigate clinical features of elderly acromegaly (elderly-ACRO) and to identify the risk factors for the occurrence of comorbidities in elderly-ACRO., Materials and Methods: A retrospective and multi-center study was performed on acromegaly patients. Acromegaly comorbidities were compared among elderly-ACRO (>65 years), young acromegaly patients (young-ACRO if ≤65 years) and a control group of age and gender-matched subjects., Result: Fifty of the 189 enrolled patients were elderly-ACRO (26.5%). Cardiovascular, metabolic, neurological/psychiatric and joint/articular disorders, nodular thyroid disease, sleep apnoea syndrome and skeletal fragility occurred more frequently in elderly-ACRO as compared to controls. Cardiovascular and metabolic disorders, nodular thyroid disease occurred significantly more frequently in elderly-ACRO as compared to young-ACRO and controls. On the other hand, neurological/psychiatric, joint/articular disorders and bone fragility occur with a similar frequency among elderly and young-ACRO. We found that elderly-ACRO had an increased risk for the occurrence of systemic arterial hypertension (p < 0.001, OR: 5.4 95%IC:2.6-10.9), left ventricular hypertrophy (p = 0.01, OR: 3 95%IC: 1.5-5.8) and metabolic disorders (p = 0.006, OR: 4.1 95%IC: 2-8.3)., Conclusion: Our results may suggest that some acromegaly comorbidities may be predominantly due to acromegaly "per-se" rather than to aging. On the contrary, cardiovascular and metabolic disorders seem to be due to aging as well., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Cardiovascul diseases are the most common comorbidities in acromegaly. Potential parameters in pathology of cardiovascular comorbidities are changes in levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) as well as body composition parameters., Purpose: The aim of this study was to examine morphological and functional parameters of the cardiovascular system by echocardiography and to assess its relationship with disease activity and body composition parameters., Methods: We prospectively enroled 129 acromegalic patients (82 females, 47 males) and 80 healthy controls (53 females, 27 males) matched for age, gender, and BMI. All patients underwent two-dimensional echocardiography. Body composition parameters were assessed by dual-energy X-ray absorptiometry., Results: Acromegaly patients presented with higher left ventricle mass (LVM) compared to controls (LVMI: 123 ± 45 g/m 2 vs 83 ± 16 g/m 2 , P < 0.001). Prevalence of left ventricle hypertrophy in acromegaly patients was 67% (78% concentric, 22% eccentric). IGF -1 levels, BMI, and lean mass positively correlated with LVM in all acromegaly patients (P < 0.001). Fat mass positively correlated with LVM in females (R = 0.306, P = 0.005), but this correlation was not found in males. We did not find any difference in size of the left and right ventricle between acromegaly patients and controls. Acromegaly patients presented with left atrium enlargement, diastolic dysfunction and low incidence of systolic dysfunction. Valvopathy was found in 43% of patients with predominant (31%) prevalence of mitral regurgitation., Conclusion: Our study demonstrates higher prevalence of cardiovascular comorbidities in acromegaly patients and the impact of IGF-1 levels and body composition parameters in pathology in some of these comorbidities., (© 2022. The Author(s).)

Purpose: Current treatment of acromegaly restores a normal life expectancy in most cases. So, the study of persistent complications affecting patients' quality of life (QoL) is of paramount importance, especially motor disability and depression. In a large cohort of acromegalic patients we aimed at establishing the prevalence of depression, to look for clinical and sociodemographic factors associated with it, and to investigate the respective roles (and interactions) of depression and arthropathy in influencing QoL., Methods: One hundred and seventy-one acromegalic patients (95 women and 76 men, aged 20-85 years) among those recruited in a cross-sectional Italian multicentric study were investigated. Each patient filled in three validated questionnaires: AcroQoL, WOMAC (measuring articular pain, stiffness and functionality), and AIMS (evaluating articular symptoms and depression)., Results: A very high (up to 28%) depression rate was detected in acromegalic subjects. Two patients showing pathological AIMS depression scores, committed suicide during the three years observational period. In our population poor psychological status was significantly associated with female sex. Furthermore, a significant strong correlation was found between AIMS depression score and WOMAC score. Both depression and arthropathy-related motor disability turned out to independently contribute with similar strength to the impairment of QoL., Conclusions: We report a high prevalence of depression in acromegaly, which is associated with female sex and arthropathy. Both depression and arthropathy strongly and independently contribute to the impaired QoL of patients. Our study shows that assessment and monitoring of psychological status is mandatory in acromegaly, also suggesting an inexpensive tool for this assessment., (© 2022. The Author(s).)

Purpose: To investigate the prevalence of cancer in patients with acromegaly and the variables associated with malignant and premalignant lesions detected by cancer screening., Methods: The data of 214 patients diagnosed with acromegaly in our institution were evaluated retrospectively. Prevalence of cancer was compared with national rates to estimate standardized incidence ratios (SIRs). The relationships of malignant and premalignant lesions detected by cancer screening with demographic, clinical, and radiological variables were also analyzed., Results: Cancer was detected in 24 (13.4%) of 179 patients enrolled in the study. Compared to the general population, the incidence of all malignancies was increased in both women and men with acromegaly (SIR: 4.78, 95% CI: 2.43-8.53, p = 0.002 and SIR: 8.97, 95% CI: 5.51-14.7, p < 0.001, respectively). The most common cancers were thyroid, colorectal, breast, kidney, gastric, and testicular cancer, respectively. Duration of disease was the only independent risk factor for the development of cancer (OR: 1.007, 95% CI: 1.002-1.011, p = 0.002). Malignant/premalignant lesions were detected in 21.5% of the patients with a colonoscopy scanning procedure and in 20.8% with an esophagogastroduodenoscopy procedure, and current age was found to be higher among the patients with malignant/premalignant lesions (p = 0.023 and p = 0.003, respectively). Breast cancer was detected in 3.7% of screening tests performed with mammography., Conclusion: In this study, it was shown that the prevalence of cancer increases with acromegaly and this increase is associated with disease duration. Considering the increase in the number of premalignant lesions, the scope of cancer screening recommendations in the guidelines should be expanded to ensure early diagnosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To reveal distinctive features of vitamin D metabolism in patients with active acromegaly compared to healthy individuals, particularly in the setting of cholecalciferol treatment., Methods: The study group included 34 adults with active acromegaly, and the control group included 30 apparently healthy adults with similar age, sex, and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D 3 , 25(OH)D 2 , 1,25(OH) 2 D 3 , 3-epi-25(OH)D 3 and 24,25(OH) 2 D 3 ), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3, and 7 after the administration. All data were analyzed with nonparametric statistics., Results: Patients with acromegaly had tendency to lower baseline 25(OH)D 3 levels (p = 0.05) and lower 25(OH)D 3 levels (p < 0.05) during the follow-up. They were also characterized by PTH suppression (lower baseline PTH levels and lower prevalence of secondary hyperparathyroidism), altered production of main vitamin D metabolites (higher 1,25(OH) 2 D 3 and lower 24,25(OH) 2 D 3 levels with corresponding lower 25(ОН)D 3 /1,25(ОН) 2 D 3 and higher 25(ОН)D 3 /24,25(ОН) 2 D 3 ratios) as well as concordant biochemical features (higher levels of serum phosphorus and albumin-adjusted calcium levels) throughout the study (p < 0.05). The acromegaly group showed an increase in DBP levels after cholecalciferol intake as opposed to the control group (p < 0.05) and had lower increase in free 25(OH)D levels (p < 0.05). Δ25(OH)D 3 was similar between the groups (p > 0.05), showed a negative correlation with the disease activity markers-both IGF-1 levels (r = -0.44, p < 0.05) and fasting GH levels (r = -0.56, p < 0.05)-and lacked correlation with BMI in the acromegaly group (p > 0.05)., Conclusion: Patients with active acromegaly have dysregulated vitamin D metabolism characterized by higher 1,25(ОН) 2 D 3 , lower 24,25(ОН) 2 D 3 and altered DBP production. The response to vitamin D supplementation in acromegaly patients might be influenced by hormonal excess. Obtained results require reproducibility check and further study to develop specific clinical recommendations., Trial Registration: NCT04844164 (release date: April 9, 2021; retrospectively registered)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: An increased prevalence of vertebral fractures (VFs) has been reported in previous studies. The aim of this study was to evaluate the association between bone mineral density (BMD), bone turnover markers, serum sclerostin levels, and vertebral fractures (VFs) in acromegaly patients. We also evaluated the effects of gonadal status, disease activity, treatment modality, age, sex, and body mass index (BMI) on skeletal endpoints., Design: Case-control study., Patients and Measurements: Seventy acromegaly patients (M/F:36/34, mean age 45.5 ± 11.9 years) and 70 controls (M/F:31/39; mean age 45.66 ± 11.9 years) were included. VFs, BMD, calcium metabolism, markers of bone turnover, and sclerostin levels were evaluated. BMD was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500). Conventional lateral radiography of the spine was performed and the Genant method was used for the assessment of fractures of T4-L5 vertebrae., Results: The prevalence of vertebral fractures was higher in acromegalic patients as compared with the control group (72.9 vs. 20%; p < 0.001). Serum phosphate (P) levels (3.46 ± 0.59 mg/dl vs. 3.11 ± 0.44 mg/dl; p < 0.001) and b-cross laps (CTx) levels (0.47 µg/l, range 0.04-2.38 vs. 0.28 µg/l, range 0.11-0.80; p < 0.001) were significantly higher in acromegaly patients than control subjects. Serum sclerostin levels were similar between either acromegaly patients and control subjects or acromegaly patients with VF and without VF. In the means of treatment modality, VFs were more frequent in patients treated with adjuvant gamma knife radiosurgery (GKS) (p = 0.07). In the binary logistic regression analysis, the age of the acromegaly patients, the presence of hypogonadism, and GKS treatment were the factors significantly correlated with the occurrence of spinal fractures., Conclusions: The prevalence of VFs in patients with acromegaly is higher than in control subjects. Since advanced age, the presence of hypogonadism and GKS treatment were the factors predicting VFs in acromegaly; radiological evaluations should be considered as an emerging tool especially in those patients. Although markers of bone turnover elevated in acromegaly, they were not useful for the prediction of fractures. Serum sclerostin levels showed no discrepancy between the two groups and further studies are required for assessment of sclerostin role in this form of secondary osteoporosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Diabetes mellitus (DM) represents one of the most frequent comorbidities in patients with acromegaly. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent an important class for diabetes management. However, limited data is reported regarding the use of this class in patients with acromegaly and diabetes., Methods: Reporting data regarding patients with acromegaly and diabetes under treatment with SGLT2i., Results: 29 acromegalic patients with diabetes were identified. Treatment with SGLT-2i was documented in nine patients, out of them 5 females and 4 males with a mean age (SD) of 61 ± 12 yr. The mean (SD) duration of treatment with SGLT2i was 27.5 ± 7.3 months. Mean HbA1c before and after SGLT-2i initiation was 8.1 ± 1.1 and 7.0 ± 0.9% respectively. Mean IGF-1 level (SD) before SGLT-2i initiation was 177 ± 68 ng/mL and the mean GH level (SD) was 0.7 ± 0.5 µg/L. All nine patients are still under treatment with SGLT2i and none of them had reported any adverse reaction related to SGLT2i., Conclusions: The present article provides us for the first time with new data regarding the use of SGLT2i among acromegalic patients with diabetes.

Purpose: Acromegaly is a rare disease due to growth hormone (GH)-secreting pituitary adenoma. GH and IGF-1 levels are usually congruent, indicating either remission or active disease; however, a discrepancy between GH and IGF-1 may occur. We aimed to evaluate the outcome of diabetes mellitus (DM) and hypertension (HT) in acromegalic patients with congruent GH and/or IGF-1 levels vs. discordant biochemical parameters., Methods: Retrospective analysis of the data of 3173 patients from the Liege Acromegaly Survey (LAS) allowed us to include 190 patients from 8 tertiary referral centers across Europe, treated by surgery, with available data concerning DM and HT both at diagnosis and at the last follow-up (LFU). We recorded the number of anti-HT and anti-DM drugs used at the first evaluation and at LFU for every patient., Results: Ninety-nine patients belonged to the REM group (concordant parameters), 65 patients were considered as GH dis (high random GH/controlled IGF-1), and 26 patients were considered as IGF-1 dis (high IGF-1/controlled random GH). At diagnosis, 72 patients (37.8%) had HT and 54 patients had DM (28.4%). There was no statistically significant difference in terms of the number of anti-HT and anti-DM drugs at diagnosis versus LFU (mean duration: 7.3 ± 4.5 years) between all three groups., Conclusion: The long-term outcome of DM and HT in acromegaly does not tend to be more severe in patients with biochemical discordance in comparison with patients considered as in remission on the basis of concordant biological parameters, suggesting that patients with biochemical discordance do not require a closer follow-up.

Posterior pituitary tumors are rare nonneuroendocrine neoplasms originating in the neurohypophysis that lack hormonal secretory capacity. Surprisingly, these tumors are relatively frequently associated with adenohypophyseal syndromes of hormonal hypersecretion such as Cushing's disease and acromegaly. Fifteen cases of posterior pituitary tumor associated with hypercortisolism have been reported to date, 13 of them were pituicytomas (Pi) and 2 were granular cell tumors (GCT). Six patients with posterior pituitary tumor associated with acromegaly have been reported (4 Pi and 2 GCT). The main forms of clinical presentation and the possible pathophysiological mechanisms of this association are reviewed.

Purpose: Acromegaly is considered an important cause of secondary osteoporosis. However, studies on bone mineral density (BMD) have yielded conflicting results and there are few studies that evaluate an accurate imaging method for early diagnosis of osteoporosis in these patients. The objective of this study was to assess whether entropy and uniformity on computed tomography (CT) scans are useful parameters for optimization of assessment of bone fragility in patients with acromegaly., Methods: We included 34 patients and 36 controls matched for age and sex in a cross-sectional study. Patients and controls underwent CT scan of the lumbosacral spine, dual-energy x-ray absorptiometry (DXA) and blood tests. A software was developed to calculate the entropy and uniformity by a region of interest (ROI) of the trabecular bone of the first lumbar vertebra (L1)., Results: The acromegalic group presented higher mean bone entropy (6.87 ± 0.98 vs. 6.03 ± 1.68, p = 0.013) and lower mean bone uniformity (0.035 ± 0.704 vs. 0.113 ± 0.205, p = 0.035) than control group. Analyzing only acromegalics, mean bone entropy was higher and bone uniformity was lower in patients with hypogonadism than patients without hypogonadism (7.28 ± 0.36 vs. 6.74 ± 1.08, p = 0.038 and 0.008 ± 0.002 vs. 0.043 ± 0.079, p = 0.031) respectively. Patients with acromegaly presented higher BMD and Z-score in the femoral neck than control group (1.156 ± 0.108 vs. 0.925 ± 0.326 g/cm 2 , p = 0.043 and 0.6 ± 0.6 vs. -0.05 ± 0.8, p = 0.041, respectively). Entropy was negatively correlated with T-score of the lumbar spine (r p  = -0.357, p = 0.033) in control group and uniformity was positively correlated with T-score of the lumbar spine, neck, and total hip, respectively (r p  = 0.371, p = 0.031; r p  = 0.348, p = 0.043 and r p  = 0.341, p = 0.049) in acromegalic group., Conclusions: The study identified that entropy and uniformity are a relevant parameters data in bone fragility assessment in acromegalic patients.

Background: Acromegaly is a rare disease characterized by a chronic exposition to growth hormone (GH) and insulin-like growth factor-1 (IGF-1), caused in most cases by a pituitary GH-secreting adenoma. Chronic GH excess induces systemic complications (metabolic, cardiovascular, respiratory, neoplastic, and musculoskeletal) and increased mortality if not appropriately treated. Recent epidemiological data report an improved life span of patients with acromegaly probably due to better acromegaly management; additionally, the number of pituitary incidentaloma in general population also increased over time due to more frequent imaging. Therefore, the number of elderly patients, newly diagnosed with acromegaly or in follow-up, is expected to grow in the coming years and clinicians will need to be aware of particularities in managing these patients., Purpose: This review aims to explore different aspects of acromegaly of the elderly patients, focusing on epidemiology, diagnosis, clinical presentation, complications, and management options., Methods: Available literature has been assessed through PubMed (data until August 2019) by specific keywords., Conclusions: Available data on acromegaly in the elderly patient are sparse, but point to important differences. Further studies are needed comparing elderly with younger patients with acromegaly to better define a tailored diagnostic and therapeutic management.

Purpose: In the general population, sleep disorders are associated with an increased risk of cognitive impairment. The prevalence of sleep disorders, such as sleep apnea, in acromegalic patients is higher than in the general population, and they may have additional risk of cognitive impairment due to acromegaly treatment and comorbidities. We aim to study the relationship between sleep disturbances and cognitive dysfunction in a group of acromegalic patients., Methods: We studied 67 consecutive acromegalic patients. We performed a neurocognitive assessment and patients completed the Acromegaly Quality of Life Questionnaire (AcroQoL), Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index., Results: Of the 67 acromegaly patients in the study, 38.8% were male and median age at the neurological examination was 56 (IQR 48, 65). Approximately 6-10% of patients had impaired cognitive assessment, depending on the test. In linear regression models adjusted for age, sex, BMI, disease duration, and disease activity, poorer sleep quality was associated with lower global cognitive z-score (B = -0.03, 95% CI -0.06, -0.002). Daytime somnolence was associated with poorer physical AcroQoL sub-score (B = -0.04, 95% CI -0.08, -0.002). Sleep quality was associated with poorer overall AcroQoL (B = -0.03, 95% CI -0.05, -0.006), physical AcroQoL (B = -0.04, 95% CI -0.07, -0.005), psychological AcroQoL (B = -0.02, 95% CI -0.04, -0.001), and social AcroQoL (B = -0.02, 95% CI -0.04, -0.0009)., Conclusions: In acromegaly patients, we found robust evidence that poor sleep quality is associated with poorer quality of life, and some evidence that it is associated with poorer cognitive function.

Purpose: To explore the effects of pegvisomant (PEGV) on glucose metabolism in patients with acromegaly within ACROSTUDY, an international, observational, prospective safety surveillance study., Methods: Patients were retrospectively divided into two cohorts, with (DM group) or without diabetes mellitus (no-DM). Parameters of glucose metabolism and IGF-I values were analyzed yearly both cross-sectionally for 4 years (yrs) and longitudinally at 1 and 4-5 yrs of PEGV treatment., Results: Among 1762 patients, 510 (28.9%) had DM before PEGV start. At cross-sectional analyses, in the DM group mean blood glucose was 140.0 ± 58.7 mg/dl at baseline, 116.4 ± 44.8 mg/dl at year 1 and 120.0 ± 44.3 mg/dl at yr 4. Mean HbA1c was 6.6 ± 1.2 % at yr 1 vs. 7.0 ± 1.4 % at baseline. HbA1c was above 6.5% in 61.9% at baseline and ranged from 45.4 to 53.8% at subsequent yearly time points. At the 4-yr longitudinal analysis, in the DM group (n = 109), mean blood glucose decreased by 20.2 mg/dl at yr 4, mean HbA1c was 7.0 ± 1.5% at baseline vs. 6.8 ± 1.4%. Patients achieved IGF-I normalization in 52.1% and 57.4% of cases in the DM and no-DM groups, respectively at 1 year. The mean daily PEGV dose (mg/day) was higher in the DM group (18.2 vs. 15.3) while the absolute change of IGF-I values from baseline was similar in both groups. PEGV was well tolerated in both groups without any unexpected AEs., Conclusions: Patients with DM had a moderate decrease in mean fasting glucose values during PEGV treatment.

Purpose: Patients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis., Methods: Cross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients' follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea investigations., Results: Of the 259 participants, 75 (29%) were diagnosed with sleep apnea before the study start. In 43 (57%) of these patients, sleep apnea had been diagnosed before the diagnosis of acromegaly. After clinical assessment and sleep studies, sleep apnea was diagnosed in an additional 20 patients, yielding a total sleep apnea prevalence of 37%. Higher sleep apnea risk was associated with higher BMI, waist circumference, and index finger circumference. Sleep apnea was more frequent among patients with S-IGF-1 levels in the highest quartile., Conclusion: Sleep apnea is common among patients with acromegaly, and is often diagnosed prior to their acromegaly diagnosis. These results support early screening for sleep apnea in patients with acromegaly and awareness for acromegaly in patients with sleep apnea.

Purpose: To evaluate the incidence of obstructive sleep apnea-hypopnea syndrome (OSAHS), explore the structural changes in pharyngeal soft tissue underlying OSAHS development and analyze the correlation between hormone levels and pharyngeal soft tissue changes in patients with untreated acromegaly., Methods: Twenty-five patients with untreated acromegaly were prospectively enrolled. Pituitary hormones were tested, sellar magnetic resonance imaging was confirmed, overnight polysomnography was conducted, and upper airway computed tomography was performed on these patients., Results: Patients with untreated acromegaly had a high incidence of OSAHS (52.0%, 13/25). The average age of the patients with OSAHS was 12 years older than that of patients without OSAHS (47.0 ± 8.5 years vs. 35.1 ± 9.5 years, p = 0.003). The posterior pharyngeal soft tissues were thicker in four different planes, including the planes of the soft palate, uvula, tongue and epiglottis (p = 0.003, 0.008, 0.027, and 0.003, respectively), and the soft palate (p = 0.024) was more hypertrophic in patients with acromegaly presenting with OSAHS than patients without OSAHS. The posterior pharyngeal wall thickness (cm) positively correlated with the serum insulin-like growth factor 1 (IGF-1) level (ng/ml) in the planes of the soft palate (slope = 0.001, p = 0.006) and epiglottis (slope = 0.002, p = 0.039)., Conclusions: OSAHS is a common complication in patients with untreated acromegaly, and advanced age is a risk factor. Posterior pharyngeal soft tissue thickening and soft palate hypertrophy are structural changes underlying OSAHS development in patients with acromegaly. Higher IGF-1 levels predict an increase in the posterior pharyngeal soft tissue thickness in patients with acromegaly.

Purpose: Oro-dental pathologies (ODP) such as enlargement of the tongue, mandibular prognathism, and spaced teeth are characteristic features of acromegaly. Their frequency of occurrence during the course of the disease is largely unresolved. Purpose of this study was to assess ODP and oro-dental treatments in patients with acromegaly with regard to the length of the diagnostic process, tumor histology, and quality of life (QoL)., Methods: Single-center retrospective survey study using questionnaires on dental symptoms, diagnostic process, and treatment in patients with acromegaly operated on a growth hormone-secreting pituitary adenoma. The association between ODP and QoL was assessed using the Short-Form 36 (SF-36) Health Survey., Results: 145/314 patients completed the questionnaires. 80.7% were affected by any ODP, most frequently enlargement of the tongue (57.9%), spaced teeth (42.8%), mandibular growth (24.1%), and mandibular prognathism (22.1%). ODP were significantly more frequent in patients with sparsely vs. densely granulated adenomas (p = 0.045). Early diagnosis within 2 years was associated with significantly fewer ODP than later diagnosis (68.5 vs. 87.2%, p = 0.009). Treatments included dental crowns (16.6%), dental bridges (12.4%), dental implants (9.7%), dental prostheses (3.4%), orthodontal (i.e., braces, 6.9%), and surgical correction of the teeth (2.1%). Physical QoL was significantly lower in patients with ODP than in those without (p = 0.014)., Conclusion: In our large series of patients, four of five patients were affected by ODP at any time during the course of the disease. The results highlight the importance of early identification and treatment of oro-dental problems in patients with acromegaly as hallmarks of the disease.

Purpose: Recent epidemiologic studies suggest a high prevalence of acromegaly. The prevalence of obstructive sleep apnea syndrome (OSAS) in acromegaly patients ranges from 47 to 70%. A recent study identified 2 patients with acromegaly among 567 OSAS patients. However, it remains unclear whether screening for acromegaly among OSAS patients is necessary. The aim was to screen for acromegaly among OSAS patients by measuring IGF-1 levels and performing confirmatory tests if necessary., Methods: We performed a prospective cross-sectional diagnostic study on the prevalence of acromegaly in patients with OSAS. A total of 507 patients with a confirmed diagnosis of OSAS (357 male, 150 female) were screened., Results: Seven male and three female patients (1.97% of total) were positively screened for elevated IGF-1 levels. Nine out of ten patients suppressed growth hormone levels during OGTT excluding acromegaly, whereas one individual was identified to have acromegaly according to established criteria (1/507, prevalence 0.2%). Analysis of the data showed no correlation between elevated IGF-1 values and the severity of OSAS or BMI., Conclusions: Our data demonstrate a low prevalence of acromegaly in patients with OSAS. Until data from population-based studies is available we suggest restricting screening for acromegaly in OSAS to those patients who have additional clinical features of acromegaly.

Purpose: To evaluate the gonadal functions and related factors in female patients with acromegaly at the time of diagnosis, the course of gonadal dysfunctions and pregnancies during the follow-up period, and the investigation of ovarian reserve with serum anti-Mullerian hormone (AMH) levels in patients with reproductive age., Methods: Patients who were not menopausal at the time of acromegaly diagnosis (n = 47) were included in this study. Baseline gonadal status was evaluated retrospectively. Patients were divided into three groups: normal gonadal function (group 1), gonadal dysfunction without central hypogonadism (group 2), and central hypogonadism (group 3). Group 1 and group 2 were compared in terms of clinical and laboratory findings. AMH levels were studied in patients who were ≤ 45 years old (n = 14) at the time of the study. Data related to pregnancies (n = 13) were evaluated retrospectively., Results: Group 1 included 18 patients (38%), group 2 included 18 patients (38%), and group 3 included 11 patients (24%). The estimated duration of acromegaly was longer, and baseline PRL levels were higher, in group 2 than group 1 (p = 0.002 and p = 0.015, respectively). Gonadal functions recovered in 66% of patients. AMH levels were low in 64% of patients. The frequency of maternal diabetes and hypertension was 7.7%, and there was no tumoral growth in any of the pregnancies., Conclusion: The most important factors affecting gonadal functions, excluding central hypogonadism, are hyperprolactinemia and the duration of the indolent period before diagnosis of acromegaly. AMH levels in the majority of patients were found to be lower than the expected age. Despite the decreased ovarian reserve, fertilization and normal birth can be achieved with careful surveillance.

Purpose: To investigate the characteristics of difficult intubation and identify novel efficient predictors in patients with acromegaly., Methods: Patients with either untreated acromegaly or non-functional pituitary adenomas were enrolled. Patients with acromegaly underwent hormone assays, upper airway computed tomography and magnetic resonance imaging examinations and preoperative overnight polysomnography. The modified Mallampati classification, mouth opening, neck circumference, and neck extension were assessed, and the Cormack-Lehane grades and the time of tracheal intubation were recorded., Results: Patients with acromegaly had a higher incidence of difficult intubation (62.5%). The time of tracheal intubation was prolonged, the neck circumference was enlarged, and the neck extension was confined. In patients with acromegaly and difficult intubation, the insulin-like growth factor 1 levels and apnea/hypoxia index were significantly higher compared to patients without difficult intubation (1115.40 ± 253.73 vs. 791.67 ± 206.62 ng/ml, P = 0.020; 22.17 ± 23.25 vs. 2.47 ± 2.84, P = 0.026, respectively). The bilateral regression analysis revealed that high levels of insulin-like growth factor 1 were an independent risk factor for developing difficult intubation (p = 0.042, Exp B = 1.006). The modified Mallampati classification was positively correlated with apnea/hypoxia index and could be calculated using the following logarithmic equation: MMC = 0.2982 * ln (AHI) + 2.1836., Conclusions: In patients with acromegaly, neck movement is confined, the time of tracheal intubation is prolonged, and the neck circumference is enlarged, and these patients suffer from an increased incidence of difficult intubation (62.5%) during anesthesia induction. The apnea/hypoxia index and insulin-like growth factor 1 levels are both increased in acromegalic patients with difficult intubation, and elevated insulin-like growth factor 1 levels are an independent risk factor of difficult intubation in acromegalic patients.

Comorbidities related to the cardiovascular system are one of the most prevalent in patients with acromegaly, and contribute to an increased risk of morbidity and all-cause mortality. Specifically, hypertension, cardiomyopathy, heart valve disease, arrhythmias, atherosclerosis, coronary artery disease, and cardiac dysfunction may be frequent findings. Although the underlying physiopathology for each comorbidity may not be fully elucidated, uncontrolled growth hormone/insulin-like growth factor 1 excess, age, prolonged disease duration, and coexistence of other cardio-vascular risk factors are significant influencing variables. A simple diagnostic approach to screen for the presence of these comorbidities may allow prompt treatment and arrest the progression of cardiac abnormalities. In this article, we revise the most prevalent cardiovascular comorbidities and their pathophysiology in acromegalic patients, and we address some recommendations for their prompt diagnosis, management and treatment. Strengths and pitfalls of different diagnostic techniques that are currently being used and how different treatments can affect these complications will be further discussed.

Pathogenesis and long-term outcome of obstructive sleep apnea syndrome (OSAS) in acromegalic patients are still under debate. The aim of the study was to assess the prevalence and long-term follow-up of a series of acromegalic patients with OSAS and to investigate site, degree, and possible causes of upper airway obstruction by morphological study. Cross-sectional and longitudinal study was conducted in 58 acromegalic patients (33 active, 25 controlled) with polysomnography in all subjects, repeated in 25 patients with OSAS, and echocardiography. Morphological study including fiberoptic nasopharyngoscopy with the Müller maneuver (FNMM), magnetic resonance imaging (MRI), with 3-dimensional (3D) elaboration was also performed. The prevalence of OSAS was 58.6 % in the whole series: 63.6 % in the active group and 52 % in the controlled one. Left ventricular hypertrophy was more prevalent in patients with OSAS. OSAS improved in 62.5 % of active patients after achieving hormonal control, whereas it persisted or got worse in 66.6 % of the controlled ones. The uvula and tongue base were the main site of obstruction assessed by FNMM. Uvula diameters obtained by MRI study correlated with the severity of upper airway collapse assessed by FNMM and tongue measure with apnea-hypopnea index (p = 0.044). A greater narrowing and a smaller total volume of upper airways were confirmed by 3D-MRI in patients with more severe OSAS. Uvula and tongue hypertrophy plays a relevant role in the pathogenesis and severity of OSAS. Intensive treatment of acromegaly needs to be promptly adopted in order to reverse it.

Evaluation of cognitive function in acromegaly has revealed contradictory findings; some studies report normal cognition in patients with long-term cured acromegaly, while others show attention and memory deficits. Moreover, the presence of affective disorders in these patients is common. Our aim was to evaluate memory and decision making in acromegalic patients and explore their relationship with affective disorders like anxiety and depressive symptoms. Thirty-one patients with acromegaly (mean age 49.5 ± 8.5 years, 14 females and 17 males) and thirty-one healthy controls participated in this study. The Iowa Gambling Task (IGT), Rey Auditory Verbal Learning Test, State-Trait Anxiety Inventory, and Beck Depression Inventory-II (BDI-II) were used to evaluate decision making, verbal memory, anxiety, and depressive symptoms, respectively. Acromegalic patients showed impairments in delayed verbal memory (p < 0.05) and more anxiety and depressive symptoms (p < 0.05) than controls. In the IGT, acromegalic patients presented an altered decision-making strategy compared to controls, choosing a lower number of the safer cards (p < 0.05) and higher number of the riskier cards (p < 0.05). Moreover, multiple correlations between anxiety and depressive symptoms and performance in memory and decision making were found. Impaired delayed memory and decision making observed in acromegalic patients are related to anxiety and depressive symptoms. Providing emotional support to the patients could improve their cognitive function. A key clinical application of this research is the finding that depressive symptoms and anxiety are essentially modifiable factors.

To summarize all available data on pregnancy outcome of acromegaly patients exposed to the growth hormone receptor antagonist pegvisomant (PEGV) during pregnancy as present in the Pfizer's Global Safety Database. Pfizer's Global Safety Database contains adverse event data obtained from the following sources: spontaneous reports, health authorities, Pfizer-sponsored post-marketing surveillance program (ACROSTUDY), customer engagement programs, and clinical studies, reported regardless of outcome. The safety database was searched up to 10th March 2014. From the 35 pregnancy cases, 27 involved maternal [mean age (range) 33.3 years (23-41) and 8 paternal (33.7 years (32-38)] PEGV exposure. Two female patients were reported with two pregnancy cases each. Fetal outcome was normal in 14 (4 paternal) of the 18 reported as live birth, while 4 cases (1 paternal) did not specify the birth outcome. At conception, PEGV mean dose (range) was 15.3 mg/d (4.3-30). In 3 cases of maternal exposure of the 18 cases reporting live birth, PEGV was continued throughout the pregnancy in a dose of 12.1 mg/d (10-15). In 5 cases (all maternal) an elective termination of the pregnancy was performed with no reported fetal abnormalities, 2 cases (maternal) reported a non-PEGV-related spontaneous abortion and in 1 maternal case an ectopic pregnancy occurred. In 9 cases (3 paternal), the fetal outcome was not reported. Three women reported gestational diabetes; one woman continued PEGV treatment during pregnancy. Although the number of reported pregnancies with exposure to PEGV is very small, the presented data reflect the largest series of data available to date and do not suggest adverse consequences of PEGV on pregnancy outcome. Nevertheless, it should be stressed that PEGV should not be used during pregnancy unless absolutely necessary.

The purpose of this study was to evaluate the safety of the oral glucose tolerance test (OGTT) and its capacity to suppress growth hormone (GH) in diabetic patients without acromegaly. A total of 135 diabetic patients submitted to the OGTT for GH suppression were studied. The following selection criteria were applied: age between 20 and 70 years; body mass index≥18.5 and ≤27 kg/m2; absence of kidney, liver, or thyroid disease; no use of estrogens, androgens, corticosteroids, or levothyroxine. Adequate suppression of GH was defined as a nadir below the cut-off established for a sample of 200 normoglycemic subjects (<0.25 µg/L for men, <0.74 µg/L for premenopausal women, and <0.5 µg/L for postmenopausal women). Acromegaly was diagnosed in five patients. Among the 130 diabetic patients without known pituitary disease or a clinical suspicion of acromegaly, 95.5% of men, 94% of premenopausal women, and 96.6% of postmenopausal women presented adequate GH suppression (vs 97.5% of normoglycemic controls). In all patients without acromegaly, the lowest GH levels (nadir) were achieved after the administration of glucose and not during baseline measurement. None of the patients had acute complications [ketoacidosis, hyperosmolar state, and symptomatic marked hyperglycemia (>300 mg/dL)] on the day of the test and up to 3 days thereafter. We demonstrated the safety of the OGTT and its capacity to suppress GH in diabetic patients without acromegaly. In addition, we suggest the adoption of a protocol to prevent possible risks of the OGTT in patients with diabetes.

Several studies have shown that acromegaly is associated with increased psychological morbidity. However, it is not known whether this is attributed to acromegaly per se or to its chronicity as a debilitating disease affecting quality of life (QoL). The aim of this study was to assess psychological profile in acromegalics compared with those suffering from other serious chronic diseases and healthy controls. Secondary end points were QoL assessment and its association with mood disturbances. Comparative, cross-sectional study conducted in Northern Greece (2011-2012). The Greek versions of the Profile of Mood States (POMS) and AcroQoL questionnaires were used to assess psychological status and QoL, respectively. Forty acromegalics, 40 age- and sex-matched people with other chronic diseases and 80 healthy controls were included. No significant differences were identified between acromegalics and those suffering from other chronic diseases, regarding tension, anger, depression, confusion, fatigue and vigor. Compared with healthy controls, acromegalics suffered more from depression and anger, which remained significant after controlling for age, gender and marital status (p = 0.003 and p = 0.048, respectively). Negative predictors were female gender, macroadenomas and radiotherapy. AcroQoL scores were negatively associated with POMS subscales. Males had better QoL than females. Other than a negative association between AcroQoL-relationships subscale and disease duration, no association with other parameters was observed. Acromegaly has a negative impact on psychological status, which is worse than that of general population, but comparable to other chronic diseases. Mood disturbances are associated with impaired QoL, mainly in females and those with longer disease duration.

Prediction of ischemic cardiovascular events (ICE) in acromegalic patients stratified accordingly with Framingham (FS) and Agatston score (AS). 32 patients with active (group A (0)) and 20 with controlled (group B (0)) acromegaly have been enrolled. During the 5-year follow-up, 19 out of 32 patients in group A (0) reached disease control. At entry, FS and AS, by an eight-slice MDCT scanner, were calculated in all patients. ICE were diagnosed by autopsy, if lethal, and by electrocardiography and/or echocardiography, if non-lethal. Overall, 9.6 % of patients died for lethal ICE. AS >400, but not high FS at entry, was associated with increased risk of lethal ICE. Lethal ICE had occurred in two patients of group A (0) and three of group B (0) (p NS), while a non-lethal ICE had occurred in two cases of the former and in other two of the latter group (p NS). Either FS or AS was correlated with the risk for ICE overall (p < 0.02), but only AS correlated with that of lethal ICE (p < 0.0003). Survival analysis demonstrated reduced life expectancy in patients with high FS (p < 0.02). In acromegalics, AS >400 is associated with increased risk of lethal ICE, while high FS is associated with reduced life expectancy, regardless of disease control.

Pituitary adenomas (PAs) represent 15 % of all brain tumors. One-sixth of these are reported to cause acromegaly via excess growth hormone secretion. These tumors have been associated with multiple comorbidities, including neuropsychiatric and cognitive dysfunction. We aimed to assess patient perception of cognitive deficits and the relationship of cognitive changes to active acromegaly (AA) versus controlled acromegaly (CA) versus non-functional PAs (NFPA). A modified FACT-Cog survey was used, which focused on the prevalence and severity of perceived dysfunction in five areas of cognitive function: ability to learn, concentration/distractibility, mental agility, memory and recall, and verbal recall. Patient perception of current health and health change over the previous 12 months was also assessed. The overall perceived prevalence and severity of cognitive dysfunction were the highest among NFPA groups, particularly in the areas of mental agility, verbal recall, and memory/recall. Patients with AA reported greater prevalence and severity of dysfunction with respect to concentration/distractibility and ability to learn. Patients with AA reported the best overall current health, though patients with CA reported the greatest improvement in health over the previous year. These findings may indicate that PAs can affect cognitive function regardless of whether excess growth hormone is present. Acromegaly and NFPA patients perceive specific areas of cognitive dysfunction that may require further evaluation and treatment. Further research may be useful regarding patient quality of life, patient functionality during normal daily activities, and perceived dysfunction despite biological disease control.

Thyroid diseases are frequently seen in patients with acromegaly. The aim of this study is to evaluate thyroid diseases and thyroid cancer in acromegalic patients followed in a single institution. The data of 92 acromegalic (43 male, 49 female) patients followed over 12 years were retrieved retrospectively from the hospital recordings. All available data for gender, age, body weight and height, duration of acromegaly, age at diagnosis of acromegaly, treatment methods for acromegaly and history of thyroid disease, serum GH, IGF-1, thyroid function tests, thyroid ultrasonography (US), thyroid scintigraphy and thyroid fine needle aspiration biopsy (FNAB) results were recorded for the patients. The mean age of the patients was 43.9 ± 10.8 years and the mean disease duration was 12 ± 6.9 years. Thyroid US was performed in 64 patients who had nodular or diffuse goiter on palpation during the post-treatment follow-up and nodules were found in 44 (47.8 %) patients. Final diagnosis in 64 patients with thyroid US results and thyroid function tests including 26 patients with FNAB were as follows: 31 (48.4 %) benign multinodular goiter (MNG), 6 (9.4 %) simple nodular goiter, 1 (1.6 %) toxic MNG, 1 (1.6 %) Hurthle cell adenoma, and 5 (7.8 %) differentiated thyroid cancer. In addition, 9 (14.1 %) patients had diffuse goiter. One of the patients with diffuse goiter had amiodarone induced thyrotoxicosis. Eleven (17.1 %) patients had normal thyroid US and no other thyroid disease. Patients with nodules had longer disease duration than patients without nodules (14.2 ± 6.6 vs. 9.4 ± 3.4 years, p = 0.043). Thyroid volume was positively correlated with post-treatment GH and post-treatment IGF-1 levels (r = 0.309, p = 0.041 and r = 0.423, p = 0.004), respectively. We found that 7.8 % of our acromegalic patients with thyroid US results were diagnosed with thyroid cancer. Therefore, acromegalic patients must be considered as a high risk group for the development of thyroid cancer and must be closely followed for thyroid nodules and tumors.

Acromegaly is associated with a variety of cardiovascular disturbances such as left ventricular hypertrophy, diastolic cardiac dysfunction, and hypertension. Left ventricular (LV) dyssynchrony means the impairment of synchronicity and is defined as the loss of the simultaneous peak contraction of corresponding cardiac segments. The objective of this study was to investigate whether acromegalic patients have left ventricular dyssynchrony. Dyssynchrony was evaluated in 30 patients with active acromegaly and 30 controls. All the patients and controls were subjected to a tissue synchronization imaging. The time to regional peak systolic tissue velocity (Ts) in LV by the six-basal-six-mid-segmental model was measured on ejection phase TSI images and four TSI parameters of systolic dyssynchrony were computed. All TSI parameters of LV dyssynchrony increased in patients with acromegaly compared to the controls: the standard deviation (SD) of the 12 LV segments Ts (43.5 ± 13.5 vs 26.2 ± 12.5, p < 0.001); the maximal difference in Ts between any 2 of the 12 LV segments (133.3 ± 38 vs 84.6 ± 37.6, p < 0.001); the SD of the 6 basal LV segments (41.1 ± 15.9 vs 25.4 ± 14.8, p = 0.001); and the maximal difference in Ts between any 2 of the 6 basal LV segments (102.6 ± 37.5 vs 65.2 ± 36.9, p = 0.001). In addition, there were significant relationships between the levels of growth hormone/insulin-like growth factor-1 and Ts-SD-12. LV synchronicity has been impaired in patients with acromegaly. Left ventricular dyssynchrony is associated with disease activity and it may contribute to the harmful cardiovascular effects of acromegaly.

Acromegaly is a chronic endocrinopathy characterized by the hypersecretion of growth hormone and insulin-like growth factor-1. Musculoskeletal pain is a frequent problem encountered in acromegaly and is associated with a reduction in the quality of life. In this study, the presence of inflammatory and degenerative rheumatologic diseases in acromegaly has been retrospectively evaluated. Forty patients with acromegaly who were in remission according to laboratory findings, but still having joint and back pain problems, were referred to rheumatology outpatient clinic and all the patients were examined by clinical, radiological, and laboratory data. Mean age was 47.1 years (22-75). When the radiological data were evaluated, erosions of the left sacroiliac joint were found by means of magnetic resonance imaging in 1 patient and degenerative joint changes were observed in 24 patients by X-ray imaging. However, there was no pathology in the radiological data of 15 patients. Laboratory data revealed antinuclear antibody positivity (3 nucleolar and 1 homogeneous) in 4 patients, rheumatoid factor positivity in 4, and cyclic citrullinated peptide positivity only in 1 patient. The diagnosis of an inflammatory rheumatologic disease, including rheumatoid arthritis, ankylosing spondylitis, or undifferentiated connective tissue disease was made in 3 patients. Besides, the diagnosis of diffuse idiopathic skeletal hyperostosis was also established in 6 patients. While degenerative joint diseases were frequently observed in our group similar to the literature, inflammatory rheumatologic diseases were also found in three patients. Distinguishing these two diseases is important because response to medical treatment is dramatically better in inflammatory diseases than in degenerative pathologies. A multidisciplinary approach is imperative for appropriate management of these patients.

Acromegaly is a rare condition caused by a pituitary adenoma that secretes growth hormone. The mortality rate is 72 % higher in patients with acromegaly than in the general population according to meta-analyses. Mortality analysis has shown as many as 60 % of acromegalic patients die due to cardiovascular disease. Sudden cardiac death may occur in patients with acromegaly and malignant ventricular arrhythmia may play an important role in this fatal complication; however, the precise mechanism is not fully known. QT dispersion (dQT) is an electrophysiological factor known to be associated with a tendency for ventricular arrhythmia and sudden cardiac death. This study aimed to evaluate dQT as an early predictor of ventricular tachyarrhythmia, as sudden cardiac death commonly occurs in acromegalic patients. This cross-sectional case-control study enrolled 20 patients (10 female and 10 male) with acromegaly and 20 healthy controls (11 female and 9 male) after exclusion criteria were applied. Each participant underwent 12-lead electrocardiography, including ≥3 QRS complexes, at a speed of 25 mm/s after a 15-min rest. In each participant, the QT interval (beginning of the Q wave to the end of the T wave) was corrected (QTc) for heart rate using Bazett's formula [Formula: see text] QTc dispersion (dQTc) (QTc max - QTc min) was also calculated. There was no significant difference in median dQTc between the acromegalic patients (0.79 s) and the controls (0.45 s) (p > 0.05). Active acromegalic patients (n = 14) were estimated to have a median dQTc of 0.82 s, after excluding from the analysis six patients that were under full biochemical control, and that had randomly obtained growth hormone levels <0.4 ng/mL, GH <1 ng/mL based on oral glucose tolerance test, and normal IGF-I for age and gender. A significant difference was noted in median dQTc between the active acromegalic patients and the controls (p = 0.015). The dQT in active acromegalic patients was longer than that in the control group, which indicates that patients with active acromegaly might have an elevated risk for ventricular arrhythmia. We think that a non-invasive, simple and inexpensive marker-measurement of dQT-as part of cardiac monitoring could be valuable for screening complications in acromegalic patients.

Acromegaly is frequently complicated by fragility vertebral fractures and diabetes mellitus. Since type 2 diabetes mellitus is a cause of secondary osteoporosis in the general population, in this cross-sectional study we aimed at investigating the association between diabetes mellitus and vertebral fractures in males with acromegaly. Fifty-seven patients (median age 47 years, range: 24-85) with active (21 cases) and controlled (36 cases) acromegaly and 57 control subjects were evaluated for bone mineral density (BMD) by DXA and vertebral fractures by a quantitative morphometric analysis. Diabetes mellitus was found in 18 patients and 18 control subjects. The prevalence of vertebral fractures was higher in acromegalic patients as compared with the control subjects (50.9 vs. 10.5%; χ(2): 21.8; P < 0.001). Acromegalic patients with fractures had serum IGF-I values significantly higher (P = 0.009), longer duration of active disease (P < 0.001) and higher prevalence of active acromegaly (P = 0.007) and diabetes mellitus (P = 0.04) as compared to patients who did not fracture. When acromegaly was active, the prevalence of vertebral fractures was high independently of the coexistent diabetes mellitus. On the contrary, when acromegaly was controlled the prevalence of vertebral fractures was significantly higher in patients with diabetes as compared to patients without diabetes (62.6 vs. 28.0%; P = 0.04). In both diabetic and non diabetic patients, vertebral fractures occurred independently of BMD. In conclusion, this study suggests that diabetes mellitus may be associated with an increased prevalence of vertebral fractures in males with acromegaly. However, this effect seems to be relatively attenuated in the presence of persistent GH hypersecretion.

McCune-Albright syndrome (MAS) is a sporadic disorder characterized by the classic triad of polyostotic fibrous dysplasia, café-au-lait' skin pigmentation, and hyperfunctional endocrinopathy. It is caused by embryonic somatic mutations leading to the substitution of His or Cys for Arg at amino acid 201 of the alpha-subunit of the signal transduction protein Gs (Gsalpha). A 32-year-old man was diagnosed as McCune-Albright syndrome with the following findings: polyostotic fibrous dysplasia, café-au-lait' spots and acromegaly. An ultrasonic examination showed that he had left-pleural effusion, which disappeared after almost a year without special treatment. Genomic DNA was isolated from the peripheral blood, bone tissue, skin lesion and pleura samples of the patient. Then PCR and direct sequencing were performed. An activating mutation of the Gsalpha gene (Arg201Cys) was found in the genomic DNA isolated from the peripheral blood and the bone tissue, but not in genomic DNA isolated from the skin and pleura samples.

Carbohydrate intolerance is a common feature of acromegaly. Frank diabetes mellitus is seen in about 10-20% of patients. There is no report of acromegaly presenting with diabetic ketoacidosis (DKA), associated with retinitis pigmentosa (RP), in the literature. We report the occurrence of DKA and RP in a patient with acromegaly. A 39-year-old Turkish man was admitted to the emergency ward with a 1-mo history of thirst, polyuria, weight loss of 10 kg, and loss of consciousness for 2 d. Physical examination revealed findings suggestive of acromegaly, including coarse facial features and enlargement of his hands and feet. At ophthalmological examination, funduscopy showed RP. Laboratory studies confirmed the diagnoses of DKA and acromegaly. Magnetic resonance imaging disclosed the presence of a pituitary adenoma. During the medical treatment with octreotide, symptomatic sinusoidal bradycardia was developed (pulse rate 45 bpm, and blood pressure 70/40 mmHg). Octreotide therapy was stopped. Pituitary adenoma was removed surgically. For treatment of DKA, insulin need was very high in the first days after the onset of ketoacidosis, but decreased after initiation of treatment with octreotide and after successful operation. Insulin was stopped 7 d after surgery. Follow-up showed normalization of growth hormone levels and plasma glucose levels. Only six other cases of DKA associated with acromegaly and only three other cases of RP associated with acromegaly were found in the medical literature. In conclusion, to our knowledge, the present case is a first report of DKA and RP in patient with acromegaly.

In this study, we investigated gingival enlargement in patients with acromegaly as a component of the disease. Eleven patients (5 males, 6 females) were evaluated. Diagnosis was confirmed with typical clinical features and laboratory. Oral examinations were carried out by the same periodontist. During the examination, plaque index, gingival index, probing pocket depths, and gingival enlargement values were evaluated. Duration of the disease was between 0.2 and 13 yr. Seven patients had pituitary macroadenomas and four had microadenomas during their initial diagnosis. Only one patient was newly diagnosed. The other patients had previously undergone surgery. Gingival enlargement was found in eight patients. Seven patients with gingival enlargement also had prognathism, and one patient had prognathism associated with gingival enlargement. These findings demonstrate that acromegaly that results in overgrowth in various organs should be considered one of the causes of gingival enlargement.