Binge Eating and Compulsive Buying During Cabergoline Treatment for Prolactinoma: A Case Report.

Prolactinomas are the most prevalent functional pituitary adenomas. They are usually treated clinically with dopamine agonists. The most widely used and suitable drug is cabergoline (CAB), a specific D2 dopamine agonists. Patients in prolactinoma treatment with CAB commonly report physical side effects, but aberrant behavioral changes such as increased impulsivity have also been reported recently. We report the case of a 47-year-old Brazilian woman with prolactinoma that developed compulsive buying, binge eating, and hypersexuality after four years of CAB treatment. In her psychiatric evaluation, the patient scored high levels on the following scales: Compulsive Buying Scale (CBS), Binge Eating Scale (BES), and Barratt Impulsiveness Scale-11 (BIS11). She also reported financial problems and weight gain in addition to her social and clinical problems. Impulsivity disorders may appear with the use of CAB and other dopamine agonists. We suggest that more observational studies with a large patient sample and specific regular psychiatric evaluations during treatment are necessary for patients in use of CAB, especially those treated for several years.

Identification of mutant K-RAS in pituitary macroadenoma.

PURPOSE: RAS genes are among the most frequently mutated genes in cancer, where their mutation frequency varies according to the distinct RAS isoforms and tumour types. Despite occurring more prevalent in malignant tumours, RAS mutations were also observed in few benign tumours. Pituitary adenomas are examples of benign tumours which vary in size and aggressiveness. The present study was performed to investigate, via liquid biopsy and tissue analysis, the presence of K-RAS mutations in a pituitary macroadenoma. METHODS: Molecular analysis was performed to investigate K-RAS mutations using the droplet digital PCR (ddPCR) method by evaluating both plasma (liquid biopsy) and the solid tumour of a patient diagnosed with a giant clinically non-functioning pituitary tumour. RESULTS: The patient underwent surgical resection due to visual loss, and the histopathological analysis showed a gonadotrophic pituitary macroadenoma. The molecular analysis revealed the presence of mutant K-RAS both in the plasma and in the tumour tissue which, to our knowledge, has not been previously reported in the literature. CONCLUSION: Our findings highlight the exceptional capacity of the digital PCR in detecting low frequency mutations (below 1%), since we detected, for the first time, K-RAS mutations in pituitary macroadenoma. The potential impact of K-RAS mutations in these tumours should be further investigated.

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism.

Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

What is the potential function of microRNAs as biomarkers and therapeutic targets in COVID-19?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19, a pandemic associated with substantial morbidity and mortality. Despite of this, no vaccine or approved drug is available to eradicate the virus. In this manuscript, we present an alternative study area that may contribute to development of diagnostic biomarkers and therapeutic targets for COVID-19. We analyzed sixty SARS-CoV-2 genomes to identify regions that could work as virus-encoded miRNA seed sponges and potentially bind to human miRNA seed sites and prevent interaction with their native targets thereby relieving native miRNA suppression. MicroRNAs (miRNAs) are evolutionally conserved single-stranded RNAs that regulate gene expression at the posttranscriptional level by disrupting translation. MiRNAs are key players in variety of biological processes that regulate differentiation, development and activation of immune cells in both innate and adaptive immunity. We find 34 miRNAs for positive-sense viral RNA and 45 miRNAs for negative-sense that can strongly bind to certain key SARS-CoV-2 genes. The disruption and dysfunction of miRNAs may perturb the immune response and stimulate the release of inflammatory cytokines altering the cellular response to viral infection. Previous studies demonstrate that miRNAs have the potential to be used as diagnostic and therapeutic biomarkers. Therefore, its discovery and validation are essential for improving the diagnosis of infection and clinical monitoring in COVID-19.

Determinants of morbidities and mortality in acromegaly

ABSTRACT Acromegaly is a systemic disease associated with increased morbidity, presenting cardiovascular, metabolic, respiratory, neoplastic, endocrine, articular and bone complications. Most of these comorbidities can be prevented or delayed with adequate disease treatment and, more recent studies with the use of modern treatments of acromegaly, have shown a change in the severity and prevalence of these complications. In addition, acromegaly is associated with increased mortality, but recent studies (especially those published in the last decade) have shown a different scenario than older studies, with mortality no longer being increased in adequately controlled patients and a change in the main cause of death from cardiovascular disease to malignancy. In this review, we discuss this changing face of acromegaly summarizing current knowledge and evidence on morbimortality of the disease. Arch Endocrinol Metab. 2019;63(6):630-7

The effectiveness of a therapist-oriented home rehabilitation program for a patient with acromegaly: A case study.

BACKGROUND: Acromegaly causes numerous functional limitations that negatively impact patients' performance of activities of daily living (ADLs) and contribute to the deterioration of health-related quality of life (HRQoL). Thus, the purpose of the present case study was to evaluate the effect of therapist-oriented home rehabilitation (TOHR) for a patient with acromegaly. CASE DESCRIPTION: We report the case of a 53-year-old man who was diagnosed with primary acromegaly 17 years ago. He complained of difficulties performing tasks that involved his hands, pain in the lower limbs, and fatigue when he climbed a few flights of stairs. Although he performed ADLs independently, he reported some difficulties or discomfort when performing them. INTERVENTION AND OUTCOME: The patient underwent a booklet-guided physical exercise program that lasted two months (three times per week, 60 minutes per session). The activities included overall stretching, muscle strengthening, and endurance exercises, along with aerobic conditioning through functional circuit training. After two months of exercise, he reported improved HRQoL as assessed with the Acromegaly Quality of Life Questionnaire, with increases in quadriceps muscle strength and 6-min walking distance. However, none of these benefits remained when the patient was assessed after a 1-month washout period. CONCLUSION: This study showed that patients with acromegaly may benefit markedly from TOHR, which could provide a novel therapeutic approach as an adjunct to hormone control therapy.

Brazilian multicenter study on pegvisomant treatment in acromegaly.

OBJECTIVE: Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. SUBJECTS AND METHODS: Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. RESULTS: 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. CONCLUSIONS: In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.

Brazilian multicenter study on pegvisomant treatment in acromegaly

ABSTRACT Objective Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. Subjects and methods Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. Results 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. Conclusions In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.

Determinants of morbidities and mortality in acromegaly.

Acromegaly is a systemic disease associated with increased morbidity, presenting cardiovascular, metabolic, respiratory, neoplastic, endocrine, articular and bone complications. Most of these comorbidities can be prevented or delayed with adequate disease treatment and, more recent studies with the use of modern treatments of acromegaly, have shown a change in the severity and prevalence of these complications. In addition, acromegaly is associated with increased mortality, but recent studies (especially those published in the last decade) have shown a different scenario than older studies, with mortality no longer being increased in adequately controlled patients and a change in the main cause of death from cardiovascular disease to malignancy. In this review, we discuss this changing face of acromegaly summarizing current knowledge and evidence on morbimortality of the disease. Arch Endocrinol Metab. 2019;63(6):630-7.

Computed tomography airway lumen volumetry in patients with acromegaly: Association with growth hormone levels and lung function.

INTRODUCTION: The segmentation and skeletonisation of images via computed tomography (CT) airway lumen volumetry provide a new perspective regarding the incorporation of this technique in medical practice. Our aim was to quantify morphological changes in the large airways of patients with acromegaly through CT and, secondarily, to correlate these findings with hormone levels and pulmonary function testing (PFT) parameters. METHODS: This was a cross-sectional study in which 28 non-smoker patients with acromegaly and 15 control subjects underwent CT analysis of airway lumen volumetry with subsequent image segmentation and skeletonisation. Moreover, all participants were subjected to PFT. RESULTS: Compared with the controls, patients with acromegaly presented higher diameters in the trachea, right main bronchus and left main bronchus. The patients with acromegaly also showed a higher tracheal sinuosity index (the deviation of a line from the shortest path, calculated by dividing total length by shortest possible path) than the controls [1.06 (1.02-1.09) vs. 1.03 (1.02-1.04), P = 0.04], and tracheal stenosis was observed in 25% of these individuals. The tracheal area was correlated with the levels of growth hormone (rs  = 0.45, P = 0.02) and insulin-like growth factor type I (rs  = 0.38, P = 0.04). The ratio between the forced expiratory flow and forced inspiratory flow at 50% of the forced vital capacity was correlated with the tracheal area (rs  = 0.36, P = 0.02) and Δ tracheal diameters (rs  = 0.58, P < 0.0001). CONCLUSION: Patients with acromegaly exhibit tracheobronchomegaly and tracheal sinuosity/stenosis. Moreover, there are associations between the results of CT airway lumen volumetry, hormone levels and functional parameters of large airway obstruction.

Balance Control and Peripheral Muscle Function in Aging: A Comparison Between Individuals with Acromegaly and Healthy Subjects.

Advances in the knowledge of acromegaly are leading to an increase in the survival rate of acromegalic subjects. This study was conducted to evaluate balance control, risk of falls, and peripheral muscle function in acromegalic older adults. Seventeen older subjects with acromegaly (67 [63-73] years) and 20 paired control subjects were evaluated with balance scales, force platform, and knee isokinetic dynamometry tests. There were significant differences between the groups on several balance and gait scales, with a worse performance and greater risk of falls in the acromegalic older adults. Acromegalic older adults had lower values for peak torque, maximum repetition of the total work, and total work during extension at 240°/s. The acromegalic older adults had higher values in the medial-lateral range. Acromegaly subjects had lateral instability that compromises their body balance and increases the risk of falls. Moreover, there was a propensity for muscle fatigue in these individuals.

What is the effect of peripheral muscle fatigue, pulmonary function, and body composition on functional exercise capacity in acromegalic patients?

[Purpose] The six-minute walk test (6MWT) is increasingly being used as an important tool for analyzing functional capacity in patients with multisystem disorders. The aim of this study was to evaluate the effect of body composition, peripheral muscle function, and pulmonary function on the six-minute walk distance (6MWD) in acromegalic patients. [Subjects and Methods] Thirty-two patients with active acromegaly, with a mean age of 48.6 ± 12.1 years, underwent an evaluation of body composition using electrical bioimpedance, isometric dynamometry with surface electromyography, tests of pulmonary function, and the 6MWT. [Results] The mean ± SD values for the 6MWD, fat-free mass (FFM), and maximal expiratory pressure (MEP) were 65.5 ± 11.7% predicted, 55.1 ± 10.6 kg, and 55.2 ± 16.8% predicted, respectively. There was a significant correlation between the 6MWD and the following parameters: the angle of the linear regression line obtained using the values of the median frequency electromyography signal over time during the fatigability test for the vastus medialis muscle (MDF, r=0.65), FFM (r=0.62), MEP (r=0.60), height((2))/resistance index (r=0.52), resistance (r=-0.50), and forced expiratory volume in 1 second (r=0.50). Multivariate analysis showed that MDF, FFM, and MEP were independent predictors of the 6MWD (R(2)=0.52). [Conclusion] The fatigability of the peripheral muscles, FFM, and MEP are the primary determinants of the 6MWD in acromegalics.

Posture and balance control in patients with acromegaly: results of a cross-sectional study.

Acromegaly is a chronic debilitating disease that presents with multiple systemic manifestations, including changes in body composition, joint abnormalities, muscular impairment and visual disturbances. This study aimed to assess posture and body balance in acromegalic patients and to establish the correlation between these measures. Twenty-eight acromegalic patients and a similar number of control subjects matched for sex, age, weight, height and body mass index underwent postural evaluation using the photogrammetry and measurement of balance using the stabilometry in two tasks: feet apart, eyes open and feet together, eyes closed. In comparison with the control group, the acromegalic group presented postural deviations in lateral views in the vertical alignment of the trunk (P=0.001 for the right side and P=0.021 for the left), the hip angle (P=0001 for the right side and P=0.016 for the left side) and horizontal alignment of the pelvis (P=0.017 for the right and P<0.001 for the left side). Compared with healthy subjects, the acromegalic patients presented displacement of the centre of pressure in both the anterior-posterior direction and the medial-lateral direction in both evaluated tasks. We observed significant correlations between balance measures and the following posture evaluation variables: distance between the lower limbs, horizontal alignment of the head and vertical alignment of the head. Our results suggest that posture and balance need to be evaluated for acromegalic patients in clinical practice, as there are significant postural imbalances and deviations in these patients.

Prevalence of obstructive sleep apnea in patients with prolactinoma before and after treatment with dopamine agonists.

OBJECTIVES: Obesity is the main risk factor for the development of obstructive sleep apnea (OSA). Hyperprolactinemia has also been related to obesity. To determine the OSA prevalence in patients with prolactinoma before and after dopamine agonist (DA) and to evaluate the correlation between the apnea-hypopnea index (AHI) and prolactin levels, body mass index (BMI), waist circumference (WC), visceral fat volume (VFV), subcutaneous fat volume, and other metabolic parameters. METHODS: Thirty-five patients with prolactinoma at baseline and twenty-one who completed the 6-month DA treatment were submitted to clinical/laboratorial evaluations, polysomnography and abdominal imaging. RESULTS: Before treatment, the prevalence of obesity/overweight and OSA were, respectively, 68.5 and 34.2 %. We found a positive correlation between AHI and weight (r = 0.57; p < 0.001), BMI (r = 0.56; p < 0.001), WC (r = 0.61; p < 0.001), VFV (r = 0.55; p = 0.002), insulin levels (r = 0.57; p < 0.001), and HOMA-IR index (r = 0.57; p < 0.001); and a negative correlation between AHI and HDL-cholesterol (r = -0.47; p = 0.005). After multivariate analysis, VFV and insulin levels were the most important predictors for AHI (p = 0.001 and p = 0.02, respectively). After DA, the obesity/overweight and OSA prevalence did not change. CONCLUSIONS: The OSA prevalence in patients with prolactinoma is similar to the obese subjects and did not change after treatment. Higher BMI and visceral obesity, but not prolactin levels, seem to be the major factor involved in the occurrence of OSA in these patients.

Prevalence of thyroid diseases in patients with acromegaly: experience of a Brazilian center / Prevalência das doenças tireoidianas em pacientes com acromegalia: experiência de um centro brasileiro

OBJECTIVES: Acromegaly is frequently associated with thyroid diseases. In this study, we evaluated the frequency of thyroid disorders in a series of acromegalic patients. SUBJECTS AND METHODS: We evaluated 106 acromegalic patients using thyroid ultrasonography (US) and measurements of GH, IGF-I, free T4, TSH and anti-thyroperoxidase antibody levels. IGF-I was expressed in mass units and age-related standard deviation scores (SD-scores). Fine-needle aspiration biopsy (FNAB) was performed on thyroid nodules with a diameter greater than one centimeter or with suspicious characteristics. RESULTS: Thyroid disorders were found in 75 patients. Eleven patients had diffuse goiter, 42 patients had nodular goiter, and 22 patients had unspecific morphological abnormalities. Four patients (3.8%) had thyroid carcinoma. Considering the patients with diffuse or nodular goiter, thyroid volume was greater in patients with active acromegaly, and was positively correlated with GH, IGF-I, and IGF-I SD-score. CONCLUSIONS: Our study confirmed that benign thyroid diseases are frequent in acromegalic patients. The prevalence of thyroid cancer was higher than in the overall population. We suggest that thyroid US should be routinely performed in patients with acromegaly.

OBJETIVOS: Acromegalia está frequentemente associada a doenças tireoidianas. Neste estudo, avaliamos a presença de tireoidopatias em uma série de pacientes acromegálicos. SUJEITOS E MÉTODOS: Foram avaliados 106 pacientes por ultrassonografia (US) e dosagens de GH, IGF-1, T4 livre, TSH e anticorpo antitireoperoxidase. O IGF-I foi expresso em unidades de massa e desvio-padrão (DP-IGF-I). Punção aspirativa por agulha fina (PAAF) foi realizada quando os nódulos eram maiores que um centímetro ou tinham características suspeitas. RESULTADOS: Alterações tireoidianas foram encontradas em 75 pacientes. Onze apresentavam bócio difuso, 42, bócio nodular e 22, alterações morfológicas inespecíficas. Houve quatro casos (3,8%) de câncer diferenciado de tireoide. Considerando os pacientes com bócio difuso ou nodular, o volume tireoidiano foi maior naqueles com acromegalia em atividade e correlacionou-se positivamente com os níveis de GH, IGF-1 e DP-IGF-1. CONCLUSÕES: Nosso estudo confirmou que as doenças tireoidianas benignas são frequentes nos pacientes acromegálicos. A prevalência de câncer diferenciado de tireoide foi maior que na população geral. Sugerimos que US de tireoide seja realizado rotineiramente nos pacientes com acromegalia.

Pulmonary function testing and chest tomography in patients with acromegaly.

BACKGROUND: Despite the gradual improvement in treatment procedures and cure rates of acromegaly, a steady increase in the mortality rate due to respiratory disease has been documented in recent decades. In this study, our objectives were to describe the abnormalities in lung structure and function that occur in acromegalic patients and to correlate these changes with hormonal levels. METHODS: This cross-sectional study included 20 acromegalic patients and 20 age-and height-matched control subjects, all non-smokers. All subjects underwent spirometry, whole body plethysmography, carbon monoxide diffusing capacity, and respiratory muscle strength. Acromegalic patients also performed high-resolution computed tomography (HRCT). RESULTS: Most patients were female (65%), with a mean age of 52.5 ± 13 years. Acromegalic patients showed lower values of maximum expiratory pressure (55.9 ± 17.1 vs. 103.7 ± 19.2%; p < 0.001) and maximum inspiratory pressure (71.4 ± 27.8 vs. 85.3 ± 24.1%; p = 0.005) compared to control subjects. The values of forced vital capacity (107.1 ± 15.9 vs. 98.9 ± 21.4%; p = 0.028), total lung capacity - TLC (107.3 ± 12.9 vs. 93.7 ± 7.60%; p = 0.002), residual volume (114.1 ± 22.7 vs. 90.0 ± 14.6%; p < 0.001), and airways' resistance (3.82 vs. 2.31 cmH2O/L/s; p = 0.039) were greater in acromegalic patients than in control subjects. The difference between the TLC measured by plethysmography and the VA (alveolar volume) measured during the DLCO maneuver was higher in acromegalic patients than in control subjects (0.69 ± 0.46 vs. 0.19 ± 0.61 L; p = 0.021). The main findings in HRCT in acromegalic patients were air trapping, airway calcification and bronchiectasis, which were observed in 60%, 40% and 35% of cases, respectively. There was no significant correlation between the levels of growth hormone and insulin-like growth factor I, the lung function and the air trapping. CONCLUSIONS: Acromegalic patients show changes consistent with the involvement of the small airways and ventilation inhomogeneity, both in terms of lung function and structure. However, air trapping cannot be explained either by hormone levels or changes in lung function.

ZAC1 and SSTR2 are downregulated in non-functioning pituitary adenomas but not in somatotropinomas.

INTRODUCTION: There are few data regarding ZAC1 expression in clinically non-functioning pituitary adenomas (NFPA). Because somatotropinomas and NFPA behave differently with respect to tumor shrinkage during somatostatin analogs (SA) therapy, we sought to compare the ZAC1 and somatostatin receptor (sstr) types 1, 2, 3 and 5 mRNA expression in these two pituitary adenoma subtypes and in normal human pituitaries. METHODS: ZAC1 and SSTR mRNA expression levels were evaluated using real-time RT-PCR (TaqMan) in 20 NFPA and compared with the expression levels in 23 somatotropinomas and five normal pituitaries. The NFPA invasiveness was evaluated using magnetic resonance imaging with Hardy's modified criteria. Ki-67 and p53 were evaluated using immunohistochemistry. RESULTS: A total of 20 patients with NFPA [6 males, median age 56 years (range: 30-78)], 23 with acromegaly [12 males, median age 43 years (range: 24-57)] and five normal pituitaries [4 males, median age 48 years (range: 36-54)] were included. Four of the patients (20%) had Hardy's grade 2 tumors; all of the others had Hardy's grade 3 tumors. The Ki-67 median expression was 2.35 (range: 0.2-9.23), and only four of the tumors (20%) were positive for p53. The ZAC1 mRNA expression was significantly lower in NFPA than in somatotropinomas and in normal pituitaries (p<0.001 for both), as well as the SSTR2 (p=0.001 and 0.01, respectively). The SSTR3 expression was higher in the NFPA than in the somatotropinomas and in the normal pituitaries (p=0.03 and 0.02, respectively). No correlation was found between the ZAC1 mRNA expression and the tumor invasiveness, Ki-67 and p53. CONCLUSION: ZAC1 and SSTR2 are underexpressed and SSTR3 is overexpressed in NFPA compared to those in somatotropinomas and in normal pituitaries, which might explain the lack of tumor shrinkage that is observed in response to commercially available SA therapy in patients with NFPA.

Functional evaluation of the joints in acromegalic patients and associated factors.

This study aims to evaluate the presence of arthropathy in the large peripheral joints most commonly affected in acromegaly and to classify the severity according to the functional assessment of each joint to identify any factor that could predict the development of arthropathy and its level of severity. Seventy-one acromegalic patients were interviewed and underwent a physical examination of the knees, hips, and shoulders to identify the presence of arthropathy. The disease was functionally classified as more severe or less severe, according to a specific functional scale. We studied 21 males (29.5%) and 50 females (70.5%) with a mean age of 49.5 ± 14.5 years. Arthropathy in the studied joints was observed in 40 patients (prevalence of 56%), and a statistically significant association with the presence of arthropathy was observed for three of the evaluated factors: increased body mass index (BMI), older age at diagnosis of acromegaly, and female gender. There was no association with disease control or other factors related to acromegaly. We classified 19 patients as having more functionally severe arthropathy and identified two factors associated with its development: increased BMI and lower levels of insulin-like growth factor type I. The relationship of factors such as female sex and BMI, which are also related to osteoarthritis, with arthropathy in acromegalic patients suggested a high prevalence of irreversible joint disease present at diagnosis of acromegaly. We highlight the BMI, which was associated with either the presence of arthropathy or more severe arthropathy, which demonstrates the importance of body weight control in the management of acromegalic patients.

Acromegaly has a negative influence on trabecular bone, but not on cortical bone, as assessed by high-resolution peripheral quantitative computed tomography.

INTRODUCTION: Acromegaly is one of the causes of secondary osteoporosis, although studies of bone mineral density (BMD) have yielded conflicting results and none of them have evaluated the bone properties. OBJECTIVES AND PATIENTS: Our objective was to correlate, in a cohort of 82 acromegalic patients, BMD and bone microarchitecture, using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography, with the presence of type 2 diabetes mellitus (T2DM), disease activity, and gonadal status and to compare these bone parameters between 45 eugonadal acromegalic patients and 45 healthy controls. RESULTS: Acromegalic patients with T2DM had lower trabecular density and trabecular bone volume to tissue volume ratio in the distal tibia. Patients with active acromegaly exhibited a higher BMD and T-score in the lumbar spine (P = .02 for both) and a higher cortical density in the distal tibia when compared with those with controlled acromegaly (P = .001). After multiple linear regression (including age, presence of T2DM, acromegaly activity, and gonadal status), eugonadism remained the main determinant of bone parameters. The 45 acromegalic patients with eugonadism were compared with 45 age- and sex-matched controls and exhibited lower trabecular densities and impaired microstructures. CONCLUSIONS: Acromegaly appears to have a deleterious effect on trabecular bone microarchitecture, and in this specific population, the gonadal status might be more important than T2DM or acromegaly activity in determining bone health. High-resolution peripheral quantitative computed tomography seems promising for evaluating acromegalic bone properties and for addressing the limitations posed by dual-energy x-ray absorptiometry.

Prevalence of thyroid diseases in patients with acromegaly: experience of a Brazilian center.

OBJECTIVES: Acromegaly is frequently associated with thyroid diseases. In this study, we evaluated the frequency of thyroid disorders in a series of acromegalic patients. SUBJECTS AND METHODS: We evaluated 106 acromegalic patients using thyroid ultrasonography (US) and measurements of GH, IGF-I, free T4, TSH and anti-thyroperoxidase antibody levels. IGF-I was expressed in mass units and age-related standard deviation scores (SD-scores). Fine-needle aspiration biopsy (FNAB) was performed on thyroid nodules with a diameter greater than one centimeter or with suspicious characteristics. RESULTS: Thyroid disorders were found in 75 patients. Eleven patients had diffuse goiter, 42 patients had nodular goiter, and 22 patients had unspecific morphological abnormalities. Four patients (3.8%) had thyroid carcinoma. Considering the patients with diffuse or nodular goiter, thyroid volume was greater in patients with active acromegaly, and was positively correlated with GH, IGF-I, and IGF-I SD-score. CONCLUSIONS: Our study confirmed that benign thyroid diseases are frequent in acromegalic patients. The prevalence of thyroid cancer was higher than in the overall population. We suggest that thyroid US should be routinely performed in patients with acromegaly.